Quantitative Biology

In the pregnant mother and her fetus, chronic prenatal stress results in entrainment of the fetal heartbeat by the maternal heartbeat, quantified by the fetal stress index (FSI). Deep learning (DL) is capable of pattern detection in complex medical data with high accuracy in noisy real-life environments, but little is known about DL's utility in non-invasive biometric monitoring during pregnancy. A recently established self-supervised learning (SSL) approach to DL provides emotional recognition from electrocardiogram (ECG). We hypothesized that SSL will identify chronically stressed mother-fetus dyads from the raw maternal abdominal electrocardiograms (aECG), containing fetal and maternal ECG. Chronically stressed mothers and controls matched at enrolment at 32 weeks of gestation were studied. We validated the chronic stress exposure by psychological inventory, maternal hair cortisol and FSI. We tested two variants of SSL architecture, one trained on the generic ECG features for emotional recognition obtained from public datasets and another transfer-learned on a subset of our data. Our DL models accurately detect the chronic stress exposure group (AUROC=0.982+/-0.002), the individual psychological stress score (R2=0.943+/-0.009) and FSI at 34 weeks of gestation (R2=0.946+/-0.013), as well as the maternal hair cortisol at birth reflecting chronic stress exposure (0.931+/-0.006). The best performance was achieved with the DL model trained on the public dataset and using maternal ECG alone. The present DL approach provides a novel source of physiological insights into complex multi-modal relationships between different regulatory systems exposed to chronic stress. The final DL model can be deployed in low-cost regular ECG biosensors as a simple, ubiquitous early stress detection and monitoring tool during pregnancy. This discovery should enable early behavioral interventions.

Summary: Hydrogen deuterium exchange mass spectrometry (HDX-MS) is becoming increasing routine for monitoring changes in the structural dynamics of proteins. Differential HDX-MS allows comparison of individual protein states, such as in the absence or presence of a ligand. This can be used to attribute changes in conformation to binding events, allowing the mapping of entire con-formational networks. As such, the number of necessary cross-state comparisons quickly increas-es as additional states are introduced to the system of study. There are currently very few software packages available that offer quick and informative comparison of HDX-MS datasets and even few-er which offer statistical analysis and advanced visualization. Following the feedback from our origi-nal software Deuteros, we present Deuteros 2.0 which has been redesigned from the ground up to fulfil a greater role in the HDX-MS analysis pipeline. Deuteros 2.0 features a repertoire of facilities for back exchange correction, data summarization, peptide-level statistical analysis and advanced data plotting features. Availability: Deuteros 2.0 can be downloaded from this https URL under the Apache 2.0 license. Installation of Deuteros 2.0 requires the MATLAB Runtime Library available free of charge from MathWorks (this https URL) and is available for both Windows and Mac operating systems.

Background: In the United States, 5.7 million patients are admitted annually to intensive care units (ICU), with costs exceeding $82 billion. Although close monitoring and dynamic assessment of patient acuity are key aspects of ICU care, both are limited by the time constraints imposed on healthcare providers. Methods: Using the University of Florida Health (UFH) Integrated Data Repository as Honest Broker, we created a database with electronic health records data from a retrospective study cohort of 38,749 adult patients admitted to ICU at UF Health between 06/01/2014 and 08/22/2019. This repository includes demographic information, comorbidities, vital signs, laboratory values, medications with date and timestamps, and diagnoses and procedure codes for all index admission encounters as well as encounters within 12 months prior to index admission and 12 months follow-up. We developed algorithms to identify acuity status of the patient every four hours during each ICU stay. Results: We had 383,193 encounters (121,800 unique patients) admitted to the hospital, and 51,073 encounters (38,749 unique patients) with at least one ICU stay that lasted more than four hours. These patients requiring ICU admission had longer median hospital stay (7 days vs. 1 day) and higher in-hospital mortality (9.6% vs. 0.4%) compared with those not admitted to the ICU. Among patients who were admitted to the ICU and expired during hospital admission, more deaths occurred in the ICU than on general hospital wards (7.4% vs. 0.8%, respectively). Conclusions: We developed phenotyping algorithms that determined patient acuity status every four hours while admitted to the ICU. This approach may be useful in developing prognostic and clinical decision-support tools to aid patients, caregivers, and providers in shared decision-making processes regarding resource use and escalation of care.

