Optimization of Potent and Selective Cyclohexyl Acid ERAP1 Inhibitors Using Structure- and Property-Based Drug Design.

Endoplasmic reticulum aminopeptidase 1 (ERAP1) cleaves the -terminal amino acids of peptides, which can then bind onto major histocompatibility class I (MHC-I) molecules for presentation onto the cell surface, driving the activation of adaptive immune responses. In cancer, overtrimming of mature antigenic peptides can reduce cytotoxic T-cell responses, and ERAP1 can generate self-antigenic peptides which contribute to autoimmune cellular responses. Therefore, modulation of ERAP1 activity has potential therapeutic indications for cancer immunotherapy and in autoimmune disease.

An international core outcome set for primary progressive aphasia (COS-PPA): Consensus-based recommendations for communication interventions across research and clinical settings.

Introduction: Interventions to treat speech-language difficulties in primary progressive aphasia (PPA) often use word accuracy as a highly comparable outcome. However, there are more constructs of importance to people with PPA that have received less attention.

Methods: Following Core Outcome Set Standards for Development Recommendations (COSSTAD), this study comprised: Stage 1 - systematic review to identify measures; Stage 2 - consensus groups to identify important outcome constructs for people with PPA (n = 82) and care partners (n = 91); Stage 3 - e-Delphi consensus with 57 researchers.

The role of advocacy in sustaining male contraceptive research and development.

Novel male contraceptives have been in development for well over half a century, and despite a robust predicted global market for new methods, funding for research and development has been extremely limited. While the pharmaceutical industry previously supported male contraceptive research and development, industry partners are only spectators in the current space, awaiting a product that has been de-risked by the public sector before re-entering the field. Current male contraceptive development efforts are thus primarily funded by nonprofit, non-governmental, and government agencies who also act as the primary advocates for the field.

Naming in a multilingual context: Norms for the ICMR-Manipal colour picture corpus in Kannada from the Indian context.

There have been many published picture corpora. However, more than half of the world's population speaks more than one language and, as language and culture are intertwined, some of the items from a picture corpus designed for a given language in a particular culture may not fit another culture (with the same or different language). There is also an awareness that language research can gain from the study of bi-/multilingual individuals who are immersed in multilingual contexts that foster inter-language interactions.