Building trust and inclusion with under-served groups: a public involvement project employing a knowledge mobilisation approach.

Background: Certain groups are commonly under-served by health research due to exclusionary models of research design/delivery. Working in partnership with under-served groups is key to improving inclusion. This project aimed to explore the use of a knowledge mobilisation approach to start building partnerships with under-served groups based on trust and mutual understanding.

A simplified G-CSF-free procedure allows for in vivo HSC gene therapy of sickle cell disease in a mouse model.

We have reported the direct repair of the sickle cell mutation in vivo in a disease model using vectorized prime editors after hematopoietic stem cell (HSC) mobilization with granulocyte colony-stimulating factor (G-CSF)/AMD3100. The use of G-CSF for HSC mobilization is a hurdle for the clinical translation of this approach. Here, we tested a G-CSF-free mobilization regimen using WU-106, an inhibitor of integrin α4β1, plus AMD3100 for in vivo HSC prime editing in sickle cell disease (SCD) mice.

Assessing the Cost-Effectiveness of Next-Generation Sequencing as a Biomarker Testing Approach in Oncology and Policy Implications: A Literature Review.

Objective: A key hurdle in broader next-generation sequencing (NGS) biomarker testing access in oncology is the ongoing debate on NGS's cost-effectiveness. We conducted a systematic review of existing evidence of the costs of NGS as a biomarker testing strategy in oncology and developed policy suggestions.

Methods: We searched multiple databases for studies reporting cost comparisons and cost-effectiveness of NGS across oncology indications and geographies between 2017 and 2022, inclusive.

Clinical consensus recommendations for the non-surgical treatment of children with Perthes' disease in the UK.

Aims: The aim of this study was to produce clinical consensus recommendations about the non-surgical treatment of children with Perthes' disease. The recommendations are intended to support clinical practice in a condition for which there is no robust evidence to guide optimal care.

Methods: A two-round, modified Delphi study was conducted online.

Supporting patients to prepare for total knee replacement: Evidence-, theory- and person-based development of a 'Virtual Knee School' digital intervention.

Introduction: Digital delivery of pre-operative total knee replacement (TKR) education and prehabilitation could improve patient outcomes pre- and post-operatively. Rigorously developing digital interventions is vital to help ensure they achieve their intended outcomes whilst mitigating their potential drawbacks.

Objective: To develop a pre-operative TKR education and prehabilitation digital intervention, the 'Virtual Knee School' (VKS).

In vivo HSC prime editing rescues sickle cell disease in a mouse model.

Sickle cell disease (SCD) is a monogenic disease caused by a nucleotide mutation in the β-globin gene. Current gene therapy studies are mainly focused on lentiviral vector-mediated gene addition or CRISPR/Cas9-mediated fetal globin reactivation, leaving the root cause unfixed. We developed a vectorized prime editing system that can directly repair the SCD mutation in hematopoietic stem cells (HSCs) in vivo in a SCD mouse model (CD46/Townes mice).

Stable HIV decoy receptor expression after in vivo HSC transduction in mice and NHPs: Safety and efficacy in protection from SHIV.

We aim to develop an in vivo hematopoietic stem cell (HSC) gene therapy approach for persistent control/protection of HIV-1 infection based on the stable expression of a secreted decoy protein for HIV receptors CD4 and CCR5 (eCD4-Ig) from blood cells. HSCs in mice and a rhesus macaque were mobilized from the bone marrow and transduced by an intravenous injection of HSC-tropic, integrating HDAd5/35++ vectors expressing rhesus eCD4-Ig. In vivo HSC transduction/selection resulted in stable serum eCD4-Ig levels of ∼100 μg/mL (mice) and >20 μg/mL (rhesus) with half maximal inhibitory concentrations (ICs) of 1 μg/mL measured by an HIV neutralization assay.

Content and delivery of pre-operative interventions for patients undergoing total knee replacement: a rapid review.

Background: Total knee replacement (TKR) is a common operation typically performed for end-stage knee osteoarthritis. Patients awaiting TKR often have poor health-related quality of life. Approximately 20% of patients experience persistent pain post-TKR.

In vivo base editing by a single i.v. vector injection for treatment of hemoglobinopathies.

Individuals with β-thalassemia or sickle cell disease and hereditary persistence of fetal hemoglobin (HPFH) possessing 30% fetal hemoglobin (HbF) appear to be symptom free. Here, we used a nonintegrating HDAd5/35++ vector expressing a highly efficient and accurate version of an adenine base editor (ABE8e) to install, in vivo, a -113 A>G HPFH mutation in the γ-globin promoters in healthy CD46/β-YAC mice carrying the human β-globin locus. Our in vivo hematopoietic stem cell (HSC) editing/selection strategy involves only s.

