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

Hypertension is a global health concern with an increasing prevalence, underscoring the need for effective monitoring and analysis of blood pressure (BP) dynamics. We analyzed a substantial BP dataset comprising 75,636,128 records from 2,054,462 unique patients collected between 2000 and 2022 at Emory Healthcare in Georgia, USA, representing a demographically diverse population. We examined and compared population-wide statistics of bivariate changes in systolic BP (SBP) and diastolic BP (DBP) across sex, age, and race/ethnicity. The analysis revealed that males have higher BP levels than females and exhibit a distinct BP profile with age. Notably, average SBP consistently rises with age, whereas average DBP peaks in the forties age group. Among the ethnic groups studied, Blacks have marginally higher BPs and a greater standard deviation. We also discovered a significant correlation between SBP and DBP at the population level, a phenomenon not previously researched. These results emphasize the importance of demography-specific BP analysis for clinical diagnosis and provide valuable insights for developing personalized, demography-specific healthcare interventions.

Retrieval augmented generation (RAG) provides the capability to constrain generative model outputs, and mitigate the possibility of hallucination, by providing relevant in-context text. The number of tokens a generative large language model (LLM) can incorporate as context is finite, thus limiting the volume of knowledge from which to generate an answer. We propose a two-layer RAG framework for query-focused answer generation and evaluate a proof-of-concept for this framework in the context of query-focused summary generation from social media forums, focusing on emerging drug-related information. The evaluations demonstrate the effectiveness of the two-layer framework in resource constrained settings to enable researchers in obtaining near real-time data from users.

To develop a harmonized multicenter clinical and electroencephalography (EEG) database for acute hypoxic-ischemic brain injury research involving patients with cardiac arrest., info:eu-repo/semantics/published

Blind source separation (BSS) techniques have revealed to be promising approaches for, among other, biomedical signal processing applications. Specifically, for the noninvasive extraction of fetal cardiac signals from maternal abdominal recordings, where conventional filtering schemes have failed to extract the complete fetal ECG components. From previous studies, it is now believed that a carefully selected array of electrodes well-placed over the abdomen of a pregnant woman contains the required `information' for BSS, to extract the complete fetal components. Based on this idea, in previous works array recording systems and sensor selection strategies based on the Mutual Information (MI) criterion have been developed. In this paper the previous works have been extended, by considering the 3-dimensional aspects of the cardiac electrical activity. The proposed method has been tested on simulated and real maternal abdominal recordings. The results show that the new sensor selection strategy together with the MI criterion, can be effectively used to select the channels containing the most `information' concerning the fetal ECG components from an array of 72 recordings. The method is hence believed to be useful for the selection of the most informative channels in online applications, considering the different fetal positions and movements.

Objective: Gaussian Processes (GP)-based filters, which have been effectively used for various applications including electrocardiogram (ECG) filtering can be computationally demanding and the choice of their hyperparameters is typically ad hoc. Methods: We develop a data-driven GP filter to address both issues, using the notion of the ECG phase domain -- a time-warped representation of the ECG beats onto a fixed number of samples and aligned R-peaks, which is assumed to follow a Gaussian distribution. Under this assumption, the computation of the sample mean and covariance matrix is simplified, enabling an efficient implementation of the GP filter in a data-driven manner, with no ad hoc hyperparameters. The proposed filter is evaluated and compared with a state-of-the-art wavelet-based filter, on the PhysioNet QT Database. The performance is evaluated by measuring the signal-to-noise ratio (SNR) improvement of the filter at SNR levels ranging from -5 to 30dB, in 5dB steps, using additive noise. For a clinical evaluation, the error between the estimated QT-intervals of the original and filtered signals is measured and compared with the benchmark filter. Results: It is shown that the proposed GP filter outperforms the benchmark filter for all the tested noise levels. It also outperforms the state-of-the-art filter in terms of QT-interval estimation error bias and variance. Conclusion: The proposed GP filter is a versatile technique for preprocessing the ECG in clinical and research applications, is applicable to ECG of arbitrary lengths and sampling frequencies, and provides confidence intervals for its performance.

