Imputing Missing Observations with Time Sliced Synthetic Minority Oversampling Technique

We present a simple yet novel time series imputation technique with the goal of constructing an irregular time series that is uniform across every sample in a data set. Specifically, we fix a grid defined by the midpoints of non-overlapping bins (dubbed slices ) of observation times and ensure that each sample has values for all of the features at that given time. This allows one to both impute fully missing observations to allow uniform time series classification across the entire data and, in special cases, to impute individually missing features. To do so, we slightly generalize the well-known class imbalance algorithm SMOTE \cite{smote} to allow component wise nearest neighbor interpolation that preserves correlations when there are no missing features. We visualize the method in the simplified setting of 2-dimensional uncoupled harmonic oscillators. Next, we use tSMOTE to train an Encoder/Decoder long-short term memory (LSTM) model with Logistic Regression for predicting and classifying distinct trajectories of different 2D oscillators. After illustrating the the utility of tSMOTE in this context, we use the same architecture to train a clinical model for COVID-19 disease severity on an imputed data set. Our experiments show an improvement over standard mean and median imputation techniques by allowing a wider class of patient trajectories to be recognized by the model, as well as improvement over aggregated classification models

The impact of maternal SARS-CoV-2 infection and COVID-19 vaccination on maternal-fetal outcomes.

The rapidly evolving COVID-19 pandemic has resulted in an upsurge of scientific productivity to help address the global health crisis. One area of active research is the impact of COVID-19 on pregnancy. Here, we provide an epidemiological overview about what is known about the effects of maternal SARS-CoV-2 infection and COVID-19 vaccination on maternal-fetal outcomes, and identify gaps in knowledge. Pregnant people are at increased risk for severe COVID-19, and maternal SARS-CoV-2 infection increases the risk of negative maternal-fetal outcomes. Despite this elevated risk, there have been high rates of vaccine hesitancy, heightened by the initial lack of safety and efficacy data for COVID-19 vaccination in pregnancy. In response, retrospective cohort studies were performed to examine the impact of COVID-19 vaccination during pregnancy. Here, we report the vaccine\u27s efficacy during pregnancy and its impact on maternal-fetal outcomes, as well as an overview of initial studies on booster shots in pregnancy. We found that pregnant people are at risk for more severe COVID-19 outcomes, maternal SARS-CoV-2 infection is associated with worse birth outcomes, COVID-19 vaccine hesitancy remains prevalent in the pregnant population, and COVID-19 vaccination and boosters promote better maternal-fetal outcomes. The results should help reduce vaccine hesitancy by alleviating concerns about the safety and efficacy of administering the COVID-19 vaccine during pregnancy. Overall, this review provides an introduction to COVID-19 during pregnancy. It is expected to help consolidate current knowledge, accelerate research of COVID-19 during pregnancy and inform clinical, policy, and research decisions regarding COVID-19 vaccination in pregnant people

The effect of maternal SARS-CoV-2 infection timing on birth outcomes: a retrospective multicentre cohort study.

BACKGROUND: The impact of maternal SARS-CoV-2 infection remains unclear. In this study, we evaluated the risk of maternal SARS-CoV-2 infection on birth outcomes and how this is modulated by the pregnancy trimester in which the infection occurs. We also developed models to predict gestational age at delivery for people following a SARS-CoV-2 infection during pregnancy. METHODS: We did a retrospective cohort study of the impact of maternal SARS-CoV-2 infection on birth outcomes. We used clinical data from Providence St Joseph Health electronic health records for pregnant people who delivered in the USA at the Providence, Swedish, or Kadlec sites in Alaska, California, Montana, Oregon, or Washington. The SARS-CoV-2 positive cohort included people who had a positive SARS-CoV-2 PCR-based test during pregnancy, subdivided by trimester of infection. No one in this cohort had been vaccinated for COVID-19 at time of infection. The SARS-CoV-2 negative cohort were people with at least one negative SARS-CoV-2 PCR-based test and no positive tests during pregnancy. Cohorts were matched on common covariates impacting birth outcomes, and univariate and multivariate analysis were done to investigate risk factors and predict outcomes. The primary outcome was gestational age at delivery with annotation of preterm birth classification. We trained multiple supervised learning models on 24 features of the SARS-CoV-2 positive cohort to evaluate performance and feature importance for each model and discuss the impact of SARS-CoV-2 infection on gestational age at delivery. FINDINGS: Between March 5, 2020, and July 4, 2021, 73 666 pregnant people delivered, 18 335 of whom had at least one SARS-CoV-2 test during pregnancy before Feb 14, 2021. We observed 882 people infected with SARS-CoV-2 during their pregnancy (first trimester n=85; second trimester n=226; and third trimester n=571) and 19 769 people who have never tested positive for SARS-CoV-2 and received at least one negative SARS-CoV-2 test during their pregnancy. SARS-CoV-2 infection indicated an increased risk of preterm delivery (p INTERPRETATION: These results suggest that pregnant people would benefit from increased monitoring and enhanced prenatal care after first or second trimester SARS-CoV-2 infection, regardless of acute COVID-19 severity. FUNDING: US National Institutes of Health

