106 results on '"Murray BA"'
Search Results
2. Epidemiology of systemic sclerosis in Quebec, Canada: a population-based studyResearch in context
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Anastasiya Muntyanu, Katherine Aw, Mohammed Kaouache, Elham Rahme, Mohamed Osman, Murray Baron, Stephanie Ghazal, and Elena Netchiporouk
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Systemic sclerosis ,Incidence ,Prevalence ,Mortality ,Epidemiology ,Populational ,Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: Systemic sclerosis (SSc) is a systemic life-threatening autoimmune rheumatic disease. We aimed to assess the incidence, prevalence, mortality and spatiotemporal trends of SSc in Quebec, Canada with stratification by sex and age. Methods: SSc cases were identified from Quebec populational databases from 1989 to 2019. Negative Binomial (NB) Generalized Linear Models were used for age-standardized incidence rates (ASIR) analyses and NB random walk for prevalence and mortality. A Poisson Besag-York-Mollié regression model was used for spatial analysis. Findings: 8180 incident SSc cases were identified between 1996 and 2019 with an average age of 57.3 ± 16.3 years. The overall ASIR was 4.14/100,000 person-years (95%, Confidence Interval (CI) 4.05–4.24) with a 4:1 female predominance. ASIR increased steadily over time with an Average Annual Percent Change (AAPC) of 3.94% (95% CI 3.49–4.38). While the highest incidence rates were in those aged 60–79 years old among females and >80 years old among males, the highest AAPC (∼10%) was seen in children. Standarized incidence ratios varied geographically between 0.52 to 1.64. The average prevalence was 28.96/100,000 persons (95% CI 28.72–29.20). The Standardized Mortality Ratio (SMR) decreased from 4.18 (95% CI 3.64–4.76) in 1996 to 2.69 (95% CI 2.42–2.98) in 2019. Females had a greater SMR until 2007 and males thereafter. The highest SMR was in children and young adults [31.2 (95% CI 8.39–79.82) in the 0–19-year age group]. Interpretation: We showed an increasing trend in SSc incidence and prevalence and a decline in SMR over a 25-year period in Quebec. An uneven geographic distribution of SSc incidence was demonstrated. Funding: National Scleroderma Foundation, Canadian Dermatology Foundation/Canadian Institutes of Health Research.
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- 2024
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3. Sludge Pasteurisation - an Alternative Sludge Disinfection Process
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Australian Water and Wastewater Association. Federal Convention (13th : 1989 : Canberra, A.C.T.), Murray, BA, Law, IB, and Tuft, RG
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- 1989
4. Load Management Developments in Queensland
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Engineering Conference (1980 : Adelaide, S.A.), Abercrombie, WJ, Bartlett, SC, and Murray, BA
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- 1980
5. Exposure to silica and systemic sclerosis: A retrospective cohort study based on the Canadian Scleroderma Research Group
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Anastasiya Muntyanu, Raymond Milan, Elham Rahme, Avery LaChance, Lydia Ouchene, Maxime Cormier, Ivan V. Litvinov, Marie Hudson, Murray Baron, Elena Netchiporouk, the Canadian Scleroderma Research Group, M. Baron, M. Hudson, G. Gyger, J. Pope, M. Larche, N. Khalidi, A. Masetto, E. Sutton, T. S. Rodriguez Reyna, N. Maltez, C. Thorne, P. R. Fortin, A. Ikic, D. Robinson, N. Jones, S. LeClercq, P. Docherty, D. Smith, and M. J. Fritzler
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systemic sclerosis ,silica ,environmental triggers ,occupation ,mortality ,gastrointestinal disease ,Medicine (General) ,R5-920 - Abstract
IntroductionSystemic sclerosis (SSc) is thought to be induced by an environmental trigger in genetically predisposed individuals. This study assessed the demographic and clinical characteristics and disease severity of silica exposed SSc patients.MethodsData was obtained from the Canadian Scleroderma Research Group (CSRG) cohort, containing 1,439 patients (2004–2019). Univariate and multivariate logistic regression analyses were performed, to determine the phenotype and severity of silica-exposed SSc patients. Mortality was assessed using Cox Survival Regression and Kaplan-Meier analyses.ResultsAmong 1,439 patients (86.7% females), 95 patients reported exposure to silica. Those exposed were younger, of male sex and with more severe disease. Sex differences were observed where male patients exposed to silica were more likely to be Caucasian and smokers whereas female patients were younger at SSc diagnosis compared to unexposed. Multivariate regression, controlled for multiple confounders, showed that silica exposure was associated with a younger age at diagnosis and worse disease severity and mortality.ConclusionExposure to silica was reported in ∼7% of CSRG cohort and ∼20% of male patients and was associated with a worse prognosis in terms of age of diagnosis, organ involvement and mortality. Hence, screening for silica exposure among higher risk individuals may be beneficial and these patients may require closer monitoring for systemic disease.
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- 2022
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6. Interactive Strategic Planning and Community Development: The Northern Ireland Experience
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John V. Greer BA(Hons), MSc, Mrtpi, Mipi and Michael R. Murray BA(Hons), MSc, PhD, Mrtpi, Mipi
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Strategic planning ,Economic growth ,Public Administration ,Sociology and Political Science ,Divided society ,business.industry ,Development ,Public relations ,Northern ireland ,Rural development ,Argument ,General partnership ,Political science ,Community development ,business ,Economic change - Abstract
This paper discusses a model of community development practice that involves an interactive relationship between organized rural residents and outside technical facilitators. A central argument is that a strategic plan in a multi-community planning situation benefits from a series of specific community development inputs. The discussion draws upon a case study in Northern Ireland where, in a deeply divided society, community-led rural development not only contributes to social and economic change, but also helps promote mutual understanding and reconciliation between contesting cultural traditions. The paper identifies three key issues of wider interest: engaging in strategic planning, supporting multi-community activity, and forging new partnership arrangements. It points to some mechanisms for replication elsewhere.
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- 1997
7. Special Issue 'Rheumatic Diseases: Pathophysiology, Targeted Therapy, Focus on Vascular and Pulmonary Manifestations 2022'
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Barbara Ruaro, Murray Baron, Edoardo Rosato, Romeo Martini, and Marco Confalonieri
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n/a ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
This Special Issue, titled “Rheumatic Diseases: Pathophysiology, Targeted Therapy, Focus on Vascular and Pulmonary Manifestations”, aims to demonstrate recent and new advances and future trends in the field of rheumatic diseases [...]
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- 2023
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8. Immunosuppressive treatment in diffuse cutaneous systemic sclerosis is associated with an improved composite response index (CRISS)
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Boyang Zheng, Marie Hudson, Mianbo Wang, Murray Baron, and for the Canadian Scleroderma Research Group
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Systemic sclerosis ,Scleroderma ,Immunosuppression ,Outcomes ,CRISS ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Outcomes of therapeutic studies in diffuse cutaneous systemic sclerosis (dcSSc) have mainly been measured for specific organs, particularly the skin and lungs. A new composite response index in dcSSc (CRISS) has been developed for clinical trials. The goal of this study was to determine whether, in an observational dcSSc cohort, immunosuppression was associated with global disease improvement measured with the CRISS. Methods We conducted a retrospective cohort study in a multi-centered SSc registry comparing 47 patients newly exposed to immunosuppression for ≥ 1 year to 254 unexposed patients. Inverse probability of treatment weighting (IPTW) was performed to create comparable exposed and unexposed groups by balancing for age, sex, disease duration, modified Rodnan skin score (mRSS), forced vital capacity, patient and physician global assessments, and Health Assessment Questionnaire score. A CRISS score ≥ 0.6 at 1 year was defined as improvement. Results Exposed patients had shorter disease duration (5.5 versus 11.7 years, p
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- 2020
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9. Relationships Between Allopurinol Dose, Oxypurinol Concentration and Urate‐Lowering Response—In Search of a Minimum Effective Oxypurinol Concentration
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Lisa K. Stamp, Peter T. Chapman, Murray Barclay, Anne Horne, Christopher Frampton, Tony R. Merriman, Daniel F. B. Wright, Jill Drake, and Nicola Dalbeth
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Therapeutics. Pharmacology ,RM1-950 ,Public aspects of medicine ,RA1-1270 - Abstract
The aims of this study were to determine factors that predict serum urate (SU) lowering response to allopurinol and the conversion of allopurinol to oxypurinol, and to determine a minimum therapeutic oxypurinol concentration. Data from 129 participants in a 24‐month open, randomized, controlled, parallel‐group, comparative clinical trial were analyzed. Allopurinol dose, SU, and plasma oxypurinol concentrations were available at multiple time points. The slope for the association between allopurinol dose and SU was calculated as a measure of sensitivity to allopurinol. The slope for the association between allopurinol dose and oxypurinol was calculated as a measure of allopurinol metabolism. Receiver operating characteristic (ROC) curves were used to identify a minimum oxypurinol concentration predictive of SU
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- 2020
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10. The effect of kidney function on the urate lowering effect and safety of increasing allopurinol above doses based on creatinine clearance: a post hoc analysis of a randomized controlled trial
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Lisa K. Stamp, Peter T. Chapman, Murray Barclay, Anne Horne, Christopher Frampton, Paul Tan, Jill Drake, and Nicola Dalbeth
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Allopurinol ,Chronic kidney disease ,Gout ,Serum urate ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background The use of allopurinol in people with chronic kidney disease (CKD) remains one of the most controversial areas in gout management. The aim of this study was to determine the effect of baseline kidney function on safety and efficacy of allopurinol dose escalation to achieve serum urate (SU)
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- 2017
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11. Sudden Cardiac Death in Systemic Sclerosis: Diagnostics to Assess Risk and Inform Management
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Laura Ross, Elizabeth Paratz, Murray Baron, André La Gerche, and Mandana Nikpour
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systemic sclerosis (scleroderma) ,heart disease ,cardiac ,sudden cardiac death ,arrhythmia ,Medicine (General) ,R5-920 - Abstract
Cardiac disease is a leading cause of death in systemic sclerosis (SSc) and sudden cardiac death (SCD) is thought to occur more commonly in SSc than in the general population. Diffuse myocardial fibrosis, myocarditis and ischaemic heart disease are all prevalent in SSc and can be reasonably hypothesised to contribute to an increased risk of SCD. Despite this, SCD remains a relatively understudied area of SSc with little understood about SSc-specific risk factors and opportunities for primary prevention. In this review, we present an overview of the possible mechanisms of SCD in SSc and our current understanding of how each of these mechanisms may contribute to cardiac death. This review highlights the need for a future research agenda that addresses the underlying epidemiology of SCD in SSc and identifies opportunities for intervention to modify the disease course of heart disease in SSc.
