Rational engineering of minimally immunogenic nucleases for gene therapy.

Genome editing using CRISPR-Cas systems is a promising avenue for the treatment of genetic diseases. However, cellular and humoral immunogenicity of genome editing tools, which originate from bacteria, complicates their clinical use. Here we report reduced immunogenicity (Red)(i)-variants of two clinically relevant nucleases, SaCas9 and AsCas12a.

Structural and functional determination of peptide versus small molecule ligand binding at the apelin receptor.

We describe a structural and functional study of the G protein-coupled apelin receptor, which binds two endogenous peptide ligands, apelin and Elabela/Toddler (ELA), to regulate cardiovascular development and function. Characterisation of naturally occurring apelin receptor variants from the UK Genomics England 100,000 Genomes Project, and AlphaFold2 modelling, identifies T89 as important in the ELA binding site, and R168 as forming extensive interactions with the C-termini of both peptides. Base editing to introduce an R/H168 variant into human stem cell-derived cardiomyocytes demonstrates that this residue is critical for receptor binding and function.

Perspectives on Technology Use in the Context of Caregiving for Persons With Dementia: Qualitative Interview Study.

Background: Examining ways to support persons with dementia and their caregivers to help minimize the disease's impact on individuals, families, and society is critical. One emerging avenue for support is technology (eg, smartphones and smart homes).

Objective: Given the increasing presence of technology in caregiving, it is pertinent to appreciate whether and how technology can be most useful to a care partner's everyday life.

Effectiveness of palliative hemostatic radiotherapy for hemoptysis: a prospective single-arm observation study.

Background: Palliative radiotherapy (RT) is commonly used for malignancy-associated hemoptysis. This study aims to determine RT control probability, durability, and influencing factors.

Methods: This single-institution prospective observational study included patients ≥18 years old with any lung malignancy and active hemoptysis.

Pre and post diagnostic dementia care in four Scottish prisons.

Background And Purpose: The number of older people in prisons is increasing across the globe. Many have poor physical and mental health, higher prevalence of head injury, cognitive impairment and dementia than found in community populations. Meeting the complex needs of this vulnerable group has become an increasing concern for prison and prison healthcare services.