Individuals with suspected rare genetic disorders often undergo multiple clinical evaluations, imaging studies, laboratory tests and genetic tests, to find a possible answer over a prolonged period of multiple years. Addressing this diagnostic odyssey thus have substantial clinical, psychosocial, and economic benefits. Many rare genetic diseases have distinctive facial features, which can be used by artificial intelligence algorithms to facilitate clinical diagnosis, in prioritizing candidate diseases to be further examined by lab tests or genetic assays, or in helping the phenotype-driven reinterpretation of genome/exome sequencing data. However, existing methods using frontal facial photo were built on conventional Convolutional Neural Networks (CNNs), rely exclusively on facial images, and cannot capture non-facial phenotypic traits and demographic information essential for guiding accurate diagnoses. Here we introduce GestaltMML, a multimodal machine learning (MML) approach solely based on the Transformer architecture. It integrates the facial images, demographic information (age, sex, ethnicity), and clinical notes of patients to improve prediction accuracy. Furthermore, we also introduce GestaltGPT, a GPT-based methodology with few-short learning capacities that exclusively harnesses textual inputs using a range of large language models (LLMs) including Llama 2, GPT-J and Falcon. We evaluated these methods on a diverse range of datasets, including 449 diseases from the GestaltMatcher Database, several in-house datasets on Beckwith-Wiedemann syndrome, Sotos syndrome, NAA10-related syndrome (neurodevelopmental syndrome) and others. Our results suggest that GestaltMML/GestaltGPT effectively incorporate multiple modalities of data, greatly narrow down candidate genetic diagnosis of rare diseases, and may facilitate the reinterpretation of genome/exome sequencing data.
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Accurate and reliable registration of longitudinal spine images is essential for assessment of disease progression and surgical outcome. Implementing a fully automatic and robust registration is crucial for clinical use, however, it is challenging due to substantial change in shape and appearance due to lesions. In this paper we present a novel method to automatically align longitudinal spine CTs and accurately assess lesion progression. Our method follows a two-step pipeline where vertebrae are first automatically localized, labeled and 3D surfaces are generated using a deep learning model, then longitudinally aligned using a Gaussian mixture model surface registration. We tested our approach on 37 vertebrae, from 5 patients, with baseline CTs and 3, 6, and 12 months follow-ups leading to 111 registrations. Our experiment showed accurate registration with an average Hausdorff distance of 0.65 mm and average Dice score of 0.92.
Eulerian Formulation of the Tensor-Based Morphology Equations for Strain-Based Blood Damage Modeling
The development of blood-handling medical devices, such as ventricular assist devices, requires the analysis of their biocompatibility. Among other aspects, this includes hemolysis, i.e., red blood cell damage. For this purpose, computational fluid dynamics (CFD) methods are employed to predict blood flow in prototypes. The most basic hemolysis models directly estimate red blood cell damage from fluid stress in the resulting flow field. More advanced models explicitly resolve cell deformation. On the downside, these models are typically written in a Lagrangian formulation, i.e., they require pathline tracking. We present a new Eulerian description of cell deformation, enabling the evaluation of the solution across the whole domain. The resulting hemolysis model can be applied to any converged CFD simulation due to one-way coupling with the fluid velocity field. We discuss the efficient numerical treatment of the model equations in a stabilized finite element context. We validate the model by comparison to the original Lagrangian formulation in selected benchmark flows. Two more complex test cases demonstrate the method's capabilities in real-world applications. The results highlight the advantages over previous hemolysis models. In conclusion, the model holds great potential for the design process of future generations of medical devices.
In medical and epidemiological studies, one of the most common settings is studying the effect of a treatment on a time-to-event outcome, where the time-to-event might be censored before end of study. A common parameter of interest in such a setting is the marginal hazard ratio (MHR). When a study is based on observational data, propensity score (PS) based methods are often used, in an attempt to make the treatment groups comparable despite having a non-randomized treatment. Previous studies have shown censoring to be a factor that induces bias when using PS based estimators. In this paper we study the magnitude of the bias under different rates of non-informative censoring when estimating MHR using PS weighting or PS matching. A bias correction involving the probability of event is suggested and compared to conventional PS based methods.
