Publications by authors named "LEVER J"

This study describes the training demands of highly trained male youth basketball players, based on training year, term and playing position. Data was collected from 41 male youth basketballers over two seasons from all on-court coach-led training sessions utilising an LPS. Linear mixed-models and pairwise comparisons were used to analyse by training year (Y1, Y2 and Y3), term (T1, T2, T3 and T4) and playing position (Backcourt, Frontcourt).

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Cigarette smoking is associated with COVID-19 prevalence and severity, but the mechanistic basis for how smoking alters SARS-CoV-2 pathogenesis is unknown. A potential explanation is that smoking alters the expression of the SARS-CoV-2 cellular receptor and point of entry, angiotensin converting enzyme-2 (ACE-2), and its cofactors including transmembrane protease serine 2 (TMPRSS2). We investigated the impact of cigarette smoking on the expression of ACE-2, TMPRSS2, and other known cofactors of SARS-CoV-2 infection and the resultant effects on infection severity in vitro.

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Unlabelled: The distal bronchioles in Idiopathic Pulmonary Fibrosis (IPF) exhibit histopathological abnormalities such as bronchiolization, peribronchiolar fibrosis and honeycomb cysts that contribute to the overall architectural remodeling of lung tissue seen in the disease. Here we describe an additional histopathologic finding of epithelial desquamation in patients with IPF, wherein epithelial cells detach from the basement membrane of the distal bronchioles. To understand the mechanism driving this pathology, we performed spatial transcriptomics of the epithelial cells and spatial proteomics of the basement membrane of the distal bronchioles from IPF patients and patients with no prior history of lung disease.

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Rationale: The role of MUC5B mucin expression in IPF pathogenesis is unknown. Bleomycin-exposed rodent models do not exhibit sustained fibrosis or airway remodeling. Unlike mice, ferrets have human-like distribution of MUC5B expressing cell types and natively express the risk-conferring variant that induces high MUC5B expression in humans.

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Article Synopsis
  • The mucociliary transport apparatus plays a crucial role in lung health by using coordinated cilia movement to clear mucus and particles through a process called metachrony.
  • Researchers hypothesized that disruptions in calcium signaling would hinder metachrony and reduce mucociliary transport (MCT), and they tested this using imaging techniques on human and ferret tracheae.
  • Results showed that metachrony significantly enhances MCT by 48% in both species and that calcium signaling is essential for maintaining this coordinated movement.
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Complex systems ranging from societies to ecological communities and power grids may be viewed as networks of connected elements. Such systems can go through critical transitions driven by an avalanche of contagious change. Here we ask, where in a complex network such a systemic shift is most likely to start.

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Micrometeorites are estimated to represent the main part of the present flux of extraterrestrial matter found on the Earth's surface and provide valuable samples to probe the interplanetary medium. Here, we describe large and representative collections of micrometeorites currently available to the scientific community. These include Antarctic collections from surface ice and snow, as well as glacial sediments from the eroded top of nunataks-summits outcropping from the icesheet-and moraines.

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Lever, JR, Duffield, R, Murray, A, Bartlett, JD, and Fullagar, HHK. Longitudinal internal training load and exposure in a high-performance basketball academy. J Strength Cond Res 38(8): 1464-1471, 2024-This study describes the longitudinal training exposure (session counts) and internal training load (Rating of Perceived Exertion [RPE] and Session Rating of Perceived Exertion [sRPE]) of youth basketball players at a high-performance academy, based on the training year, training term, and playing position.

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Physician–scientists who become parents during their long period of training need additional funding and support for lactation, childcare and healthcare, to ensure an equitable workforce.

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Theory suggests that increasingly long, negative feedback loops of many interacting species may destabilize food webs as complexity increases. Less attention has, however, been paid to the specific ways in which these 'delayed negative feedbacks' may affect the response of complex ecosystems to global environmental change. Here, we describe five fundamental ways in which these feedbacks might pave the way for abrupt, large-scale transitions and species losses.

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Background: Nourishing Beginnings is an integrated referral and service delivery model supporting Medicaid-eligible pregnant individuals by providing increased nutritional food access throughout pregnancy up to three months postpartum, through community health workers (CHW), who simultaneously address and provide support for social service needs of the client.

Methods: To study the impact of possible interventions on food security, the program includes two distinct interventions each paired with traditional CHW services, nutrition educational materials, and provision of basic essential cooking tools. Interventions consist of either bi-weekly home food delivery from the local food bank or bi-weekly financial assistance with healthy food access navigation.

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Inferring knowledge from known relationships between drugs, proteins, genes, and diseases has great potential for clinical impact, such as predicting which existing drugs could be repurposed to treat rare diseases. Incorporating key biological context such as cell type or tissue of action into representations of extracted biomedical knowledge is essential for principled pharmacological discovery. Existing global, literature-derived knowledge graphs of interactions between drugs, proteins, genes, and diseases lack this essential information.

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Kidney macrophages are comprised of both monocyte-derived and tissue resident populations; however, the heterogeneity of kidney macrophages and factors that regulate their heterogeneity are poorly understood. Herein, we performed single cell RNA sequencing (scRNAseq), fate mapping, and parabiosis to define the cellular heterogeneity of kidney macrophages in healthy mice. Our data indicate that healthy mouse kidneys contain four major subsets of monocytes and two major subsets of kidney resident macrophages (KRM) including a population with enriched expression, suggesting monocyte origin.

