In order to evaluate whether rare regulatory variants in the vicinity of promoters are likely to impact gene expression, we conducted a novel burden test for enrichment of rare variants at the extremes of expression. After sequencing 2-kb promoter regions of 472 genes in 410 healthy adults, we performed a quadratic regression of rare variant count on bins of peripheral blood transcript abundance from microarrays, summing over ranks of all genes. After adjusting for common eQTLs and the major axes of gene expression covariance, a highly significant excess of variants with minor allele frequency less than 0.05 at both high and low extremes across individuals was observed. Further enrichment was seen in sites annotated as potentially regulatory by RegulomeDB, but a deficit of effects was associated with known metabolic disease genes. The main result replicates in an independent sample of 75 individuals with RNA-seq and whole-genome sequence information. Three of four predicted large-effect sites were validated by CRISPR/Cas9 knockdown in K562 cells, but simulations indicate that effect sizes need not be unusually large to produce the observed burden. Unusually divergent low-frequency promoter haplotypes were observed at 31 loci, at least 9 of which appear to be derived from Neandertal admixture, but these were not associated with divergent gene expression in blood. The overall burden test results are consistent with rare and private regulatory variants driving high or low transcription at specific loci, potentially contributing to disease.

We investigated the dynamics of illness among household members of SARS-CoV-2 infected children that received medical care (n=32). We identified 144 household contacts (HCs): 58 children and 86 adults. Forty-six percent of HCs developed symptoms consistent with COVID-19 disease. Child-to-adult transmission was suspected in 7 cases.

Pituitary adenomas are tumors that arise in the anterior pituitary gland. They are the third most common cause of central nervous system (CNS) tumors among adults. Most adenomas are benign and exert their effect via excess hormone secretion or mass effect. Clinical presentation of pituitary adenoma varies based on their size and hormone secreted. Here, we review some of the most common types of pituitary adenomas, their clinical presentation, and current diagnostic and therapeutic strategies.

A paucity of data exists evaluating a guardian’s intent to vaccinate their child against COVID-19 in the United States. We administered 102 first (April–November 2020) and 45 second (December–January 2020–2021) surveys to guardians of children (<18 years) who had a laboratory-confirmed diagnosis of COVID-19 and assessed their intent to give a COVID-19 vaccine to their child, when one becomes available. The first and second surveys of the same cohort of guardians were conducted before and following the press releases detailing the adult Pfizer-BioNTech and Moderna Phase 3 results. Both surveys included an intent-to-vaccinate question using the subjective language of “if a safe and effective vaccine” became available, and a second question was added to second surveys using the objective language of “would prevent 19 of 20 people from getting disease”. When using subjective language, 24 of 45 (53%) guardians endorsed vaccine administration for their children in the first survey, which decreased to 21 (46%) in the second survey. When adding objective language, acceptance of vaccination increased to 31 (69%, p = 0.03). Common reasons for declining vaccination were concerns about adverse effects and/or vaccine safety. Providing additional facts on vaccine efficacy increased vaccine acceptance. Evidence-based strategies are needed to increase pediatric COVID-19 vaccine uptake.

No abstract