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Barrett’s esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC), but its cellular origin and mechanism of neoplastic progression remain unresolved. Notch signaling, which plays a key role in regulating intestinal stem cell maintenance, has been implicated in a number of cancers. The kinase Dclk1 labels epithelial post-mitotic tuft cells at the squamo-columnar junction (SCJ), and has also been proposed to contribute to epithelial tumor growth. Here, we find that genetic activation of intracellular Notch signaling in epithelial Dclk1-positive tuft cells resulted in the accelerated development of metaplasia and dysplasia in a mouse model of BE (pL2.Dclk1.N2IC mice). In contrast, genetic ablation of Notch receptor 2 in Dclk1-positive cells delayed BE progression (pL2.Dclk1.N2fl mice), and led to increased secretory cell differentiation. The accelerated BE progression in pL2.Dclk1.N2IC mice correlated with changes to the transcriptomic landscape, most notably for the activation of oncogenic, proliferative pathways in BE tissues, in contrast to upregulated Wnt signalling in pL2.Dclk1.N2fl mice. Collectively, our data show that Notch activation in Dclk1-positive tuft cells in the gastric cardia can contribute to BE development.

A pilot cross-sectional online study attempts to clarify the role of implicit sociocultural attitudes in future thinking and tests a hypothesis that the implicit activation of Individualism / Collectivism concepts changes the content and other characteristics of self-relevant images of the future — self-defining future projections (SDFPs). The study performed in 2019-2020 involved 191 people, mean age — M = 36.9 (SD = 10.4) years. Group 1 underwent Individualism priming: 108 people (11.2% of males), mean age — M = 37.6 (SD = 1.04) years. Group 2 underwent Collectivism priming: 83 people (22.9% of males), age — M = 36 years (SD = 1.13). No significant sociodemographic between-group differences were found (p<0.05). Two versions of the online survey (one with an Individualism priming task and another with a Collectivism priming task) were randomly sent to students and teachers of Russian higher education institutions. After completing the priming task, the respondents constructed SDFPs in line with the definition provided and evaluated their quality. Experts rated SDFP thematic content, integration of meaning and specificity in accordance with valid coding pro¬cedures. Collectivism / Individualism levels were assessed using the INDCOL test. The priming procedure had a small significant effect on SDFP thematic content, interpersonal orientation, and specificity. It was more prominent in the Collectivism priming, although expected correlations between the Individualism and feelings of the Autonomy and Competence need satisfaction in SDFPs were also found. Collectivism seemed to strengthen future thinking overgenerality and to hinder the capacity to reflect on one’s own future. On the contrary, Individualism involves taking personal responsibility, but it seemed to enhance the need for Relatedness and social support (a protective factor in depressive conditions) in a compensatory manner. The data contributes to a further understanding of implicit influences on future thinking and suggest that it is the balance of the Collectivism and Individualism values that is crucial for mental health.

Introduction Although pharmacogenetic tests provide the information on a genotype and the predicted phenotype, these tests themselves do not provide the interpretation of data for a physician. There are currently approximately two dozen pharmacogenomic clinical decision support systems used in psychiatry. Implementation of clinical decision support systems capable of forming recommendations on drug and dose selection according to the results of pharmacogenetic testing is an urgent task. Fulfillment of this task may allow increasing the efficacy of therapy and decreasing the risk of undesirable side effects. Materials and methods The study included 51 male patients (21 in the main group and 30 in the control group) with alcohol withdrawal syndrome. To evaluate the efficacy and safety of therapy, several international psychometric scales and rating scales to measure side effects were used. Genotyping was performed using real‐time polymerase chain reaction with allele‐specific hybridization. Pharmacogenetic test results were interpreted using free software PGX2 (http://www.pgx2.com). Results Statistically significant differences between the scores derived from all psychometric scales were revealed. For instance, the total score on CIWA‐Ar scale by day 3 was 13.5 [11.2; 16.0] for the main group and 18.0 [17.0; 22.0] (p < 0.001) for the control group; by day 5, it was 6.5 [4.2; 8.0] for the main group and 15.0 [14.0; 16.0] (p < 0.001) for the control group. The UKU side effect rating scale (UKU) also revealed a statistically significant difference. The total score on UKU scale by day 3 was 6.0 [5.0; 7.0] for the main group and 7.0 [6.0; 8.0] (p < 0.001) for the control group; by day 5, this difference grew significantly: 5.5 [3.0; 9.0] for the main group and 14.0 [12.0; 19.0] (p < 0.001) for the control group. The groups were representative (there was no difference between the scores at the inclusion of patients). Conclusion Pharmacogenetic‐guided personalization of drug dose in patients with alcohol withdrawal syndrome can reduce the risk of undesirable side effects and pharmacoresistance. It allows recommending the use of pharmacogenomic clinical decision support systems for optimizing drug dosage.