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J Med Chem
January 2025
Epics Therapeutics SA, rue Adrienne Bolland 47, Gosselies 6041, Belgium.
METTL3 is the RNA methyltransferase predominantly responsible for the addition of N-methyladenosine (mA), the most abundant modification to mRNA. The prevalence of mA and the activity and expression of METTL3 have been linked to the appearance and progression of acute myeloid leukemia (AML), thereby making METTL3 an attractive target for cancer therapeutics. We report herein the discovery and optimization of small-molecule inhibitors of METTL3, culminating in the selection of as an proof-of-concept compound.
View Article and Find Full Text PDFOper Neurosurg (Hagerstown)
November 2024
Department of Neurosurgery, University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Background And Objectives: IDH-wildtype glioblastoma multiforme (GBM) and grade 4 IDH-mutant astrocytoma are challenging to manage in oncology. This study explores the contrast between gross total resection (GTR) and supratotal resection (SupTR) for IDH-wildtype GBM and grade 4 IDH-mutant astrocytoma, aiming to summarize their influence on crucial clinical outcomes.
Methods: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.
Oper Neurosurg (Hagerstown)
November 2024
Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Background And Objectives: Accurate intraoperative assessment of coronal alignment is critical to achieving favorable clinical outcomes in adult spinal deformity surgery. However, surgical positioning creates challenges in predicting standing coronal alignment. Gravity-based plumblines require an upright posture and are not possible intraoperatively.
View Article and Find Full Text PDFJ Cereb Blood Flow Metab
January 2025
Department of Applied Physics and Electronics, Umeå University, Umeå, Sweden.
Variations in cerebral blood flow and blood volume interact with intracranial pressure and cerebrospinal fluid dynamics, all of which play a crucial role in brain homeostasis. A key physiological modulator is respiration, but its impact on cerebral blood flow and volume has not been thoroughly investigated. Here we used 4D flow MRI in a population-based sample of 65 participants (mean age = 75 ± 1) to quantify these effects.
View Article and Find Full Text PDFPLoS One
January 2025
Division of Hepatobiliary and Transplantation Surgery, Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Background And Objectives: Urological complications after kidney transplantation, due to the ureteroneocystostomy, are associated with significant morbidity, prolonged hospital stay and even mortality. Ureteral stents can minimize the number of complications but are not consistently used, as previous studies were retrospective in nature. We aim to prospectively determine the most effective stenting approach.
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