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- 2021
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12. Evidence for heterophilic adhesion of embryonic retinal cells and neuroblastoma cells to substratum-adsorbed NCAM
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Murray, BA, primary and Jensen, JJ, additional
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- 1992
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13. A comparison of health-related quality of life (HRQoL) across four systemic autoimmune rheumatic diseases (SARDs).
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Julia Greenfield, Marie Hudson, Evelyne Vinet, Paul R Fortin, Vivian Bykerk, Christian A Pineau, Mianbo Wang, Sasha Bernatsky, Murray Baron, and Canadian Scleroderma Research Group and Canadian Inflammatory Myopathy Study Group
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Medicine ,Science - Abstract
To compare physical and mental health-related quality of life (HRQoL) across four systemic autoimmune rheumatic diseases (SARD).Incident subjects enrolled in four SARD cohorts, namely systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA) and idiopathic inflammatory myopathies (IIM) were studied. The outcomes of interest were baseline Short Form Health Survey physical (PCS) and mental (MCS) component summary scores. Multivariate analysis was conducted to determine whether PCS and MCS scores differed across SARD type.The study included 118 SLE (93% women, mean age 36 years), 108 SSc (79% women, mean age 55), 64 RA (63% women, mean age 58) and 25 IIM (68% women, mean age 49) subjects. Mean PCS scores were 38.9 ± 12.2 in SLE, 37.1 ± 13.3 in RA, 35.0 ± 13.6 in SSc and 28.0 ± 15.4 in IIM. Mean MCS scores were 45.0 ± 13.3 in RA, 44.4 ± 14.7 in SSc, 40.1 ± 14.3 in SLE and 33.6 ± 18.7 in IIM. SARD type was an independent predictor of HRQoL with, in some cases, the magnitude of the differences reaching one standard deviation (IIM worse PCS scores compared to SLE (β -12.23 [95% CI -18.11, -6.36; p
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- 2017
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14. Targeted Therapy in Systemic Sclerosis
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Murray Baron
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Drug treatment ,scleroderma ,systemic sclerosis ,targeted ,Medicine ,Medicine (General) ,R5-920 - Abstract
Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma) has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc. The well-known properties of transforming growth factor (TGF)-β in promoting collagen synthesis and secretion has led to a small trial of fresolimumab, a human IgG4 monoclonal antibody capable of neutralizing TGF-β. Evidence supporting important roles for interleukin-6 in the pathogenesis of SSc have led to a large trial of tocilizumab in SSc. Soluble guanylate cyclase (sGC) is an enzyme that catalyzes the production of cyclic guanosine monophosphate (cGMP) upon binding of nitric oxide (NO) to the sGC molecule. Processes such as cell growth and proliferation are regulated by cGMP. Evidence that sGC may play a role in SSc has led to a trial of riociguat, a molecule that sensitizes sGC to endogenous NO. Tyrosine kinases (TKs) are involved in a wide variety of physiologic and pathological processes including vascular remodeling and fibrogenesis such as occurs in SSc. This has led to a trial of nintedanib, a next-generation tyrosine-kinase (TK) inhibitor which targets multiple TKs, in SSc.
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- 2016
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15. An assessment of the measurement equivalence of English and French versions of the Center for Epidemiologic Studies Depression (CES-D) Scale in systemic sclerosis.
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Vanessa C Delisle, Linda Kwakkenbos, Marie Hudson, Murray Baron, Brett D Thombs, and Canadian Scleroderma Research Group
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Medicine ,Science - Abstract
Center for Epidemiologic Studies Depression (CES-D) Scale scores in English- and French-speaking Canadian systemic sclerosis (SSc) patients are commonly pooled in analyses, but no studies have evaluated the metric equivalence of the English and French CES-D. The study objective was to examine the metric equivalence of the CES-D in English- and French-speaking SSc patients.The CES-D was completed by 1007 English-speaking and 248 French-speaking patients from the Canadian Scleroderma Research Group Registry. Confirmatory factor analysis (CFA) was used to assess the factor structure in both samples. The Multiple-Indicator Multiple-Cause (MIMIC) model was utilized to assess differential item functioning (DIF).A two-factor model (Positive and Negative affect) showed excellent fit in both samples. Statistically significant, but small-magnitude, DIF was found for 3 of 20 CES-D items, including items 3 (Blues), 10 (Fearful), and 11 (Sleep). Prior to accounting for DIF, French-speaking patients had 0.08 of a standard deviation (SD) lower latent scores for the Positive factor (95% confidence interval [CI]-0.25 to 0.08) and 0.09 SD higher scores (95% CI-0.07 to 0.24) for the Negative factor than English-speaking patients. After DIF correction, there was no change on the Positive factor and a non-significant increase of 0.04 SD on the Negative factor for French-speaking patients (difference = 0.13 SD, 95% CI-0.03 to 0.28).The English and French versions of the CES-D, despite minor DIF on several items, are substantively equivalent and can be used in studies that combine data from English- and French-speaking Canadian SSc patients.
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- 2014
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16. Systemic sclerosis immunoglobulin induces growth and a pro-fibrotic state in vascular smooth muscle cells through the epidermal growth factor receptor.
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Monique R Arts, Murray Baron, Nidaa Chokr, Marvin J Fritzler, Canadian Scleroderma Research Group (CSRG), and Marc J Servant
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Medicine ,Science - Abstract
It has been suggested that autoantibodies in systemic sclerosis (SSc) may induce the differentiation of cultured fibroblasts into myofibroblasts through platelet-derived growth factor receptor (PDGFR) activation. The present study aims to characterize the effects of SSc IgG on vascular smooth muscle cells (VSMCs) and to determine if stimulatory autoantibodies directed to the PDGFR can be detected, and whether they induce a profibrotic response in primary cultured VSMCs.Cultured VSMCs were exposed to IgG fractions purified from SSc-patient or control sera. VSMC responses were then analyzed for ERK1/2 and Akt phosphorylation, PDGFR immunoprecipitation, cellular proliferation, protein synthesis, and pro-fibrotic changes in mRNA expression.Stimulatory activity in IgG fractions was more prevalent and intense in the SSc samples. SSc IgG immunoprecipitated the PDGFR with greater avidity than control IgG. Interestingly, activation of downstream signaling events (e.g. Akt, ERK1/2) was independent of PDGFR activity, but required functional EGFR. We also detected increased protein synthesis in response to SSc IgG (p
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- 2014
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17. The comparability of English, French and Dutch scores on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F): an assessment of differential item functioning in patients with systemic sclerosis.
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Linda Kwakkenbos, Linda M Willems, Murray Baron, Marie Hudson, David Cella, Cornelia H M van den Ende, Brett D Thombs, and Canadian Scleroderma Research Group
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Medicine ,Science - Abstract
The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is commonly used to assess fatigue in rheumatic diseases, and has shown to discriminate better across levels of the fatigue spectrum than other commonly used measures. The aim of this study was to assess the cross-language measurement equivalence of the English, French, and Dutch versions of the FACIT-F in systemic sclerosis (SSc) patients.The FACIT-F was completed by 871 English-speaking Canadian, 238 French-speaking Canadian and 230 Dutch SSc patients. Confirmatory factor analysis was used to assess the factor structure in the three samples. The Multiple-Indicator Multiple-Cause (MIMIC) model was utilized to assess differential item functioning (DIF), comparing English versus French and versus Dutch patient responses separately.A unidimensional factor model showed good fit in all samples. Comparing French versus English patients, statistically significant, but small-magnitude DIF was found for 3 of 13 items. French patients had 0.04 of a standard deviation (SD) lower latent fatigue scores than English patients and there was an increase of only 0.03 SD after accounting for DIF. For the Dutch versus English comparison, 4 items showed small, but statistically significant, DIF. Dutch patients had 0.20 SD lower latent fatigue scores than English patients. After correcting for DIF, there was a reduction of 0.16 SD in this difference.There was statistically significant DIF in several items, but the overall effect on fatigue scores was minimal. English, French and Dutch versions of the FACIT-F can be reasonably treated as having equivalent scoring metrics.
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- 2014
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18. Cross-language measurement equivalence of the Center for Epidemiologic Studies Depression (CES-D) scale in systemic sclerosis: a comparison of Canadian and Dutch patients.
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Linda Kwakkenbos, Erin Arthurs, Frank H J van den Hoogen, Marie Hudson, Wim G J M van Lankveld, Murray Baron, Cornelia H M van den Ende, Brett D Thombs, and Canadian Scleroderma Research Group
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Medicine ,Science - Abstract
Increasingly, medical research involves patients who complete outcomes in different languages. This occurs in countries with more than one common language, such as Canada (French/English) or the United States (Spanish/English), as well as in international multi-centre collaborations, which are utilized frequently in rare diseases such as systemic sclerosis (SSc). In order to pool or compare outcomes, instruments should be measurement equivalent (invariant) across cultural or linguistic groups. This study provides an example of how to assess cross-language measurement equivalence by comparing the Center for Epidemiologic Studies Depression (CES-D) scale between English-speaking Canadian and Dutch SSc patients.The CES-D was completed by 922 English-speaking Canadian and 213 Dutch SSc patients. Confirmatory factor analysis (CFA) was used to assess the factor structure in both samples. The Multiple-Indicator Multiple-Cause (MIMIC) model was utilized to assess the amount of differential item functioning (DIF).A two-factor model (positive and negative affect) showed excellent fit in both samples. Statistically significant, but small-magnitude, DIF was found for 3 of 20 items on the CES-D. The English-speaking Canadian sample endorsed more feeling-related symptoms, whereas the Dutch sample endorsed more somatic/retarded activity symptoms. The overall estimate in depression scores between English and Dutch was not influenced substantively by DIF.CES-D scores from English-speaking Canadian and Dutch SSc patients can be compared and pooled without concern that measurement differences may substantively influence results. The importance of assessing cross-language measurement equivalence in rheumatology studies prior to pooling outcomes obtained in different languages should be emphasized.
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- 2013
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19. Sociodemographic and disease correlates of body image distress among patients with systemic sclerosis.