Multimodality and multichannel monitoring have become increasingly popular and accessible in engineering, Internet of Things, wearable devices, and biomedical applications. In these contexts, given the diverse and complex nature of data modalities, the relevance of sensor fusion and sensor selection is heightened. In this note, we study the problem of channel/modality selection and fusion from an information theoretical perspective, focusing on linear and nonlinear signal mixtures corrupted by additive Gaussian noise. We revisit and extend well-known properties of linear noisy data models in estimation and information theory, providing practical insights that assist in the decision-making process between channel (modality) selection and fusion. Using the notion of multichannel signal-to-noise ratio, we derive conditions under which, selection or fusion of multimodal/multichannel data can be beneficial or redundant. This contributes to a better understanding of how to optimize sensor fusion and selection from a theoretical standpoint, aiming to enhance multimodal/multichannel system design, especially for biomedical multichannel/multimodal applications.

In this study, we present a deep learning framework designed to integrate with our previously developed system that facilitates large-scale 1D fetal Doppler data collection, aiming to enhance data quality. This system, tailored for traditional Indigenous midwives in low-resource communities, leverages a cost-effective Android phone to improve the quality of recorded signals. We have shown that the Doppler data can be used to identify fetal growth restriction, hypertension, and other concerning issues during pregnancy. However, the quality of the signal is dependent on many factors, including radio frequency interference, position of the fetus, maternal body habitus, and usage of the Doppler by the birth attendants. In order to provide instant feedback to allow correction of the data at source, a signal quality metric is required that can run in real-time on the mobile phone. In this study, 191 DUS signals with durations mainly in the range between 5 to 10 minutes were evaluated for quality and classified into five categories: Good, Poor, (Radiofrequency) Interference, Talking, and Silent, at a resolution of 3.75 seconds. A deep neural network was trained on each 3.75-second segment from these recordings and validated using five-fold cross-validation. An average micro F1 = 97.4\% and macro F1 = 94.2\% were achieved, with F1 = 99.2\% for `Good' quality data. These results indicate that the algorithm, which will now be implemented in the midwives' app, should allow a significant increase in the quality of data at the time of capture., Comment: Extended Abstract presented at Machine Learning for Health (ML4H) symposium 2023, December 10th, 2023, New Orleans, United States, 11 pages

Machine learning (ML) and deep learning models are extensively used for parameter optimization and regression problems. However, not all inverse problems in ML are ``identifiable,'' indicating that model parameters may not be uniquely determined from the available data and the data model's input-output relationship. In this study, we investigate the notion of model parameter identifiability through a case study focused on parameter estimation from motion sensor data. Utilizing a bipedal-spring mass human walk dynamics model, we generate synthetic data representing diverse gait patterns and conditions. Employing a deep neural network, we attempt to estimate subject-wise parameters, including mass, stiffness, and equilibrium leg length. The results show that while certain parameters can be identified from the observation data, others remain unidentifiable, highlighting that unidentifiability is an intrinsic limitation of the experimental setup, necessitating a change in data collection and experimental scenarios. Beyond this specific case study, the concept of identifiability has broader implications in ML and deep learning. Addressing unidentifiability requires proven identifiable models (with theoretical support), multimodal data fusion techniques, and advancements in model-based machine learning. Understanding and resolving unidentifiability challenges will lead to more reliable and accurate applications across diverse domains, transcending mere model convergence and enhancing the reliability of machine learning models.

Cardiovascular diseases are a major cause of mortality globally, and electrocardiograms (ECGs) are crucial for diagnosing them. Traditionally, ECGs are printed on paper. However, these printouts, even when scanned, are incompatible with advanced ECG diagnosis software that require time-series data. Digitizing ECG images is vital for training machine learning models in ECG diagnosis and to leverage the extensive global archives collected over decades. Deep learning models for image processing are promising in this regard, although the lack of clinical ECG archives with reference time-series data is challenging. Data augmentation techniques using realistic generative data models provide a solution. We introduce ECG-Image-Kit, an open-source toolbox for generating synthetic multi-lead ECG images with realistic artifacts from time-series data. The tool synthesizes ECG images from real time-series data, applying distortions like text artifacts, wrinkles, and creases on a standard ECG paper background. As a case study, we used ECG-Image-Kit to create a dataset of 21,801 ECG images from the PhysioNet QT database. We developed and trained a combination of a traditional computer vision and deep neural network model on this dataset to convert synthetic images into time-series data for evaluation. We assessed digitization quality by calculating the signal-to-noise ratio (SNR) and compared clinical parameters like QRS width, RR, and QT intervals recovered from this pipeline, with the ground truth extracted from ECG time-series. The results show that this deep learning pipeline accurately digitizes paper ECGs, maintaining clinical parameters, and highlights a generative approach to digitization. This toolbox currently supports data augmentation for the 2024 PhysioNet Challenge, focusing on digitizing and classifying paper ECG images.

