tbuckley/cabot-search huggingface dataset:
The effect of migration within the European Union/European Economic Area on the distribution of tuberculosis, 2007 to 2013
Authors: Vahur Hollo, Saara Magdalena Kotila, Csaba Ködmön, Phillip Zucs, Marieke Johanna van der Werf
Journal: Eurosurveillance (2016)

Immigration from tuberculosis (TB) high-incidence countries is known to contribute notably to the TB burden in low-incidence countries. However, the effect of migration enabled by the free movement of persons within the European Union (EU)/European Economic Area (EEA) on TB notification has not been analysed. We analysed TB surveillance data from 29 EU/EEA countries submitted for the years 2007-2013 to The European Surveillance System. We used place of birth and nationality as proxy indicators for native, other EU/EEA and non-EU/EEA origin of the TB cases and analysed the characteristics of the subgroups by origin. From 2007-2013, a total of 527,467 TB cases were reported, of which 129,781 (24.6%) were of foreign origin including 12,566 (2.4%) originating from EU/EEA countries other than the reporting country. The countries reporting most TB cases originating from other EU/EEA countries were Germany and Italy, and the largest proportion of TB cases in individuals came from Poland (n=1,562) and Romania (n=6,285). At EU/EEA level only a small proportion of foreign TB cases originated from other EU/EEA countries, however, the uneven distribution of this presumed importation may pose a challenge to TB programmes in some countries.
P2-03-03: An Insulin-Like Growth Factor I (IGF-I)-Induced Gene, Solute Carrier Family 7 Member 11 (SLC7A11)/xCT, Mediates IGF-I-Induced Biological Behaviors in Breast Cancer Cells.
Authors: Y Yang, MA Becker, D Yee
Journal: Cancer Research (2011)

Abstract Our laboratory studied the gene expression profiles of a series of T47D variant cell lines with differential insulin receptor substrate (IRS) adaptor protein expression to develop predictive IGF-I pathway biomarkers. We identified an IGF-I-induced gene, SLC7A11 (or xCT), which is specifically regulated through IRS-1. xCT encodes the cystine/glutamate transporter subunit of the heterodimeric amino acid transport system xc- which is a major plasma membrane transporter for the cellular uptake of cystine in exchange for intracellular glutamate. xCT is involved in the regulations of proliferation, metastasis, and drug resistance in various cancers. However, to date, the linkage between xCT and the IGF-I signaling pathway has not been described. To study the role for xCT in mediating IGF-I-induced biology in breast cancer cell lines, we examined xCT mRNA expression upon IGF-I stimulation in two breast cancer cell lines; the MCF-7 (IRS-1 activated) and MDA-MB-231 (IRS-2 activated) cells. Significant increased xCT expression was observed only in MCF-7 cells after IGF-I treatment. Immunoblots showed that xCT protein expression was elevated after IGF-I treatment and induced glutamate/cystine exchange in MCF-7 cells. shRNA was used to downregulate xCT in MCF-7 and MDA-MB-231 cells. In MCF-7, IGF-I-stimulated cell monolayer growth was suppressed by xCT shRNA or by the xCT inhibitor sulfasalazine (SASP). In MDA-MB-231 cells, xCT downregulation did not affect IGF-mediated Boyden chamber migration. Thus, IGF-I induction of cellular xCT levels is associated with cell growth in the IRS-1 activated MCF-7 cells, while MDA-MB-231 cells were not affected by downregulation of this gene. Therefore, our data imply that xCT may mediate IGF-I induced biological functions in breast cancer cell lines through an IRS-1 dependent pathway. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-03-03.
THE IMPACT OF DIFFERENT TYPES OF AEROBIC EXERCISE ON ENDOTHELIAL FUNCTION AND ARTERIAL STIFFNESS
Authors: Gerasimos Siasos, Dimitrios Athanasiou, Gerasimos Terzis, Aggeliki Stasinaki, Panagiotis Tourikis, Efstathios Dimitropoulos, Stamatis Tsouroulas, Nikolaos Gouliopoulos, Evangelos Oikonomou, Marina Zaromitidou, Konstantinos Mourouzis, Sotirios Tsalamandris, Eleni Kokkou, Christodoulos I Stefanadis, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2015)
Dose considerations in the SO2-exposed exercising asthmatic.