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Lisa R Jewett, Marie Hudson, Vanessa L Malcarne, Murray Baron, Brett D Thombs, and Canadian Scleroderma Research Group
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Medicine ,Science - Abstract
Body image concerns are infrequently studied in systemic sclerosis (SSc), even though significant visible disfigurement is common. The objective of this study was to identify sociodemographic and disease-related correlates of dissatisfaction with appearance and social discomfort among people with SSc.SSc patients came from the 15-center Canadian Scleroderma Research Group Registry. Sociodemographic information was based on patient self-report. Disease characteristics were obtained via physician examinations. The Brief-SWAP was used to assess dissatisfaction with appearance and social discomfort. Structural equation models were conducted with MPlus to determine the relationship of dissatisfaction with appearance and social discomfort with age, sex, education, marital status, race/ethnicity, disease duration, skin involvement, telangiectasias, skin pigmentation changes, and hand contractures.A total of 489 SSc patients (432 female, 57 male) were included. Extent of skin involvement was significantly associated with both dissatisfaction with appearance and social discomfort (standardized regression coefficients = 0.02, p = 0.001; 0.02, p = 0.020, respectively), as was skin involvement in the face (0.18, p = 0.016; 0.23, p = 0.006, respectively). Greater social discomfort was robustly associated with younger age (-0.017, p
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- 2012
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20. Are scores on English and French versions of the PHQ-9 comparable? An assessment of differential item functioning.
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Erin Arthurs, Russell J Steele, Marie Hudson, Murray Baron, Brett D Thombs, and (CSRG) Canadian Scleroderma Research Group
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Medicine ,Science - Abstract
Medical research increasingly utilizes patient-reported outcome measures administered and scored in different languages. In order to pool or compare outcomes from different language versions, instruments should be measurement equivalent across linguistic groups. The objective of this study was to examine the cross-language measurement equivalence of the Patient Health Questionnaire-9 (PHQ-9) between English- and French-speaking Canadian patients with systemic sclerosis (SSc).The sample consisted of 739 English- and 221 French-speaking SSc patients. Multiple-Indicator Multiple-Cause (MIMIC) modeling was used to identify items displaying possible differential item functioning (DIF).A one-factor model for the PHQ-9 fit the data well in both English- and French-speaking samples. Statistically significant DIF was found for 3 of 9 items on the PHQ-9. However, the overall estimate in depression latent scores between English- and French-speaking respondents was not influenced substantively by DIF.Although there were several PHQ-9 items with evidence of minor DIF, there was no evidence that these differences influenced overall scores meaningfully. The PHQ-9 can reasonably be used without adjustment in Canadian English- and French-speaking samples. Analyses assessing measurement equivalence should be routinely conducted prior to pooling data from English and French versions of patient-reported outcome measures.
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- 2012
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21. Sexual activity and impairment in women with systemic sclerosis compared to women from a general population sample.
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Brooke Levis, Andrea Burri, Marie Hudson, Murray Baron, Brett D Thombs, and Canadian Scleroderma Research Group (CSRG)
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Medicine ,Science - Abstract
Reports of low sexual activity rates and high impairment rates among women with chronic diseases have not included comparisons to general population data. The objective of this study was to compare sexual activity and impairment rates of women with systemic sclerosis (SSc) to general population data and to identify domains of sexual function driving impairment in SSc.Canadian women with SSc were compared to women from a UK population sample. Sexual activity and, among sexually active women, sexual impairment were evaluated with a 9-item version of the Female Sexual Function Index (FSFI).Among women with SSc (mean age = 57.0 years), 296 of 730 (41%) were sexually active, 181 (61%) of whom were sexually impaired, resulting in 115 of 730 (16%) who were sexually active without impairment. In the UK population sample (mean age = 55.4 years), 956 of 1,498 women (64%) were sexually active, 420 (44%) of whom were impaired, with 536 of 1,498 (36%) sexually active without impairment. Adjusting for age and marital status, women with SSc were significantly less likely to be sexually active (OR = 0.34, 95%CI = 0.28-0.42) and, among sexually active women, significantly more likely to be sexually impaired (OR = 1.88, 95%CI = 1.42-2.49) than general population women. Controlling for total FSFI scores, women with SSc had significantly worse lubrication and pain scores than general population women.Sexual functioning is a problem for many women with scleroderma and is associated with pain and poor lubrication. Evidence-based interventions to support sexual activity and function in women with SSc are needed.
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- 2012
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22. An International, Web-Based, Prospective Cohort Study to Determine Whether the Use of ACE Inhibitors prior to the Onset of Scleroderma Renal Crisis Is Associated with Worse Outcomes—Methodology and Preliminary Results
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Marie Hudson, Murray Baron, Ernest Lo, Joanna Weinfeld, Daniel E. Furst, and Dinesh Khanna
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Background. To describe the methodology of a study designed to determine whether systemic sclerosis (SSc) patients with incident scleroderma renal crisis (SRC) on angiotensin converting enzyme (ACE) inhibitors prior to the onset of SRC have worse outcomes. Methods. Prospective, international cohort study of SRC subjects identified through an ongoing web-based survey. Every second Friday afternoon, an e-mail was sent to 589 participating physicians to identify new cases of SRC. Death or dialysis at one year after the onset of SRC will be compared in patients exposed or not to ACE inhibitors prior to the onset of SRC. Results. Fifteen months after the start of the survey, we had identified 76 incident cases of SRC. Of these, 66 (87%) had a hypertensive SRC and 10 (13%) a normotensive SRC. Twenty-two percent (22%) of the patients were on an ACE inhibitor immediately prior to the onset of the SRC. To date, we have collected one-year follow-up data on approximately 1/3 of the cohort. Of these, over 50% have died or remain on dialysis at one year. Conclusion. An international, web-based cohort study design is a feasible method of recruiting a substantial number of patients to study an infrequent vascular manifestation of SSc.
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- 2010
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23. Complete genome sequence of Enterococcus faecium strain TX16 and comparative genomic analysis of Enterococcus faecium genomes
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Qin Xiang, Galloway-Peña Jessica R, Sillanpaa Jouko, Roh Jung, Nallapareddy Sreedhar R, Chowdhury Shahreen, Bourgogne Agathe, Choudhury Tina, Muzny Donna M, Buhay Christian J, Ding Yan, Dugan-Rocha Shannon, Liu Wen, Kovar Christie, Sodergren Erica, Highlander Sarah, Petrosino Joseph F, Worley Kim C, Gibbs Richard A, Weinstock George M, and Murray Barbara E
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Microbiology ,QR1-502 - Abstract
Abstract Background Enterococci are among the leading causes of hospital-acquired infections in the United States and Europe, with Enterococcus faecalis and Enterococcus faecium being the two most common species isolated from enterococcal infections. In the last decade, the proportion of enterococcal infections caused by E. faecium has steadily increased compared to other Enterococcus species. Although the underlying mechanism for the gradual replacement of E. faecalis by E. faecium in the hospital environment is not yet understood, many studies using genotyping and phylogenetic analysis have shown the emergence of a globally dispersed polyclonal subcluster of E. faecium strains in clinical environments. Systematic study of the molecular epidemiology and pathogenesis of E. faecium has been hindered by the lack of closed, complete E. faecium genomes that can be used as references. Results In this study, we report the complete genome sequence of the E. faecium strain TX16, also known as DO, which belongs to multilocus sequence type (ST) 18, and was the first E. faecium strain ever sequenced. Whole genome comparison of the TX16 genome with 21 E. faecium draft genomes confirmed that most clinical, outbreak, and hospital-associated (HA) strains (including STs 16, 17, 18, and 78), in addition to strains of non-hospital origin, group in the same clade (referred to as the HA clade) and are evolutionally considerably more closely related to each other by phylogenetic and gene content similarity analyses than to isolates in the community-associated (CA) clade with approximately a 3–4% average nucleotide sequence difference between the two clades at the core genome level. Our study also revealed that many genomic loci in the TX16 genome are unique to the HA clade. 380 ORFs in TX16 are HA-clade specific and antibiotic resistance genes are enriched in HA-clade strains. Mobile elements such as IS16 and transposons were also found almost exclusively in HA strains, as previously reported. Conclusions Our findings along with other studies show that HA clonal lineages harbor specific genetic elements as well as sequence differences in the core genome which may confer selection advantages over the more heterogeneous CA E. faecium isolates. Which of these differences are important for the success of specific E. faecium lineages in the hospital environment remain(s) to be determined.
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- 2012
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24. The hylEfm gene in pHylEfm of Enterococcus faecium is not required in pathogenesis of murine peritonitis
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Mojica Maria F, Rincón Sandra, Montealegre Maria C, Panesso Diana, Rice Louis B, Singh Kavindra V, Murray Barbara E, and Arias Cesar A
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Microbiology ,QR1-502 - Abstract
Abstract Background Plasmids containing hylEfm (pHylEfm) were previously shown to increase gastrointestinal colonization and lethality of Enterococcus faecium in experimental peritonitis. The hylEfm gene, predicting a glycosyl hydrolase, has been considered as a virulence determinant of hospital-associated E. faecium, although its direct contribution to virulence has not been investigated. Here, we constructed mutants of the hylEfm-region and we evaluated their effect on virulence using a murine peritonitis model. Results Five mutants of the hylEfm-region of pHylEfmTX16 from the sequenced endocarditis strain (TX16 [DO]) were obtained using an adaptation of the PheS* system and were evaluated in a commensal strain TX1330RF to which pHylEfmTX16 was transferred by mating; these include i) deletion of hylEfm only; ii) deletion of the gene downstream of hylEfm (down) of unknown function; iii) deletion of hylEfm plus down; iv) deletion of hylEfm-down and two adjacent genes; and v) a 7,534 bp deletion including these four genes plus partial deletion of two others, with replacement by cat. The 7,534 bp deletion did not affect virulence of TX16 in peritonitis but, when pHylEfmTX16Δ7,534 was transferred to the TX1330RF background, the transconjugant was affected in in vitro growth versus TX1330RF(pHylEfmTX16) and was attenuated in virulence; however, neither hylEfm nor hylEfm-down restored wild type function. We did not observe any in vivo effect on virulence of the other deletions of the hylEfm-region Conclusions The four genes of the hylEfm region (including hylEfm) do not mediate the increased virulence conferred by pHylEfmTX16 in murine peritonitis. The use of the markerless counterselection system PheS* should facilitate the genetic manipulation of E. faecium in the future.