Regular blood pressure (BP) monitoring in clinical and ambulatory settings plays a crucial role in the prevention, diagnosis, treatment, and management of cardiovascular diseases. Recently, the widespread adoption of ambulatory BP measurement devices has been driven predominantly by the increased prevalence of hypertension and its associated risks and clinical conditions. Recent guidelines advocate for regular BP monitoring as part of regular clinical visits or even at home. This increased utilization of BP measurement technologies has brought up significant concerns, regarding the accuracy of reported BP values across settings. In this survey, focusing mainly on cuff-based BP monitoring technologies, we highlight how BP measurements can demonstrate substantial biases and variances due to factors such as measurement and device errors, demographics, and body habitus. With these inherent biases, the development of a new generation of cuff-based BP devices which use artificial-intelligence (AI) has significant potential. We present future avenues where AI-assisted technologies can leverage the extensive clinical literature on BP-related studies together with the large collections of BP records available in electronic health records. These resources can be combined with machine learning approaches, including deep learning and Bayesian inference, to remove BP measurement biases and to provide individualized BP-related cardiovascular risk indexes.

Objective: Murmurs are abnormal heart sounds, identified by experts through cardiac auscultation. The murmur grade, a quantitative measure of the murmur intensity, is strongly correlated with the patient's clinical condition. This work aims to estimate each patient's murmur grade (i.e., absent, soft, loud) from multiple auscultation location phonocardiograms (PCGs) of a large population of pediatric patients from a low-resource rural area. Methods: The Mel spectrogram representation of each PCG recording is given to an ensemble of 15 convolutional residual neural networks with channel-wise attention mechanisms to classify each PCG recording. The final murmur grade for each patient is derived based on the proposed decision rule and considering all estimated labels for available recordings. The proposed method is cross-validated on a dataset consisting of 3456 PCG recordings from 1007 patients using a stratified ten-fold cross-validation. Additionally, the method was tested on a hidden test set comprised of 1538 PCG recordings from 442 patients. Results: The overall cross-validation performances for patient-level murmur gradings are 86.3% and 81.6% in terms of the unweighted average of sensitivities and F1-scores, respectively. The sensitivities (and F1-scores) for absent, soft, and loud murmurs are 90.7% (93.6%), 75.8% (66.8%), and 92.3% (84.2%), respectively. On the test set, the algorithm achieves an unweighted average of sensitivities of 80.4% and an F1-score of 75.8%. Conclusions: This study provides a potential approach for algorithmic pre-screening in low-resource settings with relatively high expert screening costs. Significance: The proposed method represents a significant step beyond detection of murmurs, providing characterization of intensity which may provide a enhanced classification of clinical outcomes.

Stethoscope-recorded chest sounds provide the opportunity for remote cardio-respiratory health monitoring of neonates. However, reliable monitoring requires high-quality heart and lung sounds. This paper presents novel Non-negative Matrix Factorisation (NMF) and Non-negative Matrix Co-Factorisation (NMCF) methods for neonatal chest sound separation. To assess these methods and compare with existing single-source separation methods, an artificial mixture dataset was generated comprising of heart, lung and noise sounds. Signal-to-noise ratios were then calculated for these artificial mixtures. These methods were also tested on real-world noisy neonatal chest sounds and assessed based on vital sign estimation error and a signal quality score of 1-5 developed in our previous works. Additionally, the computational cost of all methods was assessed to determine the applicability for real-time processing. Overall, both the proposed NMF and NMCF methods outperform the next best existing method by 2.7dB to 11.6dB for the artificial dataset and 0.40 to 1.12 signal quality improvement for the real-world dataset. The median processing time for the sound separation of a 10s recording was found to be 28.3s for NMCF and 342ms for NMF. Because of stable and robust performance, we believe that our proposed methods are useful to denoise neonatal heart and lung sound in a real-world environment. Codes for proposed and existing methods can be found at: https://github.com/egrooby-monash/Heart-and-Lung-Sound-Separation., Comment: 12 pages, 4 figures, 3 tables. Paper submitted and under review for possible publication in IEEE

