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Catheter ablation is effective in reducing atrial fibrillation (AF), but the association of ablation for AF with quality of life is unclear. To evaluate whether the procedural outcome of ablation for AF is associated with quality of life (QOL) measures. This was a prespecified secondary analysis of the Substrate and Trigger Ablation for Reduction of Atrial Fibrillation-Part II (STAR AF II) prospective randomized clinical trial, which compared 3 strategies for ablation of persistent AF. This analysis included 549 of the 589 patients enrolled in the trial who underwent ablation. Enrollment occurred at 35 centers in Europe, Canada, Australia, China, and Korea from November 2010 to July 2012. Data for the current study were analyzed on December 11, 2019. Patients underwent AF ablation with 1 of 3 ablation strategies (1) pulmonary vein isolation (PVI), (2) PVI plus complex fractionated electrograms, or (3) PVI plus linear lesions. Quality of life was assessed at baseline and at 6, 12, and 18 months afternt QOL improvement occurred in all 3 study arms and regardless of AF recurrence, defined as AF episodes lasting more than 30 seconds for no recurrence, mean (SD) PCS increased from 66.5 (20.9) to 79.1 (19.4) and MCS from 35.3 (8.7) to 37.7 (7.7); for recurrence, mean (SD) PCS increased from 70.2 (20.4) to 86.4 (16.8) and MCS from 35.3 (8.6) to 37.1 (7.4) (P < .05 for all). When outcome was defined by AF burden reduction, in patients with less than 70% reduction in AF burden, the increase in PCS was significantly less than in those with greater than 70% reduction, and only 3 of 8 subscales showed significant improvement. In this secondary analysis, decreases in AF burden after ablation for AF were significantly associated with improvements in QOL. Quality of life changes were significantly associated with the percentage of AF burden reduction after ablation. ClinicalTrials.gov Identifier NCT01203748. ClinicalTrials.gov Identifier NCT01203748. Congenital cytomegalovirus infection (cCMVi) is one of the most common infections associated with childhood hearing loss. Prevention and mitigation of cCMVi-related hearing loss will require an increase in newborn screening, which is not yet available in China. To estimate the cost-effectiveness of newborn screening strategies for cCMVi from the perspective of the Chinese health care system. A decision tree for a simulated cohort population of 15 000 000 live births was developed to compare the costs and health effects of 3 mutually exclusive interventions (1) no screening, (2) targeted screening using CMV polymerase chain reaction assay for newborns who fail a universal hearing screening, and (3) universal screening for CMV among all newborns. Markov diagrams were used to evaluate the lifetime horizon (76 years). Cost, hearing-related health outcomes, and incremental cost-effectiveness ratios (ICERs) were estimated based on a direct medical costs perspective. Costs and ICERs were reported in 2018 US considered for the Chinese population. While the results are specific to China, the model may easily be adapted for other countries. To achieve cost-effectiveness and best health outcomes, universal screening could be considered for the Chinese population. While the results are specific to China, the model may easily be adapted for other countries.The COVID-19 (coronavirus disease 2019) pandemic has underscored the critical need for all countries to strengthen their health data and information systems and ensure the routes the data travel, from submission to use, are unobstructed. Timely, credible, reliable, and actionable data are key to ensuring that political decisions are data driven and facilitate understanding, monitoring, and forecasting. To ensure that critical decisions related to the wider health and socioeconomic effects of this pandemic are data driven, each country needs to develop or enhance a national data governance plan that includes a clear coordination mechanism, well-defined and documented data processes (manual or electronic), the exchange of data, and a data culture to empower users. In addition, countries should now more than ever invest and enhance their data and health information systems to ensure that all decisions are data driven and that they are prepared for what is next.The majority of the human genome encodes long noncoding RNA (lncRNA) genes, critical regulators of various cellular processes, which largely outnumber protein-coding genes. However, lncRNA-involved fusions have not been surveyed and characterized yet. Here, we present a systematic study of the lncRNA fusion landscape across cancer types and identify >30 000 high-confidence tumor-specific lncRNA fusions (using 8284 tumor and 6946 normal samples). Fusions positively correlated with DNA damage and cancer stemness and were specifically low in microsatellite instable (MSI)-High or virus-infected tumors. Moreover, fusions distribute differently among cancer molecular subtypes, but with shared enrichment in tumors that are microsatellite stable (MSS), with high somatic copy number alterations (SCNA), and with poor survival. https://www.selleckchem.com/products/rgd-arg-gly-asp-peptides.html Importantly, we find a potentially new mechanism, mediated by enhancer RNAs (eRNA), which generates secondary fusions that form densely connected fusion networks with many fusion hubs targeted by FDA-approved drugs. Finally, we experimentally validate functions of two tumor-promoting chimeric proteins derived from mRNA-lncRNA fusions, KDM4B-G039927 and EPS15L1-lncOR7C2-1. The EPS15L1 fusion protein may regulate (Gasdermin E) GSDME, critical in pyroptosis and anti-tumor immunity. Our study completes the fusion landscape in cancers, sheds light on fusion mechanisms, and enriches lncRNA functions in tumorigenesis and cancer progression.Nucleic acid therapeutics (NATs) have proven useful in promoting the degradation of specific transcripts, modifying gene expression, and regulating mRNA splicing. In each situation, efficient delivery of nucleic acids to cells, tissues and intracellular compartments is crucial-both for optimizing efficacy and reducing side effects. Despite successes in NATs, our understanding of their cellular uptake and distribution in tissues is limited. Current methods have yielded insights into distribution of NATs within cells and tissues, but the sensitivity and resolution of these approaches are limited. Here, we show that nanoscale secondary ion mass spectrometry (NanoSIMS) imaging can be used to define the distribution of 5-bromo-2'-deoxythymidine (5-BrdT) modified antisense oligonucleotides (ASO) in cells and tissues with high sensitivity and spatial resolution. This approach makes it possible to define ASO uptake and distribution in different subcellular compartments and to quantify the impact of targeting ligands designed to promote ASO uptake by cells.
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