tbuckley/cabot-search huggingface dataset:
P207 Reliability Of Measurements Using Innocor Breath By Breath Analyser During A Maximal Exercise Test In Cystic Fibrosis Patients
Authors: K. Bayfield, M. McGovern, A. Simpson, M. Embley, S. Cunningham, J. Davies, E. Alton, J. Innes
Journal: Thorax (2014)

<h3>Introduction</h3> Cardiopulmonary exercising testing (CPET) is considered the gold standard to study exercise capacity as an endpoint in clinical trials. Originally the UKCFGTC used the shuttle walk test for exercise capacity measurement but this proved inappropriate for mild, fit cystic fibrosis (CF) patients in our trial cohort (FEV<sub>1</sub> 50–90% predicted). The Innocor device uses photoacoustic gas detection technology and offers metabolic measurement but has not previously been validated for CPET in CF. <h3>Aim</h3> To compare the Innocor with known reliable CPET machines to see if it is suitable to take forward into a multi dose clinical trial of gene therapy. <h3>Methods</h3> 12 CF patients (7 Male, 14–47 years) participated in the study recruited from London and Edinburgh sites. They performed two incremental cycle ergometer exercise tests to exhaustion (adapted Godfrey protocol) with breath by breath analysis assessed using a reference system (Jaeger Masterscreen PFT, London; Pulmolink Medisoft, Edinburgh) or the Innocor device. All tests were randomly ordered, completed at least 24 h apart, with no more than two week’s separation. <h3>Results</h3> VO<sub>2</sub>max and V<sub>E </sub>max were comparable between the Innocor and reference systems (p = 0.1790 and p = 0.7642 respectively; paired t tests). For VO2max, Bland Altman analysis showed the mean difference [Reference equipment-Innocor] was -0.026 l/min and the 95% confidence interval was -0.27 to 0.22 l/min (see Figure). In our experience the Innocor heart rate (HR) recording (derived from saturation monitor) was unreliable; reading low during exercise compared to ECG-derived HR. <h3>Conclusions</h3> This small study confirms the Innocor device can produce measures of VO<sub>2</sub>max comparable (95% confidence interval) with standard calibrated exercise systems in CF patients with mild to moderate lung disease. We found the method for Innocor to derive HR (pulse oximetry) was not reliable compared to reference ECG especially during heavy exercise. We were subsequently able to overcome this problem by interfacing the Innocor device with a separate electrocardiographic heart rate monitor.
Abstract 108: FGF-2 regulates cell proliferation, migration and angiogenesis through a novel NDY1/KDM2B-miR101-EZH2 pathway
Authors: Filippos Kottakis, Christos Polytarchou, Sotirios Kampranis, Philip N. Tsichlis
Journal: Cancer Research (2011)

Abstract The histone H3K27 methyltransferase EZH2 plays an important role in oncogenesis, by mechanisms that are incompletely understood. Here we show that NDY1/KDM2B, a JmjC domain-containing histone H3K36me2, H3K36me1 and H3K4me3 demethylase synergizes with EZH2 to silence the EZH2 inhibitor miR-101. NDY1/KDM2B and EZH2 repress miR-101 by binding its promoter in concert via a process that is activated by upregulation of NDY1/KDM2B. EZH2 does not bind the miR-101 promoter when overexpressed in the absence of NDY1/KDM2B, while NDY1/KDM2B binds the miR-101 promoter when overexpressed in the absence of EZH2, but fails to repress transcription. The concerted action of NDY1/KDM2B and EZH2, triggered by the upregulation of NDY1/KDM2B, promotes the initial upregulation of EZH2 and initiates a feedforward loop that results to the gradual upregulation of EZH2 and other miR-101 targets. NDY1/KDM2B expression was induced by FGF-2 and to a lesser degree by VEGF, via CREB phosphorylation and activation, downstream of the DYRK1A kinase. The FGF-2-NDY1-miR-101-EZH2 axis was documented in primary fibroblasts in culture, and in a set of human tumor cell lines, and it was shown to be responsible for the FGF-2 and EZH2 effects on cell proliferation, migration and angiogenesis. The axis appeared to also be active in a set of transitional cell bladder carcinomas, in which NDY1/KDM2B and FGF-2 were overexpressed in concert and their upregulation correlated with the repression of miR-101 and the upregulation of EZH2. These data delineate a novel pathway that links FGF-2 signaling with the functional and transcriptional regulation of EZH2 via NDY1/KDM2B and miR-101, and contributes to oncogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 108. doi:10.1158/1538-7445.AM2011-108
Housing as Health Care — New York's Boundary-Crossing Experiment
Authors: Kelly M. Doran, Elizabeth J. Misa, Nirav R. Shah
Journal: New England Journal of Medicine (2013)

