Uri Goldsztejn

About one in ten babies is born preterm, i.e., before completing 37 weeks of gestation, which can result in permanent neurologic deficit and is a leading cause of child mortality. Although imminent preterm labor can be detected, predicting preterm births more than one week in advance remains elusive. Here, we develop a deep learning method to predict preterm births directly from electrohysterogram (EHG) measurements of pregnant mothers recorded at around 31 weeks of gestation. We developed a prediction model, which includes a recurrent neural network, to predict preterm births using short-time Fourier transforms of EHG recordings and clinical information from two public datasets. We predicted preterm births with an area under the receiver-operating characteristic curve (AUC) of 0.78 (95% confidence interval: 0.76-0.80). Moreover, we found that the spectral patterns of the measurements were more predictive than the temporal patterns, suggesting that preterm births can be predicted from short EHG recordings in an automated process. We show that preterm births can be predicted for pregnant mothers around their 31st week of gestation, prompting beneficial treatments to reduce the incidence of preterm births and improve their outcomes.

About one in ten babies is born preterm, i.e., before completing 37 weeks of gestation, which can result in permanent neurologic deficit and is a leading cause of child mortality. Although imminent preterm labor can be detected, predicting preterm births more than one week in advance remains elusive. Here, we develop a deep learning method to predict preterm births directly from electrohysterogram (EHG) recordings of pregnant mothers without symptoms of preterm labor. We developed a prediction model, which includes a recurrent neural network, to predict preterm births using short-time Fourier transforms of EHG recordings and clinical information from two public datasets. We predicted preterm births with an area under the receiver-operating characteristic curve (AUC) of 0.80 (95% confidence interval: 0.79-0.82). Moreover, we found that the spectral patterns of the measurements were more predictive than the temporal patterns, suggesting that preterm births can be predicted from short EHG recordings in an automated process. We show that, even without symptoms of preterm labor, preterm births can be predicted for pregnant mothers around their 31st week of gestation, prompting beneficial treatments to reduce the incidence of preterm births and improve their outcomes.

Cardiac radiotherapy (RT) may be effective in treating heart failure (HF) patients with refractory ventricular tachycardia (VT). The previously proposed mechanism of radiation-induced fibrosis does not explain the rapidity and magnitude with which VT reduction occurs clinically. Here, we demonstrate in hearts from RT patients that radiation does not achieve transmural fibrosis within the timeframe of VT reduction. Electrophysiologic assessment of irradiated murine hearts reveals a persistent supraphysiologic electrical phenotype, mediated by increases in Na_V1.5 and Cx43. By sequencing and transgenic approaches, we identify Notch signaling as a mechanistic contributor to Na_V1.5 upregulation after RT. Clinically, RT was associated with increased Na_V1.5 expression in 1 of 1 explanted heart. On electrocardiogram (ECG), post-RT QRS durations were shortened in 13 of 19 patients and lengthened in 5 patients. Collectively, this study provides evidence for radiation-induced reprogramming of cardiac conduction as a potential treatment strategy for arrhythmia management in VT patients.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, yet the molecular signature of the vulnerable atrial substrate is not well understood. Here, we delineated a distinct transcriptional signature in right versus left atrial cardiomyocytes (CMs) at baseline and identified chamber-specific gene expression changes in patients with a history of AF in the setting of end-stage heart failure (AF+HF) that are not present in heart failure alone (HF). We observed that human left atrial (LA) CMs exhibited Notch pathway activation and increased ploidy in AF+HF but not in HF alone. Transient activation of Notch signaling within adult CMs in a murine genetic model is sufficient to increase ploidy in both atrial chambers. Notch activation within LA CMs generated a transcriptomic fingerprint resembling AF, with dysregulation of transcription factor and ion channel genes, including Pitx2 , Tbx5 , Kcnh2 , Kcnq1 , and Kcnip2 . Notch activation also produced distinct cellular electrophysiologic responses in LA versus right atrial CMs, prolonging the action potential duration (APD) without altering the upstroke velocity in the left atrium and reducing the maximal upstroke velocity without altering the APD in the right atrium. Our results support a shared human/murine model of increased Notch pathway activity predisposing to AF.

With the COVID-19 pandemic infecting millions of people, large-scale isolation policies have been enacted across the globe. To assess the impact of isolation measures on deaths, hospitalizations, and economic output, we create a mathematical model to simulate the spread of COVID-19, incorporating effects of restrictive measures and segmenting the population based on health risk and economic vulnerability. Policymakers make isolation policy decisions based on current levels of disease spread and economic damage. For 76 weeks in a population of 330 million, we simulate a baseline scenario leaving strong isolation restrictions in place, rapidly reducing isolation restrictions for non-seniors shortly after outbreak containment, and gradually relaxing isolation restrictions for non-seniors. We used 76 weeks as an approximation of the time at which a vaccine will be available. In the baseline scenario, there are 235,724 deaths and the economy shrinks by 34.0%. With a rapid relaxation, a second outbreak takes place, with 525,558 deaths, and the economy shrinks by 32.3%. With a gradual relaxation, there are 262,917 deaths, and the economy shrinks by 29.8%. We also show that hospitalizations, deaths, and economic output are quite sensitive to disease spread by asymptomatic people. Strict restrictions on seniors with very gradual lifting of isolation for non-seniors results in a limited number of deaths and lesser economic damage. Therefore, we recommend this strategy and measures that reduce non-isolated disease spread to control the pandemic while making isolation economically viable.