Metformin reduces the clonal fitness of Dnmt3aR878H hematopoietic stem and progenitor cells by reversing their aberrant metabolic and epigenetic state.

Clonal hematopoiesis (CH) arises when a hematopoietic stem cell (HSC) acquires a mutation that confers a competitive advantage over wild-type (WT) HSCs, resulting in its clonal expansion. Individuals with CH are at an increased risk of developing hematologic neoplasms and a range of age-related inflammatory illnesses1-3. Therapeutic interventions that suppress the expansion of mutant HSCs have the potential to prevent these CH-related illnesses; however, such interventions have not yet been identified. The most common CH driver mutations are in the DNA methyltransferase 3 alpha (DNMT3A) gene with arginine 882 (R882) being a mutation hotspot. Here we show that murine hematopoietic stem and progenitor cells (HSPCs) carrying the Dnmt3aR878H/+ mutation, which is equivalent to human DNMT3AR882H/+, have increased mitochondrial respiration compared with WT cells and are dependent on this metabolic reprogramming for their competitive advantage. Importantly, treatment with metformin, an oral anti-diabetic drug with inhibitory activity against complex I in the electron transport chain (ETC), reduced the fitness of Dnmt3aR878H/+ HSCs. Through a multi-omics approach, we discovered that metformin acts by enhancing the methylation potential in Dnmt3aR878H/+ HSPCs and reversing their aberrant DNA CpG methylation and histone H3K27 trimethylation (H3K27me3) profiles. Metformin also reduced the fitness of human DNMT3AR882H HSPCs generated by prime editing. Our findings provide preclinical rationale for investigating metformin as a preventive intervention against illnesses associated with DNMT3AR882 mutation-driven CH in humans.

Developing a Multi-Criteria Decision Making approach to compare types of classroom furniture considering mismatches for anthropometric measures of university students.

The mismatch between students' anthropometric measures and school furniture dimensions have been investigated in many countries. In Iran, collegians spend at least a quarter of the day hours at university in the sitting position, so it is essential to evaluate furniture mismatch among university students. In Iranian universities, the use of chairs with an attached table is widespread, while the study of mismatches in these chairs among the collegian community is rare. This study was aimed to compare and rank different classroom furniture types based on the mismatch between collegians' anthropometric measures and the dimensions of classroom furniture among Industrial Engineering students by developing a Multi-Criteria Decision Making approach in an integrated Methodology. The sample consisted of 111 participants (71 males, 40 females). Ten anthropometric measures were gathered, together with eight furniture dimensions for four types of chairs. Mismatch analyses were carried out using mismatch equations, and the Simple Additive Weighting method was used as a base method to solve the decision-making problem. The results indicated that Underneath Desk Height and Seat to Desk Clearance showed the highest levels of the match, while Seat Width presents the highest levels of low mismatch. According to the results, Type 1 and Type 3 were the best current classroom furniture. The Sensitivity Analysis was performed in two ways: changing the weights of criteria in nine scenarios and comparing the results with five other MCDM methods. The proposed MCDM approach can be used widely in furniture procurement processes and educational environments.

The Relationship Between Attachment Styles, Self-Monitoring and Cybercrime in Social Network Users.

BACKGROUND: The anonymity in the cyberspace environment, as well as the rapid advent of and improvements to online activities has increased cybercrime. OBJECTIVES: The aim of this paper was to survey the relationship between attachment styles, self-monitoring and cybercrime in social network users. PATIENTS AND METHODS: The Collins and Read Adult Attachment Scale, and the Snyder self-monitoring and cybercrime scales were sent to 500 social network users. Of these, 203 users (103 men and 100 women) filled out the questionnaires. RESULTS: The results showed that women achieved higher scores in self-monitoring and the anxious attachment style, and men achieved higher scores in cybercrime and the anxious attachment style. There was a negative correlation between self-monitoring and cybercrime, and the anxious attachment style had a positive correlation with cybercrime and a negative correlation with self-monitoring. The secure attachment style had a positive correlation with self-monitoring and a negative correlation with cybercrime. The dependent attachment style had a positive correlation with self-monitoring and a negative correlation with cybercrime. All correlations were significant. CONCLUSIONS: Attachment styles have significant relationships with both self-monitoring and cybercrime. Self-monitoring and attachment styles are significant predictors of cybercrimes.