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- 2011
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25. Bicarbonate enhances expression of the endocarditis and biofilm associated pilus locus, ebpR-ebpABC, in Enterococcus faecalis
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Thomson L Charlene, Bourgogne Agathe, and Murray Barbara E
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Microbiology ,QR1-502 - Abstract
Abstract Background We previously identified ebpR, encoding a potential member of the AtxA/Mga transcriptional regulator family, and showed that it is important for transcriptional activation of the Enterococcus faecalis endocarditis and biofilm associated pilus operon, ebpABC. Although ebpR is not absolutely essential for ebpABC expression (100-fold reduction), its deletion led to phenotypes similar to those of an ebpABC mutant such as absence of pili at the cell surface and, consequently, reduced biofilm formation. A non-piliated ebpABC mutant has been shown to be attenuated in a rat model of endocarditis and in a murine urinary tract infection model, indicating an important participation of the ebpR-ebpABC locus in virulence. However, there is no report relating to the environmental conditions that affect expression of the ebpR-ebpABC locus. Results In this study, we examined the effect of CO2/HCO3-, pH, and the Fsr system on the ebpR-ebpABC locus expression. The presence of 5% CO2/0.1 M HCO3- increased ebpR-ebpABC expression, while the Fsr system was confirmed to be a weak repressor of this locus. The mechanism by which the Fsr system repressed the ebpR-ebpABC locus expression appears independent of the effects of CO2- bicarbonate. Furthermore, by using an ebpA::lacZ fusion as a reporter, we showed that addition of 0.1 M sodium bicarbonate to TSBG (buffered at pH 7.5), but not the presence of 5% CO2, induced ebpA expression in TSBG broth. In addition, using microarray analysis, we found 73 genes affected by the presence of sodium bicarbonate (abs(fold) > 2, P < 0.05), the majority of which belong to the PTS system and ABC transporter families. Finally, pilus production correlated with ebpA mRNA levels under the conditions tested. Conclusions This study reports that the ebp locus expression is enhanced by the presence of bicarbonate with a consequential increase in the number of cells producing pili. Although the molecular basis of the bicarbonate effect remains unclear, the pathway is independent of the Fsr system. In conclusion, E. faecalis joins the growing family of pathogens that regulates virulence gene expression in response to bicarbonate and/or CO2.
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- 2010
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26. Using the Delphi Method to Elucidate Patient and Caregiver Experiences of Cancer Care
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Janet Ellis MBBChir, MD, FRCPC, Miriam von Mücke Similon MD, Melissa B Korman BSc (Hons), MSc (Candidate), Sophia den Otter-Moore BSc, MSc, Alva Murray BA, MSW, RSW, Kevin Higgins MSc, MD, FACS, FRCSC, Danny Enepekides MD, FRCSC, MPH, and Marlene Jacobson PhD, S-LP (C) reg.CASLPO
- Subjects
Medicine (General) ,R5-920 - Abstract
Objective: Identify the most salient elements of the head and neck cancer (HNC) care experience described by patients and caregivers in focus group interviews. Methods: Three focus groups of patients and caregivers were facilitated by research assistants and clinicians. Open-ended guiding questions captured/elicited aspects of care that were appreciated, warranted improvement, or enhanced communication and information. A four-step Delphi process derived consensus among focus group facilitators (n = 5) regarding salient discussion points from focus group conversations. Results: Seven salient themes were identified: (1) information provision, (2) burden related to symptoms and treatment side effects, (3) importance of social support, (4) quality of care at both hospital and provider levels, (5) caring for the person, not just treating cancer, (6) social and emotional impact of HNC, and (7) stigma and insufficient information regarding human papillomavirus-related HNC. Conclusion: Participants reported varying needs and support preferences, a desire for individualized communication, and to feel cared for as both a person and a patient. Findings illuminate the intricate details underlying high-quality, compassionate, person-centered HNC cancer care.
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- 2022
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27. Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma
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Michele Ceccarelli, Floris P. Barthel, Tathiane M. Malta, Thais S. Sabedot, Sofie R. Salama, Bradley A. Murray, Olena Morozova, Yulia Newton, Amie Radenbaugh, Stefano M. Pagnotta, Samreen Anjum, Jiguang Wang, Ganiraju Manyam, Pietro Zoppoli, Shiyun Ling, Arjun A. Rao, Mia Grifford, Andrew D. Cherniack, Hailei Zhang, Laila Poisson, Carlos Gilberto Carlotti, Daniela Pretti da Cunha Tirapelli, Arvind Rao, Tom Mikkelsen, Ching C. Lau, W.K. Alfred Yung, Raul Rabadan, Jason Huse, Daniel J. Brat, Norman L. Lehman, Jill S. Barnholtz-Sloan, Siyuan Zheng, Kenneth Hess, Ganesh Rao, Matthew Meyerson, Rameen Beroukhim, Lee Cooper, Rehan Akbani, Margaret Wrensch, David Haussler, Kenneth D. Aldape, Peter W. Laird, David H. Gutmann, Houtan Noushmehr, Antonio Iavarone, Roel G.W. Verhaak, Harindra Arachchi, J. Todd Auman, Miruna Balasundaram, Saianand Balu, Gene Barnett, Stephen Baylin, Sue Bell, Christopher Benz, Natalie Bir, Keith L. Black, Tom Bodenheimer, Lori Boice, Moiz S. Bootwalla, Jay Bowen, Christopher A. Bristow, Yaron S.N. Butterfield, Qing-Rong Chen, Lynda Chin, Juok Cho, Eric Chuah, Sudha Chudamani, Simon G. Coetzee, Mark L. Cohen, Howard Colman, Marta Couce, Fulvio D’Angelo, Tanja Davidsen, Amy Davis, John A. Demchok, Karen Devine, Li Ding, Rebecca Duell, J. Bradley Elder, Jennifer M. Eschbacher, Ashley Fehrenbach, Martin Ferguson, Scott Frazer, Gregory Fuller, Jordonna Fulop, Stacey B. Gabriel, Luciano Garofano, Julie M. Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, Caterina Giannini, William J. Gibson, Angela Hadjipanayis, D. Neil Hayes, David I. Heiman, Beth Hermes, Joe Hilty, Katherine A. Hoadley, Alan P. Hoyle, Mei Huang, Stuart R. Jefferys, Corbin D. Jones, Steven J.M. Jones, Zhenlin Ju, Alison Kastl, Ady Kendler, Jaegil Kim, Raju Kucherlapati, Phillip H. Lai, Michael S. Lawrence, Semin Lee, Kristen M. Leraas, Tara M. Lichtenberg, Pei Lin, Yuexin Liu, Jia Liu, Julia Y. Ljubimova, Yiling Lu, Yussanne Ma, Dennis T. Maglinte, Harshad S. Mahadeshwar, Marco A. Marra, Mary McGraw, Christopher McPherson, Shaowu Meng, Piotr A. Mieczkowski, C. Ryan Miller, Gordon B. Mills, Richard A. Moore, Lisle E. Mose, Andrew J. Mungall, Rashi Naresh, Theresa Naska, Luciano Neder, Michael S. Noble, Ardene Noss, Brian Patrick O’Neill, Quinn T. Ostrom, Cheryl Palmer, Angeliki Pantazi, Michael Parfenov, Peter J. Park, Joel S. Parker, Charles M. Perou, Christopher R. Pierson, Todd Pihl, Alexei Protopopov, Nilsa C. Ramirez, W. Kimryn Rathmell, Xiaojia Ren, Jeffrey Roach, A. Gordon Robertson, Gordon Saksena, Jacqueline E. Schein, Steven E. Schumacher, Jonathan Seidman, Kelly Senecal, Sahil Seth, Hui Shen, Yan Shi, Juliann Shih, Kristen Shimmel, Hugues Sicotte, Suzanne Sifri, Tiago Silva, Janae V. Simons, Rosy Singh, Tara Skelly, Andrew E. Sloan, Heidi J. Sofia, Matthew G. Soloway, Xingzhi Song, Carrie Sougnez, Camila Souza, Susan M. Staugaitis, Huandong Sun, Charlie Sun, Donghui Tan, Jiabin Tang, Yufang Tang, Leigh Thorne, Felipe Amstalden Trevisan, Timothy Triche, David J. Van Den Berg, Umadevi Veluvolu, Doug Voet, Yunhu Wan, Zhining Wang, Ronald Warnick, John N. Weinstein, Daniel J. Weisenberger, Matthew D. Wilkerson, Felicia Williams, Lisa Wise, Yingli Wolinsky, Junyuan Wu, Andrew W. Xu, Lixing Yang, Liming Yang, Travis I. Zack, Jean C. Zenklusen, Jianhua Zhang, Wei Zhang, Jiashan Zhang, Erik Zmuda, Ceccarelli, M, Barthel, Fp, Malta, Tm, Sabedot, T, Salama, Sr, Murray, Ba, Morozova, O, Newton, Y, Radenbaugh, A, Pagnotta, Sm, Anjum, S, Wang, Jg, Manyam, G, Zoppoli, P, Ling, S, Rao, Aa, Grifford, M, Cherniack, Ad, Zhang, Hl, Poisson, L, Carlotti, Cg, Tirapelli, Dpd, Rao, A, Mikkelsen, T, Lau, Cc, Yung, Wka, Rabadan, R, Huse, J, Brat, Dj, Lehman, Nl, Barnholtz-Sloan, J, Zheng, S, Hess, K, Rao, G, Meyerson, M, Beroukhim, R, Cooper, L, Akbani, R, Wrensch, M, Haussler, D, Aldape, Kd, Laird, Pw, Gutmann, Dh, Noushmehr, H, Iavarone, A, Verhaak, Rgw, and Neurosurgery
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0301 basic medicine ,Adult ,X-linked Nuclear Protein ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Epigenesis, Genetic ,Transcriptome ,03 medical and health sciences ,Diffuse Glioma ,Glioma ,medicine ,Cluster Analysis ,Humans ,Promoter Regions, Genetic ,Gene ,Telomerase ,ATRX ,Cell Proliferation ,Pilocytic astrocytoma ,Biochemistry, Genetics and Molecular Biology(all) ,Brain Neoplasms ,MUTAÇÃO GENÉTICA ,DNA Helicases ,Nuclear Proteins ,DNA Methylation ,Middle Aged ,Telomere ,medicine.disease ,Isocitrate Dehydrogenase ,3. Good health ,030104 developmental biology ,DNA demethylation ,DNA methylation ,Mutation ,Cancer research ,Signal Transduction - Abstract
Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.
- Published
- 2016
28. Utilizing NMR fecal metabolomics as a novel technique for detecting the physiological effects of food shortages in waterfowl.