Authors: A V Colucci, R P Strieter
Journal: Environmental Health Perspectives (1983)

In this study we have demonstrated that by combining data from several recent controlled human exposure studies it is possible systematically to relate increases in airways resistance to the rate of SO2 exposure (Dmin) in the exercising asthmatic. It was determined that the mode of SO2 exposure (oral vs. oronasal) greatly influences the degree of response in the asthmatic. Forced oral breathing consistently produces larger percentage increases in SRaw per unit increase in SO2 exposure rate. We have demonstrated further that while the dose/effect relationship which describes the increases in specific airways resistance (SRaw) versus exposure rate (Dmin) of SO2 is most consistently exponential in character, a linear (more conservative) model also can be used to fit the data. Using both the linear and exponential model, we have constructed a matrix which allows direct estimation of the combined minute ventilation (VE) and SO2 concentration (as ppm or microgram/L) required to achieve various levels of specific airways resistance increase. In this report this matrix is constructed only on subjects breathing in an unencumbered (oronasal) manner. Future reports will explore these relationships in the asthmatic breathing in an encumbered (oral) manner.
Abstract LB-411: Genotype and haplotype analysis of cell cycle genes and the risks of sporadic colorectal and pancreatic cancers in the Czech Republic
Authors: Pavel E. Vodicka, Alessio Naccarati, Barbara Pardini, Veronika Polakova, Zdenek Smerhovsky, Ludmila Vodickova
Journal: Cancer Research (2010)

Abstract The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. Pancreatic carcinoma represents the fourth leading cause of cancer-related deaths in the country, with a minimum of patients surviving 5 years. The etiology and molecular pathogenesis of above cancers are weakly understood. TP53 plays a role in cell cycle and apoptosis and is frequently mutated in solid tumors, including colorectal and pancreatic. Assuming that genetic variation may affect susceptibility to cancer development, the role of polymorphisms and haplotypes of TP53, CDKN1A and CDKN2A in modulating the cancer risk was addressed. We investigated selected polymorphisms in TP53 (rs17878362:A1&amp;gt;A2, rs1042522:G&amp;gt;C, rs12947788:C&amp;gt;T, and rs17884306:G&amp;gt;A), CDKN1A (rs1801270:C&amp;gt;A and rs1059234:C&amp;gt;T), and CDKN2A (rs3731249:G&amp;gt;A, rs11515:C&amp;gt;G, and rs3088440:C&amp;gt;T) genes in 614 hospital-based cases and 614 matched controls from the country for association with colorectal cancer and 240 cases and controls (for a total of 1827 individuals) for association with pancreatic cancer risk. For CRC, none of the studied polymorphisms was strongly associated with risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P&amp;lt;0.0001). In comparison to the most common haplotype (A1GCG), the haplotype A2CCG was associated with an increased risk (OR 1.40, 95% CI 1.07-1.82), while four other less frequent haplotypes A1CCG, A2GCG A1GTG, and A1GCA were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon and rectal cancers. No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. For pancreatic cancer: carriers of the variant C allele of rs1042522 polymorphism were at an increased risk of (OR 1.73; 95% CI 1.26-2.39; p=0.001). The A2CCG haplotype in comparison with the most common haplotype (A1GCG) was associated with an increased risk (OR 1.39; 95% CI 1.02-1.88; p=0.034), and the A1CCG with a reduced risk (OR 0.30; 95% CI 0.12 -0.76; p=0.011) for this cancer. Genetic variation in TP53 may contribute, alone or in concert with other risk factors, to modify the inherited susceptibility to both colorectal and pancreatic cancers, as well as to other gastrointestinal cancers. Supported by GACR 310/07/1430. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 LB-411.