Objective: To determine if a realistic, but computationally efficient model of the electrocardiogram can be used to pre-train a deep neural network (DNN) with a wide range of morphologies and abnormalities specific to a given condition - T-wave Alternans (TWA) as a result of Post-Traumatic Stress Disorder, or PTSD - and significantly boost performance on a small database of rare individuals. Approach: Using a previously validated artificial ECG model, we generated 180,000 artificial ECGs with or without significant TWA, with varying heart rate, breathing rate, TWA amplitude, and ECG morphology. A DNN, trained on over 70,000 patients to classify 25 different rhythms, was modified the output layer to a binary class (TWA or no-TWA, or equivalently, PTSD or no-PTSD), and transfer learning was performed on the artificial ECG. In a final transfer learning step, the DNN was trained and cross-validated on ECG from 12 PTSD and 24 controls for all combinations of using the three databases. Main results: The best performing approach (AUROC = 0.77, Accuracy = 0.72, F1-score = 0.64) was found by performing both transfer learning steps, using the pre-trained arrhythmia DNN, the artificial data and the real PTSD-related ECG data. Removing the artificial data from training led to the largest drop in performance. Removing the arrhythmia data from training provided a modest, but significant, drop in performance. The final model showed no significant drop in performance on the artificial data, indicating no overfitting. Significance: In healthcare, it is common to only have a small collection of high-quality data and labels, or a larger database with much lower quality (and less relevant) labels. The paradigm presented here, involving model-based performance boosting, provides a solution through transfer learning on a large realistic artificial database, and a partially relevant real database., Comment: Presented at the University of Chicago Data Science Institute Dec 6th 2021. See: https://www.youtube.com/watch?v=B36CGi8ODCw and https://datascience.uchicago.edu/events/dss-gari-clifford

The fetal electrocardiogram (fECG) was first recorded from the maternal abdominal surface in the early 1900s. During the past fifty years, the most advanced electronics technologies and signal processing algorithms have been used to convert noninvasive fetal electrocardiography into a reliable technology for fetal cardiac monitoring. In this chapter, the major signal processing techniques, which have been developed for the modeling, extraction and analysis of the fECG from noninvasive maternal abdominal recordings are reviewed and compared with one another in detail. The major topics of the chapter include: 1) the electrophysiology of the fECG from the signal processing viewpoint, 2) the mathematical model of the maternal volume conduction media and the waveform models of the fECG acquired from body surface leads, 3) the signal acquisition requirements, 4) model-based techniques for fECG noise and interference cancellation, including adaptive filters and semi-blind source separation techniques, and 5) recent algorithmic advances for fetal motion tracking and online fECG extraction from few number of channels.

Digital stethoscopes in combination with telehealth allow chest sounds to be easily collected and transmitted for remote monitoring and diagnosis. Chest sounds contain important information about a newborn's cardio-respiratory health. However, low-quality recordings complicate the remote monitoring and diagnosis. In this study, a new method is proposed to objectively and automatically assess heart and lung signal quality on a 5-level scale in real-time and to assess the effect of signal quality on vital sign estimation. For the evaluation, a total of 207 10s long chest sounds were taken from 119 preterm and full-term babies. Thirty of the recordings from ten subjects were obtained with synchronous vital signs from the Neonatal Intensive Care Unit (NICU) based on electrocardiogram recordings. As reference, seven annotators independently assessed the signal quality. For automatic quality classification, 400 features were extracted from the chest sounds. After feature selection using minimum redundancy and maximum relevancy algorithm, class balancing, and hyper-parameter optimization, a variety of multi-class and ordinal classification and regression algorithms were trained. Then, heart rate and breathing rate were automatically estimated from the chest sounds using adapted pre-existing methods. The results of subject-wise leave-one-out cross-validation show that the best-performing models had a mean squared error (MSE) of 0.49 and 0.61, and balanced accuracy of 57% and 51% for heart and lung qualities, respectively. The best-performing models for real-time analysis (<200ms) had MSE of 0.459 and 0.67, and balanced accuracy of 57% and 46%, respectively. Our experimental results underscore that increasing the signal quality leads to a reduction in vital sign error, with only high-quality recordings having a mean absolute error of less than 5 beats per minute, as required for clinical usage., Comment: 13 pages, 8 figures, 3 tables. Paper submitted and under review in IEEE Access

