Search

Following publication of the original article [1], the authors reported two errors in Fig. 1B and Fig. 2B. 1. The two EP + siGLO and DS + siGLO brightfield/β-gal images from Fig. 2A were accidentally duplicated in Fig. 1B. The images in Fig. 2A are correct. The images in Fig. 1B are replaced with representative images of untransfected EP and DS cells. The incorrect and the correct figure are given below. The incorrect Fig. 1: (Figure presented.) The correct Fig. 1: (Figure presented.) The replacement of these images does not change any of the other data in this figure, nor the conclusion of this figure. 2. The authors also noticed that the panels in Fig. 2B labelled with “DS” were incorrectly labelled. The bar charts and figure legend correctly state that these images are “DS + siGLO” images. These panels are now relabelled as “DS + siGLO”. This proposed relabelling does not change any of the other data in this figure, nor the conclusion of Fig. 2B. The incorrect and the correct figure are given below. The incorrect Fig. 2: (Figure presented.) The correct Fig. 2: (Figure presented.) In both instances, these errors do not change any data associated with these figures, nor do they change the conclusions of the corresponding figures and the paper.

BackgroundCellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. Here, we perform methylome analysis of actively dividing and deeply senescent normal human epithelial cells.ResultsWe identify senescence-associated differentially methylated positions (senDMPs) from multiple experiments using cells from one donor. We find that human senDMP epigenetic signatures are positively and significantly correlated with both cancer and ageing-associated methylation dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, which are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that a single senDMP signature can be effectively reversed in a newly-developed protocol of transient senescence reversal.ConclusionsThe senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that may lead to cancer and age-related diseases in humans.

Background: This study aimed to describe treatment patterns and overall survival (OS) in patients with advanced non–small cell lung cancer (aNSCLC) in three countries between 2011 and 2020. Methods: Three databases (US, Canada, Germany) were used to identify incident aNSCLC patients. OS was assessed from the date of incident aNSCLC diagnosis and, for patients who received at least a first line of therapy (1LOT), from the date of 1LOT initiation. In multivariable analyses, we analyzed the influence of index year and type of prescribed treatment on OS. Findings: We included 51,318 patients with an incident aNSCLC diagnosis. The percentage of patients treated with a 1LOT differed substantially between countries, whereas the number of patients receiving immunotherapies/targeted treatments increased over time in all three countries. Median OS from the date of incident diagnosis was 9.9 months in the United States vs. 4.1 months in Canada. When measured from the start of 1LOT, patients had a median OS of 10.7 months in the United States, 10.9 months in Canada, and 10.9 months in Germany. OS from the start of 1LOT improved in all three countries from 2011 to 2020 by approximately 3 to 4 months. Conclusions: Observed continuous improvement in OS among patients receiving at least a 1LOT from 2011 to 2020 was likely driven by improved care and changes in the treatment landscape. The difference in the proportion of patients receiving a 1LOT in the observed countries requires further investigation. Observed continuous improvement in overall survival among patients receiving at least a first line of therapy from 2011 to 2020 was likely driven by improved care and changes in treatment landscape. The difference in the proportion of patients receiving a first line of therapy in the observed countries requires further investigation. [ABSTRACT FROM AUTHOR]

Across its clinical development program, ocrelizumab demonstrated efficacy in improving clinical outcomes in multiple sclerosis, including annualized relapse rates and confirmed disability progression. However, as with any new treatment, it was unclear how this efficacy would translate into real‐world clinical practice. The objective of this study was to systematically collate the published real‐world clinical effectiveness data for ocrelizumab in relapsing remitting multiple sclerosis and primary progressive multiple sclerosis. A search strategy was developed in MEDLINE and Embase to identify articles reporting real‐world evidence in people with relapsing remitting multiple sclerosis or primary progressive multiple sclerosis receiving treatment with ocrelizumab. The search focused on English language articles only but was not limited by the country in which the study was conducted or the time frame of the study. Additional manual searches of relevant websites were also performed. Fifty‐two studies were identified reporting relevant evidence. Real‐world effectiveness data for ocrelizumab were consistently favorable, with reductions in relapse rate and disease progression rates similar to those reported in the OPERA I/OPERA II and ORATORIO clinical trials, including in studies with more diverse patient populations not well represented in the pivotal trials. Although direct comparisons are confounded by lack of randomization of treatments, outcomes reported suggest that ocrelizumab has a similar or greater efficacy than other therapy options. Initial real‐world effectiveness data for ocrelizumab appear favorable and consistent with results reported in clinical trials, providing clinicians with an efficacious option to treat patients with multiple sclerosis. [ABSTRACT FROM AUTHOR]

Migraine with aura is a common, debilitating, recurrent headache disorder associated with transient and reversible focal neurological symptoms (1). A role has been suggested for the two-pore domain (K2P) potassium channel, TWIK-related spinal cord potassium channel (TRESK, encoded by KCNK18), in pain pathways and general anaesthesia (2). We therefore examined whether TRESK is involved in migraine by screening the KCNK18 gene in subjects diagnosed with migraine. Here we report a frameshift mutation, F139WfsX24, which segregates perfectly with typical migraine with aura in a large pedigree. We also identified prominent TRESK expression in migraine-salient areas such as the trigeminal ganglion. Functional characterization of this mutation demonstrates that it causes a complete loss of TRESK function and that the mutant subunit suppresses wild-type channel function through a dominant-negative effect, thus explaining the dominant penetrance of this allele. These results therefore support a role for TRESK in the pathogenesis of typical migraine with aura and further support the role of this channel as a potential therapeutic target., Migraine is a common recurrent headache disorder, with an annual prevalence estimated at 18.2% in females and 6.5% in males (1). One third of attacks, which can last from 4 [...]