Publications by authors named "Keegan J"

Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell-B cell interactions. Expansion of T follicular helper (T) and T peripheral helper (T) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE. Human T and T cells characteristically produce high levels of the B cell chemoattractant CXCL13 (refs.

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Lupus nephritis (LN) is a frequent manifestation of systemic lupus erythematosus, and fewer than half of patients achieve complete renal response with standard immunosuppressants. Identifying non-invasive, blood-based pathologic immune alterations associated with renal injury could aid therapeutic decisions. Here, we used mass cytometry immunophenotyping of peripheral blood mononuclear cells in 145 patients with biopsy-proven LN and 40 healthy controls to evaluate the heterogeneity of immune activation in patients with LN and to identify correlates of renal parameters and treatment response.

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Telomere maintenance and elongation allows cells to gain replicative immortality and evade cellular senescence during cancer development. While most cancers use telomerase to maintain telomere lengths, a subset of cancers engage the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. ALT is present in 5%-10% of all cancers, although the prevalence is dramatically higher in certain cancer types, including complex karyotype sarcomas, isocitrate dehydrogenase-mutant astrocytoma (WHO grade II-IV), pancreatic neuroendocrine tumours, neuroblastoma and chromophobe hepatocellular carcinomas.

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Introduction: The purpose of our research was to explore how parents and their adolescent children make decisions about the human papillomavirus (HPV) vaccine, and to inform future interventions that aim to facilitate inclusive decision-making processes.

Method: Purposive and snowball sampling strategies targeted parents and their adolescent children (ages = 11-13) in a large city in Australia. We conducted separate and joint semistructured interviews in 2013 with six mother-adolescent dyads (50% female adolescents and 50% male).

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Novel therapeutics are urgently needed to prevent opportunistic infections in immunocompromised individuals undergoing cancer treatments or other immune-suppressive therapies. Trained immunity is a promising strategy to reduce this burden of disease. We previously demonstrated that mesenchymal stromal cells (MSCs) preconditioned with a class A CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) agonist, can augment emergency granulopoiesis in a murine model of neutropenic sepsis.

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Background: Traditional school-based sexuality education has a myriad of problems with its successful delivery, including access to comprehensive sexuality curricula, access to trained facilitators, and community and parental fears. As an alternative form of sexuality education, The Sex Wrap podcast is released in weekly episodes of about 20-45min, providing listeners with diverse, evidence-based sexual health information.

Methods: Participants in a larger mixed-methods study evaluating The Sex Wrap were invited to participate in qualitative in-depth interviews to explore their experiences with sexuality education, including The Sex Wrap , and how they relate to information received through the podcast.

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Rheumatoid arthritis (RA) is a systemic autoimmune disease with currently no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in 'At-Risk' populations prior to clinical disease onset is crucial to establishing effective prevention strategies. Here, we applied mass cytometry to deeply characterize the immunophenotypes in blood from At-Risk individuals identified through the presence of serum antibodies to citrullinated protein antigens (ACPA) and/or first-degree relative (FDR) status (n=52), as compared to established RA (n=67), and healthy controls (n=48).

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The telomeric repeat-containing RNA, TERRA, associates with both telomeric DNA and telomeric proteins, often forming RNA:DNA hybrids (R-loops). TERRA is most abundant in cancer cells utilizing the alternative lengthening of telomeres (ALT) pathway for telomere maintenance, suggesting that persistent TERRA R-loops may contribute to activation of the ALT mechanism. Therefore, we sought to identify the enzyme(s) that regulate TERRA metabolism in mammalian cells.

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Background And Objective: Shared decision-making (SDM) aligns patient preferences with health care team treatment goals. This quality improvement initiative implemented a standardized SDM bundle within a neurocritical care unit (NCCU), where unique demands make existing, provider-driven SDM practices challenging.

Methods: An interprofessional team defined key issues, identified barriers, and created change ideas to drive implementation of an SDM bundle using the Institute for Healthcare Improvement Model for Improvement framework incorporating Plan-Do-Study-Act cycles.

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Dogs are an important part of life for many people. Dog ownership can confer various health benefits to their owners, but it also presents some risks. In order to establish if dog owners were aware of these risks, an online survey of dog ownership practices was carried out.

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Introduction: Trauma alters the immune response in numerous ways, affecting both the innate and adaptive responses. Macrophages play an important role in inflammation and wound healing following injury. We hypothesize that macrophages mobilize from the circulation to the site of injury and secondary sites after trauma, with a transition from proinflammatory (M1) shortly after trauma to anti-inflammatory (M2) at later time points.

