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Androgens are the obligatory precursors of estrogens. In humans, classic androgen biosynthesis yields testosterone, thought to represent the predominant circulating active androgen both in men and women. However, recent work has shown that 11-ketotestosterone, derived from the newly described 11-oxygenated androgen biosynthesis pathway, makes a substantial contribution to the active androgen pool in women. Considering that classic androgens are the obligatory substrates for estrogen biosynthesis catalyzed by cytochrome P450 aromatase, we hypothesized that 11-oxygenated androgens are aromatizable. Here we use steroid analysis by tandem mass spectrometry to demonstrate that human aromatase generates 11-oxygenated estrogens from 11-oxygenated androgens in 3 different cell-based aromatase expression systems and in human ex vivo placenta explant cultures. We also show that 11-oxygenated estrogens are generated as a byproduct of the aromatization of classic androgens. We show that 11β-hydroxy-17β-estradiol binds and activates estrogen receptors α and β and that 11β-hydroxy-17β-estradiol and the classic androgen pathway-derived active estrogen, 17β-estradiol, are equipotent in stimulating breast cancer cell line proliferation and expression of estrogen-responsive genes. 11-oxygenated estrogens were, however, not detectable in serum from individuals with high aromatase levels (pregnant women) and elevated 11-oxygenated androgen levels (patients with congenital adrenal hyperplasia or adrenocortical carcinoma). Our data show that while 11-oxygenated androgens are aromatizable in vitro and ex vivo, the resulting 11-oxygenated estrogens are not detectable in circulation, suggesting that 11-oxygenated androgens function primarily as androgens in vivo.<br />Virtual consults have replaced in-person visits for many home-isolated patients with COVID-19 disease.<br />To describe the natural history, clinical management and outcomes of community-dwelling patients with COVID-19, who received support from a family medicine-led, virtual CovidCare@Home program in Toronto, Ontario, Canada.<br />Observational, descriptive study conducted by retrospective chart review of 98 patients enrolled during the first 5 weeks of program implementation (8 April-11 May 2020); 73 patients with laboratory-confirmed COVID-19, with symptom onset ≤ 14 days before initial consult were included for analysis. Patients were classified as mild, moderate or severe based on WHO Criteria.<br />All patients in the program experienced mild (88%) or moderate (12.3%) disease. No patients were hospitalized or died. Patients were mainly female (70%); with mean age of 43.3 years. Most patients (82.2%) worked in higher risk, healthcare settings. Almost 40% had no medical co-morbidities. Common symptoms were cough (65.8%), fatigue (60.3%), headache (42.5%) and myalgia (39.7%), followed by fever (32.9%), sore throat (21.9%), nasal congestion (21.9%) and rhinorrhea (20.5%). Headache (51%) and anosmia (45.1%) were common among females; fever and breathlessness among males (40.9%). Nine patients (12.3%) experienced worsening of symptoms (mainly respiratory) or exacerbation of co-morbidities, which required care outside the virtual service.<br />Patients with mild to moderate COVID-19 disease can be managed safely and effectively in a family medicine-led virtual program. Some sex differences in symptoms were observed. Future work should focus on long-term follow up in view of the existence of so-called 'long-haulers'.<br />Patients with mild to moderate COVID-19 disease can be managed safely and effectively in a family medicine-led virtual program. Some sex differences in symptoms were observed. Future work should focus on long-term follow up in view of the existence of so-called 'long-haulers'.A large number of studies are being conducted to evaluate the efficacy and safety of candidate vaccines against novel coronavirus disease-2019 (COVID-19). [https://www.selleckchem.com/products/as601245.html AS601245 nmr] Most Phase 3 tri- als have adopted virologically confirmed symptomatic COVID-19 disease as the primary efficacy endpoint, although laboratory-confirmed SARS-CoV-2 is also of interest. In addi- tion, it is important to evaluate the effect of vaccination on disease severity. To provide a full picture of vaccine efficacy and make efficient use of available data, we propose using SARS-CoV-2 infection, symptomatic COVID-19, and severe COVID-19 as dual or triple pri- mary endpoints. We demonstrate the advantages of this strategy through realistic simulation studies. Finally, we show how this approach can provide rigorous interim monitoring of the trials and efficient assessment of the durability of vaccine efficacy.Epithelial-mesenchymal transition (EMT) has been shown to be linked to a poor prognosis, particularly in patients with non-small-cell lung cancer. Nevertheless, little is known regarding the existence of EMT-related gene signatures and their prognostic values in lung adenocarcinoma (LUAD). In the current study, we systematically profiled the mRNA expression data of patients with LUAD in The Cancer Genome Atlas and Gene Expression Omnibus databases using a total of 1,184 EMT-related genes. The prognostic values of the EMT-related genes used to develop risk score models for overall survival were determined using LASSO and Cox regression analyses. A prognostic signature that consisted of nine unique EMT-related genes was generated using a training set. A nomogram, incorporating this EMT-related gene signature and clinical features of patients with LUAD, was constructed for potential clinical use. Calibration plots, decision-making curves, and receiver operating characteristic curve analysis showed that this model had a good ability to predict the survival of patients with LUAD. The EMT-associated gene signature and prognostic nomogram established in this study were reliable in predicting the survival of patients with LUAD. Thus, we first identified a novel EMT-related gene signature and developed a nomogram for predicting the prognosis of patients with LUAD.<br />The use of platelet-rich fibrin (PRF) membranes has been evaluated for different purposes. However, few studies aimed to assess the effect of PRF membranes on peri-implant mucosal thickness augmentation. Thus, the aim was to evaluate whether the use of PRF membranes placed using the same surgical procedure of single implant installation in the anterior area of the maxilla can result in peri-implant mucosal thickness increase.<br />Eight patients received single maxillary implants (anterior area), covered by three PRF membranes (2,500 rpm/12 minutes, RCFmax = 719.71 g). Clinical parameters (baseline and 3 months postoperative) and patient-centered parameters were evaluated. The buccal peri-implant mucosal thickness (BMT) and ridge defect (RD) parameters showed a statistically significant difference, with a gain of 0.7 ± 0.3 mm in BMT and reduction of 0.8 ± 0.3 mm in RD. Supracrestal tissue height (STH) was &gt;3 mm after 3 months. Postoperative pain and number of analgesics showed low values (0.95 ± 1.06 and 1.