Drug Development.

Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.

Amyloidosis and Heart Transplantation in a New Era.

Background: The prognosis in patients with advanced cardiac amyloidosis (CA) remains poor.

Objectives: We sought to describe survival post heart transplantation (HT) in amyloid compared with non-amyloid recipients, highlight waitlist times within the new allocation system across three Organ Procurement and Transplantation Network (OPTN) regions, and describe multiorgan transplantation (MOT) in hereditary amyloidosis.

Methods: This is a retrospective review of end-stage CA patients who underwent HT at Mayo Clinic from January 2007 to December 2020.

Single unit-derived connectivity networks in tuberous sclerosis complex reveal propensity for network hypersynchrony driven by tuber-tuber interactions.

Network hypersynchrony is emerging as an important system-level mechanism underlying seizures, as well as cognitive and behavioural impairments, in children with structural brain abnormalities. We investigated patterns of single neuron action potential behaviour in 206 neurons recorded from tubers, transmantle tails of tubers and normal looking cortex in 3 children with tuberous sclerosis. The patterns of neuronal firing on a neuron-by-neuron (autocorrelation) basis did not reveal any differences as a function of anatomy.

Cancer mutations rewire the RNA methylation specificity of METTL3-METTL14.

Chemical modification of RNAs is important for posttranscriptional gene regulation. The METTL3-METTL14 complex generates most -methyladenosine (mA) modifications in messenger RNAs (mRNAs), and dysregulated methyltransferase expression has been linked to cancers. Here we show that a changed sequence context for mA can promote oncogenesis.

Methodological report of a cross-sectional survey of abortion-related knowledge, attitudes and practices amongst health professionals in Britain, strategies adopted and lessons learned: evidence from the SACHA Study.

Background: Most surveys examining health professionals' knowledge, attitudes and practices around abortion have used convenience samples and have targeted doctors. Our goal in the SACHA Study, drawing on evidence-based strategies to maximise response rates, was to achieve a representative sample of a wider range of health professionals, working in general practice, maternity services, pharmacies, sexual and reproductive health (SRH) clinics and specialist abortion services in Britain, to explore the knowledge, attitudes and experience of abortion care and views on future models of delivery.

Methods: A cross-sectional questionnaire-based survey of midwives, doctors, nurses and pharmacists in England, Scotland and Wales was undertaken between November, 2021 and July, 2022.