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These effects were associated with modulation of genes involved in cell adhesion and Epithelial to Mesenchymal Transition (EMT). Conclusions In GBM, MEG3 acts as a tumor-suppressor mainly regulating cell adhesion, EMT and cell proliferation, thus providing a potential candidate for novel GBM therapies.Importance Individuals with low socioeconomic status (SES) bear a disproportionate share of the coronary heart disease (CHD) burden, and CHD remains the leading cause of mortality in low-income US counties. Objective To estimate the excess CHD burden among individuals in the United States with low SES and the proportions attributable to traditional risk factors and to other factors associated with low SES. Design, setting, and participants This computer simulation study used the Cardiovascular Disease Policy Model, a model of CHD and stroke incidence, prevalence, and mortality among adults in the United States, to project the excess burden of early CHD. The proportion of this excess burden attributable to traditional CHD risk factors (smoking, high blood pressure, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, type 2 diabetes, and high body mass index) compared with the proportion attributable to other risk factors associated with low SES was estimated. Model inputs were d0% of these excess events; the remaining 60% of these events were attributable to other factors associated with low SES. Among a simulated cohort of 1.3 million adults with low SES who were 35 years old in 2015, the model projected that 250 000 individuals (19%) will develop CHD by age 65 years, with 119 000 (48%) of these CHD cases occurring in excess of those expected for individuals with higher SES. Conclusions and relevance This study suggested that, for approximately one-quarter of US adults aged 35 to 64 years, low SES was substantially associated with early CHD burden. Although biomedical interventions to modify traditional risk factors may decrease the disease burden, disparities by SES may remain without addressing SES itself.Objectives Uterine lesions with plexiform morphology are uncommon lesions with debated histogenesis. Despite being an incidental and usually benign finding (plexiform tumorlet), some cases can pose diagnostic problems. Their paucity in the recent literature adds to these difficulties and often causes ambiguities. The objective of this study is to systematically review published cases to highlight the historical aspects of their recognition, reappraising their morphology, histogenesis, and differential diagnosis. Methods English literature is reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and 32 reports are analyzed. Results Most cases are reported in the fourth to sixth decades. In most cases (66.7%), plexiform lesions are incidental findings while 33.3% of cases have been the chief pathology. Size varies from 0.5 to 195 mm. Plexiform foci were solitary in 78.2% cases and multiple in 21.8%. In 67.8% of cases, the lesions are reported as myometrial, while 32.2% are arising from endometrial stroma. Immunohistochemistry shows smooth muscle and no sex cord marker expression. They are usually benign lesions, but worrisome features include plexiform morphology in disseminated peritoneal leiomyomatosis, intravenous leiomyomatosis, and diffuse uterine leiomyomatosis. Conclusions Plexiform lesions represent a diverse pathology varying from epithelioid leiomyomas to epithelioid smooth muscle metaplasia of endometrial type of stroma.The universal L-shaped tertiary structure of tRNAs is maintained with the help of nucleotide modifications within the D- and T-loops, and these modifications are most extensive within hyperthermophilic species. The obligate-commensal Nanoarchaeum equitans and its phylogenetically-distinct host Ignicoccus hospitalis grow physically coupled under identical hyperthermic conditions. We report here two fundamentally different routes by which these archaea modify the key conserved nucleotide U54 within their tRNA T-loops. In N. equitans, this nucleotide is methylated by the S-adenosylmethionine-dependent enzyme NEQ053 to form m5U54, and a recombinant version of this enzyme maintains specificity for U54 in Escherichia coli. In N. equitans, m5U54 is subsequently thiolated to form m5s2U54. In contrast, I. hospitalis isomerizes U54 to pseudouridine prior to methylating its N1-position and thiolating the O4-position of the nucleobase to form the previously uncharacterized nucleotide m1s4Ψ. The methyl and thiol groups in m1s4Ψ and m5s2U are presented within the T-loop in a spatially identical manner that stabilizes the 3'-endo-anti conformation of nucleotide-54, facilitating stacking onto adjacent nucleotides and reverse-Hoogsteen pairing with nucleotide m1A58. Thus, two distinct structurally-equivalent solutions have evolved independently and convergently to maintain the tertiary fold of tRNAs under extreme hyperthermic conditions.Background HIV-positive men who have sex with men (MSM) are at high risk of hepatitis C virus (HCV) reinfection following clearance of HCV, but risk factors specifically for reinfection have never been comprehensively assessed. Methods Using data from a prospective observational cohort study among HIV-positive MSM with an acute HCV infection (MOSAIC), the incidence of HCV reinfection following spontaneous clearance or successful treatment was assessed. A univariable Bayesian exponential survival model was used to identify risk factors associated with HCV reinfection. Results 122 HIV-positive MSM who had a spontaneously cleared or successfully treated HCV infection between 2003 and 2017 were included. During a median follow-up of 1.4 years (interquartile range 0.5-3.8), 34 HCV reinfections were observed in 28 patients. The incidence of HCV reinfection was 11.5/100 person-years and among those with reinfection, median time to reinfection was 1.3 years (interquartile range 0.6-2.7). NMS-873 HCV reinfection was associated with receptive condomless anal intercourse, sharing of sex toys, group sex, anal rinsing before sex, ≥10 casual sex partners in the last 6 months, nadir CD4 cell count less then 200 cells/mm3, and recent CD4 cell count less then 500 cells/mm3. Conclusions Incidence of HCV reinfection was high and strongly associated with sexual risk behavior, highlighting the need for interventions to reduce risk behavior and prevent HCV reinfections among HIV-positive MSM.

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