Interview with Dr. Nirav Shah on New York State's decision to address housing needs as a social determinant of health. (10:56)Download The role of social determinants of health, and the business case for addressing them, is clear when it comes to homelessness and housing. New York State is undertaking an experiment that uses Medicaid funds for supportive housing for high-risk, homeless Medicaid recipients.
Injuries Due to Firearms in Three Cities
Authors: Arthur L. Kellermann, Frederick P. Rivara, Roberta K. Lee, Joyce G. Banton, Peter Cummings, Bela B. Hackman, Grant Somes
Journal: New England Journal of Medicine (1996)

To describe the incidence and outcome of injuries due to firearms, we conducted a population-based study of fatal and nonfatal gunshot wounds in three cities: Memphis, Tennessee; Seattle, Washington; and Galveston, Texas.
Protection by Milk Immunoglobulin Concentrate against Oral Challenge with Enterotoxigenic<i>Escherichia coli</i>
Authors: Carol O. Tacket, Genevieve Losonsky, Harriet Link, Yen Hoang, Pierre Guesry, Helmut Hilpert, Myron M. Levine
Journal: New England Journal of Medicine (1988)

Enterotoxigenic Escherichia coli is a common cause of traveler's diarrhea. Prophylaxis against traveler's diarrhea has been associated with side effects from bismuth subsalicylate and the development of resistance to antimicrobial agents. We undertook a double-blind controlled trial in which a bovine milk immunoglobulin concentrate with high titers of antibodies against enterotoxigenic E. coli was used as prophylaxis against E. coli challenge in volunteers. Lyophilized milk immunoglobulins were prepared from the colostrum of cows immunized with several enterotoxigenic E. coli serotypes and fimbria types, E. coli heat-labile enterotoxin, and cholera toxin. As a control, an immunoglobulin concentrate with no anti-E. coli activity was prepared. Ten volunteers received buffered immunoglobulin concentrate against enterotoxigenic E. coli, and 10 received the control immunoglobulin concentrate, dissolved in water, three times a day. No side effects were observed. On the third day of immunoglobulin prophylaxis, the volunteers were given 109 colony-forming units of enterotoxigenic E coli H10407 (O78:H11). This strain produces colonization factor antigen I and heat-labile and heat-stable enterotoxins. None of the 10 volunteers receiving the immunoglobulin concentrate against E. coli had diarrhea, but 9 of the 10 controls did (P<0.0001). All volunteers excreted E. coli H10407. We conclude from these preliminary results that milk immunoglobulin concentrate may be an effective prophylaxis against traveler's diarrhea. (N Engl J Med 1988; 318:1240–3.)
SP0145 Mri: Introduction to Image Acquisition and Basic Physics
Authors: M. Østergaard
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Magnetic resonance imaging (MRI) is getting increasingly clinically important in the diagnosis and management of patients with peripheral and axial inflammatory joint diseases. A minimal knowledge of MRI acquisition techniques and the physics behind them increases the ability to have a meaningful discussion with the radiologists. This presentation will in an easily understandable way introduce participants to the basic physics of MRI. Furthermore, the most common MRI acquisition techniques, and their advantages and disadvantages, will be reviewed. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6333
Abstract 1000: Rad6B induced β-catenin stabilization requires intact Wnt signaling
Authors: Brigitte Gerard, Larry Tait, Seema Shah, Pratima Nangia-Makker, Malathy PV Shekhar
Journal: Cancer Research (2010)

