Transscleral Pars Plana Choroid Ablation Using the Iridex Laser System Yields Improvements for Surgical Insertion of the Port Delivery Implant in a Minipig Model.

Purpose: To evaluate an alternative surgical approach for Port Delivery System with ranibizumab (PDS) implant and a novel application of Iridex laser system in Gottingen minipig model.

Methods: A total of seventeen male minipigs (Part 1: 9 animals in non-recovery and Part 2: 8 animals observed for 8-days post-surgery Part 2) received PDS implant insertion into each eye. The effect of Iridex 810 nm infrared diode laser with varying energy (power or duration) on transscleral pars plana ablation, surrounding ocular tissue and postsurgical vitreous hemorrhage (VH) was investigated.

Semorinemab Pharmacokinetics and The Effect on Plasma Total Tau Pharmacodynamics in Clinical Studies.

Background: Semorinemab is a monoclonal antibody that targets the N-terminal domain of the tau protein that is in clinical development for the treatment of Alzheimer's disease.

Objectives: To perform model-based evaluations of the observed pharmacokinetics in serum and the total plasma tau target-engagement dynamics from clinical studies evaluating semorinemab.

Design: The observed semorinemab pharmacokinetics and plasma tau target engagement from phase 1 and 2 clinical studies were modeled using a non-linear mixed effect target-mediated drug disposition model.

Primate cerebrospinal fluid CHI3L1 reflects brain TREM2 agonism.

Introduction: Triggering receptor expressed on myeloid cells 2 (TREM2) agonists are being clinically evaluated as disease-modifying therapeutics for Alzheimer's disease. Clinically translatable pharmacodynamic (PD) biomarkers are needed to confirm drug activity and select the appropriate therapeutic dose in clinical trials.

Methods: We conducted multi-omic analyses on paired non-human primate brain and cerebrospinal fluid (CSF), and stimulation of human induced pluripotent stem cell-derived microglia cultures after TREM2 agonist treatment, followed by validation of candidate fluid PD biomarkers using immunoassays.

Assessment of Color Reproducibility and Mitigation of Color Variation in Whole Slide Image Scanners for Toxicologic Pathology.

Digital pathology workflows in toxicologic pathology rely on whole slide images (WSIs) from histopathology slides. Inconsistent color reproduction by WSI scanners of different models and from different manufacturers can result in different color representations and inter-scanner color variation in the WSIs. Although pathologists can accommodate a range of color variation during their evaluation of WSIs, color variability can degrade the performance of computational applications in digital pathology.