The effect of COVID-19 vaccination and booster on maternal-fetal outcomes: a retrospective multicenter cohort study.

Background: COVID-19 infection in pregnant people has previously been shown to increase the risk for poor maternal-fetal outcomes. Despite this, there has been a lag in COVID-19 vaccination in pregnant people due to concerns over the potential effects of the vaccine on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and booster on maternal COVID-19 breakthrough infections and birth outcomes. Methods: This was a retrospective multicenter cohort study on the impact of COVID-19 vaccination on maternal-fetal outcomes for people that delivered (n=86,833) at Providence St. Joseph Health across Alaska, California, Montana, Oregon, New Mexico, Texas, and Washington from January 26, 2021 through July 11, 2022. Cohorts were defined by vaccination status at time of delivery: unvaccinated (n=48,492), unvaccinated propensity score matched (n=26,790), vaccinated (n=26,792; two doses of mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech), and/or boosted (n=7,616). The primary outcome was maternal COVID-19 infection. COVID-19 vaccination status at delivery, COVID-19 infection-related health care, preterm birth (PTB), stillbirth, very low birth weight (VLBW), and small for gestational age (SGA) were evaluated as secondary outcomes. Findings: Vaccinated pregnant people were significantly less likely to have a maternal COVID-19 infection than unvaccinated matched (p1,500 g; 0.31). Vaccinated people who were boosted had significantly lower rates of maternal COVID-19 infections (p Interpretation: COVID-19 vaccination protects against adverse maternal-fetal outcomes with booster doses conferring additional protection against COVID-19 infection. It is therefore important for pregnant people to have high priority status for vaccination, and for them to stay current with their COVID-19 vaccination schedule. Funding: This study was funded by the National Institute for Child Health & Human Development and the William O. and K. Carole Ellison Foundation

Effect of COVID-19 vaccination and booster on maternal-fetal outcomes: a retrospective cohort study.

BACKGROUND: COVID-19 in pregnant people increases the risk for poor maternal-fetal outcomes. However, COVID-19 vaccination hesitancy remains due to concerns over the vaccine\u27s potential effects on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and boosters on maternal SARS-CoV-2 infections and birth outcomes. METHODS: This was a retrospective multicentre cohort study on the impact of COVID-19 vaccination on maternal-fetal outcomes for people who delivered (n=106 428) at Providence St Joseph Health across seven western US states from Jan 26, 2021 to Oct 26, 2022. Cohorts were defined by vaccination status at delivery: vaccinated (n=35 926; two or more doses of mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech), unvaccinated (n=55 878), unvaccinated propensity score matched (n=16 771), boosted (n=10 927; three or more doses), vaccinated unboosted (n=13 243; two doses only), and vaccinated unboosted with propensity score matching (n=4414). We built supervised machine learning classification models, which we used to determine which people were more likely to be vaccinated or boosted at delivery. The primary outcome was maternal SARS-CoV-2 infection. COVID-19 vaccination status at delivery, COVID-19-related health care, preterm birth, stillbirth, and very low birthweight were evaluated as secondary outcomes. FINDINGS: Vaccinated people were more likely to conceive later in the pandemic, have commercial insurance, be older, live in areas with lower household composition vulnerability, and have a higher BMI than unvaccinated people. Boosted people were more likely to have more days since receiving the second COVID-19 vaccine dose, conceive earlier in the pandemic, have commercial insurance, be older, and live in areas with lower household composition vulnerability than vaccinated unboosted people. Vaccinated pregnant people had lower rates of COVID-19 during pregnancy (4·0%) compared with unvaccinated matched people (5·3%; p INTERPRETATION: COVID-19 vaccination protects against adverse maternal-fetal outcomes, with booster doses conferring additional protection. Pregnant people should be high priority for vaccination and stay up to date with their COVID-19 vaccination schedule. FUNDING: National Institute for Child Health & Human Development and the William O and K Carole Ellison Foundation

Multiomic signatures of body mass index identify heterogeneous health phenotypes and responses to a lifestyle intervention.