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Murray BA and Machin KL
- Abstract
Metabolomics is the study of small, endogenous metabolites that participate in metabolic reactions, including responses to stressors. Anthropogenic and environmental changes that alter habitat and food supply can act as stressors in wild waterfowl. These alterations invoke a series of physiological processes to provide energy to restore homeostasis and increase survival. In this study, we utilized fecal metabolomics to measure metabolites and identify pathways related to a 6-day feed restriction in captive mallard ducks ( Anas platyrhynchos , n = 9). Fecal samples were collected before (baseline) and during feed restriction (treatment). H
1 Nuclear Magnetic Resonance (NMR) spectroscopy was performed to identify metabolites. We found that fecal metabolite profiles could be used to distinguish between the feed-restricted and baseline samples. We identified metabolites related to pathways for energy production and metabolism endpoints, and metabolites indicative of gut microbiota changes. We also demonstrated that mallard ducks could utilize endogenous reserves in times of limited caloric intake. Fecal metabolomics shows promise as a non-invasive novel tool in identifying and characterizing physiological responses associated with stressors in a captive wild bird species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Murray and Machin.)- Published
- 2024
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29. The effects of pre-hatch elevated corticosterone and post-hatch restrictive food availability on the HPA axis development of mallard ducks (Anas platyrhynchos).
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Murray BA, Soos C, and Machin KL
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- Animals, Female, Ducks, Pituitary-Adrenal System, Feedback, Stress, Physiological, Corticosterone pharmacology, Hypothalamo-Hypophyseal System
- Abstract
Environmental changes can be stressors (altered habitat and food supply, climate change, etc.) to wild animals. Stressors trigger the hypothalamic pituitary adrenal (HPA) axis to release corticosterone (CORT) which modifies energy homeostasis. During nesting, stressed females can deposit increased concentrations of CORT into eggs, altering egg viability and offspring characteristics, constituting a significant mechanism regulating population productivity in subsequent generations. In this study, increased maternal disposition of CORT was mimicked through a 15 ng/g in ovo injection of CORT into mallard duck eggs. Growth and HPA axis function were measured during post-hatch development. For growth, changes in mass were compared at hatch, 7 weeks and 11 weeks. The HPA axis was assessed at seven weeks by measuring CORT at baseline, followed by restraint stress, dexamethasone (negative feedback) and ACTH (maximal adrenal capacity) challenges. At eleven weeks of age, ducks were subjected to a 6-day 25% feed reduction to simulate a poor quality environment to evaluate response to a chronic stressor by comparing CORT at baseline and after restraint stress. Growth and CORT concentration did not differ between treatments at seven weeks or after feed restriction (11 weeks). The CORT dosage administered did not appear to affect HPA axis development in ducklings. Mallards are a highly adaptable species and may have overcome any early alterations to their phenotype. Further research is needed to determine the effects of increased maternal CORT on growth and the development of the HPA axis in ducks. SUMMARY STATEMENT: This study examines how maternal stress (simulated through elevated corticosterone in ovo) and post-hatch chronic stressors (food restriction) affect the development of the HPA axis in a precocial bird., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)
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- 2023
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30. Modification of hyaluronic acid to enable click chemistry photo-crosslinking of hydrogels with tailorable degradation profiles.
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Buckley C, Montgomery TR, Szank T, Murray BA, Quigley C, and Major I
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- Click Chemistry methods, Tissue Engineering methods, Glycosaminoglycans, Sulfhydryl Compounds chemistry, Hydrogels pharmacology, Hydrogels chemistry, Hyaluronic Acid chemistry
- Abstract
Hyaluronic acid (HA) is a naturally occurring mucopolysaccharide that, due to its inherent bioactivity and extracellular matrix-like structure, has the potential to be utilised extensively in tissue engineering. However, this glycosaminoglycan lacks the properties required for cellular adhesion and photo-crosslinking by UV light, which significantly hinders this polymers applicability. This research presents a method for modifying hyaluronic acid via thiolation and methacrylation to generate a novel photo-crosslinkable polymer with improved physicochemical properties, biocompatibility and the potential to customize biodegradability according to the ratio of monomers used. A decrease in stiffness proportional to increasing thiol concentration was observed when testing the compressive strength of hydrogels. Conversely, it was noted that the storage moduli of hydrogels increased proportionally to thiol concentration indicating a greater degree of cross-linking with the addition of thiol. The addition of thiol to HA increased the biocompatibility of the material in both neuronal and glial cell lines and improved the degradability of methacrylated HA. Due to the enhanced physicochemical properties and biocompatibility imparted by the introduction of thiolated HA, this novel hydrogel system could have numerous bioengineering applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ciara Buckley reports financial support was provided by the Irish Research Council., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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31. Reducing Power Sector Emissions under the 1990 Clean Air Act Amendments: A Retrospective on 30 Years of Program Development and Implementation.
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LaCount MD, Haeuber RA, Macy TR, and Murray BA
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- 2021
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32. Exercise restriction is protective for genotype-positive family members of arrhythmogenic right ventricular cardiomyopathy patients.
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Wang W, Tichnell C, Murray BA, Agafonova J, Cadrin-Tourigny J, Chelko S, Tandri H, Calkins H, and James CA
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- Adolescent, Adult, Child, Family, Female, Genotype, Humans, Male, Middle Aged, Mutation, Plakophilins genetics, Young Adult, Arrhythmogenic Right Ventricular Dysplasia diagnosis, Arrhythmogenic Right Ventricular Dysplasia genetics, Exercise
- Abstract
Aims: In arrhythmogenic right ventricular cardiomyopathy (ARVC) patients, exercise worsens disease course, so exercise restriction is recommended. However, recommendations for genotype-positive ARVC family members is incompletely resolved. We aimed to provide evidence for exercise recommendations for genotype-positive ARVC family members., Methods and Results: Arrhythmogenic right ventricular cardiomyopathy family members inheriting a pathogenic desmosomal variant were interviewed about exercise history from age 10. Exercise was characterized by duration, intensity, and dose (duration*intensity). Associations between exercise and (i) diagnosis by 2010 Task Force Criteria and (ii) development of sustained ventricular arrhythmias were examined. The study included 101 family members (age: 40.5 ± 19.3 years, male: 41%, Plakophilin-2 variant: 81%). Forty-four individuals (44%) met diagnostic criteria and 16 (16%) experienced sustained ventricular arrhythmia. Individuals who met diagnostic criteria had significantly higher average exercise duration and dose, but not peak intensity than those who did not. Only one individual who exercised below the American Heart Association recommended minimum (650 metabolic equivalent of task-hours/year) met diagnostic criteria or experienced sustained ventricular arrhythmia as opposed to 50% of individuals who exceeded it (adjusted odds ratio = 0.03, 95% confidence interval 0.003-0.26). The difference in exercise exposure between affected and unaffected individuals was more striking in females than in males. Females who had done high-dose exercise in adolescence had the worst survival free from diagnosis (P < 0.01)., Conclusions: In phenotype-negative ARVC family members with a pathogenic desmosomal variant, athletic activities should be limited, particularly exercise dose. Exercise may play a greater role in promoting disease in female family members., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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33. A Dairy-Derived Ghrelinergic Hydrolysate Modulates Food Intake In Vivo.
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Howick K, Wallace-Fitzsimons SE, Kandil D, Chruścicka B, Calis M, Murphy E, Murray BA, Fernandez A, Barry KM, Kelly PM, Ryan AM, Cryan JF, Griffin BT, and Schellekens H
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- Animals, Calcium metabolism, Caseins chemistry, Cell Line, Chromatography, High Pressure Liquid, Enzyme Activation, Enzyme Stability, Female, Ghrelin metabolism, Humans, Hydrogen-Ion Concentration, Male, Molecular Imaging methods, Rats, Receptors, Ghrelin metabolism, Caseins metabolism, Eating, Gene Expression, Receptors, Ghrelin genetics
- Abstract
Recent times have seen an increasing move towards harnessing the health-promoting benefits of food and dietary constituents while providing scientific evidence to substantiate their claims. In particular, the potential for bioactive protein hydrolysates and peptides to enhance health in conjunction with conventional pharmaceutical therapy is being investigated. Dairy-derived proteins have been shown to contain bioactive peptide sequences with various purported health benefits, with effects ranging from the digestive system to cardiovascular circulation, the immune system and the central nervous system. Interestingly, the ability of dairy proteins to modulate metabolism and appetite has recently been reported. The ghrelin receptor (GHSR-1a) is a G-protein coupled receptor which plays a key role in the regulation of food intake. Pharmacological manipulation of the growth hormone secretagogue receptor-type 1a (GHSR-1a) receptor has therefore received a lot of attention as a strategy to combat disorders of appetite and body weight, including age-related malnutrition and the progressive muscle wasting syndrome known as cachexia. In this study, a milk protein-derivative is shown to increase GHSR-1a-mediated intracellular calcium signalling in a concentration-dependent manner in vitro. Significant increases in calcium mobilisation were also observed in a cultured neuronal cell line heterologously expressing the GHS-R1a. In addition, both additive and synergistic effects were observed following co-exposure of GHSR-1a to both the hydrolysate and ghrelin. Subsequent in vivo studies monitored standard chow intake in healthy male and female Sprague-Dawley rats after dosing with the casein hydrolysate (CasHyd). Furthermore, the provision of gastro-protected oral delivery to the bioactive in vivo may aid in the progression of in vitro efficacy to in vivo functionality. In summary, this study reports a ghrelin-stimulating bioactive peptide mixture (CasHyd) with potent effects in vitro. It also provides novel and valuable translational data supporting the potential role of CasHyd as an appetite-enhancing bioactive. Further mechanistic studies are required in order to confirm efficacy as a ghrelinergic bioactive in susceptible population groups.
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- 2018
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34. Characterising cis -regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues.
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Zhang M, Lykke-Andersen S, Zhu B, Xiao W, Hoskins JW, Zhang X, Rost LM, Collins I, Bunt MV, Jia J, Parikh H, Zhang T, Song L, Jermusyk A, Chung CC, Zhu B, Zhou W, Matters GL, Kurtz RC, Yeager M, Jensen TH, Brown KM, Ongen H, Bamlet WR, Murray BA, McCarthy MI, Chanock SJ, Chatterjee N, Wolpin BM, Smith JP, Olson SH, Petersen GM, Shi J, and Amundadottir L
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- Alleles, Chromosomes, Human, Pair 9, Genome-Wide Association Study, Genotype, Humans, Nonsense Mediated mRNA Decay, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid, Sequence Analysis, RNA, ABO Blood-Group System genetics, Gene Expression, Pancreas, Pancreatic Neoplasms genetics, Quantitative Trait Loci, RNA, Neoplasm analysis, Transcriptome
- Abstract
Objective: To elucidate the genetic architecture of gene expression in pancreatic tissues., Design: We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison., Results: We identified 38 615 cis -eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis -eQTL (in 237 genes) in tumour-derived tissues (false discovery rate <0.1), with the strongest effects seen near transcriptional start sites. Approximately 23% and 42% of genes with significant cis -eQTLs appeared to be specific for tumour-derived and normal-derived tissues, respectively. Significant enrichment of cis -eQTL variants was noted in non-coding regulatory regions, in particular for pancreatic tissues (1.53-fold to 3.12-fold, p≤0.0001), indicating tissue-specific functional relevance. A common pancreatic cancer risk locus on 9q34.2 (rs687289) was associated with ABO expression in histologically normal (p=5.8×10
-8 ) and tumour-derived (p=8.3×10-5 ) tissues. The high linkage disequilibrium between this variant and the O blood group generating deletion variant in ABO (exon 6) suggested that nonsense-mediated decay (NMD) of the 'O' mRNA might explain this finding. However, knockdown of crucial NMD regulators did not influence decay of the ABO 'O' mRNA, indicating that a gene regulatory element influenced by pancreatic cancer risk alleles may underlie the eQTL., Conclusions: We have identified cis -eQTLs representing potential functional regulatory variants in the pancreas and generated a rich data set for further studies on gene expression and its regulation in pancreatic tissues., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)- Published
- 2018
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35. Raccoon roundworm (Baylisascaris procyonis) as an occupational hazard: 1. Knowledge of B. procyonis and attitudes towards it and other zoonoses among wildlife rehabilitators.
