Roche (Switzerland)

A community-validated tool for clinical outcome calculation in multiple sclerosis: Consensus development and scenario-specific recommendations

Background: Reproducibility and comparability of disability outcomes remain major challenges in multiple sclerosis (MS) research. Definitions of disability progression vary widely across studies, and calculation criteria are often insufficiently documented to enable replication....

Data-driven construction of an imine reductase library capable of broad-scope reductive amination at equimolar substrate concentrations

Reductive amination catalysed by imine reductases and reductive aminases has emerged as a powerful method for the asymmetric synthesis of chiral amines, yet the generality and practical limitations of these enzymes remain poorly understood. Here, we combine large-scale, iterative...

Neurobiological correlates of longitudinal grey matter volume changes in preclinical Alzheimer’s disease

Background: Structural brain changes during the earliest asymptomatic stages of Alzheimer's disease (AD) remain poorly understood. Previous research in preclinical AD shows heterogeneous findings, reporting both subtle neuronal loss and paradoxical increases in grey matter (GM) v...

PLCG2 downregulation impairs synaptic function and increases Alzheimer’s disease hallmarks in neuronal cultures

We developed a high-content screening to investigate how Alzheimer’s disease (AD) genetic risk factors may affect synaptic mechanisms in rat primary neuronal cultures. Of the target genes identified, we found that Plcg2 downregulation in mouse dentate gyrus neurons consistently d...

Early functional reactivity to a CEACAM5 x CD3 T cell bispecific antibody in solid tumors associates with baseline immune contexture rather than target antigen density alone

Abstract Clinical translation of T cell bispecific (TCB) therapies in solid tumors is hindered by the immunosuppressive tumor microenvironment and intratumoral heterogeneity, features poorly captured by standard preclinical models. We applied an integrated translational framework...

Ontogenically distinct mouse alveolar macrophages modulate cigarette smoke-induced lung inflammation via Spp1

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death. While airway-recruited macrophages contribute to COPD pathogenesis, the role of embryonic alveolar macrophages (Em-AM) remains unclear. Using a cigarette smoke (CS)-induced COPD mouse model, we find...

Burden, perception of stigma, and gender differences among informal care partners of individuals with mild cognitive impairment

Background Caring for individuals with mild cognitive impairment (MCI) is increasingly recognized as a significant clinical challenge. However, the latent burden, driven by perceived stigma and gender-specific vulnerabilities, remains poorly characterized during these early stage...

Quantitative biochemical profiling of GCase activity and α-synuclein proteoforms in post-mortem human brains from GBA-related and idiopathic Parkinson’s disease

Variants in GBA1 , encoding lysosomal glucocerebrosidase (GCase), are risk factors for Parkinson’s disease (PD), which is characterized by α-synuclein (αSyn) accumulation and lysosomal dysfunction. Nonetheless, the relationship between αSyn accumulation and GCase deficiency remai...

Serum Glial Fibrillary Acidic Protein Dynamics, Disease Progression, and Therapy Response in Multiple Sclerosis

Importance: Capturing individual multiple sclerosis (MS) progression is difficult; few studies have evaluated glial fibrillary acidic protein (GFAP) in large longitudinal cohorts with independent validation. Objective: To investigate whether serum GFAP levels and treatment-relate...

Obinutuzumab Induces Histological Remission and Deep Kidney Parenchymal B-Cell Depletion in Patients with Lupus Nephritis: Exploratory Analyses of the Phase III REGENCY Trial

Objectives The REGENCY trial ( NCT04221477 ) demonstrated superiority of obinutuzumab (OBI) plus standard therapy (+ST) vs placebo (PBO) +ST in achieving complete renal response (CRR) at Week 76 (W76) in adults with active lupus nephritis (LN). These exploratory analyses aimed to...