Dose‐related modulation of the synaptic proteome after short‐term treatment with XPro1595 for Alzheimer’s disease.

Background: XPro1595 (XPro) is a brain‐penetrant, recombinant protein variant of human tumor necrosis factor (TNF) rationally designed to selectively neutralize only the soluble, pro‐inflammatory form of the cytokine (solTNF). An unbiased proteomic analysis of CSF samples from an open‐label, phase‐1b study (NCT03943264) in patients with Alzheimer’s disease (AD) was conducted to assess for pharmacodynamic activity and disease‐specific target engagement.

Method: Patients with AD (n = 20) were treated for 12‐weeks with one of three doses of XPro: 0.

Built environment change for injury prevention: insights from public health professionals across public health units in Ontario, Canada.

Background: Road-related injuries and deaths are among the most significant and avoidable public health problems in Canada. Modifications to the built environment (BE) can reduce injury rates for vulnerable road users (VRUs) and other priority populations who experience disproportionate risk. This paper highlights public health professionals' experiences working in injury prevention across Ontario public health units (PHUs) navigating barriers and facilitators to BE change.

Achieving a 35-Plex Tandem Mass Tag Reagent Set through Deuterium Incorporation.

Mass spectrometry-based sample multiplexing with isobaric tags permits the development of high-throughput and precise quantitative biological assays with proteome-wide coverage and minimal missing values. Here, we nearly doubled the multiplexing capability of the TMTpro reagent set to a 35-plex through the incorporation of one deuterium isotope into the reporter group. Substituting deuterium frequently results in suboptimal peak coelution, which can compromise the accuracy of reporter ion-based quantification.