Purpose: A conventional 2D UNet convolutional neural network (CNN) architecture may result in ill-defined boundaries in segmentation output. Several studies imposed stronger constraints on each level of UNet to improve the performance of 2D UNet, such as SegNet. In this study, we investigated 2D SegNet and a proposed conditional random field insert (CRFI) for zonal prostate segmentation from clinical T2-weighted MRI data. Methods: We introduced a new methodology that combines SegNet and CRFI to improve the accuracy and robustness of the segmentation. CRFI has feedback connections that encourage the data consistency at multiple levels of the feature pyramid. On the encoder side of the SegNet, the CRFI combines the input feature maps and convolution block output based on their spatial local similarity, like a trainable bilateral filter. For all networks, 725 2D images (i.e., 29 MRI cases) were used in training; while, 174 2D images (i.e., 6 cases) were used in testing. Results: The SegNet with CRFI achieved the relatively high Dice coefficients (0.76, 0.84, and 0.89) for the peripheral zone, central zone, and whole gland, respectively. Compared with UNet, the SegNet+CRFIs segmentation has generally higher Dice score and showed the robustness in determining the boundaries of anatomical structures compared with the SegNet or UNet segmentation. The SegNet with a CRFI at the end showed the CRFI can correct the segmentation errors from SegNet output, generating smooth and consistent segmentation for the prostate. Conclusion: UNet based deep neural networks demonstrated in this study can perform zonal prostate segmentation, achieving high Dice coefficients compared with those in the literature. The proposed CRFI method can reduce the fuzzy boundaries that affected the segmentation performance of baseline UNet and SegNet models.

Patients who undergo mechanical heart valve replacements or have conditions like Atrial Fibrillation have to take Vitamin K Antagonists (VKA) drugs to prevent coagulation of blood. These drugs have narrow therapeutic range and need to be very closely monitored due to life threatening side effects. The dosage of VKA drug is determined and revised by a physician based on Prothrombin Time - International Normalised Ratio (PT-INR) value obtained through a blood test. Our work aimed at predicting the maintenance dosage of warfarin, the present most widely recommended anticoagulant drug, using the de-identified medical data collected from 109 patients from Kerala. A Support Vector Machine (SVM) Regression model was built to predict the maintenance dosage of warfarin, for patients who have been undergoing treatment from a physician and have reached stable INR values between 2.0 and 4.0.

The controversy of computed tomography (CT) use in COVID-19 screening is associated with ambiguous characteristics of chest CT as a diagnostic test. The reported values of CT sensitivity and specificity calculated using RT-PCR as a reference standard vary widely. The objective of this study was to reevaluate the diagnostic and prognostic value of CT using an alternative approach. This study included 973 symptomatic COVID-19 patients aged 42 ± 17 years, 56% females. We reviewed the disease dynamics between the initial and follow-up CT studies using a "CT0-4" grading system. Sensitivity and specificity were calculated as conditional probabilities that a patient's condition would improve or deteriorate relative to the initial CT study results. For the calculation of negative (NPV) and positive (PPV) predictive values, we estimated the COVID-19 prevalence in Moscow. We used several ARIMA and EST models with different parameters to fit the data on total cases of COVID-19 from March 6, 2020, to July 20, 2020, and forecast the incidence. The "CT0-4" grading scale demonstrated low sensitivity (28%) but high specificity (95%). The best statistical model for describing the pandemic in Moscow was ETS with multiplicative trend, error, and season type. According to our calculations, with the predicted prevalence of 2.1%, the values of NPV and PPV would be 98% and 10%, correspondingly. We associate the low sensitivity and PPV values with the small sample size of the patients with severe symptoms and non-optimal methodological setup for measuring these specific characteristics. The "CT0-4" grading scale was highly specific and predictive for identifying admissions to hospitals of COVID-19 patients. Despite the ambiguous accuracy, chest CT proved to be an effective practical tool for patient management during the pandemic, provided that the necessary infrastructure and human resources are available.

