bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stretching single titin molecules from failing human hearts reveals titin’s role in blunting cardiac kinetic reserve
Authors: Chen Mei-Pian , Kiduko Salome A , Saad Nancy S , Canan Benjamin D , Kilic Ahmet , Mohler Peter J , Janssen Paul M L 
Published: February 2019

Abstract

Aims
Heart failure (HF) patients commonly experience symptoms primarily during elevated heart rates, as a result of physical activities or stress. A main determinant of diastolic passive tension, the elastic sarcomeric protein titin, has been shown to be associated with HF, with unresolved involvement regarding its role at different heart rates. To determine whether titin is playing a role in the heart rate (frequency-) dependent acceleration of relaxation (FDAR). W, we studied the FDAR responses in live human left ventricular cardiomyocytes and the corresponding titin-based passive tension (TPT) from failing and non-failing human hearts.

Methods and results
Using atomic force, we developed a novel single-molecule force spectroscopy approach to detect TPT based on the frequency-modulated cardiac cycle. Mean TPT reduced upon an increased heart rate in non-failing human hearts, while this reduction was significantly blunted in failing human hearts. These mechanical changes in the titin distal Ig domain significantly correlated with the frequency-dependent relaxation kinetics of human cardiomyocytes obtained from the corresponding hearts. Furthermore, the data suggested that the higher the TPT, the faster the cardiomyocytes relaxed, but the lower the potential of myocytes to speed up relaxation at a higher heart rate. Such poorer FDAR response was also associated with a lesser reduction or a bigger increase in TPT upon elevated heart rate.

Conclusions
Our study established a novel approach in detecting dynamic heart rate relevant tension changes physiologically on native titin domains. Using this approach, the data suggested that the regulation of kinetic reserve in cardiac relaxation and its pathological changes were associated with the intensity and dynamic changes of passive tension by titin.
Macrophage-derived MMP-8 determines smooth muscle cell differentiation from adventitia stem/progenitor cells and promotes neointima hyperplasia
Authors: Yang Feng , Chen Qishan , Yang Mei , Maguire Eithne Margaret , Yu Xiaotian , He Shiping , Xiao Rui , Wang Claire S , An Weiwei , Wu Wei , Zhou Yijiang , Xiao Qingzhong , Zhang Li 
Published: February 2019

Abstract

Aims
Emerging evidence has suggested that adventitia stem/progenitor cells (AdSPCs) migrate into the intima of arteries in response to injury, where they differentiate towards smooth muscle cells (SMCs) and participate in neointimal hyperplasia. We have previously identified matrix metalloproteinase-8 (MMP8) as a key player in atherogenesis. In this study, we aimed to investigate the functional roles of macrophage-derived MMP8 in AdSPC differentiation and injury-induced arterial remodelling.

Methods and results
We first observed an important role for MMP8 in SMC differentiation from embryonic stem cells, but this effect was not seen in AdSPCs. Instead, through macrophages/AdSPCs co-culture and macrophage conditional culture medium studies, we have demonstrated that the MMP8 protein secreted from macrophages promotes SMC differentiation from AdSPCs. Mechanistically, we showed that macrophage-derived MMP8 promotes SMC differentiation from AdSPCs through modulating transforming growth factor-β activity and a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10)/Notch1 signalling. We further demonstrated that the binding site for CBF1, Suppressor of Hairless, and Lag-1 (CSL) within SMC gene promoters is responsible for Notch1 mediated SMC differentiation. Finally, we demonstrated that macrophage-derived MMP8 increased injury-induced neointimal SMC hyperplasia by activating ADAM10/Notch1 signalling.

Conclusions
We have identified macrophage-derived MMP8 as a regulator in SMC differentiation from AdSPCs and neointimal SMC hyperplasia in response to injury. Our data provide new insights into the roles of MMP8 in AdSPC differentiation and the pathogenesis of neointima formation in the context of angiographic restenosis, and therefore may aid in the development of novel therapeutic agents for the prevention of this disease.
Identification of invasive and radionuclide imaging markers of coronary plaque vulnerability using radiomic analysis of coronary computed tomography angiography
Authors: Kolossváry Márton , Park Jonghanne , Bang Ji-In , Zhang Jinlong , Lee Joo Myung , Paeng Jin Chul , Merkely Béla , Narula Jagat , Kubo Takashi , Akasaka Takashi , Koo Bon-Kwon , Maurovich-Horvat Pál 
Published: February 2019

Abstract

Aims
Identification of invasive and radionuclide imaging markers of coronary plaque vulnerability by a single, widely available non-invasive technique may provide the opportunity to identify vulnerable plaques and vulnerable patients in broad populations. Our aim was to assess whether radiomic analysis outperforms conventional assessment of coronary computed tomography angiography (CTA) images to identify invasive and radionuclide imaging markers of plaque vulnerability.

