Basic Science and Pathogenesis.

Background: The bi-directional autophagy and inflammation network becomes progressively dysregulated with age, with systemic inflammation as a biomarker of this dysregulation including in Alzheimer's Disease (AD). We hypothesize that interventions which target the shared feature of systemic inflammation in the biology of aging and AD, via regulation of the autophagy-inflammation network, will prevent the conversion to disease pathogenesis in AD as well as improve healthspan and longevity in aging populations. While previous studies report benefits of mTOR inhibition including rapamycin in transgenic mouse models of familial AD, the present studies aim to evaluate this pathway in a model of sporadic, late onset AD (LOAD) and test the contribution of AMP-activated protein kinase (AMPK) as a critical regulator of the mTOR pathway.

Basic Science and Pathogenesis.

Background: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically-engineered marmosets that carry knock-in (KI) point mutations in the presenilin-1 (PSEN1) gene that can be studied from birth throughout lifespan.

Method: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1.

Proton radiography inversions with source extraction and comparison to mesh methods.

Proton radiography is a central diagnostic technique for measuring electromagnetic (EM) fields in high-energy-density, laser-produced plasmas. In this technique, protons traverse the plasma where they accumulate small EM deflections which lead to variations in the proton fluence pattern on a detector. Path-integrated EM fields can then be extracted from the fluence image through an inversion process.

Clonal hematopoiesis of indeterminate potential (CHIP) and its association with treatment outcomes and adverse events in patients with solid tumours.

Clonal hematopoiesis of indeterminate potential (CHIP) is the clonal expansion of hematopoietic stem cells from somatic mutations. It is a common incidental finding in cell-free DNA (cfDNA). We investigated the incidence of CHIP in cfDNA from patients with solid tumours and explored its association with treatment outcomes and adverse events.

Communicative health literacy and associated variables in nine European countries: results from the HLS survey.

Our study aimed to report on variables associated with communicative health literacy (COM-HL) in European adults. The HLS survey was conducted in 2019-2021 including nine countries which measured COM-HL by using a validated questionnaire (HLS-COM-P-Q6 with a score ranging from 0 to 100). Linear regression models were used to study variables associated with COM-HL globally (multilevel model with random intercepts and slopes and at country level) and in each country.