Addressing the critical shortage of mental health resources for effective screening, diagnosis, and treatment remains a significant challenge. This scarcity underscores the need for innovative solutions, particularly in enhancing the accessibility and efficacy of therapeutic support. Embodied agents with advanced interactive capabilities emerge as a promising and cost-effective supplement to traditional caregiving methods. Crucial to these agents' effectiveness is their ability to simulate non-verbal behaviors, like backchannels, that are pivotal in establishing rapport and understanding in therapeutic contexts but remain under-explored. To improve the rapport-building capabilities of embodied agents we annotated backchannel smiles in videos of intimate face-to-face conversations over topics such as mental health, illness, and relationships. We hypothesized that both speaker and listener behaviors affect the duration and intensity of backchannel smiles. Using cues from speech prosody and language along with the demographics of the speaker and listener, we found them to contain significant predictors of the intensity of backchannel smiles. Based on our findings, we introduce backchannel smile production in embodied agents as a generation problem. Our attention-based generative model suggests that listener information offers performance improvements over the baseline speaker-centric generation approach. Conditioned generation using the significant predictors of smile intensity provides statistically significant improvements in empirical measures of generation quality. Our user study by transferring generated smiles to an embodied agent suggests that agent with backchannel smiles is perceived to be more human-like and is an attractive alternative for non-personal conversations over agent without backchannel smiles.
In the clinical treatment of mood disorders, the complex behavioral symptoms presented by patients and variability of patient response to particular medication classes can create difficulties in providing fast and reliable treatment when standard diagnostic and prescription methods are used. Increasingly, the incorporation of physiological information such as neuroimaging scans and derivatives into the clinical process promises to alleviate some of the uncertainty surrounding this process. Particularly, if neural features can help to identify patients who may not respond to standard courses of anti-depressants or mood stabilizers, clinicians may elect to avoid lengthy and side-effect-laden treatments and seek out a different, more effective course that might otherwise not have been under consideration. Previously, approaches for the derivation of relevant neuroimaging features work at only one scale in the data, potentially limiting the depth of information available for clinical decision support. In this work, we show that the utilization of multi spatial scale neuroimaging features - particularly resting state functional networks and functional network connectivity measures - provide a rich and robust basis for the identification of relevant medication class and non-responders in the treatment of mood disorders. We demonstrate that the generated features, along with a novel approach for fast and automated feature selection, can support high accuracy rates in the identification of medication class and non-responders as well as the identification of novel, multi-scale biomarkers.
With the proliferation of research means and computational methodologies, published biomedical literature is growing exponentially in numbers and volume. Cancer cell lines are frequently used models in biological and medical research that are currently applied for a wide range of purposes, from studies of cellular mechanisms to drug development, which has led to a wealth of related data and publications. Sifting through large quantities of text to gather relevant information on the cell lines of interest is tedious and extremely slow when performed by humans. Hence, novel computational information extraction and correlation mechanisms are required to boost meaningful knowledge extraction. In this work, we present the design, implementation and application of a novel data extraction and exploration system. This system extracts deep semantic relations between textual entities from scientific literature to enrich existing structured clinical data in the domain of cancer cell lines. We introduce a new public data exploration portal, which enables automatic linking of genomic copy number variants plots with ranked, related entities such as affected genes. Each relation is accompanied by literature-derived evidences, allowing for deep, yet rapid, literature search, using existing structured data as a springboard. Our system is publicly available on the web at //cancercelllines.org
In order to optimize the radiotherapy delivery for cancer treatment, especially when dealing with complex treatments such as Total Marrow and Lymph Node Irradiation (TMLI), the accurate contouring of the Planning Target Volume (PTV) is crucial. Unfortunately, relying on manual contouring for such treatments is time-consuming and prone to errors. In this paper, we investigate the application of Deep Learning (DL) to automate the segmentation of the PTV in TMLI treatment, building upon previous work that introduced a solution to this problem based on a 2D U-Net model. We extend the previous research (i) by employing the nnU-Net framework to develop both 2D and 3D U-Net models and (ii) by evaluating the trained models on the PTV with the exclusion of bones, which consist mainly of lymp-nodes and represent the most challenging region of the target volume to segment. Our result show that the introduction of nnU-NET framework led to statistically significant improvement in the segmentation performance. In addition, the analysis on the PTV after the exclusion of bones showed that the models are quite robust also on the most challenging areas of the target volume. Overall, our study is a significant step forward in the application of DL in a complex radiotherapy treatment such as TMLI, offering a viable and scalable solution to increase the number of patients who can benefit from this treatment.