Coronavirus disease 2019 (COVID-19) has caused global disruption and a significant loss of life. Existing treatments that can be repurposed as prophylactic and therapeutic agents could reduce the pandemic's devastation. Emerging evidence of potential applications in other therapeutic contexts has led to the investigation of dietary supplements and nutraceuticals for COVID-19. Such products include vitamin C, vitamin D, omega 3 polyunsaturated fatty acids, probiotics, and zinc, all of which are currently under clinical investigation. In this review, we critically appraise the evidence surrounding dietary supplements and nutraceuticals for the prophylaxis and treatment of COVID-19. Overall, further study is required before evidence-based recommendations can be formulated, but nutritional status plays a significant role in patient outcomes, and these products could help alleviate deficiencies. For example, evidence indicates that vitamin D deficiency may be associated with greater incidence of infection and severity of COVID-19, suggesting that vitamin D supplementation may hold prophylactic or therapeutic value. A growing number of scientific organizations are now considering recommending vitamin D supplementation to those at high risk of COVID-19. Because research in vitamin D and other nutraceuticals and supplements is preliminary, here we evaluate the extent to which these nutraceutical and dietary supplements hold potential in the COVID-19 crisis.

A theory for diffusivity estimation for spatially extended activator-inhibitor dynamics modelling the evolution of intracellular signaling networks is developed in the mathematical framework of stochastic reaction-diffusion systems. In order to account for model uncertainties, we extend the results for parameter estimation for semilinear stochastic partial differential equations, as developed in [PS20], to the problem of joint estimation of diffusivity and parametrized reaction terms. Our theoretical findings are applied to the estimation of effective diffusivity of signaling components contributing to intracellular dynamics of the actin cytoskeleton in the model organism Dictyostelium discoideum.

Coral reef ecosystems support significant biological activities and harbor huge diversity, but they are facing a severe crisis driven by anthropogenic activities and climate change. An important behavioral trait of the coral holobiont is coral motion, which may play an essential role in feeding, competition, reproduction, and thus survival and fitness. Therefore, characterizing coral behavior through motion analysis will aid our understanding of basic biological and physical coral functions. However, tissue motion in the stony scleractinian corals that contribute most to coral reef construction are subtle and may be imperceptible to both the human eye and commonly used imaging techniques. Here we propose and apply a systematic approach to quantify and visualize subtle coral motion across a series of light and dark cycles in the scleractinian coral Montipora capricornis. We use digital image correlation and optical flow techniques to quantify and characterize minute coral motions under different light conditions. In addition, as a visualization tool, motion magnification algorithm magnifies coral motions in different frequencies, which explicitly displays the distinctive dynamic modes of coral movement. We quantified and compared the displacement, strain, optical flow, and mode shape of coral motion under different light conditions. Our approach provides an unprecedented insight into micro-scale coral movement and behavior through macro-scale digital imaging, thus offering a useful empirical toolset for the coral research community.

A first analysis applying compressive sensing to a quantitative biological trait and its compressible "frequency domain" is presented. Consider an n -bit genetic sequence and suppose we want to discover a function that maps participating alleles (or even environmental influences) to a particular trait. Under plausible assumptions of how they evolved, certain traits can be viewed as "smooth" functions on the n -dimensional Boolean lattice of possible genomes. This allows approximation of their Fourier transforms, i.e., their gene networks, as sparse, dominated by "low-frequency" components. In turn, we can apply compressive sensing methods to collect relatively few samples, yet achieve accurate recovery. For an arbitrary quantitative trait affected by n=26 genes and with 812 meaningful gene interactions, our simulations show noisy trait measurements ( SNR=20dB ) from just M=44,336 genomes in a population of size N= 2 26 (undersample ratio M/N??.00066 ) permit discovering its gene network and predicting trait values, both with about 97.6% accuracy. More dramatic undersample ratios are possible for traits affected by more genes. Work is currently underway to see if empirical data fit the proposed model. If so, it could offer a radical reduction in the number of measurements -- from exponential to polynomial in some cases -- necessary to quantify the relationship between genomes and certain traits.