Learn Health Syst
January 2025
Introduction: Co-production approaches are increasingly being advocated for as a way of addressing the research translatory gap while including patient and public involvement in development of services they access, and particularly in disability service provision. Embedded research (ER) is a method which integrates the researcher within the target organization to better facilitate both co-production of research outputs and the reduction of the research translation gap. The aim of this reflection is to better understand the commonalities and differences between ER in a disability context to accounts published in academic literature.
View Article and Find Full Text PDFMolecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a step toward molecular subtype application in the clinic.
View Article and Find Full Text PDFCyclin-CDKs are master regulators of cell division. In addition to directly activating the CDK, the cyclin subunit regulates CDK specificity by binding short peptide "docking" motifs in CDK substrates. Here, we measure the relative binding strength of ~100,000 peptides to 11 human cyclins from five cyclin families (D, E, A, B and F).
View Article and Find Full Text PDFBackground: Estrogen receptor-positive breast cancer patients have a long-term risk of distant metastatic disease, and premenopausal patients have a higher risk. Randomized studies with long-term follow-up are essential to understand treatment benefit. We elucidated the long-term tamoxifen therapy benefit by menopausal status in the Stockholm tamoxifen trials with 20 years complete follow-up.
View Article and Find Full Text PDFUnlabelled: Transmission of genetic material from one generation to the next is a fundamental feature of all living cells. In eukaryotes, a macromolecular complex called the kinetochore plays crucial roles during chromosome segregation by linking chromosomes to spindle microtubules. Little is known about this process in evolutionarily diverse protists.
View Article and Find Full Text PDFThe flavoenzyme proline dehydrogenase (PRODH) catalyzes the first step of proline catabolism, the oxidation of l-proline to Δ-pyrroline-5-carboxylate. The enzyme is a target for chemical probe discovery because of its role in the metabolism of certain cancer cells. -propargylglycine is the first and best characterized mechanism-based covalent inactivator of PRODH.
View Article and Find Full Text PDFNaive T cells recirculate between the spleen and lymph nodes where they mount immune responses when meeting dendritic cells presenting foreign antigen. As this may happen anywhere, naive T cells ought to visit all lymph nodes. Here, deep sequencing almost-complete TCR repertoires led to a comparison of different lymph nodes within and between individual mice.
View Article and Find Full Text PDFPurpose: Lung transplantation (LTx) is a potential intervention for end-stage COVID-19 lung disease. Current literature is sparse regarding the outcomes of LTx for COVID-19 related acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). This study aims to characterize outcomes and patterns of LTx for COVID-19 related lung disease throughout the pandemic.
View Article and Find Full Text PDFBackground: As co-design and community-based participatory research gain traction in health and disability, the challenges and benefits of collaboratively conducting research need to be considered. Current literature supports using co-design to improve service quality and create more satisfactory services. However, while the 'why' of using co-design is well understood, there is limited literature on 'how' to co-design.
View Article and Find Full Text PDFHuman mixed lineage leukemia 4 (MLL4), also known as KMT2D, regulates cell type specific transcriptional programs through enhancer activation. Along with the catalytic methyltransferase domain, MLL4 contains seven less characterized plant homeodomain (PHD) fingers. Here, we report that the sixth PHD finger of MLL4 (MLL4) binds to the hydrophobic motif of ten-eleven translocation 3 (TET3), a dioxygenase that converts methylated cytosine into oxidized derivatives.
View Article and Find Full Text PDFObjective: Dental anxiety is widespread among both children and adults. To diagnose dental anxiety, standardized anxiety questionnaires are recommended. Based on the suggestive nature of the questionnaires, the study aimed to find out whether asking respondents about personal coping strategies before dental treatment influences their anxiety.
View Article and Find Full Text PDFBackground: We aimed to determine if salivary cadmium (Cd) levels had any association with breast density, hoping to establish a less invasive cost-effective method of stratifying Cd burden as an environmental breast cancer risk factor.
Methods: Salivary Cd levels were quantified from the Marin Women's Study, a Marin County, California population composite. Volumetric compositional breast density (BD ) data were measured by single x-ray absorptiometry techniques.
Introduction: Telepractice service delivery of allied health interventions to people with disability can potentially reduce access barriers and improve service equity. However, questions remain regarding telepractice functionality for people with disability. This study addressed questions related to how allied health clinicians and managers perceive telepractice as functioning in the provision of therapy services to people with disability.
View Article and Find Full Text PDFStud Health Technol Inform
January 2024
The methods and strategies utilised to facilitate focus group discussion within a co-design context have a fundamental impact on the opportunity for participants to actively engage with the content. This is a description of the strategies our project utilized including visual prompts and preparation guide to assist both service users and staff participants facilitate access to concepts discussed within our focus group sessions.
View Article and Find Full Text PDFThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the development of various vaccines. Reports have emerged suggesting a possible association between SARS-CoV-2 vaccination and the onset of thyroid diseases. This review explores the clinical aspects of thyroid disorders following SARS-CoV-2 vaccination, including a case report of a patient with concomitant subacute thyroiditis (SAT) and Graves' disease (GD) with blocking thyrotropin receptor autoantibodies (TSH-R-Ab) following SARS-CoV-2 vaccination.
View Article and Find Full Text PDFIntroduction: Telepractice has the potential to align with the directive to reduce inequalities by United Nations Sustainable Development Goal 10. Telepractice additionally addresses a national digital health strategic plan for accessible digitally enabled models of care. To plan improvements, it is essential to understand the experience of telepractice for people with disability, which may be achieved through an approach such as journey mapping.
View Article and Find Full Text PDFUnlabelled: Telepractice has existed for decades, but as a result of the COVID-19 pandemic, it gained value and increased desirability across the disability service and health sectors, as a mitigation strategy for the viral transmission risk. The increased desirability of telepractice encouraged organisations to invest and correspondingly enhance access to services delivered remotely via digital technology including allied health therapy interventions. The investment and uptake of telepractice provided greater learning opportunities and ability to investigate telepractice implementation in specific contexts such as disability services, enabling service providers the ability to tailor to specific population needs.
View Article and Find Full Text PDFThe virus life cycle depends on host-virus protein-protein interactions, which often involve a disordered protein region binding to a folded protein domain. Here, we used proteomic peptide phage display (ProP-PD) to identify peptides from the intrinsically disordered regions of the human proteome that bind to folded protein domains encoded by the SARS-CoV-2 genome. Eleven folded domains of SARS-CoV-2 proteins were found to bind 281 peptides from human proteins, and affinities of 31 interactions involving eight SARS-CoV-2 protein domains were determined (K ∼ 7-300 μM).
View Article and Find Full Text PDFThe modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) moieties is a highly dynamic process that spatiotemporally regulates nearly every important cellular program. Despite its significance, little is known about the substrate recognition and regulation modes of O-GlcNAc transferase (OGT), the primary enzyme responsible for O-GlcNAc addition. In this study, we identified the intervening domain (Int-D), a poorly understood protein fold found only in metazoan OGTs, as a specific regulator of OGT protein-protein interactions and substrate modification.
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