The immunological defects causing susceptibility to severe viral respiratory infections due to early-life dysbiosis remain ill-defined. Here, we show that influenza virus susceptibility in dysbiotic infant mice is caused by CD8 T cell hyporesponsiveness and diminished persistence as tissue-resident memory cells. We describe a previously unknown role for nuclear factor interleukin 3 (NFIL3) in repression of memory differentiation of CD8 T cells in dysbiotic mice involving epigenetic regulation of T cell factor 1 (TCF 1) expression.
View Article and Find Full Text PDFBackground: Blood lipids are dysregulated in pulmonary hypertension (PH). Lower high-density lipoproteins cholesterol (HDL-C) and low-density lipoproteins cholesterol (LDL-C) are associated with disease severity and death in PH. Right ventricle (RV) dysfunction and failure are the major determinants of morbidity and mortality in PH.
View Article and Find Full Text PDFBackground: Mepolizumab is a therapy for severe asthma. We have little knowledge of the characteristics of people in the US that discontinue mepolizumab in clinical care.
Objective: To investigate the real-world efficacy and time to clinical discontinuation of mepolizumab, we evaluated individuals with asthma started on mepolizumab at the Cleveland Clinic.
Am J Respir Cell Mol Biol
March 2023
Although modern clinical practices such as cesarean sections and perinatal antibiotics have improved infant survival, treatment with broad-spectrum antibiotics alters intestinal microbiota and causes dysbiosis. Infants exposed to perinatal antibiotics have an increased likelihood of life-threatening infections, including pneumonia. Here, we investigated how the gut microbiota sculpt pulmonary immune responses, promoting recovery and resolution of infection in newborn rhesus macaques.
View Article and Find Full Text PDFPreterm newborns are exposed to several risk factors for developing brain injury. Clinical studies have suggested that the presence of intrauterine infection is a consistent risk factor for preterm birth and white matter injury. Animal models have confirmed these associations by identifying inflammatory cascades originating at the maternofetal interface that penetrate the fetal blood-brain barrier and result in brain injury.
View Article and Find Full Text PDFPurpose: Although mobile apps are used extensively by speech-language pathologists, evidence for app-based treatments remains limited in quantity and quality. This study investigated the efficacy of app-based visual-acoustic biofeedback relative to nonbiofeedback treatment using a single-case randomization design. Because of COVID-19, all intervention was delivered via telepractice.
View Article and Find Full Text PDFFidelity monitoring is the degree to which a clinical trial intervention is implemented as intended by a research protocol. Consistent implementation of research protocols supported with extant fidelity monitoring plans contribute rigor and validity of study results. Fidelity monitoring plans should be comprehensive yet practical to accommodate the realities of conducting research, particularly a pragmatic clinical trial, in dynamic settings with heterogeneous patient populations.
View Article and Find Full Text PDFApproximately 1 in 4 pregnant women in the United States undergo labor induction. The onset and establishment of labor, particularly induced labor, is a complex and dynamic process influenced by multiple endocrine, inflammatory, and mechanical factors as well as obstetric and pharmacological interventions. The duration from labor induction to the onset of active labor remains unpredictable.
View Article and Find Full Text PDFAlthough most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation.
View Article and Find Full Text PDFBackground And Objectives: The Women's Wellness through Equity and Leadership (WEL) program was developed as a collaboration between 6 major medical associations in the United States. The goal was to contribute to the creation of equitable work environments for women physicians. The purpose of the current study was to evaluate the pilot implementation of WEL.
View Article and Find Full Text PDFEstimating the time of delivery is of high clinical importance because pre- and postterm deviations are associated with complications for the mother and her offspring. However, current estimations are inaccurate. As pregnancy progresses toward labor, major transitions occur in fetomaternal immune, metabolic, and endocrine systems that culminate in birth.
View Article and Find Full Text PDFThe Common Metrics Initiative aims to develop and field metrics to improve research processes within the national Clinical and Translational Science Award (CTSA) Consortium. A Median Accrual Ratio (MAR) common metric was developed to assess the results of efforts to increase subject accrual into a set of clinical trials within the expected time period. A pilot test of the MAR was undertaken at Tufts Clinical and Translational Science Institute (CTSI) with eight CTSA Consortium hubs.