AB0952 Subclinical Left Ventricular Dysfunction in Patients with Ankylosing Spondylitis without Clinically Evident Cardiovascular Disease: A Two-Dimensional Speckle Tracking Echocardiographic Study
Authors: N. Ustun, M. Kurt, A.E. Yagiz, H. Guler, A.D. Turhanoglu
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Cardiac involvement is common in ankylosing spondylitis (AS), which has not been previously evaluated by using speckle tracking echocardiography (STE). <h3>Objectives</h3> The objectives of this study were to evaluate the left ventricle (LV) systolic strain by STE in order to provide the subclinical myocardial dysfunction in patients with AS and to examine the relationship between LV systolic strain and disease activity indices. <h3>Methods</h3> A total of 26 patients with AS without clinically evident cardiovascular disease and 26 age-,sex-,and BMI-matched healthy controls were included in the study. Bath AS disease activity index, Bath AS fuctional index, Bath AS metrology index and Bath AS radiologic index were used as clinical indices. Conventional echocardiography, tissue Doppler imaging, color tissue Doppler derived strain/strain rate echocardiographic imaging were performed by a single cardiologist using a 2.5–3.5 MHz transducer and Vingmed System 7 (Vivid 7 Pro; Horton, Norway). All data were transferred to a workstation for further offline analysis (EchoPAC 6.1; GE Vingmed Ultrasound AS). For left ventricle color tissue Doppler dynamic images were obtained from from LV apical 4-, 3- and 2-C (chamber) views. <h3>Results</h3> There were no significant differences in baseline demographic characteristics and cardiovascular risk factors between the patients and the controls. There were no significant differences between patients and controls in terms of left ventricle diameters, ejection fraction, posterior wall thickness, interventriculer septum wall thickness, mitral deceleration time and systolic myocardial flow velocity (p&gt;0.05). AS patients were observed to have statistically significantly lower left ventricule peak longitudinal and global strain/strain rate values in the 4C, 3C, and 2C views compared with the controls (p&gt;0.05). In addition, we detected no correlation in left ventricule global strain values and AS clinical indices values (p&gt;0.05). <h3>Conclusions</h3> Myocardial systolic function assessed by STE, which is a sensitive marker of ventricular dysfunction is impaired in AS. <h3>References</h3> Teske AJ, De Boeck BW, Melman PG, Sieswerda GT, Doevendans PA, Cramer MJ. Echocardiographic quantification of myocardial function using tissue deformation imaging, a guide to image acquisition and analysis using tissue Doppler and speckle tracking. Cardiovasc Ultrasound 2007;5:27. Schiller NB, Shah PM, Crawford M, et al: American Society of Echocardiography committee on standards, subcommittee on quantitation of two-dimensional echocardiograms: Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiography 1989;2:358–367. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1961
S18 Rate Of Decline In Lung Density May Predict Long-term Outcome In Patients With Alpha 1 Antitrypsin Deficiency (aatd)
Authors: C. Green, D. Parr, R. Stockley, A. Turner
Journal: Thorax (2014)

<h3>introduction and objectives</h3> Alpha-1-Antitrypsin Deficiency (A1ATD) is a genetically determined anti-proteinase deficiency which predisposes to emphysema.<sup>1</sup> Factors predicting mortality in untreated A1ATD patients include poor FEV1, gas transfer and low lung density.<sup>1</sup> Indeed the latter has been shown to be the most sensitive measure of progression and hence has become the primary outcome in recent studies of augmentation therapy.<sup>2</sup> We hypothesised that patients with the most rapid decline in lung density would be those most at risk of death and most in need of transplantation as the only viable rescue option. <h3>Methods</h3> Augmentation naïve patients with 2 quantitative CT scans were selected from the UK A1ATD registry. The annual decline in lung density was determined using the difference between the 2 scans and patients were divided into those with no decline, a slow decline (0–2 g/l/year) or a rapid decline (&gt; 2). Subsequent death or lung transplant was noted. A univariate analysis was undertaken dividing the population into 2 groups: Alive without transplant and dead. Median baseline density was significantly higher in the living than the dead group (55.40 g/l and 39.80 g/l respectively; p = 0.002) and thus was included in a multivariate analysis, seeking association with subsequent death in a Cox regression analysis. <h3>Results</h3> 77 patients were identified with sufficient data for analysis. 