Multiomic profiling can reveal population heterogeneity for both health and disease states. Obesity drives a myriad of metabolic perturbations and is a risk factor for multiple chronic diseases. Here we report an atlas of cross-sectional and longitudinal changes in 1,111 blood analytes associated with variation in body mass index (BMI), as well as multiomic associations with host polygenic risk scores and gut microbiome composition, from a cohort of 1,277 individuals enrolled in a wellness program (Arivale). Machine learning model predictions of BMI from blood multiomics captured heterogeneous phenotypic states of host metabolism and gut microbiome composition better than BMI, which was also validated in an external cohort (TwinsUK). Moreover, longitudinal analyses identified variable BMI trajectories for different omics measures in response to a healthy lifestyle intervention; metabolomics-inferred BMI decreased to a greater extent than actual BMI, whereas proteomics-inferred BMI exhibited greater resistance to change. Our analyses further identified blood analyte-analyte associations that were modified by metabolomics-inferred BMI and partially reversed in individuals with metabolic obesity during the intervention. Taken together, our findings provide a blood atlas of the molecular perturbations associated with changes in obesity status, serving as a resource to quantify metabolic health for predictive and preventive medicine

Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with impaired kidney function.

OBIECTIVE: Bowel movement frequency (BMF) variation has been linked to changes in the composition of the human gut microbiome and to many chronic conditions, like metabolic disorders, neurodegenerative diseases, chronic kidney disease (CKD), and other intestinal pathologies like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Slow intestinal transit times (constipation) are thought to lead to compromised intestinal barrier integrity and a switch from saccharolytic to proteolytic fermentation within the microbiota, giving rise to microbially-derived toxins that may make their way into circulation and cause damage to organ systems. However, these phenomena have not been characterized in generally-healthy populations, and the connections between microbial metabolism and the early-stage development and progression of chronic disease remain underexplored. DESIGN: Here, we examine the phenotypic impact of BMF variation across a cohort of over 2,000 generally-healthy, community dwelling adults with detailed clinical, lifestyle, and multi-omic data. RESULTS: We show significant differences in key blood plasma metabolites, proteins, chemistries, gut bacterial genera, and lifestyle factors across BMF groups that have been linked, in particular, to inflammation and CKD severity and progression. DISCUSSION: In addition to dissecting BMF-related heterogeneity in blood metabolites, proteins, and the gut microbiome, we identify self-reported diet, lifestyle, and psychological factors associated with BMF variation, which suggest several potential strategies for mitigating constipation and diarrhea. Overall, this work highlights the potential for managing BMF to prevent disease. WHAT IS ALREADY KNOWN ABOUT THIS TOPIC: Constipation and diarrhea are linked to several chronic diseases, like IBD, CKD, and neurodegenerative disorders. Chronic constipation, in particular, is associated with the increased production of microbially-derived uremic toxins in the gut due to an ecosystem-wide switch from fiber fermentation to protein fermentation. A build-up of these gut-derived toxins in blood, like p-cresol, has been associated with CKD disease progression and severity. WHAT THIS STUDY ADDS: While prior work has demonstrated associations between microbially-derived uremic toxins, constipation, and CKD severity/progression, here we show similar signatures in a generally-healthy cohort. Overall, we map out the molecular phenotypic effects of aberrant BMFs across individuals without any apparent disease, and show how these effects precede, and may contribute to, the development of chronic disease. We find that certain lifestyle and dietary patterns, like higher levels of exercise, reduced anxiety levels, a more plant-based diet, and drinking more water, are associated with a more optimal BMF range. HOW THIS STUDY MIGHT AFFECT RESEARCH POLICY OR PRACTICE: Overall, we suggest that even mild levels of chronic constipation may cause damage to organ systems over time and ultimately give rise to chronic diseases, like CKD or neurodegeneration. These findings pave the way for future research into early interventions for individuals at risk of developing chronic diseases related to BMF abnormalities. Managing BMF abnormalities prior to disease development may be an important disease prevention strategy, but this will require further evidence through longitudinal human intervention trials