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Sapp SGH, Murray BA, Hoover ER, Green GT, and Yabsley MJ
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- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Animals, Wild, Ascaridida Infections transmission, Data Collection, Female, Health Knowledge, Attitudes, Practice, Humans, Internet, Male, Middle Aged, Risk Factors, Surveys and Questionnaires, Young Adult, Zoonoses, Ascaridoidea, Raccoons parasitology
- Abstract
Wildlife rehabilitators are at risk of zoonotic diseases because they often have prolonged contact with many species of wildlife and their bodily fluids. Raccoon roundworm (Baylisascaris procyonis) is a common zoonotic parasite of raccoons that has the potential to cause severe or fatal neurologic disease in a broad variety of hosts if the eggs within raccoon faeces are ingested. We administered an online survey to wildlife rehabilitators to assess their knowledge regarding aspects of transmission, biology and disease caused by B. procyonis, and also to evaluate attitudes towards wildlife diseases and B. procyonis as an occupational hazard. Knowledge was assessed using multiple choice and true-false questions; attitudes were measured using Likert-type items. A total of 659 complete or near-complete responses (missing fewer than three knowledge or attitudes items and/or non-response to some demographic fields) were collected. The median knowledge score was 7/14 questions correct (range: 0-14 correct). Generally, individuals with higher levels of education and rehabilitation experience, veterinary professionals and those who are members of professional wildlife rehabilitation groups scored above the median significantly more often (p < .01). Significantly more rehabilitators who were located in the south-east and those with part-time or infrequent commitments scored below the median overall knowledge score. There was general agreement that B. procyonis is a health risk of rehabilitators and that measures should be taken to control transmission to people and animals. Some factors explaining differences in attitudes include setting of rehabilitation (home versus animal care facility), veterinary profession, region, membership in a wildlife rehabilitation group and rehabilitation of raccoons. Findings emphasize the importance of awareness and mentorship to inform rehabilitators on the potential risks of B. procyonis and other potential zoonoses within captive wildlife settings, and the important role of professional wildlife rehabilitator groups in disseminating educational materials., (© 2017 Blackwell Verlag GmbH.)
- Published
- 2018
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36. Integrated Molecular Characterization of Uterine Carcinosarcoma.
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Cherniack AD, Shen H, Walter V, Stewart C, Murray BA, Bowlby R, Hu X, Ling S, Soslow RA, Broaddus RR, Zuna RE, Robertson G, Laird PW, Kucherlapati R, Mills GB, Weinstein JN, Zhang J, Akbani R, and Levine DA
- Subjects
- Carcinosarcoma pathology, DNA Copy Number Variations, Epithelial-Mesenchymal Transition, Female, Humans, Mutation, Uterine Neoplasms pathology, Carcinosarcoma genetics, Uterine Neoplasms genetics
- Abstract
We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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37. Letter to the Editor Regarding Equivalent Increases in Circulating GLP-1 Following Jejunal Delivery of Intact and Hydrolysed Casein: Relevance to Satiety Induction following Bariatric Surgery.
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Giblin L, McGrath BA, Murray BA, le Roux CW, Docherty NG, McSweeney PL, and Kelly AL
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- Bariatric Surgery, Humans, Obesity, Morbid, Satiation, Caseins, Glucagon-Like Peptide 1
- Published
- 2017
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38. Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.
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Fishbein L, Leshchiner I, Walter V, Danilova L, Robertson AG, Johnson AR, Lichtenberg TM, Murray BA, Ghayee HK, Else T, Ling S, Jefferys SR, de Cubas AA, Wenz B, Korpershoek E, Amelio AL, Makowski L, Rathmell WK, Gimenez-Roqueplo AP, Giordano TJ, Asa SL, Tischler AS, Pacak K, Nathanson KL, and Wilkerson MD
- Subjects
- Adult, Aged, Aged, 80 and over, DNA-Binding Proteins genetics, Female, Gene Fusion, Humans, Male, Middle Aged, Mutation, Nuclear Proteins genetics, Paraganglioma etiology, Pheochromocytoma etiology, Pol1 Transcription Initiation Complex Proteins genetics, Proto-Oncogene Proteins c-ret genetics, RNA-Binding Proteins genetics, Trans-Activators, Transcription Factors genetics, Paraganglioma genetics, Pheochromocytoma genetics
- Abstract
We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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39. A casein hydrolysate protects mice against high fat diet induced hyperglycemia by attenuating NLRP3 inflammasome-mediated inflammation and improving insulin signaling.
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Healy NP, Kirwan AM, McArdle MA, Holohan K, Nongonierma AB, Keane D, Kelly S, Celkova L, Lyons CL, McGillicuddy FC, Finucane OM, Murray BA, Kelly PM, Brennan L, FitzGerald RJ, and Roche HM
- Subjects
- 3T3-L1 Cells, Animals, Cytokines metabolism, Diabetes Mellitus, Type 2 diet therapy, Diet, High-Fat adverse effects, Hyperglycemia metabolism, Inflammation metabolism, Insulin metabolism, Insulin Resistance physiology, Interleukin-1beta metabolism, Interleukin-6 metabolism, Mice, Mice, Inbred C57BL, NLR Family, Pyrin Domain-Containing 3 Protein, NLR Proteins, Tumor Necrosis Factor-alpha drug effects, Tumor Necrosis Factor-alpha metabolism, Adipose Tissue metabolism, Caseins pharmacology, Inflammasomes metabolism, Obesity metabolism
- Abstract
Scope: Activation of the nod-like receptor protein 3 (NLRP3) inflammasome is required for IL-1β release and is a key component of obesity-induced inflammation and insulin resistance. This study hypothesized that supplementation with a casein hydrolysate (CH) would attenuate NLRP3 inflammasome mediated IL-1β secretion in adipose tissue (AT) and improve obesity-induced insulin resistance., Methods and Results: J774.2 macrophages were LPS primed (10 ng/mL) and stimulated with adenosine triphosphate (5 mM) to assess NLRP3 inflammasome activity. Pretreatment with CH (1 mg/mL; 48 h) reduced caspase-1 activity and decreased IL-1β secretion from J774.2 macrophages in vitro. 3T3-L1 adipocytes cultured with conditioned media from CH-pretreated J774.2 macrophages demonstrated increased phosphorylated (p)AKT expression and improved insulin sensitivity. C57BL/6JOLaHsd mice were fed chow or high fat diet (HFD) for 12 wk ± CH resuspended in water (0.5% w/v). CH supplementation improved glucose tolerance in HFD-fed mice as determined by glucose tolerance test. CH supplementation increased insulin-stimulated pAKT protein levels in AT, liver, and muscle after HFD. Cytokine secretion was measured from AT and isolated bone marrow macrophages cultured ex vivo. CH supplementation attenuated IL-1β, tumor necrosis factor alpha (TNF-α) and IL-6 secretion from AT and IL-1β, IL-18, and TNF-α from bone marrow macrophages following adenosine triphosphate stimulation ex vivo., Conclusion: This novel CH partially protects mice against obesity-induced hyperglycemia coincident with attenuated IL-1β secretion and improved insulin signaling., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2016
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40. Anticancer Activity of Buttermilk Against SW480 Colon Cancer Cells is Associated with Caspase-Independent Cell Death and Attenuation of Wnt, Akt, and ERK Signaling.
- Author
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Kuchta-Noctor AM, Murray BA, Stanton C, Devery R, and Kelly PM
- Subjects
- Cell Line, Cell Line, Tumor, Cell Proliferation, Cell Survival, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Dairying, Food Handling, Humans, Membrane Potential, Mitochondrial, Phospholipids analysis, Phospholipids metabolism, Phosphorylation, Pilot Projects, Protein Processing, Post-Translational, Proto-Oncogene Proteins c-akt metabolism, Sphingolipids analysis, Sphingolipids metabolism, Buttermilk analysis, Colonic Neoplasms prevention & control, Down-Regulation, Functional Food analysis, MAP Kinase Signaling System, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Wnt Signaling Pathway
- Abstract
Buttermilk is a rich source of milk fat globule membrane (MFGM) fragments assembled from bioactive polar lipids and proteins that originate from bovine mammary epithelial cells. The objective of this study was to examine growth-modulatory effects of experimental buttermilks varying in sphingolipid and phospholipid composition on a colon cancer cell line of human origin. Buttermilks were prepared from washed and unwashed cream using gravity or centrifugation. Compositional analysis showed that sphingomyelin (SM) (10.4-29.5%) and lactosylceramide (LacCer) (1.2-44.3%) were the predominant sphingolipids detected. Experimental samples inhibited in vitro growth of SW480 colon cancer cells in a dose-dependent manner. Antiproliferative activity was selective toward cancer cells. A fraction enriched in LacCer (44.3%), obtained by microfiltration induced caspase-independent cell death as evident by phosphatidylserine externalization, increased percentage of degraded DNA, and loss of mitochondrial membrane potential in SW480 cells. This fraction downregulated growth-signaling pathways mediated by β-catenin, phosphorylated Akt (serine/threonine-specific protein kinase), ERK1/2 (extracellular signal-regulated kinase), and c-myc. This study is to our knowledge the first to screen buttermilk samples that vary in polar lipid composition for antiproliferative activity in vitro.
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- 2016
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41. Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma.