27 had died and 1 was transplanted and excluded from further analysis. Slow decline in densitometry showed a trend to lower survival compared to no decline (p = 0.065) but rapid decline was significantly associated with death (p = 0.026; Figure). <h3>Conclusions</h3> Decline in lung density may be a suitable surrogate measure for survival in AATD, and as augmentation therapy slows the decline in lung density<sup>2</sup> could identify a group more likely to benefit from augmentation in the shorter term. <h3>References</h3> Dawkins P, <i>et al</i>. Mortality in alpha-1-antitrypsin deficiency in the UK. <i>Respir Med</i>. 2009 Oct;103(10):1540–7 Stockley RA, <i>et al</i>. Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry. <i>Respir Res</i>. 2010;11:136
Prophylaxis with Oral Penicillin in Children with Sickle Cell Anemia
Authors: Marilyn H. Gaston, Joel I. Verter, Gerald Woods, Charles Pegelow, John Kelleher, Gerald Presbury, Harold Zarkowsky, Elliott Vichinsky, Rathi Iyer, Jeffrey S. Lobel, Steven Diamond, C. Tate Holbrook, Frances M. Gill, Kim Ritchey, John M. Falletta
Journal: New England Journal of Medicine (1986)

Children with sickle cell anemia have an increased susceptibility to bacterial infections, especially to those caused by Streptococcus pneumoniae. We therefore conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial to test whether the regular, daily administration of oral penicillin would reduce the incidence of documented septicemia due to S.pneumoniae in children with sickle cell anemia who were under the age of three years at the time of entry. The children were randomly assigned to receive either 125 mg of penicillin V potassium (105 children) or placebo (110 children) twice daily. The trial was terminated 8 months early, after an average of 15 months of follow-up, when an 84 percent reduction in the incidence of infection was observed in the group treated with penicillin, as compared with the group given placebo (13 of 110 patients vs. 2 of 105; P = 0.0025), with no deaths from pneumococcal septicemia occurring in the penicillin group but three deaths from the infection occurring in the placebo group. On the basis of these results, we conclude that children should be screened in the neonatal period for sickle cell hemoglobinopathy and that those with sickle cell anemia should receive prophylactic therapy with oral penicillin by four months of age to decrease the morbidity and mortality associated with pneumococcal septicemia.
Performance of 18F-Fluoride PET or PET/CT for the Detection of Bone Metastases
Authors: Chen-Tian Shen, Zhong-Ling Qiu, Ting-Ting Han, Quan-Yong Luo
Journal: Clinical Nuclear Medicine (2014)

This study aimed to evaluate the diagnostic accuracy of F-fluoride PET or PET/CT compared with Tc-MDP bone scintigraphy and F-FDG PET/CT in the detection of bone metastases.An electronic search was conducted using PubMed/MEDLINE and EMBASE. The methodological quality of the included studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. All analyses were performed on Stata version 12.0 and Meta-DiSc version 1.4.Twenty articles containing 1170 patients were identified. On a patient basis, the pooled sensitivity, specificity, and the area under the summary receiver operating characteristic curve of F-fluoride PET or PET/CT were 92% (95% confidence interval [CI], 89%-95%), 93% (95% CI, 91%-95%), and 0.985, respectively. On a lesion basis, the pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve of F-fluoride PET or PET/CT were 87% (95% CI, 85%-88%), 95% (95% CI, 94%-96%), and 0.979, respectively. When compared with Tc-MDP bone scintigraphy, F-fluoride PET or PET/CT showed both higher sensitivity (96% vs. 88%, P = 0.002) and specificity (91% vs. 80%, P = 0.001). When compared with F-FDG PET/CT, F-fluoride PET/CT showed higher sensitivity (94% vs. 73%, P = 0.003), whereas no significant difference was observed in specificity (88% vs. 98%, P = 0.06).F-fluoride PET or PET/CT has an excellent diagnostic capacity for the detection of bone metastases and shows advantages when compared with Tc-MDP bone scintigraphy and F-FDG PET/CT.
