Icahn School of Medicine at Mount Sinai

About: Icahn School of Medicine at Mount Sinai is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 37488 authors who have published 76057 publications receiving 3704104 citations. The organization is also known as: Mount Sinai School of Medicine.

Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection

Abstract: BackgroundIn phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3. MethodsWe conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir–velpatasvir, in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1:1 ratio to receive sofosbuvir–velpatasvir for 12 weeks (277 patients) or sofosbuvir–ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustai...

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey: a 5-year follow-up study.

Abstract: Background Allergy to peanuts and tree nuts (TNs) is the leading cause of fatal and near-fatal food allergic reactions. Peanut allergy appears to be increasing in prevalence. Objectives We sought to determine the prevalence of self-reported peanut and TN allergy among the general population of the United States in 2002 by sex and age and to compare the results with prevalence estimates obtained 5 years earlier. Methods We performed a nationwide, cross-sectional, random telephone survey by using a standardized questionnaire. Results A total of 4855 households participated (53% participation rate), representing a census of 13,493 individuals. Peanut allergy, TN allergy, or both was self-reported in 166 (1.2%; 95% CI, 1.0%-1.4%) individuals in 155 (3.2%; 95% CI, 2.7%-3.7%) households, overall prevalence rates similar to those reported in 1997. Also similar to the 1997 survey, the severity level was high, with 79% reporting respiratory or multiple organ system reactions and 66% experiencing more than 5 lifetime reactions. Despite the severity and reaction frequency, only 74% of the children and 44% of the adults sought evaluation for the allergy, and fewer than half who did were prescribed self-injectable epinephrine. Applying conservative rules to adjust for persons with unconvincing reactions and a false-positive rate of the survey instrument (7%), a final prevalence estimate of 1.04% (95% CI, 0.9%-1.24%) was obtained. A male predominance of peanut-TN allergy was reported in children younger than 18 years (1.7% vs 0.7%, P = .02), and a female predominance was reported among adults (1.7% vs 0.9%, P = .0008). Although the rate of peanut allergy, TN allergy, or both was not significantly different from 1997 to 2002 among adults, the rate increased from 0.6% to 1.2% among children, primarily as a result of an increase in reported allergy to peanut (0.4% in 1997 to 0.8% in 2002, P = .05). Conclusions Self-reported peanut allergy has doubled among children from 1997 to 2002, and peanut allergies, TN allergies, or both continue to be reported by more than 3 million Americans. Considering that reactions are severe and the allergy is persistent, these allergies represent an increasing health concern.

Lin28 promotes transformation and is associated with advanced human malignancies

Abstract: Multiple members of the let-7 family of miRNAs are often repressed in human cancers, thereby promoting oncogenesis by derepressing targets such as HMGA2, K-Ras and c-Myc. However, the mechanism by which let-7 miRNAs are coordinately repressed is unclear. The RNA-binding proteins LIN28 and LIN28B block let-7 precursors from being processed to mature miRNAs, suggesting that their overexpression might promote malignancy through repression of let-7. Here we show that LIN28 and LIN28B are overexpressed in primary human tumors and human cancer cell lines (overall frequency approximately 15%), and that overexpression is linked to repression of let-7 family miRNAs and derepression of let-7 targets. LIN28 and LIN28b facilitate cellular transformation in vitro, and overexpression is associated with advanced disease across multiple tumor types. Our work provides a mechanism for the coordinate repression of let-7 miRNAs observed in a subset of human cancers, and associates activation of LIN28 and LIN28B with poor clinical prognosis.

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

Abstract: High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future