Effect of Glucocorticoid and 11β-Hydroxysteroid-Dehydrogenase Type 1 (11β-HSD1) in Neurological and Psychiatric Disorders.

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity is implicated as a moderator of the progression of multiple diseases and disorders in medicine and is actively subject to investigation as a therapeutic target. Here we summarize the mechanisms of the enzyme and detail the novel agents under investigation. Such agents modulate peripheral cortisol and cortisone levels in hypertension, type 2 diabetes, metabolic disorders, and Alzheimer's disease models, but there is mixed evidence for transduction into symptom management.

Independent External Validation of Artificial Intelligence Algorithms for Automated Interpretation of Screening Mammography: A Systematic Review.

Purpose: The aim of this study was to describe the current state of science regarding independent external validation of artificial intelligence (AI) technologies for screening mammography.

Methods: A systematic review was performed across five databases (Embase, PubMed, IEEE Explore, Engineer Village, and arXiv) through December 10, 2020. Studies that used screening examinations from real-world settings to externally validate AI algorithms for mammographic cancer detection were included.

Exploring the feasibility, acceptability and value of volunteer peer mentors in supporting self-management of osteoarthritis: a qualitative evaluation.

Background: Hip and knee osteoarthritis (OA) affect a large and growing proportion of the population. Treatment options are typically conservative making self-management a priority. Using trained peers to support individuals with OA has potential to improve self-management.

Understanding peer mentorship in supporting self-management of hip and knee osteoarthritis: A qualitative study of mentees' perspectives.

Background: Hip and knee osteoarthritis (OA) are common musculoskeletal conditions. Treatment is usually conservative, making self-management a priority. We developed and trialled an OA peer mentorship intervention to support self-management in older people.

Peer mentorship to improve self-management of hip and knee osteoarthritis: a randomised feasibility trial.

Objective: To determine the feasibility of conducting a randomised controlled trial (RCT) of a peer mentorship intervention to improve self-management of osteoarthritis (OA).

Design: Six-month parallel group non-blinded randomised feasibility trial.

Setting: One secondary care and one primary care UK National Health Service Trust.

Consensus on pre-operative total knee replacement education and prehabilitation recommendations: a UK-based modified Delphi study.

Background: Over 90,000 total knee replacement (TKR) procedures are performed annually in the United Kingdom (UK). Patients awaiting TKR face long delays whilst enduring severe pain and functional limitations. Almost 20% of patients who undergo TKR are not satisfied post-operatively.

The effect of using a cycling workstation on mouse dexterity.

This study investigated the effect of using a cycling workstation on mouse dexterity, including if and how this changed with practice. Thirty-four healthy adults were allocated to a sitting group (n = 17) or cycling group (n = 17). All participants completed standardised computer tasks on 6 occasions: baseline and final-all participants were seated; practice 1 to 4-sitting group participants were seated, cycling group participants pedalled on an under desk cycle.

JNK2 Is Required for the Tumorigenic Properties of Melanoma Cells.

Overexpression and activation of c-Jun N-terminal kinases (JNKs) have been observed in multiple cancer cell lines and tumor samples. Various JNK isoforms have been reported to promote lung and liver cancer, as well as keratinocyte transformation, suggesting an important role of JNK signaling in promoting tumor development. However, there are three JNK isoforms, and it is unclear how each individual isoform, especially the ubiquitously expressed JNK1 and JNK2, functions in melanoma.

The effects of unimanual and bimanual massed practice on upper limb function in adults with cervical spinal cord injury: a systematic review.

Background: Individuals with cervical spinal cord injury (cSCI) have identified improving upper limb function as their most important rehabilitation goal. Unimanual massed practice (UMP) and bimanual massed practice (BMP) may help achieve this.

Objectives: To evaluate and compare the effects of UMP and BMP on upper limb function in adults with cSCI.

Neutrophil elastase-cleaved corticosteroid-binding globulin is absent in human plasma.

Corticosteroid-binding globulin (CBG) transports glucocorticoids in blood and is a serine protease inhibitor family member. Human CBG has a reactive center loop (RCL) which, when cleaved by neutrophil elastase (NE), disrupts its steroid-binding activity. Measurements of CBG levels are typically based on steroid-binding capacity or immunoassays.

[Multicentric reticulohistiocytosis is a rare form of paraneoplasia].

A 59-year-old woman developed a rash and severe arthralgia, which primarily affected her fingers. She displayed digital arthritis and nodules on the hands, chest, face, and oral cavity. Blood samples were normal.