tbuckley/cabot-search huggingface dataset:
The effect of tensile and fluid shear stress on the in vitro degradation of magnesium alloy for stent applications
Authors: Xue-Nan Gu, Yun Lu, Fan Wang, Wenting Lin, Ping Li, Yubo Fan
Journal: Bioactive Materials (2018)

Magnesium alloys have gained great attention as biodegradable materials for stent applications. Cardiovascular stents are continuously exposed to different types of mechanical loadings simultaneously during service, including tensile, compressive and fluid shear stress. In this study, the in vitro degradation of WE43 wires was investigated under combined effect of tensile loading and fluid shear stress and compared with that experienced an individual loading condition. For the individual mechanical loading treatment, the degradation of magnesium wires was more severely affected by tensile loading than fluid shear stress. Under tensile loading, magnesium wires showed faster increment of corrosion rates, loss of mechanical properties and localized corrosion morphology with the increasing tensile loadings. With the combined stress, smaller variation of the corrosion rates as well as the slower strength degeneration was shown with increasing stress levels, in comparison with the individual treatment of tensile loading. This study could help to understand the effect of complex stress condition on the corrosion of magnesium for the optimization of biodegradable magnesium stents.
Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts
Authors: Zuelma A. Contreras, Zhanghua Chen, Theano Roumeliotaki, Isabella Annesi-Maesano, Nour Baïz, Andrea von Berg, Anna Bergström, Sarah Crozier, Liesbeth Duijts, Sandra Ekström, Esben Eller, Maria P. Fantini, Henrik Fomsgaard Kjaer, Francesco Forastiere, Beatrix Gerhard, Davide Gori, Margreet W. Harskamp-van Ginkel, Joachim Heinrich, Carmen Iñiguez, Hazel Inskip, Thomas Keil, Manolis Kogevinas, Susanne Lau, Irina Lehmann, Dieter Maier, Evelien R. van Meel, Monique Mommers, Mario Murcia, Daniela Porta, Henriëtte A. Smit, Marie Standl, Nikos Stratakis, Jordi Sunyer, Carel Thijs, Maties Torrent, Tanja G.M. Vrijkotte, Alet H. Wijga, Kiros Berhane, Frank Gilliland, Leda Chatzi
Journal: European Respiratory Journal (2018)

The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood. This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3–4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3–4 years of age. Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18–2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31–3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08–2.09). Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood.
Obesity, Hypertension, and Dyslipidemia in Childhood Are Key Modifiable Antecedents of Adult Cardiovascular Disease
Authors: Christy B. Turer, Tammy M. Brady, Sarah D. de Ferranti
Journal: Circulation (2018)

Carotid intima media thickness (cIMT) measured via ultrasound correlates with the risk of future cardiovascular events, including myocardial infarction and death. 1 Thus, researchers use cIMT as an intermediate outcome to denote atherosclerosis in younger populations that would not have time to develop clinical cardiovascular end points.In this issue of Circulation, Koskinen and colleagues 2 use data from the International Childhood Cardiovascular Cohort (i3C) consortium to identify antecedents in childhood of high cIMT (>90th study-specific percentile) in adulthood.This rich dataset includes 23.4 years of longitudinal follow-up on 2893 twelve-to 18-year-old participants from 4 studies (Cardiovascular Risk in Young Finns, Childhood Determinants of Adult Health, Bogalusa Heart, and Insulin Studies) across 3 continents.The combined i3C data show childhood obesity, hypertension, and dyslipidemia in adolescence predict the presence of high cIMT in adulthood.In the analysis, obesity is the risk factor most strongly associated with high cIMT, increasing risk 3.7 (2.0-7.0)-fold.This makes sense because adolescent obesity is highly prevalent, challenging to treat, and strongly associated with obesity and premature mortality in adulthood (Figure). 3Prevalence of childhood overweight and obesity has nearly tripled in the United States since 1988, and rates worldwide have increased 10-fold. 4Short-term weight stabilization or loss is achievable with intensive family-based behavioral approaches, but disturbingly few adolescents with obesity (2%) achieve clinically meaningful treatment responses at 3 years. 5Of even greater concern is the cooccurrence of obesity-related comorbidities: >60% of adolescents with obesity have additional risk factors such as hypertension or dyslipidemia.These risk factors improve with lifestyle changes and pharmacological treatments.For this reason, pediatric guidelines for weight management, hypertension, and hyperlipidemia recommend treating obesity-related comorbidities with intensive lifestyle counseling, coupled with effective pharmacological therapies when indicated. 6,7ypertension is strongly linked to obesity, with significant consequences for the heart and vasculature. 6Although prevalence of hypertension in US children overall is 3% to 5%, prevalence among children with obesity is much higher (up to 25%). 6s fat mass increases, so does total blood volume via central (eg, renin-angiotensin and sympathetic systems) and peripheral (eg, baroreceptors and autonomic dysregulation) mechanisms. 8The resultant increase in stroke volume, cardiac output, systemic vascular resistance, and afterload leads to elevated blood pressure, hypertension, increased left ventricular mass, and left ventricular concentric hypertrophy. 8Total blood volume and hypertension increase further in the presence of sleep apnea (present in 55% of adolescents undergoing bariatric surgery 6 ).Repeti-
Abstract 19806: Factors’ Influence Blood Pressure in 3-5 Year Old Preschool Children
Authors: Cynthia I Joiner, Deborah Ejem, Andres Azuero, Olivia Affuso, Fadi Hage, Anne Turner-Henson, Marti Rice
Journal: Circulation (2015)