Methods and results
We prospectively included patients who underwent coronary CTA, sodium-fluoride positron emission tomography (NaF18-PET), intravascular ultrasound (IVUS), and optical coherence tomography (OCT). We assessed seven conventional plaque features and calculated 935 radiomic parameters from CTA images. In total, 44 plaques of 25 patients were analysed. The best radiomic parameters significantly outperformed the best conventional CT parameters to identify attenuated plaque by IVUS [fractal box counting dimension of high attenuation voxels vs. non-calcified plaque volume, area under the curve (AUC): 0.72, confidence interval (CI): 0.65–0.78 vs. 0.59, CI: 0.57–0.62; P < 0.001], thin-cap fibroatheroma by OCT (fractal box counting dimension of high attenuation voxels vs. presence of low attenuation voxels, AUC: 0.80, CI: 0.72–0.88 vs. 0.66, CI: 0.58–0.73; P < 0.001), and NaF18-positivity (surface of high attenuation voxels vs. presence of two high-risk features, AUC: 0.87, CI: 0.82–0.91 vs. 0.65, CI: 0.64–0.66; P < 0.001).

Conclusion
Coronary CTA radiomics identified invasive and radionuclide imaging markers of plaque vulnerability with good to excellent diagnostic accuracy, significantly outperforming conventional quantitative and qualitative high-risk plaque features. Coronary CTA radiomics may provide a more accurate tool to identify vulnerable plaques compared with conventional methods. Further larger population studies are warranted.
Significant regional variation in use of implantable cardioverter-defibrillators in Denmark
Authors: Pedersen Susanne Bendesgaard , Farkas Dóra Körmendiné , Hjortshøj Søren Pihlkjær , Bøtker Hans Erik , Johansen Jens Brock , Philbert Berit Thornvig , Haarbo Jens , Thomsen Reimar Wernich , Nielsen Jens Cosedis 
Published: February 2019

Abstract

Aims
Implantable cardioverter-defibrillator (ICD) treatment prevents sudden cardiac death in high-risk patients. This study examined geographical variation in ICD implantation rates in Denmark and potential causes of variation.

Methods and results
We obtained numbers of ICD implantations in the 5 Danish regions and 98 municipalities during 2007–13 from the Danish Pacemaker and ICD Registry. Standardized implantation rates (SIRs) were computed as ICD implantations per 1 000 000 person-years, and age- and gender-standardized to the Danish population. We examined associations of the municipal SIR with mean age and Charlson Comorbidity Index score of ICD recipients, percentage of implantations with primary prophylactic indication, and distance from patient residency to ICD implanting centre. Based on 7192 ICD implantations, the nationwide SIR was 186 [95% confidence interval (CI) 182–190], ranging from 170 (95% CI 158–183) in the North Denmark Region to 206 (95% CI 195–218) in the Region of Zealand. Municipalities with higher patient comorbidity scores, higher percentages of implantations with primary prophylactic indication, and shorter distances to ICD implanting centres, had higher SIRs [differences between SIRs of municipalities in highest and lowest quartiles 22 (95% CI 10–34), 45 (95% CI 33–58), and 35 (95% CI 24–47), respectively]. Regional differences in SIRs decreased over time and had become insignificant during 2011–13.

Conclusion
Implantable cardioverter-defibrillator implantation rates in Denmark varied significantly between regions but variation decreased during 2007–13. Geographical variation was associated with differences in patient comorbidity score, variation in use of primary prophylactic ICD treatment, and distance to ICD implanting centre.
A meta-analysis of the performance of small tissue versus mechanical aortic valve prostheses
Authors: Moscarelli Marco , Fattouch Khalil , Speziale Giuseppe , Nasso Giuseppe , Santarpino Giuseppe , Gaudino Mario , Athanasiou Thanos 
Published: February 2019

Abstract

OBJECTIVES
Small aortic prosthetic valves have been associated with suboptimal performance due to patient–prosthesis mismatch (PPM). This meta-analysis compared the outcomes of patients with a small root who received tissue versus mechanical aortic valves.

