BackgroundWhole transcriptome RNA variant analyses have shown that adenosine deaminases acting on RNA (ADAR) enzymes modify a large proportion of cellular RNAs, contributing to transcriptome diversity and cancer evolution. Despite the advances in the understanding of ADAR function in breast cancer, ADAR RNA editing functional consequences are not fully addressed.ResultsWe characterized A to G(I) mRNA editing in 81 breast cell lines, showing increased editing at 3′UTR and exonic regions in breast cancer cells compared to immortalized non-malignant cell lines. In addition, tumors from the BRCA TCGA cohort show a 24% increase in editing over normal breast samples when looking at 571 well-characterized UTRs targeted by ADAR1. Basal-like subtype breast cancer patients with high level of ADAR1 mRNA expression shows a worse clinical outcome and increased editing in their 3′UTRs. Interestingly, editing was particularly increased in the 3′UTRs of ATM, GINS4 and POLH transcripts in tumors, which correlated with their mRNA expression. We confirmed the role of ADAR1 in this regulation using a shRNA in a breast cancer cell line (ZR-75-1).ConclusionsAltogether, these results revealed a significant association between the mRNA editing in genes related to cancer-relevant pathways and clinical outcomes, suggesting an important role of ADAR1 expression and function in breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s40659-018-0185-4) contains supplementary material, which is available to authorized users.
ImportanceGreater than 20% of cases and 0.4% of deaths from COVID-19 occur in children. Following demonstration of the safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial immediately expanded to adolescents.ObjectiveTo evaluate the safety, immunogenicity, and efficacy of NVX-CoV2373 in adolescents.Design, Setting, and ParticipantsThe NVX-CoV2373 vaccine was evaluated in adolescents aged 12 to 17 years in an expansion of PREVENT-19, a phase 3, randomized, observer-blinded, placebo-controlled multicenter clinical trial in the US. Participants were enrolled from April 26 to June 5, 2021, and the study is ongoing. A blinded crossover was implemented after 2 months of safety follow-up to offer active vaccine to all participants. Key exclusion criteria included known previous laboratory-confirmed SARS-CoV-2 infection or known immunosuppression. Of 2304 participants assessed for eligibility, 57 were excluded and 2247 were randomized.InterventionsParticipants were randomized 2:1 to 2 intramuscular injections of NVX-CoV2373 or placebo, 21 days apart.Main Outcomes and MeasuresSerologic noninferiority of neutralizing antibody responses compared with those in young adults (aged 18-25 years) in PREVENT-19, protective efficacy against laboratory-confirmed COVID-19, and assessment of reactogenicity and safety.ResultsAmong 2232 participants (1487 NVX-CoV2373 and 745 placebo recipients), the mean (SD) age was 13.8 (1.4) years, 1172 (52.5%) were male, 1660 (74.4%) were White individuals, and 359 (16.1%) had had a previous SARS-CoV-2 infection at baseline. After vaccination, the ratio of neutralizing antibody geometric mean titers in adolescents compared with those in young adults was 1.5 (95% CI, 1.3-1.7). Twenty mild COVID-19 cases occurred after a median of 64 (IQR, 57-69) days of follow-up, including 6 among NVX-CoV2373 recipients (incidence, 2.90 [95% CI, 1.31-6.46] cases per 100 person-years) and 14 among placebo recipients (incidence, 14.20 [95% CI, 8.42-23.93] cases per 100 person-years), yielding a vaccine efficacy of 79.5% (95% CI, 46.8%-92.1%). Vaccine efficacy for the Delta variant (the only viral variant identified by sequencing [n = 11]) was 82.0% (95% CI, 32.4%-95.2%). Reactogenicity was largely mild to moderate and transient, with a trend toward greater frequency after the second dose of NVX-CoV2373. Serious adverse events were rare and balanced between treatments. No adverse events led to study discontinuation.Conclusions and RelevanceThe findings of this randomized clinical trial indicate that NVX-CoV2373 is safe, immunogenic, and efficacious in preventing COVID-19, including the predominant Delta variant, in adolescents.Trial RegistrationClinicalTrials.gov Identifier: NCT04611802
Based on their effect on prey populations, predators can interact synergistically, additively, or antagonistically. Predator attraction by semiochemicals in response to herbivory is well documented; however, the possibility of semiochemicals mediating synergistic interactions has not been explored. Eriopis connexa (Germar) and Hippodamia variegata (Goeze) (both Coleoptera: Coccinellidae) interact synergistically with carabid species in Central Chile, a phenomenon in which semiochemicals may be involved. Moreover, olfactory behaviour in these coccinellids is unknown. Olfactometries contrasting non‐infested vs. infested plants with Acyrthosiphon pisum Harris (Hemiptera: Aphididae) were performed to study olfactory prey‐searching in E. connexa, H. variegata, and Trirammatus striatula (Fabricius) (Coleoptera: Carabidae). To evaluate whether semiochemicals can mediate synergistic predatory interactions, four experiments were established: olfactometries contrasting (1) infested plants with and without a predator, (2) uninfested plants with and without a predator; (3) predator vs. air, and (4) plants with previous physical activity of a predator vs. clean plants (nine combinations of predator species, according to whether they corresponded to the stimulus or focal individual). Hippodamia variegata and T. striatula were attracted to infested plants when contrasted with non‐infested plants. Infested plants with a conspecific and H. variegata elicited attraction in E. connexa, whereas T. striatula preferred infested plants with E. connexa or H. variegata. Treatments with only predators (with or without the plant) did not elicit responses, except in E. connexa which was repelled by conspecifics and H. variegata, perhaps indicating an antagonistic interaction between them; plants with previous physical activity of predators did not elicit responses. These results corroborated the importance of semiochemicals produced by herbivory in the prey‐searching behaviour of aphidophagous predators. In addition, presence of predators on the foliage may favour emission of aphid alarm pheromones, which could attract E. connexa and T. striatula. Volatiles can intervene in synergistic interactions between carabids and coccinellids; this should be replicable in other systems where predator‐facilitation between aphidophagous predators is observed.
BackgroundVaginitis is a common complaint in primary care. In uncomplicated candidal vaginitis, there are no differences in effectiveness between oral or vaginal treatment. Some studies describe that the preferred treatment is the oral one, but a Cochrane's review points out inconsistencies associated with the report of the preferred way that limit the use of such data. Risk factors associated with recurrent vulvovaginal candidiasis still remain controversial.Methods/DesignThis work describes a protocol of a multicentric prospective observational study with one year follow up, to describe the women's reasons and preferences to choose the way of administration (oral vs topical) in the treatment of not complicated candidal vaginitis. The number of women required is 765, they are chosen by consecutive sampling. All of whom are aged 16 and over with vaginal discharge and/or vaginal pruritus, diagnosed with not complicated vulvovaginitis in Primary Care in Madrid.The main outcome variable is the preferences of the patients in treatment choice; secondary outcome variables are time to symptoms relief and adverse reactions and the frequency of recurrent vulvovaginitis and the risk factors. In the statistical analysis, for the main objective will be descriptive for each of the variables, bivariant analysis and multivariate analysis (logistic regression).. The dependent variable being the type of treatment chosen (oral or topical) and the independent, the variables that after bivariant analysis, have been associated to the treatment preference.DiscussionClinical decisions, recommendations, and practice guidelines must not only attend to the best available evidence, but also to the values and preferences of the informed patient.
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