Introduction: It is estimated that 2-3 million children in the US have diagnosed hypertension that can track to adulthood and is a risk factor for cardiovascular disease (CVD). However, the prevalence of instance elevations of blood pressure (BP) in children is estimated to greatly exceed the prevalence of hypertension. There is increasing evidence that risk factors for CVD, including hypertension and instance elevations in BP, begin in childhood. It is unclear when the elevations in BP first appear in children and what factors influence BP. Few studies have examined instance elevations in BP in preschool children and/or what factors influence BP. Hypothesis: The purpose of this study was to determine the prevalence of elevated BP readings in a group of rural and urban preschool children and to determine if there were differences in BP status (normal, prehypertensive, or hypertensive range) based on race, gender, location, prematurity status, or body mass index (BMI) status. Methods: A cross-sectional comparative design was used to address the purpose. A convenience sample of 56 3-5 year old children (27 rural, 29 urban; 37 male, 19 female; 33 Black, 21 White) were recruited from Head Start Centers. Height, weight, and BP were collected according to protocols at the Centers. Results: Based on pediatric percentiles, 30% of the children had elevated BP readings; 14% Pre-Hypertensive readings (6 males; 2 female; 4 Black; 4 White); 16% Hypertensive readings (6 males; 3 females; 5 Black, 4 White). Seventy-six percent of elevated BP readings were systolic BP (SBP); 47% of those with elevated BP readings had diastolic elevations, while 23.5% had elevations in both SBP and DBP. Nine participants were overweight; 5 were obese. Over 65% of the children with BP elevations were normoweight. There were no differences in BP status based on race, gender, location, prematurity or BMI Status. There was a small effect size for the relationship between race, BMI status, prematurity and BP status. Conclusions: Thirty percent of 3-5 year-old children in this sample had elevated BP readings, the majority of which were SBP. BP should be measured in children at each visit to health care providers and elevations in BP readings addressed early to prevent later hypertension and other CVDs.
Epidemiology of heart failure in Sweden : a retrospective population-based cohort study
Authors: Krister Lindmark, Kurt Boman, Mona Olofsson, G. Wikstrom, G. J. Bergman, M. Tornblom, E. Gullberg, D. Johansson, R. Schlienger, J. Stalhammar
Journal: European Journal of Heart Failure (2017)
Atypical Femur Fractures: Review of Epidemiology, Relationship to Bisphosphonates, Prevention, and Clinical Management
Authors: Dennis M Black, Bo Abrahamsen, Mary L Bouxsein, Thomas Einhorn, Nicola Napoli
Journal: Endocrine Reviews (2018)

Bisphosphonates (BPs) are highly effective in treating osteoporosis and reducing hip, vertebral, and other fractures by as much as 50% to 70%. However, since 2006, atypical femur fractures (AFFs) emerged as potential side effects of BPs and other treatments. These fractures have unusual radiologic features and occur with little trauma. Public concern has led to a >50% decrease in BP usage. AFFs are rare: for each AFF, >1200 fractures, including 135 hip fractures, are prevented. Case definition criteria were updated by the American Society of Bone and Mineral Research in 2014. Many epidemiologic studies have been reported, and although methodologically challenging, generally support a BP-AFF association. However, the magnitude of the association between BPs and AFFs is uncertain: estimates of relative risk for AFFs among BP users vs nonusers range from 1 to 65 with a meta-analysis estimate of 1.7. Although mechanistic studies have proposed several hypotheses explaining how BPs might decrease bone strength, AFF pathogenesis remains uncertain and cannot explain the paradox of efficacy of reduction of common fractures while increasing risk for rare fractures at one site. There are several consistent risk factors, including Asian race (in North America), femoral bowing, and glucocorticoid use, whereas others remain unclear. Consensus is emerging about strategies to prevent AFFs in BP users (including drug holidays after 5 years' use in some patients). In conclusion, AFFs can be devastating, but even under the most pessimistic assumptions, the benefit/risk ratio is highly positive for BPs, particularly during 3 to 5 years of use. As understanding of AFFs increases, it is becoming increasingly possible to maximize BP benefits while minimizing AFF risk.
Transcriptome profiling reveals the complexity of pirfenidone effects in idiopathic pulmonary fibrosis
Authors: Grazyna Kwapiszewska, Anna Gungl, Jochen Wilhelm, Leigh M. Marsh, Helene Thekkekara Puthenparampil, Katharina Sinn, Miroslava Didiasova, Walter Klepetko, Djuro Kosanovic, Ralph T. Schermuly, Lukasz Wujak, Benjamin Weiss, Liliana Schaefer, Marc Schneider, Michael Kreuter, Andrea Olschewski, Werner Seeger, Horst Olschewski, Malgorzata Wygrecka
Journal: European Respiratory Journal (2018)