METHODS
A systematic literature review identified 7 candidate studies; of these, 5 met the meta-analysis criteria. We analysed outcomes for a total of 680 patients (227 tissue valves and 453 mechanical valves) using random effects modelling. Each study was assessed for heterogeneity and quality. The primary end point was mortality at follow-up. Secondary end points included intraoperative and postoperative outcomes, the rate of PPM and left ventricle mass regression and major cardiac and prosthesis-related adverse events at follow-up.

RESULTS
There was no between-group difference in mortality at follow-up [incidence rate ratio 1, 95% confidence interval (CI) 0.50–2.01; P = 0.99]. The tissue group had a higher rate of PPM (odds ratio 17.19, 95% CI 8.6–25.78; P = 0.002) and significantly less reduction in ventricular mass (weighted mean difference 40.79, 95% CI 4.62–76.96; P = 0.02). There were no significant differences in the incidence of structural valve disease at follow-up compared to that in the mechanical valve group. There was also no between-group difference in aggregated adverse events at follow-up (P = 0.68).

CONCLUSIONS
Tissue and mechanical valves were associated with similar mortality rates; however, patients receiving tissue valves had a higher rate of PPM and significantly less left ventricle mass regression. These findings indicate that patients receiving small tissue valves may require closer clinical surveillance than those receiving mechanical valves.
Board games for teaching English prosody to advanced EFL learners
Authors: Łodzikowski Kacper , Jekiel Mateusz 
Published: February 2019

Abstract
This exploratory study fills the gap in research on using print board games to teach English prosody to advanced EFL learners at university level. We developed three in-class print-and-play board games that accompanied three prosody-related topics in a course in English phonetics and phonology at a Polish university. For those topics, compared to topics without any board games, learners reported higher in-class engagement and obtained higher post-class quiz scores. At the end of the course, learners rated board games as equally or more useful than some of the other teaching aids. Although traditional printed worksheets were still rated as the most useful teaching aid, learners expressed their preference for using extra classroom time for playing board games instead of completing extra worksheet exercises. We hope these promising results will encourage teachers to experiment with implementing these and other board games in their advanced curricula.
Reasons for hospitalization and risk of mortality in patients with atrial fibrillation treated with dabigatran or warfarin in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial
Authors: Alak Aiman , Hohnloser Stefan H , Fräßdorf Mandy , Reilly Paul , Ezekowitz Michael , Healey Jeff S , Brueckmann Martina , Yusuf Salim , Connolly Stuart J 
Published: February 2019

Aims
Hospitalizations are common among patients with atrial fibrillation. This article aimed to analyse the causes and consequences of hospitalizations occurring during the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial.

Methods and results
The RE-LY database was used to evaluate predictors of hospitalization using multivariate regression modelling. The relationship between hospitalization and subsequent major adverse cardiac events was evaluated in a time dependent Cox proportional-hazard modelling. Of the 18 113 patients in RE-LY, 7200 (39.8%) were hospitalized at least once during a mean follow-up of 2 years. First hospitalization rates were 2312 (39.5%) for dabigatran etexilate (DE) 110, 2430 (41.6%) for DE 150, and 42.6% (N = 2458) for warfarin. Hospitalization was associated with post-discharge death [absolute event rate 9.1% vs. 2.2%; adjusted hazard ratio (HR) 3.6, 95% confidence interval (CI) 3.2–4.0, P < 0.0001], vascular death (adjusted HR 2.9, 95% CI 2.5–3.3, P < 0.0001), and sudden cardiac death (adjusted HR 2.3; 95% CI 1.8–2.9, P < 0.0001). Cardiovascular hospitalization was also associated with an increased risk of post-discharge death (adjusted HR 2.8, 95% CI 2.5–3.2, P < 0.0001), vascular death (adjusted HR 2.8, 95% CI 2.4–3.2, P < 0.0001), and sudden cardiac death (adjusted HR 2.1, 95% CI 1.6–2.7, P < 0.0001) compared with patients not hospitalized for any cardiovascular reason.

