Desmoplastic small round cell tumor (DSRCT) is characterized by the EWSR1-WT1 t(11;22) (p13q12) translocation. Few additional putative drivers have been identified, and research has suffered from a lack of model systems. Next-generation sequencing (NGS) data from 68 matched tumor-normal samples, whole-genome sequencing data from 10 samples, transcriptomic and affymetrix array data, and a bank of DSRCT patient-derived xenograft (PDX) are presented. EWSR1-WT1 fusions were noted to be simple, balanced events. Recurrent mutations were uncommon, but were noted in TERT (3%), ARID1A (6%), HRAS (5%), and TP53 (3%), and recurrent loss of heterozygosity (LOH) at 11p, 11q, and 16q was identified in 18%, 22%, and 34% of samples, respectively. Comparison of tumor-normal matched versus unmatched analysis suggests overcalling of somatic mutations in prior publications of DSRCT NGS data. Alterations in fibroblast growth factor receptor 4 (FGFR4) were identified in 5 of 68 (7%) of tumor samples, whereas differential overexpreon, and recurrent activating mutations.Activating protein 2 alpha (AP-2α; encoded by TFAP2A) functions as a tumor suppressor and influences response to therapy in several cancer types. We aimed to characterize regulation of the transcriptome by AP-2α in colon cancer. CRISPR-Cas9 and short hairpin RNA were used to eliminate TFAP2A expression in HCT116 and a panel of colon cancer cell lines. AP-2α target genes were identified with RNA sequencing and chromatin immunoprecipitation sequencing. Effects on cell cycle were characterized in cells synchronized with aphidicolin and analyzed by FACS and Premo FUCCI. Effects on invasion and tumorigenesis were determined by invasion assay, growth of xenografts, and phosphorylated histone H3 (PHH3). Knockout of TFAP2A induced significant alterations in the transcriptome including repression of TGM2, identified as a primary gene target of AP-2α. Loss of AP-2α delayed progression through S-phase into G2-M and decreased phosphorylation of AKT, effects that were mediated through regulation of TGM2. Buparlisib (BKM120) repressed in vitro invasiveness of HCT116 and a panel of colon cancer cell lines; however, loss of AP-2α induced resistance to buparlisib. Similarly, buparlisib repressed PHH3 and growth of tumor xenografts and increased overall survival of tumor-bearing mice, whereas, loss of AP-2α induced resistance to the effect of PI3K inhibition. Loss of AP-2α in colon cancer leads to prolonged S-phase through altered activation of AKT leading to resistance to the PI3K inhibitor, Buparlisib. The findings demonstrate an important role for AP-2α in regulating progression through the cell cycle and indicates that AP-2α is a marker for response to PI3K inhibitors. IMPLICATIONS AP-2α regulated cell cycle through the PI3K cascade and activation of AKT mediated through TGM2. AP-2α induced sensitivity to Buparlisib/BKM120, indicating that AP-2α is a biomarker predictive of response to PI3K inhibitors.

Regulation of nicotine vaping products (NVPs) varies between countries, impacting the availability and use of these products. This study updated the analyses of O’Connor

on types of NVPs used and examined changes in NVP features used over 18 months in four countries with differing regulatory environments.

Data are from 4734 adult current vapers in Australia, Canada, England and the USA from Waves 1 (2016) and 2 (2018) of the International Tobacco Control Four Country Smoking and Vaping Survey. NVP characteristics included device description, adjustable voltage, nicotine content and tank size. Longitudinal analyses (n=1058) assessed movement towards or away from more complex/modifiable NVPs. A logistic regression was used to examine factors associated with changes in device description from 2016 to 2018.

Like 2016, box-tanks were the most popular NVP (37.3%) in all four countries in 2018. Over 80% of vapers continued using the same NVP and nicotine content between waves, though movement tended towards more complex/modifiable devices (14.4% of vapers). Box-tank users, exclusive daily vapers and older vapers were most likely to continue using the same device description. Certain NVPs and features differed by country, such as higher nicotine contents in the USA (11.5% use 21+ mg/mL) and greater device stability over time in Australia (90.8% stability).

Most vapers continued using the same vaping device and features over 18 months. Differences in NVP types and features were observed between countries, suggesting that differing NVP regulations affect consumer choices regarding the type of vaping device to use.

Most vapers continued using the same vaping device and features over 18 months. Differences in NVP types and features were observed between countries, suggesting that differing NVP regulations affect consumer choices regarding the type of vaping device to use.

Studies examining perceptions of ‘modified risk tobacco product’ (MRTP) messages for e-cigarettes and smokeless tobacco have indicated consumers want statistics and quantification of harm reduction. However, limited research exists on reactions to quantitative MRTP messages.

We conducted 12 focus groups in the USA in 2019-6 focused on e-cigarette messages and 6 on snus messages. Eight groups were with current smokers (ages 21-66) and four with young adult (ages 18-25) non-smokers (n=57). Participants discussed messages stating that use of snus and vaping products have been estimated by scientists to be about 90% and 95% less harmful than smoking cigarettes, respectively.

Several participants agreed the messages strongly communicated that the products are less harmful than cigarettes, were attention getting and could be ‘convincing’. However, participants expressed scepticism about the source and accuracy of the stated figures, and some noted the claims could be misleading and attractive to young people.sage limitations and aim to mitigate unintended consequences.Understanding how and where in the brain sentence-level meaning is constructed from words presents a major scientific challenge. Selleckchem Tozasertib Recent advances have begun to explain brain activation elicited by sentences using vector models of word meaning derived from patterns of word co-occurrence in text corpora. These studies have helped map out semantic representation across a distributed brain network spanning temporal, parietal, and frontal cortex. However, it remains unclear whether activation patterns within regions reflect unified representations of sentence-level meaning, as opposed to superpositions of context-independent component words. This is because models have typically represented sentences as “bags-of-words” that neglect sentence-level structure. To address this issue, we interrogated fMRI activation elicited as 240 sentences were read by 14 participants (9 female, 5 male), using sentences encoded by a recurrent deep artificial neural-network trained on a sentence inference task (InferSent). Recurrent connections and nonlinear filters enable InferSent to transform sequences of word vectors into unified “propositional” sentence representations suitable for evaluating intersentence entailment relations.