Despite the beneficial effects of pirfenidone in treating idiopathic pulmonary fibrosis (IPF), it remains unclear if lung fibroblasts (FB) are the main therapeutic target. To resolve this question, we employed a comparative transcriptomic approach and analysed lung homogenates (LH) and FB derived from IPF patients treated with or without pirfenidone. In FB, pirfenidone therapy predominantly affected growth and cell division pathways, indicating a major cellular metabolic shift. In LH samples, pirfenidone treatment was mostly associated with inflammation-related processes. In FB and LH, regulated genes were over-represented in the Gene Ontology node “extracellular matrix”. We identified lower expression of cell migration-inducing and hyaluronan-binding protein (CEMIP) in both LH and FB from pirfenidone-treated IPF patients. Plasma levels of CEMIP were elevated in IPF patients compared to healthy controls and decreased after 7 months of pirfenidone treatment. CEMIP expression in FB was downregulated in a glioma-associated oncogene homologue-dependent manner and CEMIP silencing in IPF FB reduced collagen production and attenuated cell proliferation and migration. Cumulatively, our approach indicates that pirfenidone exerts beneficial effects via its action on multiple pathways in both FB and other pulmonary cells, through its ability to control extracellular matrix architecture and inflammatory reactions.
Human tryptophanyl-tRNA synthetase is an IFN-γ–inducible entry factor for Enterovirus
Authors: Man Lung Yeung, Lilong Jia, Cyril C. Y. Yip, Jasper F. W. Chan, Jade L. L. Teng, Kwok-Hung Chan, Jian-Piao Cai, Chaoyu Zhang, Anna J. Zhang, Wan-Man Wong, Kin-Hang Kok, Susanna K. P. Lau, Patrick C. Y. Woo, Janice Y. C. Lo, Dong-Yan Jin, Shin-Ru Shih, Kwok-Yung Yuen
Journal: Journal of Clinical Investigation (2018)

Enterovirus A71 (EV-A71) receptors that have been identified to date cannot fully explain the pathogenesis of EV-A71, which is an important global cause of hand, foot, and mouth disease and life-threatening encephalitis. We identified an IFN-γ-inducible EV-A71 cellular entry factor, human tryptophanyl-tRNA synthetase (hWARS), using genome-wide RNAi library screening. The importance of hWARS in mediating virus entry and infectivity was confirmed by virus attachment, in vitro pulldown, antibody/antigen blocking, and CRISPR/Cas9-mediated deletion. Hyperexpression and plasma membrane translocation of hWARS were observed in IFN-γ-treated semipermissive (human neuronal NT2) and cDNA-transfected nonpermissive (mouse fibroblast L929) cells, resulting in their sensitization to EV-A71 infection. Our hWARS-transduced mouse infection model showed pathological changes similar to those seen in patients with severe EV-A71 infection. Expression of hWARS is also required for productive infection by other human enteroviruses, including the clinically important coxsackievirus A16 (CV-A16) and EV-D68. This is the first report to our knowledge on the discovery of an entry factor, hWARS, that can be induced by IFN-γ for EV-A71 infection. Given that we detected high levels of IFN-γ in patients with severe EV-A71 infection, our findings extend the knowledge of the pathogenicity of EV-A71 in relation to entry factor expression upon IFN-γ stimulation and the therapeutic options for treating severe EV-A71-associated complications.
New method for non-invasive detection of coronary inflammation using computed tomography angiography predicts residual cardiovascular risk
Authors: E Oikonomou, M Marwan, D Y Milind, J Mancio, A Alashi, E Hutt Centeno, S Thomas, L Herdman, C Kotanidis, K Thomas, B P Griffin, S D Flamm, A Antonopoulos, C Shirodaria, N Sabharwal, J Deanfield, S Neubauer, J Hopewell, K Channon, S Achenbach, C Antoniades
Journal: The Lancet (2018)
Abstract 19065: Circulating Cells Contribute to Post-infarction Myocardial Repair by Adopting Mature Cardiomyocyte and Endothelial Cell Fates
Authors: Cassandra E Burnett, Andrew B Goldstone, Jeff E Cohen, Jay B Patel, Bryan E Edwards, Anahita Eskandari, Sang-Ging Ong, John W MacArthur, Judith A Shizuru, Joseph Woo
Journal: Circulation (2015)

