Single-Chain Nanobody Inhibition of Notch and Avidity Enhancement Utilizing the β-Pore-Forming Toxin Aerolysin.

Notch plays critical roles in developmental processes and disease pathogenesis, which have led to numerous efforts to modulate its function with small molecules and antibodies. Here we present a nanobody inhibitor of Notch signaling derived from a synthetic phage-display library targeting the Notch negative regulatory region (NRR). The nanobody inhibits Notch signaling in a luciferase reporter assay with an IC of about 5 μM and in a Notch-dependent hematopoietic progenitor cell differentiation assay, despite a modest 19 μM affinity for the Notch NRR.

Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes.

The CD2-depleting drug alefacept (LFA3-Ig) preserved beta cell function in new-onset type 1 diabetes (T1D) patients. The most promising biomarkers of response were late expansion of exhausted CD8 T cells and rare baseline inflammatory islet-reactive CD4 T cells, neither of which can be used to measure responses to drug in the weeks after treatment. Thus, we investigated whether early changes in T cell immunophenotypes could serve as biomarkers of drug activity.

Glycerol intoxication syndrome in young children, following the consumption of slush ice drinks.

Introduction: Slush ice drinks are commonly available refreshments, aimed at children and young people. Glycerol is used to maintain the slush effect in the absence of a high sugar content.

Objective: To describe a series of children who became acutely unwell shortly after consuming a slush ice drink; their presentation mimics specific inherited metabolic diseases (IMDs).

A N-of-1 social network approach to study the social dynamics of alcohol consumption.

Introduction: The aim of this study was to investigate how the dynamics of the social environment impacted the alcohol consumption of individuals who self-identified as heavy drinkers.

Methods: A mixed methods approach including N-of-1 study with daily Ecological Momentary Assessment (EMA) followed by a social network egonet interview. Qualitative data was analysed using deductive and inductive approaches.

Treatment Outcomes From Erlotinib and Gefitinib in Advanced Epidermal Growth Factor Receptor-Mutated Nonsquamous Non-Small Cell Lung Cancer in Aotearoa New Zealand From 2010 to 2020: Nationwide Whole-of-Patient-Population Retrospective Cohort Study.

Background: Health care system-wide outcomes from routine treatment with erlotinib and gefitinib are incompletely understood.

Objective: The aim of the study is to describe the effectiveness of erlotinib and gefitinib during the first decade of their routine use for treating advanced epidermal growth factor receptor (EGFR) mutation-positive nonsquamous non-small cell lung cancer in the entire cohort of patients treated in Aotearoa New Zealand.

Methods: Patients were identified, and data collated from national pharmaceutical dispensing, cancer registration, and mortality registration electronic databases by deterministic data linkage using National Health Index numbers.