Conclusion
Hospitalizations are associated an increased risk of with death and cardiovascular death in patients with atrial fibrillation.
Status quo bias and health behavior: findings from a cross-sectional study
Authors: Karl Florian M , Holle Rolf , Schwettmann Lars , Peters Annette , Laxy Michael 
Published: February 2019

Abstract

Background
Status quo bias (SQB) has often been referred to as an important tool for improving public health. However, very few studies were able to link SQB with health behavior.

Methods
Analysis were based on data from the population-based KORA S4 study (1999–2001, n = 2309). We operationalized SQB through two questions. The first asked whether participants switched their health insurance for financial benefits since this was enabled in 1996. Those who did were assigned a ‘very low SQB’ (n = 213). Participants who did not switch were asked a second hypothetical question regarding switching costs. We assigned ‘low SQB’ to those who indicated low switching costs (n = 1035), ‘high SQB’ to those who indicated high switching costs (n = 588), and ‘very high SQB’ to those who indicated infinite switching costs (n = 473). We tested the association between SQB and physical activity, diet, smoking, alcohol consumption, the sum of health behaviors, and body mass index (BMI) using logistic, Poisson and ordinary least square regression models, respectively. Models were adjusted for age, sex, education, income, satisfaction with current health insurance and morbidity.

Results
SQB was associated with a higher rate of physical inactivity [OR = 1.22, 95% CI (1.11; 1.35)], a higher sum of unhealthy lifestyle factors [IRR = 1.05, 95% CI (1.01; 1.10)] and a higher BMI [β = 0.30, 95% CI (0.08; 0.51)].

Conclusion
A high SQB was associated with unfavorable health behavior and higher BMI. Targeting SQB might be a promising strategy for promoting healthy behavior.
The influence of patient case mix on public health area statistics for cancer stage at diagnosis: a cross-sectional study
Authors: Barclay Matthew E , Abel Gary A , Elliss-Brookes Lucy , Greenberg David C , Lyratzopoulos Georgios 
Published: February 2019

Abstract

Background
Summary statistics comparing the stage at diagnosis of geographically defined populations of cancer patients are increasingly used in public reporting to monitor geographical inequalities but may be confounded by patient case mix. We explore the impact of case-mix adjustment on a publicly reported measure of early stage at diagnosis in England.

Methods
We analyzed data used for publicly reported statistics about the stage of patients diagnosed with 1 of 11 solid tumours in 2015 in England, including information on cancer site (bladder, breast, colon, rectum, kidney, lung, melanoma, non-Hodgkin lymphoma, ovarian, prostate, endometrial), age, gender, income deprivation and population-based commissioning organization. We investigated how cancer site and other patient characteristics influence organizational comparisons and attainment of early-stage targets (≥60% of all cases diagnosed in TNM stages I–II).

Results
Adjusting for patient case mix reduced between-organization variance by more than 50%, resulting in appreciable discordance in organizational ranks (Kendall’s tau = 0.53), with 18% (37/207) of organizations being reclassified as meeting/failing the early-stage target due to case mix.

Conclusion
Summary statistics on stage of cancer diagnosis for geographical populations currently used as public health surveillance tools to monitor organizational inequalities need to account for patient sociodemographic characteristics and cancer site case mix.
Trends in disease mortality before and during the Great Recession in individuals employed in Spain in 2001
Authors: Regidor Enrique , Ronda Elena , Tapia Granados José A , Viciana-Fernández Francisco J , de la Fuente Luis , Barrio Gregorio 
Published: February 2019

Abstract

Background
Previous studies on economic recessions and mortality due to cancer and other chronic diseases have yielded inconsistent findings. We investigated the trend in all-disease mortality and mortality due to several specific diseases before and during the Great Recession of 2008 in individuals who were employed in 2001, at the beginning of follow-up.

Methods
We follow in a nationwide longitudinal study over 15 million subjects who had a job in Spain in 2001. The analysed outcomes were mortality at ages 25–64 years due to all diseases, cancer and other chronic diseases. We calculated annual mortality rates from 2003 to 2011, and the annual percentage change (APC) in mortality rates during 2003–07 and 2008–11, as well as the effect size, measured by the APC difference between the two periods.

