ACK1 and BRK non-receptor tyrosine kinase deficiencies are associated with familial systemic lupus and involved in efferocytosis.

Systemic lupus erythematosus (SLE) is an autoimmune disease, the pathophysiology and genetic basis of which are incompletely understood. Using a forward genetic screen in multiplex families with SLE, we identified an association between SLE and compound heterozygous deleterious variants in the non-receptor tyrosine kinases (NRTKs) and . Experimental blockade of ACK1 or BRK increased circulating autoantibodies in vivo in mice and exacerbated glomerular IgG deposits in an SLE mouse model.

A national survey of the provision of prehabilitation for oesophagogastric cancer patients in the UK.

Introduction: Studies have demonstrated that prehabilitation in oesophagogastric cancer (OGC) improves body composition, physical fitness and quality of life, and can reduce surgical complications. However, it is not offered in all OGC centres. Furthermore, definitions, funding and access to services vary.

Exploring physiotherapy staff's perceptions of physiotherapy delivery in acute stroke rehabilitation.

Objective: To explore physiotherapists' perspectives on current and alternative models of physiotherapy delivery in acute stroke rehabilitation.

Design: Qualitative service evaluation.

Setting: An acute stroke rehabilitation unit within a London teaching hospital in the UK.

Managing diabetic chronic kidney disease in pregnancy: Current clinical practice and uncertainties.

Background: Pre-gestational diabetes occurs in approximately 1% of pregnancies in the UK and increases the risk of adverse maternal and fetal outcomes. More women with type 2 than type 1 diabetes are now becoming pregnant and tend to have higher rates of obesity and other multi-morbidities. Chronic kidney disease (CKD) affects approximately 5%-10% of pregnant women with type 1 diabetes and about 2%-3% with type 2 diabetes.

Lived experiences of older adults within an integrated hospital-at-home service: an interpretive phenomenological analysis.

Background: The Hospital at Home (HaH) service has developed and evolved over the past few years with the Covid-19 pandemic and improved the integration of care in the community from acute hospital settings. Despite these advancements, there remains a limited understanding of patients' lived experiences with the HaH service. This study aims to explore the experiences and perceptions of older adults who have received HaH services to inform future quality improvement initiatives.

Pathogenic PDE12 variants impair mitochondrial RNA processing causing neonatal mitochondrial disease.

Pathogenic variants in either the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial function. Within this group, an increasing number of families have been identified, where Mendelian genetic disorders implicate defective mitochondrial RNA biology. The PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs.

Scoping review of review methodologies used for guiding evidence-based practice in critical care: a protocol.

Introduction: A literature review provides a synthesis on a selection of papers about a specific topic. This is used by health practitioners in critical care as in other specialities when making clinical practice decisions. The task of knowledge transfer through the review process of scientific papers involves a variety of methodologies with differing expectations on the quality and rigour that is applied.

Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells.

NKG2D ligands (NKG2DLs) are broadly expressed in cancer. To target these, we describe an adaptor chimeric antigen receptor (CAR) termed NKG2D/Dap10-12. Herein, T cells are engineered to co-express NKG2D with a fusion protein that comprises Dap10 joined to a Dap12 endodomain.

Explorations of strategies for inclusion for newly qualified physiotherapists from racially minoritised groups in a large, urban NHS Trust, UK.

Objectives: The study aimed to i) understand the experiences of newly qualified physiotherapists from racially minoritised backgrounds in a large hospital physiotherapy department and ii) co-create and implement inclusive strategies to affect work culture.

Design: The project used an action research design with co-creation principles and was in 3 phases. Phase 1 explored the experiences of inclusion for newly qualified racially minoritised staff, using focus groups and transcripts analysed thematically.

UKHCDO gene therapy taskforce: Guidance for implementation of haemophilia gene therapy into routine clinical practice for adults.

Introduction: 2022 was a landmark year with two adeno-associated viral vectors (AAVs) receiving conditional marketing authorization from EMA for the treatment of persons with severe haemophilia A and severe to moderately severe haemophilia B and a third in 2024. Gene therapy is a transformative, irreversible treatment with long-lasting effects, necessitating development of new clinical pathways to ensure optimal outcomes.

Aim: To develop a consensus framework and service specification for delivery of AAV gene therapy for haemophilia in adults within the UK using the hub-and-spoke model proposed by the European Association of Haemophilia and Allied Disorders and the European Haemophilia Consortium.

Self-Induced Nasal Septal Perforation: Rhinotillexomania-A Different Entity From Nose Picking.

Background: Nose picking is a common habit that rarely leads to mutilating self-injury. It is important to distinguish between rhinotillexomania (compulsive nose picking) as a disease and nose picking that results in or contributes to nasal septal perforation (NSP). The aim of this study is to investigate the impact of rhinotillexomania and NSP repair on sinonasal symptoms and quality of life (QoL).

External validation of a multimodality deep-learning normal tissue complication probability model for mandibular osteoradionecrosis trained on 3D radiation distribution maps and clinical variables.

Background And Purpose: While the inclusion of spatial dose information in deep learning (DL)-based normal-tissue complication probability (NTCP) models has been the focus of recent research studies, external validation is still lacking. This study aimed to externally validate a DL-based NTCP model for mandibular osteoradionecrosis (ORN) trained on 3D radiation dose distribution maps and clinical variables.

Methods And Materials: A 3D DenseNet-40 convolutional neural network (3D-mDN40) was trained on clinical and radiation dose distribution maps on a retrospective class-balanced matched cohort of 184 subjects.

Discharging the duty of candor following delayed post-endoscopy cancer diagnosis.

Endoscopic examination is not risk free. Not only are there well-known complications associated with the procedure, but malignant and pre-malignant lesions can be missed due to human factors or failures in organizational process. Duty of candor (DoC) is a legal requirement if significant harm occurs in delivery of healthcare.