SP0028 Personalised Treatment for Shoulder Pain
Authors: R. Buchbinder
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Shoulder pain is a prevalent complaint and a frequent reason for seeking medical care. By far the most common cause of shoulder pain is rotator cuff disease; while other causes include adhesive capsulitis, glenohumeral arthritis, calcific tendinitis and acute rotator cuff tear. This presentation will discuss their evidence-based management as well as known evidence-practice gaps. Studies suggest that primary care physicians lack confidence in making specific diagnoses. In addition there is a high and generally unwarranted overreliance upon imaging (especially X-Ray and ultrasound), image-guided injection and specialist referral. Key messages include: the diagnosis can usually be made by history and physical examination alone; imaging is not required in the majority of cases and exposes patients to potential harm; shoulder pain can frequently be managed with a conservative approach and often improves over time irrespective of the cause; and image-guided glucocorticoid injections are no more efficacious than anatomically guided injections. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6282
SAT0033 Anti-Citrullinated Proteins Antibodies Promote Synovial Fibroblast Migration in Rheumatoid Arthritis
Authors: M. Sun, A. Haj Hensvold, V. Malmström, K. Amara, H. Wähämaa, A.I. Catrina
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The presence of anti-citrullinated proteins antibodies (ACPAs) in RA is associated with aggressive disease phenotype and bone destruction. <h3>Objectives</h3> As synovial fibroblasts (SFs) are considered key players of both synovial inflammation and bone destruction in rheumatoid arthritis (RA), we studied the effect of ACPAs on fibroblasts migration. <h3>Methods</h3> Human dermal fibroblasts (HDFs) were obtained from PromoCell. SFs were isolated from synovial tissue of RA patients (RASFs) by enzymatic digestion. ACPA positive and negative IgGs were separated from plasma of RA patients and monoclonal anti-citrullinated antibodies were generated from synovial fluid single B-cells. Migration scratch assays were performed using either RASFs or HDFs to test the effect of ACPAs, anti-citrullinated protein monoclonal antibodies and appropriate negative controls. The effect of a phosphoinositide 3-kinase (PI3K) inhibitor (wortmanin), G-protein coupled receptor (GPCR) inhibitor (pertussis toxin), focal adhesion kinase (FAK) inhibitor (PF-573228) and peptidylarginine deiminases (PAD) inhibitor (Cl-Amidine) was tested. Light microscopy images were taken at base line and after 6 hours incubation and analyzed using NIH ImageJ to calculate migration index. Cytotoxicity and proliferation assay were done in parallel with migration assays. <h3>Results</h3> ACPAs but not others IgGs than ACPAs induced a 3.9±0.5 (mean ± SD) fold increase in HDFs and a 2.6±0.5 (mean ± SD) fold increase in RASFs migration (p&lt;0.05). GPCR blocking completely abolished ACPAs effects. PI3K but not FAK blocking abolished ACPAs effects, with minimal residual fold increase of 1.4±0.4 (mean ± SD). Inhibition experiments suggest that ACPAs mediated RASFs migration via GPCR-PI3K pathway. Pre-inactivited PAD totally abolished ACPAs effects suggesting that citrullination is crucial for ACPAs mediated RASFs migration. No difference in either cytotoxicity or proliferation rate were observed between different treatments. One out of three different anti-citrullinated monoclonal antibodies displayed similar migration promoting effects. <h3>Conclusions</h3> We describe a novel effect of ACPAs, providing a link between synovial fibroblasts and the adaptive immune system. We further suggest that different fine specificities of the ACPAs might have distinct impact on disease pathogenesis. <h3>Disclosure of Interest</h3> None declared