Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia.

DNA methylation, a key epigenetic driver of transcriptional silencing, is universally dysregulated in cancer. Reversal of DNA methylation by hypomethylating agents, such as the cytidine analogs decitabine or azacytidine, has demonstrated clinical benefit in hematologic malignancies. These nucleoside analogs are incorporated into replicating DNA where they inhibit DNA cytosine methyltransferases DNMT1, DNMT3A and DNMT3B through irreversible covalent interactions.

Melanins as Sustainable Resources for Advanced Biotechnological Applications.

Melanins are a class of biopolymers that are widespread in nature and have diverse origins, chemical compositions, and functions. Their chemical, electrical, optical, and paramagnetic properties offer opportunities for applications in materials science, particularly for medical and technical uses. This review focuses on the application of analytical techniques to study melanins in multidisciplinary contexts with a view to their use as sustainable resources for advanced biotechnological applications, and how these may facilitate the achievement of the United Nations Sustainable Development Goals.

Characterization of fecal sludge as biomass feedstock for thermal treatment in the southern Indian state of Tamil Nadu.

: Transformative sanitation technologies aim to treat fecal sludge (FS) by thermal processes and recover resources from it. There is a paucity of data describing the relevant properties of FS as viable feedstock for thermal treatment in major geographical target areas, such as India. : This study characterized FS collected from septic tanks in two cities located in the Indian southern state of Tamil Nadu.

and induction of fetal hemoglobin with a reversible and selective DNMT1 inhibitor.

Pharmacological induction of fetal hemoglobin (HbF) expression is an effective therapeutic strategy for the management of beta-hemoglobinopathies such as sickle cell disease. DNA methyltransferase (DNMT) inhibitors 5-azacytidine (5-aza) and 5-aza-2'-deoxycytidine (decitabine) have been shown to induce fetal hemoglobin expression in both preclinical models and clinical studies, but are not currently approved for the management of hemoglobinopathies. We report here the discovery of a novel class of orally bioavailable DNMT1-selective inhibitors as exemplified by GSK3482364.

Out-of-hospital Times Using Helicopters Versus Ground Services for Emergency Patients.

Objective: Minimizing out-of-hospital time reduces morbidity and mortality in patients with severe trauma, acute coronary syndrome, or acute stroke. Our objective was to compare out-of-hospital times by helicopter versus ground services when the estimated time of arrival on the scene was over 20 minutes.

Methods: We proposed a retrospective observational monocentric study following 2 cohorts.