Objective: Whether bone marrow derived circulating cells engraft in ischemic myocardium and adopt non-hematopoietic fates remains controversial. Discordance may result from limitations of parabiosis models for fate tracking. Using a bone marrow chimera model, we hypothesized that circulating cells do, in fact, contribute to mature vessel formation and myocardial regeneration. Methods: Recipient C57BL/6 (n=16) or C57BL/6-GFP mice (n=13) were lethally irradiated (10 Gy) and transplanted with 5x10 6 whole bone marrow cells from C57BL/6-DsRed donors. Four weeks post transplant, animals underwent acute myocardial infarction (MI) by ligation of the left anterior descending artery. Hearts were explanted 3 weeks post MI and were examined histologically. Individual cells were sorted after Langendorff isolation with FACS (Fig 1A). Results: Bone marrow transplant reproducibly yielded &gt;90% chimerism in peripheral blood and in the hematopoietic stem cell population. The majority of DsRed+ circulating cells adopted mature hematopoietic fates in ischemic myocardium, of which 82.3±1.54% were CD11b monocytes. However, DsRed+ circulating cells directly contributed to mature vessel formation, incorporating as cells expressing the endothelial markers, CD31 and von Willebrand factor (Fig 1B). In fact, 1.85±0.36% of the isolated CD31+ cells expressed DsRed. Fate tracking also demonstrated that circulating cells facilitate myocardial regeneration (Fig 1C) through cell fusion with native cardiomyocytes (0.03±0.01%), and to a lesser extent through transdifferentiation (0.00043±0.00029%). Conclusions: Bone marrow derived circulating cells engraft in the ischemic heart and directly repair myocardium by adopting mature endothelial and cardiomyocyte fates. Mechanistic insight into the endogenous governance of circulating cell transdifferentiation and fusion post MI is essential to realizing the full potential of cytokine and progenitor cell based therapies.
Abstract P277: ‘Catalytic’ Doses of Fructose Improve Glycemic Control but Not Insulin Resistance: A Systematic Review and Meta-Analysis of Controlled Feeding Trials
Authors: Jarvis Noronha, Catherine Braunstein, Sonia Blanco Mejia, Adrian Cozma, Andrea Glenn, John Sievenpiper
Journal: Circulation (2016)

Objective: Contrary to concerns that fructose may have adverse metabolic effects, an emerging literature has shown that low-dose fructose at a level obtainable from fruit ( &lt; 40-g/day) may benefit glycemic control. This effect appears to be mediated by upregulation of glucokinase, leading to increased hepatic glycogen synthesis. Whether this ‘catalytic’ mechanism of fructose will manifest as an increase in hepatic insulin sensitivity is unclear. To address this question, we synthesized evidence from controlled feeding trials assessing the effect of small ‘catalytic’ fructose doses on HbA1c, fasting blood glucose, and homeostasis model assessment of insulin resistance (HOMA-IR). Methods: We searched MEDLINE, EMBASE, and Cochrane Library through October 6, 2015. We included controlled feeding trials of &gt; 7 days investigating the effect of small ‘catalytic’ fructose doses ( &lt; 40-g/day) in isoenergetic exchange for other carbohydrates. Two independent reviewers extracted relevant data and risk of bias (Cochrane Risk of Bias Tool). Data were pooled using the generic inverse variance method and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q statistic) and quantified (I 2 statistic). Results: Nine trials (n= 153) met the eligibility criteria. ‘Catalytic’ doses of fructose significantly reduced HbA1c (MD= -0.40% [95% CI -0.72 to -0.08%]) and fasting blood glucose (MD= -0.18 mmol/L [95% CI -0.35 to -0.02 mmol/L]). There was no effect on HOMA-IR (MD= 0.04 [95% CI -0.14 to 0.22]). Limitations: The available trials were small (median sample size, n= 20) and of short duration (median follow-up, 2 weeks). Conclusion: Pooled analyses indicate that small ‘catalytic’ doses of fructose in isoenergetic exchange for other carbohydrates improve aspects of glycemic control, but the effect does not appear to be mediated through an improvement in hepatic insulin sensitivity. There is a need for larger and longer ( &gt; 6 months) high quality randomized trials to confirm these results.
On the Prospects for a (Deep) Learning Health Care System
Authors: C. David Naylor
Journal: JAMA (2018)

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