Discovery and clinical translation of ceperognastat, an O-GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease.

Introduction: The aggregation and spread of hyperphosphorylated, pathological tau in the human brain is hypothesized to play a key role in Alzheimer's disease (AD) as well as other neurogenerative tauopathies. O-GlcNAcylation, an important post-translational modification of tau and many other proteins, is significantly decreased in brain tissue of AD patients relative to healthy controls. Increased tau O-GlcNAcylation has been shown to reduce tau pathology in mouse in vivo tauopathy models.

Placenta accreta spectrum disorders: A Canadian tertiary care centre's experience over 10 years.

Objectives: The placenta accreta spectrum disorders (PASD) are associated with significant maternal and neonatal morbidity and mortality worldwide. As cesarean delivery rates increase, so does the rate of PASD. PASD antepartum diagnosis and perioperative management are evolving, and we primarily aimed to share our tertiary care centre's institutional approach and outcomes over a decade.

Paleomagnetic evidence for Neoarchean plate mobilism.

Plate tectonics is a unique feature of Earth, but its proposed time of initiation is still controversial, with published estimates ranging from ca. 4.2 to 0.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.