Abstract Aberrant activation of Wnt signaling results from stabilization and transcriptional activation of β-catenin and is often associated with carcinogenesis. Clinical evidence suggests that β-catenin accumulation occurs in breast cancer although activating mutations are rare. We have previously shown that Rad6B positively regulates β-catenin stability and transcriptional activity in breast cancer cells by inducing stable polyubiquitin modifications. Here we show that Rad6B physically interacts with β-catenin within the β-catenin amino acid segment containing the first armadillo repeat, which is also a binding site for casein kinase 1 (CK1). β-catenin phosphorylation by GSK3β and subsequent ubiquitination and proteasomal degradation is dependent upon CK1-mediated initiating phosphorylation of β-catenin at Ser45. In vitro kinase assays showed that Rad6B inhibits Ser45 phosphorylation by CK1, and Ser45 phosphorylated β-catenin is decreased in Rad6B overexpressing breast cancer cells. In vitro and in vivo mapping, and site-directed mutation analysis identified K394 of β-catenin as the predominant site for ubiquitination by Rad6B. MCF-7 breast cancer cells engineered to express myc-tagged K394R-β-catenin showed decreased steady-state levels and β-catenin transcriptional activity as compared to cells expressing wild type β-catenin. We also determined whether Rad6B-mediated β-catenin stabilization occurs independently of the canonical Wnt signaling pathway. MDA-MB-231 breast cancer cells overexpressing endogenous Rad6B were isolated on the basis of Rad6B promoter activity, and the consequences of Wnt disruption on β-catenin levels, transcriptional activity and Rad6B expression were determined by expressing a dominant negative mutant of Wnt coreceptor, LRP6. Disruption of Wnt signaling inhibited Rad6B expression and β-catenin accumulation. Both Wnt signaling disruption and Rad6B silencing separately enhanced localization of β-catenin on the cell membranes and decreased intracellular β-catenin accumulation. In summary, our data suggest that the Rad6B overexpression frequently observed in breast carcinomas contribute to β-catenin stabilization and transcriptional activation by inhibiting the CK1-mediated initiating phosphorylation and by ubiquitinating K394. However, the Rad6B induced β-catenin stabilization requires intact Wnt signaling. Supported by DOD W81XWH07-1-0562. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1000.
Does Calcium Supplementation Prevent Postmenopausal Bone Loss?
Authors: Bente Rus, Karsten Thomsen, Claus Christiansen
Journal: New England Journal of Medicine (1987)

During a two-year study, we examined the effect of calcium supplementation on postmenopausal bone loss in 43 women in the early postmenopausal period who were assigned to one of three treatment groups: (1) percutaneous 17β-estradiol (combined with progesterone during the second year), (2) oral calcium (2000 mg daily), and (3) placebo. All participants were examined every three months. Bone mineral content in the forearm (measured by single-photon absorptiometry) and in the entire body and spine (measured by dual-photon absorptiometry) remained constant in the estrogen-treated group but decreased significantly in the groups receiving calcium and placebo. In the calcium-treated group, we observed a tendency toward a slowed loss of compact bone (in the proximal forearm and total skeleton) as compared with the placebo group, while the rate of loss of trabecular bone (the distal forearm and spine) was the same as in the placebo group. Our preliminary data suggest that calcium supplementation in the dosage we used is not as effective as estrogen therapy for the prevention of early postmenopausal bone loss. Calcium supplementation may have had a minor effect on the loss of cortical bone, but it had no effect on the trabecular bone. (N Engl J Med 1987; 316:173–7.)
ECHOCARDIOGRAPHIC FINDINGS PREDICT IN-HOSPITAL AND 1-YEAR MORTALITY IN LEFT-SIDED NATIVE VALVE STAPHYLOCOCCUS AUREUS ENDOCARDITIS: AN ANALYSIS FROM THE INTERNATIONAL COLLABORATION ON ENDOCARDITIS- PROSPECTIVE ECHO COHORT STUDY
Authors: Trine K. Lauridsen, Lawrence Park, Christine Selton-Suty, Gail Peterson, Enrico Cecchi, Luis Afonso, Gilbert Habib, Carlos Pare, Syahidah Tamin, Stuart Dickerman, Magnus Johanssen, Mar Moreno, Vivian Chu, Zainab Samad, Niels E. Bruun, Vance G. Fowler, Anna Lisa Crowley
Journal: Journal of the American College of Cardiology (2014)
AB0388 Treat to target: normal cholesterol values in low disease activity established RA
Authors: I. Meek, H. Vonkeman, M. van de Laar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Over the past decades many reports have demonstrated the association between RA and dyslipidemia, the unfavourable lipid profiles having been observed &gt;10 years before disease onset. Some have reported an association between disease activity and low HDL cholesterol levels, however in other studies no associations between disease duration or activity and lipid spectrum abnormalities could be found. Also, after treatment with biologicals improvement, as well as deterioration of lipid profiles has been observed. Dislipidemia might contribute to the observed raised cardiovascular mortality in RA, therefore more data concerning lipid profiles in currently treated RA patients are needed. <h3>Objectives</h3> To compare the lipid profiles of RA outpatients with the general population, and to investigate risk factors for an artherogenic lipid profile in RA. <h3>Methods</h3> Comparison of lipid profiles, i.e. total cholesterol (TC), HDL cholesterol (HDL), and TC/HDL-ratio in a cohort of consecutive patients between 36 and 75 years of age attending the Arthritis Center Twente (ACT), a large rheumatology outpatient department in The Netherlands (n=546), and a sample of the general population (GP) from the same geographic region (n=4523). Multivariate analysis of the relationship between potential risk factors, i.e. disease activity (remission by DAS-28 or expert opinion), ESR, disease duration, biological use, and smoking and TC/HDL-ratio. Data were collected by direct measurements in 2009 (ACT), and from 2003 to 2007 (GP) respectively. Analyses were sex-specific and standardised by age. <h3>Results</h3> The RA cohort consisted of 341 women and 205 men, mean age 56 years, and mean disease duration 81 months, 19% being treated with biologicals, and 69% being in remission of RA. Preliminary analyses show that RA patients had similar frequencies of hypercholesterolemia (TC&gt;6.5 mmol/L and/or use of lipid lowering medication; GP 18%, OR<sub>ACT</sub> 1.1, 95% CI 0.9-1.4) and lowered HDL&lt;1.0 mmol/L; GP 7.2%, OR<sub>ACT</sub> 1.0, 95% CI 0.7-1.4) compared to the GP. TC/HDL ratios were lower in RA patients (GP 4.2, RA 3.9, p&lt;0.05). In RA patients non-smoking and biological use were associated with lower TC/HDL ratios (p&lt;0.05), controlling for lipid lowering therapy. <h3>Conclusions</h3> dislipidemia is not increased in low disease activity RA patients. Non-smoking and biological use are associated with lower TC/HDL ratios. <h3>Disclosure of Interest</h3> None Declared
Relation of Protease Inhibitor Phenotypes to Obstructive Lung Diseases in a Community
Authors: James O. Morse, Michael D. Lebowitz, Ronald J. Knudson, Benjamin Burrows
Journal: New England Journal of Medicine (1977)