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Purpose: Variable heart rate during single-cycle inversion-recovery Late Gadolinium-Enhanced (LGE) scanning degrades image quality, which can be mitigated using Variable Inversion Times (VTIs) in real-time response to R-R interval changes. We investigate in vivo and in simulations an extension of a single-cycle VTI method previously applied in 3D LGE imaging, that now fully models the longitudinal magnetisation (fmVTI).

Methods: The VTI and fmVTI methods were used to perform 3D LGE scans for 28 3D LGE patients, with qualitative image quality scores assigned for left atrial wall clarity and total ghosting.

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Obesity is accompanied by inflammation in adipose tissue, impaired glucose tolerance, and changes in adipose leukocyte populations. These studies of adipose tissue from humans and mice revealed that increased frequencies of T-bet B cells in adipose tissue depend on invariant NKT cells and correlate with weight gain during obesity. Transfer of B cells enriched for T-bet cells exacerbates metabolic disorder in obesity, while ablation of Tbx21 specifically in B cells reduces serum IgG2c levels, inflammatory cytokines, and inflammatory macrophages in adipose tissue, ameliorating metabolic symptoms.

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Objectives: To investigate the immune cell profiles of patients with systemic lupus erythematosus (SLE), and to identify longitudinal changes in those profiles over time.

Methods: We employed mass cytometry with 3 different panels of 38-39 markers (an immunophenotyping panel, a T cell/monocyte panel, and a B cell panel) in cryopreserved peripheral blood mononuclear cells (PBMCs) from 9 patients with early SLE, 15 patients with established SLE, and 14 controls without autoimmune disease. We used machine learning-driven clustering, flow self-organizing maps, and dimensional reduction with t-distributed stochastic neighbor embedding to identify unique cell populations in early SLE and established SLE.

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CD4 regulatory T cells (Tregs) activate and expand in response to different types of injuries, suggesting that they play a critical role in controlling the immune response to tissue and cell damage. This project used multi-dimensional profiling techniques to comprehensively characterize injury responsive Tregs in mice. We show that CD44 Tregs expand in response to injury and were highly suppressive when compared to CD44 Tregs.

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Objectives: We investigated the holistic experiences of university students during the pandemic.

Participants: Thirty-eight students in a public university system in New York City (NYC) purposively selected from neighborhoods highly affected by the pandemic based on level of self-reported impact.

Methods: We conducted virtual in-depth interviews from May to August 2021 and analyzed data using thematic coding and constant comparison techniques informed by grounded theory.

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Fatigue is a predisposing risk factor for injury commonly investigated in elite football populations. Little evidence advocates the most beneficial recovery strategies including contemporary cooling applications. The aim of the study was to examine immediate effects of the Game Ready on physiological and biomechanical measures in a population of elite male academy footballers, following a fatiguing training session mid-competitive season.

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Background: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined.

Methods: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors.

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Objectives: This study sought to identify patients with repaired tetralogy of Fallot (rTOF) at high risk of death and malignant ventricular arrhythmia (VA).

Background: To date there is no robust risk stratification scheme to predict outcomes in adults with rTOF.

Methods: Consecutive patients were prospectively recruited for late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) to define right and left ventricular (RV, LV) fibrosis in addition to proven risk markers.

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Semi-supervised learning provides great significance in left atrium (LA) segmentation model learning with insufficient labelled data. Generalising semi-supervised learning to cross-domain data is of high importance to further improve model robustness. However, the widely existing distribution difference and sample mismatch between different data domains hinder the generalisation of semi-supervised learning.

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Myelodysplastic syndromes (MDS) are clonal neoplasms of the hematopoietic stem cell that result in aberrant differentiation of hematopoietic lineages caused by a wide range of underlying genetic, epigenetic, and other causes. Despite the myriad origins, a recognizable MDS phenotype has been associated with miRNA aberrant expression. A model of aberrant myeloid maturation that mimics MDS was generated using a stable knockdown of miR-378-3p.

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A total of 120 internet bought stainless-steel utensil samples intended for food serving were analysed for their release of Cr, Ni, Al, Fe, Mn, Cu, Zn, and Mo. Samples were extracted using simulants under continuous and discontinuous test conditions, extracts were analysed by ICP-MS, and metallic compositions of utensils were indicated by XRF analysis. values for all analytes were determined between 0.

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