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Zheng S, Cherniack AD, Dewal N, Moffitt RA, Danilova L, Murray BA, Lerario AM, Else T, Knijnenburg TA, Ciriello G, Kim S, Assie G, Morozova O, Akbani R, Shih J, Hoadley KA, Choueiri TK, Waldmann J, Mete O, Robertson AG, Wu HT, Raphael BJ, Shao L, Meyerson M, Demeure MJ, Beuschlein F, Gill AJ, Sidhu SB, Almeida MQ, Fragoso MCBV, Cope LM, Kebebew E, Habra MA, Whitsett TG, Bussey KJ, Rainey WE, Asa SL, Bertherat J, Fassnacht M, Wheeler DA, Hammer GD, Giordano TJ, and Verhaak RGW
- Published
- 2016
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42. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas.
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Campbell JD, Alexandrov A, Kim J, Wala J, Berger AH, Pedamallu CS, Shukla SA, Guo G, Brooks AN, Murray BA, Imielinski M, Hu X, Ling S, Akbani R, Rosenberg M, Cibulskis C, Ramachandran A, Collisson EA, Kwiatkowski DJ, Lawrence MS, Weinstein JN, Verhaak RG, Wu CJ, Hammerman PS, Cherniack AD, Getz G, Artyomov MN, Schreiber R, Govindan R, and Meyerson M
- Subjects
- Antigens, Neoplasm, DNA Copy Number Variations, Humans, Recurrence, Adenocarcinoma genetics, Carcinoma, Squamous Cell genetics, Genome, Human, Lung Neoplasms genetics
- Abstract
To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined the exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor-normal pairs. Recurrent alterations in lung SqCCs were more similar to those of other squamous carcinomas than to alterations in lung ADCs. New significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. New amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase-Ras-Raf pathway alterations had mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least five predicted neoepitopes. Although targeted therapies for lung ADC and SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes.
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- 2016
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43. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.
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Ceccarelli M, Barthel FP, Malta TM, Sabedot TS, Salama SR, Murray BA, Morozova O, Newton Y, Radenbaugh A, Pagnotta SM, Anjum S, Wang J, Manyam G, Zoppoli P, Ling S, Rao AA, Grifford M, Cherniack AD, Zhang H, Poisson L, Carlotti CG Jr, Tirapelli DP, Rao A, Mikkelsen T, Lau CC, Yung WK, Rabadan R, Huse J, Brat DJ, Lehman NL, Barnholtz-Sloan JS, Zheng S, Hess K, Rao G, Meyerson M, Beroukhim R, Cooper L, Akbani R, Wrensch M, Haussler D, Aldape KD, Laird PW, Gutmann DH, Noushmehr H, Iavarone A, and Verhaak RG
- Subjects
- Adult, Brain Neoplasms metabolism, Cell Proliferation, Cluster Analysis, DNA Helicases genetics, DNA Methylation, Epigenesis, Genetic, Glioma metabolism, Humans, Isocitrate Dehydrogenase genetics, Middle Aged, Mutation, Nuclear Proteins genetics, Promoter Regions, Genetic, Signal Transduction, Telomerase genetics, Telomere, X-linked Nuclear Protein, Brain Neoplasms genetics, Brain Neoplasms pathology, Glioma genetics, Glioma pathology, Transcriptome
- Abstract
Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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44. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.
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Linehan WM, Spellman PT, Ricketts CJ, Creighton CJ, Fei SS, Davis C, Wheeler DA, Murray BA, Schmidt L, Vocke CD, Peto M, Al Mamun AA, Shinbrot E, Sethi A, Brooks S, Rathmell WK, Brooks AN, Hoadley KA, Robertson AG, Brooks D, Bowlby R, Sadeghi S, Shen H, Weisenberger DJ, Bootwalla M, Baylin SB, Laird PW, Cherniack AD, Saksena G, Haake S, Li J, Liang H, Lu Y, Mills GB, Akbani R, Leiserson MD, Raphael BJ, Anur P, Bottaro D, Albiges L, Barnabas N, Choueiri TK, Czerniak B, Godwin AK, Hakimi AA, Ho TH, Hsieh J, Ittmann M, Kim WY, Krishnan B, Merino MJ, Mills Shaw KR, Reuter VE, Reznik E, Shelley CS, Shuch B, Signoretti S, Srinivasan R, Tamboli P, Thomas G, Tickoo S, Burnett K, Crain D, Gardner J, Lau K, Mallery D, Morris S, Paulauskis JD, Penny RJ, Shelton C, Shelton WT, Sherman M, Thompson E, Yena P, Avedon MT, Bowen J, Gastier-Foster JM, Gerken M, Leraas KM, Lichtenberg TM, Ramirez NC, Santos T, Wise L, Zmuda E, Demchok JA, Felau I, Hutter CM, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Zhang J, Ayala B, Baboud J, Chudamani S, Liu J, Lolla L, Naresh R, Pihl T, Sun Q, Wan Y, Wu Y, Ally A, Balasundaram M, Balu S, Beroukhim R, Bodenheimer T, Buhay C, Butterfield YS, Carlsen R, Carter SL, Chao H, Chuah E, Clarke A, Covington KR, Dahdouli M, Dewal N, Dhalla N, Doddapaneni HV, Drummond JA, Gabriel SB, Gibbs RA, Guin R, Hale W, Hawes A, Hayes DN, Holt RA, Hoyle AP, Jefferys SR, Jones SJ, Jones CD, Kalra D, Kovar C, Lewis L, Li J, Ma Y, Marra MA, Mayo M, Meng S, Meyerson M, Mieczkowski PA, Moore RA, Morton D, Mose LE, Mungall AJ, Muzny D, Parker JS, Perou CM, Roach J, Schein JE, Schumacher SE, Shi Y, Simons JV, Sipahimalani P, Skelly T, Soloway MG, Sougnez C, Tam A, Tan D, Thiessen N, Veluvolu U, Wang M, Wilkerson MD, Wong T, Wu J, Xi L, Zhou J, Bedford J, Chen F, Fu Y, Gerstein M, Haussler D, Kasaian K, Lai P, Ling S, Radenbaugh A, Van Den Berg D, Weinstein JN, Zhu J, Albert M, Alexopoulou I, Andersen JJ, Auman JT, Bartlett J, Bastacky S, Bergsten J, Blute ML, Boice L, Bollag RJ, Boyd J, Castle E, Chen YB, Cheville JC, Curley E, Davies B, DeVolk A, Dhir R, Dike L, Eckman J, Engel J, Harr J, Hrebinko R, Huang M, Huelsenbeck-Dill L, Iacocca M, Jacobs B, Lobis M, Maranchie JK, McMeekin S, Myers J, Nelson J, Parfitt J, Parwani A, Petrelli N, Rabeno B, Roy S, Salner AL, Slaton J, Stanton M, Thompson RH, Thorne L, Tucker K, Weinberger PM, Winemiller C, Zach LA, and Zuna R
- Subjects
- Carcinoma, Papillary genetics, CpG Islands physiology, DNA Methylation, Humans, Kidney Neoplasms genetics, MicroRNAs chemistry, NF-E2-Related Factor 2 genetics, Phenotype, Proto-Oncogene Proteins c-met chemistry, Proto-Oncogene Proteins c-met genetics, RNA, Messenger chemistry, RNA, Neoplasm chemistry, Sequence Analysis, RNA, Signal Transduction physiology, Carcinoma, Papillary metabolism, Kidney Neoplasms metabolism, Mutation, NF-E2-Related Factor 2 metabolism, Proto-Oncogene Proteins c-met metabolism
- Abstract
Background: Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist., Methods: We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis., Results: Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH)., Conclusions: Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).
- Published
- 2016
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45. Nursing Students' Experiences of Health Care in Swaziland: Transformational Processes in Developing Cultural Understanding.
- Author
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Murray BA
- Subjects
- Communication Barriers, Emotions, Eswatini, Female, Humans, Interviews as Topic, United States, Young Adult, Cultural Competency, Education, Nursing, Baccalaureate, International Educational Exchange, Students, Nursing psychology
- Abstract
Background: This study examined the experiences of nursing students following a service-learning placement in Swaziland. Students worked in a hospital and implemented community health clinics., Method: Six students were interviewed 1 month after their return from the overseas study experience. A thematic analysis was performed., Results: Four themes emerged. The first theme was transitions-students experienced personal hardships, emotional reactions, and language difficulties that created discomfort. The second theme was perceptions-cultural dissonance was encountered between the health care and nursing cultures of Swaziland and the United States. The third theme was internalization-discomfort and cultural dissonance activated coping mechanisms within students that generated a process of change in attitudes and beliefs. The fourth theme was incorporation-personal and professional growth were demonstrated with greater awareness, compassion, resourcefulness, and comfort with diversity., Conclusion: The stress and cultural dissonance experienced by students led to an increase in cultural understanding and awareness., (Copyright 2015, SLACK Incorporated.)
- Published
- 2015
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46. The Value of Cardiac Magnetic Resonance Imaging in Evaluation of Pediatric Patients for Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.
- Author
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Te Riele ASJM, Marcus FI, James CA, Murray BA, Tichnell C, Zimmerman SL, Kamel IR, Crosson J, Cramer MJM, Velthuis BK, Hauer RNW, Tandri H, Bluemke DA, and Calkins H
- Subjects
- Female, Humans, Male, Arrhythmogenic Right Ventricular Dysplasia diagnosis, Magnetic Resonance Imaging standards
- Published
- 2015
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47. A Prospective Clinical Trial of Telecytopathology for Rapid Interpretation of Specimens Obtained During Endobronchial Ultrasound-Fine Needle Aspiration.
