Sentiment Analysis on Twitter: Role of Healthcare Professionals in the Global Conversation during the AstraZeneca Vaccine Suspension.

The vaccines against COVID-19 arrived in Spain at the end of 2020 along with vaccination campaigns which were not free of controversy. The debate was fueled by the adverse effects following the administration of the AstraZeneca-Oxford (AZ) vaccine in some European countries, eventually leading to its temporary suspension as a precautionary measure. In the present study, we analyze the healthcare professionals' conversations, sentiment, polarity, and intensity on social media during two periods in 2021: the one closest to the suspension of the AZ vaccine and the same time frame 30 days later. We also analyzed whether there were differences between Spain and the rest of the world. Results: The negative sentiment ratio was higher (U = 87; p = 0.048) in Spain in March (Med = 0.396), as well as the daily intensity (U = 86; p = 0.044; Med = 0.440). The opposite happened with polarity (U = 86; p = 0.044), which was higher in the rest of the world (Med = -0.264). Conclusions: There was a general increase in messages and interactions between March and April. In Spain, there was a higher incidence of negative messages and intensity compared to the rest of the world during the March period that disappeared in April. Finally, it was found that the dissemination of messages linked to negative emotions towards vaccines against COVID-19 from healthcare professionals contributed to a negative approach to primary prevention campaigns in the middle of the pandemic.

Histone Modifications Drive Aberrant Notch3 Expression/Activity and Growth in T-ALL.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood cancer caused by the deregulation of key T-cell developmental pathways, including Notch signaling. Aberrant Notch signaling in T-ALL occurs by NOTCH1 gain-of-function mutations and by NOTCH3 overexpression. Although NOTCH3 is assumed as a Notch1 target, machinery driving its transcription in T-ALL is undefined in leukemia subsets lacking Notch1 activation. Here, we found that the binding of the intracellular Notch3 domain, as well as of the activated Notch1 fragment, to the NOTCH3 gene locus led to the recruitment of the H3K27 modifiers JMJD3 and p300, and it was required to preserve transcriptional permissive/active H3K27 marks and to sustain NOTCH3 gene expression levels. Consistently, pharmacological inhibition of JMJD3 by GSKJ4 treatment or of p300 by A-485 decreased the levels of expression of NOTCH3, NOTCH1 and of the Notch target genes DELTEX1 and c-Myc and abrogated cell viability in both Notch1- and Notch3-dependent T-cell contexts. Notably, re-introduction of exogenous Notch1, Notch3 as well as c-Myc partially rescued cells from anti-growth effects induced by either treatment. Overall our findings indicate JMJD3 and p300 as general Notch1 and Notch3 signaling co-activators in T-ALL and suggest further investigation on the potential therapeutic anti-leukemic efficacy of their enzymatic inhibition in Notch/c-Myc axis-related cancers and diseases.

Chalcones and Chalcone-mimetic Derivatives as Notch Inhibitors in a Model of T-cell Acute Lymphoblastic Leukemia.

Based on hit-likeness and chemical diversity, a number of chalcones and chalcone-mimetic compounds were selected as putative Notch inhibitors. The evaluation of the antiproliferative effect combined with the inhibition of Notch1 expression in KOPTK1 cell line identified compound 18, featuring a tetrahydronaphthalene-based scaffold, as a new promising Notch-blocking agent.