Results
All-disease mortality increased from 2003 to 2007 in both men and women; then, between 2008 and 2011, all-disease mortality decreased in men and reached a plateau in women. In men, the APC in the all-disease mortality rate was 1.6 in 2003–07 and −1.4 in 2008–11 [effect size −3.0, 95% confidence interval (CI) −3.7 to −2.2]; in women it was 2.5 and −0.3 (effect size −2.8, 95% CI −4.2 to −1.3), respectively. Cancer mortality and mortality due to other chronic diseases revealed similar trends.

Conclusions
In the group of individuals with a job in 2001 the Great Recession reversed or stabilized the upward trend in all-disease mortality.
Exposure to second-hand smoke in the context of tobacco policy changes in Estonia, 1996–2016
Authors: Reile Rainer , Pärna Kersti 
Published: February 2019

Abstract

Background
Exposure to second-hand smoke (SHS) is a preventable cause of disease and disability that can effectively be tackled by tobacco legislation. The aim of the study was to analyse the trends of SHS exposure and its sociodemographic patterning during 1996–2016 in the context of tobacco policy changes in Estonia.

Methods
Nationally representative data from biennial health surveys in 1996–2016 (n = 14 629) were used to present prevalence ratios for SHS exposure among non-smokers in Estonia. Joinpoint regression and multivariable logistic regression were used to study the sociodemographic and socio-economic differences in SHS exposure and its changes during the period.

Results
Exposure to SHS among non-smoking men and women has declined 3.6 and 5 times, respectively, during 1996–2016. While the rate of change was constant among men throughout the period, the decline in SHS exposure among women became significantly faster after 2006 compared with the previous period. However, 15.6% [95% confidence interval (CI) 13.1–18.3%] of men and 8.8% (95% CI 7.1–10.6%) of women were still exposed to SHS in 2016 with higher odds found for younger age groups, non-Estonians and those with lower education and income.

Conclusions
The consistently declining prevalence of SHS exposure among non-smoking population can be at least partially attributed to implementation of tobacco legislations in 2000s. However, the existing sociodemographic and socio-economic differences in SHS exposure require further attention as those in more vulnerable positions are also more exposed to SHS-related health harms.
Parent hazardous drinking and their children’s alcohol use in early and mid-adolescence: prospective cohort study
Authors: Sharmin Sonia , Kypri Kypros , Wadolowski Monika , Bruno Raimondo , Khanam Masuma , Aiken Alexandra , Hutchinson Delyse , Najman Jackob M , Slade Tim , McBride Nyanda , Attia John , Palazzi Kerrin , Oldmeadow Christopher , Mattick Richard P 
Published: February 2019

Abstract

Background
Why adolescents’ drinking is associated with their parents’ drinking remains unclear. We examined associations in a prospective cohort study, adjusting for socio-demographic characteristics and family factors.

Methods
We recruited 1927 children from grade 7 classes (mean age 13 years), and one of their parents, in three Australian states, contacted participants annually from 2010 to 2014, and analysed data from assessments at ages 13, 14, 15 and 16 years. We used the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) subscale to identify hazardous drinking in parents (score ≥5) and children (score ≥3) and constructed mixed-effect logistic regression models, accounting for clustering within school and adjusting for likely confounders. We evaluated the sensitivity of estimates by imputing missing values assuming the data were missing at random vs. missing not at random.

Results
Parent hazardous drinking predicted mid-adolescent hazardous drinking, e.g. 15 years olds whose parents [adjusted odds ratio (aOR) 2.00; 95% confidence interval 1.51–2.64] or parents’ partners (aOR 1.94; 1.48–2.55) were hazardous drinkers had higher odds of being hazardous drinkers at age 16. The magnitude of univariate associations changed little after adjusting for covariates, and sensitivity analyses confirmed the robustness of the association, across a wide range of assumptions about the missing data.

Conclusions
The associations between parents’ and their adolescent children’s hazardous drinking are unlikely to be due to confounding by socio-demographic and family factors. Parents should be encouraged, and supported by public policy, to reduce their own alcohol consumption in order to reduce their children’s risk of becoming hazardous drinkers.