To examine the relative risk for the development of obstructive lung disease in persons heterozygous for alpha1-antitrypsin deficiency, we determined protease inhibitor phenotypes in 2944 subjects in a general community population. Phenotype M was found in 89.5 per cent, MS in 7.1 per cent, and MZ in 3.0 per cent of the population. There were two persons of phenotype Z and six of phenotype SZ. The study also included respiratory questionnaires and spirometry. There were no statistically significant differences in the prevalence of respiratory symptoms and diagnoses or of ventilatory impairment among the three major phenotype groups (M, MS and MZ), nor were there differences in the rates of deterioration of function with age or smoking. Consequently, we do not consider population screening for heterozygous alpha1-antitrypsin deficiency to be worthwhile.
Weighing dispositional and situational factors in accounting for suicide terrorism
Authors: David C. Funder
Journal: Behavioral and Brain Sciences (2014)

Abstract Lankford's book makes the important point that analyses of suicide terrorists often commit the error of overestimating the importance of situational causes of behavior and underestimating dispositional causes, such as underlying pathology. Personality and individual differences are important; suicide terrorists are not ordinary people driven by situational pressures. However, citation of empirical evidence is haphazard; the scholarly argument is not well-developed.
TCT-699 The Effect of Tricuspid Regurgitation and Right Ventricular Dysfunction on Mortality in High Risk Patients Undergoing Transcatheter Aortic Valve Replacement: An Analysis of the PARTNER II Inoperable Cohort
Authors: Alan Zajarias, Michael Mack, Rakesh M. Suri, Wael Jaber, E. Murat Tuzcu, Vinod Thourani, Ke Xu, Darshan Doshi, Martin Leon, Brian R. Lindman
Journal: Journal of the American College of Cardiology (2014)
Thrombosis and Acute Coronary-Artery Lesions in Sudden Cardiac Ischemic Death
Authors: Michael John Davies, Anthony Thomas
Journal: New England Journal of Medicine (1984)

The nature of the pathologic lesion in sudden cardiac ischemic death is in dispute. Among 100 subjects who died of ischemic heart disease in less than six hours, coronary thrombi were found in 74. There was no difference in incidence between those who died in less than 15 minutes, those who died in 15 to 60 minutes, and those who died after one hour. Among 26 cases without an intraluminal thrombus, plaque fissuring was found in 21; thus, in only 5 cases was no acute arterial lesion demonstrated. No intraluminal thrombi were found in age-matched controls. Forty-eight of the 74 thrombi were found at sites of preexisting high-grade stenosis; 14 were found at points of previous stenosis of less than 50 per cent of the diameter of the lumen. Forty-seven per cent of the thrombi were found in the right coronary artery. Only 30 per cent were found in the left anterior descending coronary artery. The pathologic process in sudden ischemic death involves a rapidly evolving coronary-artery lesion in which plaque fissuring and resultant thrombus formation are present. These findings have implications for the prevention of sudden cardiac death by antithrombotic therapy. (N Engl J Med 1984; 310:1137–40.)
Genes, hosts, goals: Disentangling causal dependencies
Authors: Bjorn Merker
Journal: Behavioral and Brain Sciences (2014)