View Article and Find Full Text PDFFailure to accrue participants into clinical trials incurs economic costs, wastes resources, jeopardizes answering research questions meaningfully, and delays translating research discoveries into improved health. This paper reports the results of a pilot test of the Median Accrual Ratio (MAR) metric developed as a part of the Common Metrics Initiative of the NIH's National Center for Advancing Translational Science (NCATS) Clinical and Translational Science Award (CTSA) Consortium. Using the metric is intended to enhance the ability of the CTSA Consortium and its "hubs" to increase subject accrual into trials within expected timeframes.
View Article and Find Full Text PDFTo understand the disparities in spontaneous preterm birth (sPTB) and/or its outcomes, biologic and social determinants as well as healthcare practice (such as those in neonatal intensive care units) should be considered. Disparities in sPTB have been largely intractable and remain obscure in most cases, despite a myriad of identified risk factors for and causes of sPTB. We still do not know how they lead to the different outcomes at different gestational ages and if they are independent of NICU practices.
View Article and Find Full Text PDFAsthma physiology affects respiratory function and inflammation, factors that may contribute to elevated resting energy expenditure (REE) and altered body composition. We hypothesized that asthma would present with elevated REE compared to weight-matched healthy controls. Adults with asthma ( = 41) and healthy controls ( = 20) underwent indirect calorimetry to measure REE, dual-energy X-ray absorptiometry (DEXA) to measure body composition, and 3-day diet records.
View Article and Find Full Text PDFThe biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.
View Article and Find Full Text PDFThe dense network of interconnected cellular signalling responses that are quantifiable in peripheral immune cells provides a wealth of actionable immunological insights. Although high-throughput single-cell profiling techniques, including polychromatic flow and mass cytometry, have matured to a point that enables detailed immune profiling of patients in numerous clinical settings, the limited cohort size and high dimensionality of data increase the possibility of false-positive discoveries and model overfitting. We introduce a generalizable machine learning platform, the immunological Elastic-Net (iEN), which incorporates immunological knowledge directly into the predictive models.
View Article and Find Full Text PDFHigh-throughput single-cell analysis technologies produce an abundance of data that is critical for profiling the heterogeneity of cellular systems. We introduce VoPo (https://github.com/stanleyn/VoPo), a machine learning algorithm for predictive modeling and comprehensive visualization of the heterogeneity captured in large single-cell datasets.
View Article and Find Full Text PDFThe Clinical and Translational Science Award (CTSA) Consortium and the National Center for Advancing Translational Science (NCATS) undertook a Common Metrics Initiative to improve research processes across the national CTSA Consortium. This was implemented by Tufts Clinical and Translational Science Institute at the 64 CTSA academic medical centers. Three metrics were collaboratively developed by NCATS staff, CTSA Consortium teams, and outside consultants for Institutional Review Board Review Duration, Careers in Clinical and Translational Research, and Pilot Award Publications and Subsequent Funding.
View Article and Find Full Text PDFPreterm birth is the leading cause of mortality in children under the age of five worldwide. Despite major efforts, we still lack the ability to accurately predict and effectively prevent preterm birth. While multiple factors contribute to preterm labor, dysregulations of immunological adaptations required for the maintenance of a healthy pregnancy is at its pathophysiological core.
View Article and Find Full Text PDFObjectives: The aim of this study was to compare the stress reduction effects of spending 25 minutes reclining in a SolTec™ Lounge between 2 intervention groups. Group 1 experienced the Lounge with multilayered music on an external speaker, while group 2 experienced the Lounge with multilayered music and synchronous vibration and magnetic stimulation from within the chair.
Subjects: In total, 110 participants with a self-reported stress level of 4 or higher on a 0- to 10-point scale were recruited from the local community including employees.
Preeclampsia is one of the most severe pregnancy complications and a leading cause of maternal death. However, early diagnosis of preeclampsia remains a clinical challenge. Alterations in the normal immune adaptations necessary for the maintenance of a healthy pregnancy are central features of preeclampsia.
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