- Author
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Bott MJ, James B, Collins BT, Murray BA, Puri V, Kreisel D, Krupnick AS, Patterson GA, Broderick S, Meyers BF, and Crabtree TD
- Subjects
- Female, Humans, Male, Middle Aged, Prospective Studies, Time Factors, Bronchoscopy, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Telepathology
- Abstract
Background: Cytopathologic interpretation of endobronchial ultrasound with fine needle aspiration (EBUS-FNA) samples by a pathologist can be time-consuming and costly, and an onsite cytopathologist may not always be readily available. A telecytopathology system was instituted and evaluated to examine the effect on operative time for EBUS., Methods: A prospective study was performed of sequential patients undergoing EBUS-FNA for the evaluation of mediastinal lymphadenopathy. Specimens for the control group were transported to the pathology laboratory, followed by remote cytologic interpretation. In a subsequent cohort, a telecytopathology system was used with intraoperative transmission of real-time live video microscopy to a remote cytopathologist (TCP group). The primary outcome was time to confirmation of cytology results., Results: Of 46 patients entered into the study, 23 underwent traditional analysis (control group), and 20 were analyzed using telecytopathology (TCP group). Lung cancer was the most common malignancy in both groups (12 TCP, 12 control). There was no difference in mean number of lymph node stations sampled (1.3 TCP vs 1.8 control, p = 0.76). Use of TCP was associated with fewer needle passes (4.9 vs 7.3, p = 0.02) and fewer slides for interpretation (8.4 vs 13.5, p = 0.01) per procedure. Time to result confirmation was significantly shorter in the TCP group (19.0 vs 46.7 minutes, p < 0.001). A diagnostic specimen was obtained in 70% of patients in the TCP group compared with 65% in the control group (p = 0.5). False-negative rates in patients undergoing EBUS-FNA and mediastinoscopy were similar between the two groups (0 in TCP vs 2 in control, p = 0.49). Mean procedural costs (excluding cost of the telecytology system and operating room time) were equivalent between the two groups ($888 TCP vs $887 control)., Conclusions: Telecytopathology provides rapid interpretation of EBUS-FNA samples with diagnostic accuracy comparable to traditional methods, shortens procedure time, and is a more efficient model for delivery of on-site EBUS-FNA interpretation., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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48. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.
- Author
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Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, Cooper LA, Rheinbay E, Miller CR, Vitucci M, Morozova O, Robertson AG, Noushmehr H, Laird PW, Cherniack AD, Akbani R, Huse JT, Ciriello G, Poisson LM, Barnholtz-Sloan JS, Berger MS, Brennan C, Colen RR, Colman H, Flanders AE, Giannini C, Grifford M, Iavarone A, Jain R, Joseph I, Kim J, Kasaian K, Mikkelsen T, Murray BA, O'Neill BP, Pachter L, Parsons DW, Sougnez C, Sulman EP, Vandenberg SR, Van Meir EG, von Deimling A, Zhang H, Crain D, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton T, Sherman M, Yena P, Black A, Bowen J, Dicostanzo K, Gastier-Foster J, Leraas KM, Lichtenberg TM, Pierson CR, Ramirez NC, Taylor C, Weaver S, Wise L, Zmuda E, Davidsen T, Demchok JA, Eley G, Ferguson ML, Hutter CM, Mills Shaw KR, Ozenberger BA, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Ayala B, Baboud J, Chudamani S, Jensen MA, Liu J, Pihl T, Raman R, Wan Y, Wu Y, Ally A, Auman JT, Balasundaram M, Balu S, Baylin SB, Beroukhim R, Bootwalla MS, Bowlby R, Bristow CA, Brooks D, Butterfield Y, Carlsen R, Carter S, Chin L, Chu A, Chuah E, Cibulskis K, Clarke A, Coetzee SG, Dhalla N, Fennell T, Fisher S, Gabriel S, Getz G, Gibbs R, Guin R, Hadjipanayis A, Hayes DN, Hinoue T, Hoadley K, Holt RA, Hoyle AP, Jefferys SR, Jones S, Jones CD, Kucherlapati R, Lai PH, Lander E, Lee S, Lichtenstein L, Ma Y, Maglinte DT, Mahadeshwar HS, Marra MA, Mayo M, Meng S, Meyerson ML, Mieczkowski PA, Moore RA, Mose LE, Mungall AJ, Pantazi A, Parfenov M, Park PJ, Parker JS, Perou CM, Protopopov A, Ren X, Roach J, Sabedot TS, Schein J, Schumacher SE, Seidman JG, Seth S, Shen H, Simons JV, Sipahimalani P, Soloway MG, Song X, Sun H, Tabak B, Tam A, Tan D, Tang J, Thiessen N, Triche T Jr, Van Den Berg DJ, Veluvolu U, Waring S, Weisenberger DJ, Wilkerson MD, Wong T, Wu J, Xi L, Xu AW, Yang L, Zack TI, Zhang J, Aksoy BA, Arachchi H, Benz C, Bernard B, Carlin D, Cho J, DiCara D, Frazer S, Fuller GN, Gao J, Gehlenborg N, Haussler D, Heiman DI, Iype L, Jacobsen A, Ju Z, Katzman S, Kim H, Knijnenburg T, Kreisberg RB, Lawrence MS, Lee W, Leinonen K, Lin P, Ling S, Liu W, Liu Y, Liu Y, Lu Y, Mills G, Ng S, Noble MS, Paull E, Rao A, Reynolds S, Saksena G, Sanborn Z, Sander C, Schultz N, Senbabaoglu Y, Shen R, Shmulevich I, Sinha R, Stuart J, Sumer SO, Sun Y, Tasman N, Taylor BS, Voet D, Weinhold N, Weinstein JN, Yang D, Yoshihara K, Zheng S, Zhang W, Zou L, Abel T, Sadeghi S, Cohen ML, Eschbacher J, Hattab EM, Raghunathan A, Schniederjan MJ, Aziz D, Barnett G, Barrett W, Bigner DD, Boice L, Brewer C, Calatozzolo C, Campos B, Carlotti CG Jr, Chan TA, Cuppini L, Curley E, Cuzzubbo S, Devine K, DiMeco F, Duell R, Elder JB, Fehrenbach A, Finocchiaro G, Friedman W, Fulop J, Gardner J, Hermes B, Herold-Mende C, Jungk C, Kendler A, Lehman NL, Lipp E, Liu O, Mandt R, McGraw M, Mclendon R, McPherson C, Neder L, Nguyen P, Noss A, Nunziata R, Ostrom QT, Palmer C, Perin A, Pollo B, Potapov A, Potapova O, Rathmell WK, Rotin D, Scarpace L, Schilero C, Senecal K, Shimmel K, Shurkhay V, Sifri S, Singh R, Sloan AE, Smolenski K, Staugaitis SM, Steele R, Thorne L, Tirapelli DP, Unterberg A, Vallurupalli M, Wang Y, Warnick R, Williams F, Wolinsky Y, Bell S, Rosenberg M, Stewart C, Huang F, Grimsby JL, Radenbaugh AJ, and Zhang J
- Subjects
- Adolescent, Adult, Aged, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Cluster Analysis, Female, Glioblastoma genetics, Glioma metabolism, Glioma mortality, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Grading, Proportional Hazards Models, Sequence Analysis, DNA, Signal Transduction, DNA, Neoplasm analysis, Genes, p53, Glioma genetics, Mutation
- Abstract
Background: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas., Methods: We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes., Results: Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma., Conclusions: The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.).
- Published
- 2015
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49. Molecular characterization of whey protein hydrolysate fractions with ferrous chelating and enhanced iron solubility capabilities.
- Author
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O'Loughlin IB, Kelly PM, Murray BA, FitzGerald RJ, and Brodkorb A
- Subjects
- Chelating Agents chemistry, Digestion, Ferrous Compounds chemistry, Humans, Iron metabolism, Milk Proteins metabolism, Models, Biological, Protein Hydrolysates chemistry, Protein Hydrolysates metabolism, Solubility, Whey Proteins, Iron chemistry, Milk Proteins chemistry
- Abstract
The ferrous (Fe2+) chelating capabilities of WPI hydrolysate fractions produced via cascade membrane filtration were investigated, specifically 1 kDa permeate (P) and 30 kDa retentate (R) fractions. The 1 kDa-P possessed a Fe2+ chelating capability at 1 g L(-1) equivalent to 84.4 μM EDTA (for 30 kDa-R the value was 8.7 μM EDTA). Fourier transformed infrared (FTIR) spectroscopy was utilized to investigate the structural characteristics of hydrolysates and molecular interactions with Fe2+. Solid-phase extraction was employed to enrich for chelating activity; the most potent chelating fraction was enriched in histidine and lysine. The solubility of ferrous sulfate solutions (10 mM) over a range of pH values was significantly (P<0.05) improved in dispersions of hydrolysate fraction solutions (10 g protein L(-1)). Total iron solubility was improved by 72% in the presence of the 1 kDa-P fraction following simulated gastrointestinal digestion (SGID) compared to control FeSO4·7H2O solutions.
- Published
- 2015
- Full Text
- View/download PDF
50. The anti-inflammatory potential of a moderately hydrolysed casein and its 5 kDa fraction in in vitro and ex vivo models of the gastrointestinal tract.
- Author
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Mukhopadhya A, Noronha N, Bahar B, Ryan MT, Murray BA, Kelly PM, O'Loughlin IB, O'Doherty JV, and Sweeney T
- Subjects
- Animals, Caco-2 Cells, Dexamethasone pharmacology, Humans, Inflammation drug therapy, Interleukin-17 genetics, Interleukin-17 metabolism, Interleukin-1alpha genetics, Interleukin-1alpha metabolism, Interleukin-1beta genetics, Interleukin-1beta metabolism, Interleukin-8 genetics, Interleukin-8 metabolism, Lipopolysaccharides, Molecular Weight, Swine, Transforming Growth Factor beta genetics, Transforming Growth Factor beta metabolism, Tumor Necrosis Factor-alpha metabolism, Anti-Inflammatory Agents pharmacology, Caseins pharmacology, Gastrointestinal Tract drug effects, Gastrointestinal Tract metabolism, Models, Biological
- Abstract
Bioactive peptides from milk can impart a wide range of physiological benefits without the allergies and intolerance associated with the consumption of whole milk. The objective of this study was to characterise the anti-inflammatory properties of intact sodium caseinate (NaCAS), a moderately hydrolysed NaCAS enzyme hydrolysate (EH) and its 5 kDa fraction (5kDaR), in both in vitro and ex vivo systems. In vitro, Caco-2 cells were stimulated with tumor necrosis factor (TNF) α and co-treated ± casein hydrolysates or dexamethasone (control). The inflammatory marker interleukin (IL)-8 was measured by ELISA in the supernatant at 24 h. Ex vivo, porcine colonic tissues were stimulated with lipopolysaccharide (LPS) and co-treated with casein hydrolysates for 3 h from which the relative expression of a panel of cytokines was measured in vitro. While the steroid dexamethasone brought about a 41.6% reduction in the IL-8 concentration in the supernatant, the 5kDaR reduced IL-8 by 59% (P < 0.05) when compared to the TNFα stimulated Caco-2 cells. In the ex vivo system, 5kDaR was associated with decreases in IL-1α, IL-1β, IL-8 and TGF-β expression and an increase in IL-17 expression (P < 0.05) relative to the LPS challenged tissues. We concluded, that a 5 kDa casein fraction demonstrates potent anti-inflammatory effects both in in vitro and ex vivo models of the gastrointestinal tract.
- Published
- 2015
- Full Text
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