Objective: Mixtures of temporally nonstationary signals are very common in biomedical applications. The nonstationarity of the source signals can be used as a discriminative property for signal separation. Herein, a semi-blind source separation algorithm is proposed for the extraction of temporally nonstationary components from linear multichannel mixtures of signals and noises. Methods: A hypothesis test is proposed for the detection and fusion of temporally nonstationary events, by using ad hoc indexes for monitoring the first and second order statistics of the innovation process. As proof of concept, the general framework is customized and tested over noninvasive fetal cardiac recordings acquired from the maternal abdomen, over publicly available datasets, using two types of nonstationarity detectors: 1) a local power variations detector, and 2) a model-deviations detector using the innovation process properties of an extended Kalman filter. Results: The performance of the proposed method is assessed in presence of white and colored noise, in different signal-to-noise ratios. Conclusion and Significance: The proposed scheme is general and it can be used for the extraction of nonstationary events and sample deviations from a presumed model in multivariate data, which is a recurrent problem in many machine learning applications., Comment: 9 pages and 5 figures

Cardiac auscultation is one of the most cost-effective techniques used to detect and identify many heart conditions. Computer-assisted decision systems based on auscultation can support physicians in their decisions. Unfortunately, the application of such systems in clinical trials is still minimal since most of them only aim to detect the presence of extra or abnormal waves in the phonocardiogram signal, i.e., only a binary ground truth variable (normal vs abnormal) is provided. This is mainly due to the lack of large publicly available datasets, where a more detailed description of such abnormal waves (e.g., cardiac murmurs) exists. To pave the way to more effective research on healthcare recommendation systems based on auscultation, our team has prepared the currently largest pediatric heart sound dataset. A total of 5282 recordings have been collected from the four main auscultation locations of 1568 patients, in the process, 215780 heart sounds have been manually annotated. Furthermore, and for the first time, each cardiac murmur has been manually annotated by an expert annotator according to its timing, shape, pitch, grading, and quality. In addition, the auscultation locations where the murmur is present were identified as well as the auscultation location where the murmur is detected more intensively. Such detailed description for a relatively large number of heart sounds may pave the way for new machine learning algorithms with a real-world application for the detection and analysis of murmur waves for diagnostic purposes., Comment: 12 pages, 6 tables, 8 figures, in IEEE Journal of Biomedical and Health Informatics

The extraction of nonstationary signals from blind and semi-blind multivariate observations is a recurrent problem. Numerous algorithms have been developed for this problem, which are based on the exact or approximate joint diagonalization of second or higher order cumulant matrices/tensors of multichannel data. While a great body of research has been dedicated to joint diagonalization algorithms, the selection of the diagonalized matrix/tensor set remains highly problem-specific. Herein, various methods for nonstationarity identification are reviewed and a new general framework based on hypothesis testing is proposed, which results in a classification/clustering perspective to semi-blind source separation of nonstationary components. The proposed method is applied to noninvasive fetal ECG extraction, as case study., Comment: 5 pages

Nowadays, shallow and deep Neural Networks (NNs) have vast applications including biomedical engineering, image processing, computer vision, and speech recognition. Many researchers have developed hardware accelerators including field-programmable gate arrays (FPGAs) for implementing high-performance and energy efficient NNs. Apparently, the hardware architecture design process is specific and time-consuming for each NN. Therefore, a systematic way to design, implement and optimize NNs is highly demanded. The paper presents a systematic approach to implement state-space models in register transfer level (RTL), with special interest for NN implementation. The proposed design flow is based on the iterative nature of state-space models and the analogy between state-space formulations and finite-state machines. The method can be used in linear/nonlinear and time-varying/time-invariant systems. It can also be used to implement either intrinsically iterative systems (widely used in various domains such as signal processing, numerical analysis, computer arithmetic, and control engineering), or systems that could be rewritten in equivalent iterative forms. The implementation of recurrent NNs such as long short-term memory (LSTM) NNs, which have intrinsic state-space forms, are another major applications for this framework. As a case study, it is shown that state-space systems can be used for the systematic implementation and optimization of NNs (as nonlinear and time-varying dynamic systems). An RTL code generating software is also provided online, which simplifies the automatic generation of NNs of arbitrary size.

A three-dimensional dynamic model of the electrical activity of the heart is presented. The model is based on the single dipole model of the heart and is later related to the body surface potentials through a linear model which accounts for the temporal movements and rotations of the cardiac dipole, together with a realistic ECG noise model. The proposed model is also generalized to maternal and fetal ECG mixtures recorded from the abdomen of pregnant women in single and multiple pregnancies. The applicability of the model for the evaluation of signal processing algorithms is illustrated using independent component analysis. Considering the difficulties and limitations of recording long-term ECG data, especially from pregnant women, the model described in this paper may serve as an effective means of simulation and analysis of a wide range of ECGs, including adults and fetuses., Iranian-French Scientific Cooperation Program, Iran Telecommunication Research Center, National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant no. R01 EB001659)