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Background Hypertension control is critical to reducing cardiovascular disease, challenging to achieve, and exacerbated by socioeconomic inequities. Few states have established statewide quality improvement (QI) infrastructures to improve blood pressure (BP) control across economically disadvantaged populations. In this study, we aimed to improve BP control by 15% for all Medicaid recipients and by 20% for non-Hispanic Black participants.

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The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2 coronavirus, is devastatingly impacting human health. A prominent component of COVID-19 is the infection and destruction of the ciliated respiratory cells, which perpetuates dissemination and disrupts protective mucociliary transport (MCT) function, an innate defense of the respiratory tract. Thus, drugs that augment MCT could improve barrier function of the airway epithelium, reduce viral replication and, ultimately, COVID-19 outcomes.

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Substantial clinical evidence supports the notion that ciliary function in the airways is important in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, the extent or nature of impairment of mucociliary transport (MCT) in in vivo models remains unknown. We hypothesize that SARS-CoV-2 infection results in MCT deficiency in the airways of golden Syrian hamsters that precedes pathological injury in lung parenchyma.

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Article Synopsis
  • Human activities like cutting down forests, climate change, and introducing new species are hurting wildlife in different ways, especially in land and water environments.
  • Scientists want to understand why these impacts are different in land versus water ecosystems by looking at four main processes: how animals and plants spread, how new species form, which species survive better, and how random changes happen.
  • They hope to find new ways to protect nature by looking at these processes and figuring out how human impacts create different problems in each ecosystem.
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Article Synopsis
  • - CIViC is a public, crowd-sourced database that compiles peer-reviewed research on the clinical significance of cancer variants to aid in cancer management.
  • - It offers structured data in real-time to facilitate global access and is designed to keep up with evolving variant interpretation guidelines and enhance collaboration with other resources.
  • - The platform has successfully expanded to include new Evidence Types related to cancer variants and now features contributions from over 300 experts, covering more than 3200 variants across 470 genes from over 3100 published studies.
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Many targeted natural product isolation approaches rely on the use of pre-existing bioactivity information to inform the strategy used for the isolation of new bioactive compounds. Bioactivity information can be available either in the form of prior assay data or via Structure Activity Relationship (SAR) information which can indicate a potential chemotype that exhibits a desired bioactivity. The work described herein utilizes a unique method of targeted isolation using structure-based virtual screening to identify potential antibacterial compounds active against MRSA within the marine sponge order Verongiida.

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Airway dehydration causes mucus stasis and bacterial overgrowth in cystic fibrosis (CF), resulting in recurrent respiratory infections and exacerbations. Strategies to rehydrate airway mucus including inhibition of the epithelial sodium channel (ENaC) have the potential to improve mucosal defense by enhancing mucociliary clearance (MCC) and reducing the risk of progressive decline in lung function. In the current work, we evaluated the effects of AZD5634, an ENaC inhibitor that shows extended lung retention and safety profile as compared with previously evaluated candidate drugs, in healthy and CF preclinical model systems.

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The kidney contains a population of resident macrophages from birth that expands as it grows and forms a contiguous network throughout the tissue. Kidney-resident macrophages (KRMs) are important in homeostasis and the response to acute kidney injury. While the kidney contains many microenvironments, it is unknown whether KRMs are a heterogeneous population differentiated by function and location.

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As guidelines, therapies, and literature on cancer variants expand, the lack of consensus variant interpretations impedes clinical applications. CIViC is a public domain, crowd-sourced, and adaptable knowledgebase of evidence for the Clinical Interpretation of Variants in Cancer, designed to reduce barriers to knowledge sharing and alleviate the variant interpretation bottleneck.

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Background: Effective management of hypertension (HTN) is a priority in primary care, necessary to decrease the costs, morbidity, and mortality associated with cardiovascular disease. Strategies to support quality improvement (QI) efforts in primary care are needed to make significant improvements in population health, especially for patients who experience socioeconomic inequalities.

Local Problem: To address the high rate (>50%) of uncontrolled HTN in the state of Ohio, a statewide QI project was implemented in high-volume Medicaid practices, aimed at improving blood pressure control and addressing racial disparities.

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Meals rich in oxalate are associated with calcium oxalate (CaOx) kidney stone disease. Hydroxy-L-proline (HLP) is an oxalate precursor found in milk and collagen-containing foods. HLP has been shown to induce CaOx crystal formation in rodents.

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Background: Inducible disruption of cilia-related genes in adult mice results in slowly progressive cystic disease, which can be greatly accelerated by renal injury.

Methods: To identify in an unbiased manner modifier cells that may be influencing the differential rate of cyst growth in injured versus non-injured cilia mutant kidneys at a time of similar cyst severity, we generated a single-cell atlas of cystic kidney disease. We conducted RNA-seq on 79,355 cells from control mice and adult-induced conditional mice (hereafter referred to as cilia mutant mice) that were harvested approximately 7 months post-induction or 8 weeks post 30-minute unilateral ischemia reperfusion injury.

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