Abstract The special sense in which the concept of “selfishness” is defined in Dawkins's popularization of basic evolutionary theory is analyzed with regard to its applicability to the relation between goals and those who entertain and pursue them. It is concluded that grounds analogous to those on which independent self-interest vis-á-vis their hosts is attributed to genes in Dawkins's sense are lacking in the case of goals in their relation to those who entertain and pursue them.
The Clinical Utility of a Diagnostic Imaging Algorithm Incorporating Low-Dose Perfusion Scans in the Evaluation of Pregnant Patients With Clinically Suspected Pulmonary Embolism
Authors: Jonathan T. Abele, Parveen Sunner
Journal: Clinical Nuclear Medicine (2012)

The aim of this study was to determine the proportion of pregnant patients with a clinical suspicion of pulmonary embolism and a normal chest radiograph who require further evaluation with perfusion scintigraphy alone compared with both perfusion scintigraphy and computed tomography (CT).All patients who had a low-dose perfusion lung scan as part of a clinical imaging algorithm to assess for clinically suspected pulmonary embolism in pregnant patients at 3 regional hospitals from September 2009 to February 2011 were retrospectively reviewed. The proportion of patients requiring a low-dose perfusion-only lung scan was compared with the proportion requiring further evaluation with both a low-dose perfusion scan and a CT scan to complete the algorithm.Seventy-four (74) patients were included. Sixty-one (61/74; 82.4%) patients had a normal low-dose perfusion-only scan and did not require further imaging. Thirteen (13/74; 17.6%) patients demonstrated an abnormal perfusion scan and required further imaging with a CT scan. One patient (1/74; 1.4%) was diagnosed with pulmonary embolism.Our results suggest that for pregnant patients with a normal chest radiograph, pulmonary embolism can be excluded in 82.4% of patients with a low-dose perfusion scan alone.
Lipoprotein-Associated Phospholipase A<sub>2</sub>as an Independent Predictor of Coronary Heart Disease
Authors: Chris J. Packard, Denis S.J. O'Reilly, Muriel J. Caslake, Alex D. McMahon, Ian Ford, Josephine Cooney, Colin H. Macphee, Keith E. Suckling, Mala Krishna, Francis E. Wilkinson, Ann Rumley, Gillian Docherty, John D. Burczak, Gordon D.O. Lowe
Journal: New England Journal of Medicine (2000)

Chronic inflammation is believed to increase the risk of coronary events by making atherosclerotic plaques in coronary vessels prone to rupture. We examined blood constituents potentially affected by inflammation as predictors of risk in men with hypercholesterolemia who were enrolled in the West of Scotland Coronary Prevention Study, a trial that evaluated the value of pravastatin in the prevention of coronary events.A total of 580 men who had had a coronary event (nonfatal myocardial infarction, death from coronary heart disease, or a revascularization procedure) were each matched for age and smoking status with 2 control subjects (total, 1160) from the same cohort who had not had a coronary event. Lipoprotein-associated phospholipase A2, C-reactive protein, and fibrinogen levels, and the white-cell count were measured at base line, along with other traditional risk factors. The association of these variables with the risk of coronary events was tested in regression models and by dividing the range of values according to quintiles.Levels of C-reactive protein, the white-cell count, and fibrinogen levels were strong predictors of the risk of coronary events; the risk in the highest quintile of the study cohort for each variable was approximately twice that in the lowest quintile. However, the association of these variables with risk was markedly attenuated when age, systolic blood pressure, and lipoprotein levels were included in multivariate models. Levels of lipoprotein-associated phospholipase A2 (platelet-activating factor acetylhydrolase), the expression of which is regulated by mediators of inflammation, had a strong, positive association with risk that was not confounded by other factors. It was associated with almost a doubling of the risk in the highest quintile as compared with the lowest quintile.Inflammatory markers are predictors of the risk of coronary events, but their predictive ability is attenuated by associations with other coronary risk factors. Elevated levels of lipoprotein-associated phospholipase A2 appear to be a strong risk factor for coronary heart disease, a finding that has implications for atherogenesis and the assessment of risk.