Electronic health records (EHR) is an inherently multimodal register of the patient's health status characterized by static data and multivariate time series (MTS). While MTS are a valuable tool for clinical prediction, their fusion with other data modalities can possibly result in more thorough insights and more accurate results. Deep neural networks (DNNs) have emerged as fundamental tools for identifying and defining underlying patterns in the healthcare domain. However, fundamental improvements in interpretability are needed for DNN models to be widely used in the clinical setting. In this study, we present an approach built on a collection of interpretable multimodal data-driven models that may anticipate and understand the emergence of antimicrobial multidrug resistance (AMR) germs in the intensive care unit (ICU) of the University Hospital of Fuenlabrada (Madrid, Spain). The profile and initial health status of the patient are modeled using static variables, while the evolution of the patient's health status during the ICU stay is modeled using several MTS, including mechanical ventilation and antibiotics intake. The multimodal DNNs models proposed in this paper include interpretable principles in addition to being effective at predicting AMR and providing an explainable prediction support system for AMR in the ICU. Furthermore, our proposed methodology based on multimodal models and interpretability schemes can be leveraged in additional clinical problems dealing with EHR data, broadening the impact and applicability of our results.
Due to the lack of quality annotation in medical imaging community, semi-supervised learning methods are highly valued in image semantic segmentation tasks. In this paper, an advanced consistency-aware pseudo-label-based self-ensembling approach is presented to fully utilize the power of Vision Transformer(ViT) and Convolutional Neural Network(CNN) in semi-supervised learning. Our proposed framework consists of a feature-learning module which is enhanced by ViT and CNN mutually, and a guidance module which is robust for consistency-aware purposes. The pseudo labels are inferred and utilized recurrently and separately by views of CNN and ViT in the feature-learning module to expand the data set and are beneficial to each other. Meanwhile, a perturbation scheme is designed for the feature-learning module, and averaging network weight is utilized to develop the guidance module. By doing so, the framework combines the feature-learning strength of CNN and ViT, strengthens the performance via dual-view co-training, and enables consistency-aware supervision in a semi-supervised manner. A topological exploration of all alternative supervision modes with CNN and ViT are detailed validated, demonstrating the most promising performance and specific setting of our method on semi-supervised medical image segmentation tasks. Experimental results show that the proposed method achieves state-of-the-art performance on a public benchmark data set with a variety of metrics. The code is publicly available.
Understanding causality helps to structure interventions to achieve specific goals and enables predictions under interventions. With the growing importance of learning causal relationships, causal discovery tasks have transitioned from using traditional methods to infer potential causal structures from observational data to the field of pattern recognition involved in deep learning. The rapid accumulation of massive data promotes the emergence of causal search methods with brilliant scalability. Existing summaries of causal discovery methods mainly focus on traditional methods based on constraints, scores and FCMs, there is a lack of perfect sorting and elaboration for deep learning-based methods, also lacking some considers and exploration of causal discovery methods from the perspective of variable paradigms. Therefore, we divide the possible causal discovery tasks into three types according to the variable paradigm and give the definitions of the three tasks respectively, define and instantiate the relevant datasets for each task and the final causal model constructed at the same time, then reviews the main existing causal discovery methods for different tasks. Finally, we propose some roadmaps from different perspectives for the current research gaps in the field of causal discovery and point out future research directions.
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