bluuebunny/crossref_metadata_2025_split huggingface dataset:
A hybrid model approach for estimating health burden from NO2 in megacities in China: a case study in Guangzhou
Authors: He Baihuiqian , Heal Mathew R , Humstad Kamilla H , Yan Liu , Zhang Qiang , Reis Stefan 
Published: October 2019

Abstract

Background: Nitrogen dioxide (NO2) poses substantial public health risks in large cities globally. Concentrations of NO2 shows high spatial variation, yet intra-urban measurements of NO2 in Chinese cities are sparse. The size of Chinese cities and shortage of some datasets is challenging for high spatial resolution modelling. The aim here was to combine advantages of dispersion and land-use regression (LUR) modelling to simulate population exposure to NO2 at high spatial resolution for health burden calculations, in the example megacity of Guangzhou. Methods: Ambient concentrations of NO2 simulated by the ADMS-Urban dispersion model at 83 ‘virtual’ monitoring sites, selected to span both the range of NO2 concentration and weighting by population density, were used to develop a LUR model of 2017 annual-mean NO2 across Guangzhou at 25 m × 25 m spatial resolution. Results: The LUR model was validated against both the 83 virtual sites (adj R
2: 0.96, RMSE: 5.48 μg m−3; LOOCV R
2: 0.96, RMSE: 5.64 μg m−3) and, independently, against available observations (n = 11, R
2:: 0.63, RMSE: 18.0 μg m−3). The modelled population-weighted long-term average concentration of NO2 across Guangzhou was 52.5 μg m−3, which contributes an estimated 7270 (6960−7620) attributable deaths. Reducing concentrations in exceedance of the China air quality standard/WHO air quality guideline of 40 μg m−3 would reduce NO2-attributable deaths by 1900 (1820–1980). Conclusions: We demonstrate a general hybrid modelling method that can be employed in other cities in China to model ambient NO2 concentration at high spatial resolution for health burden estimation and epidemiological study. By running the dispersion model with alternative mitigation policies, new LUR models can be constructed to quantify policy effectiveness on NO2 population health burden.
LRRK2 and GBA Variants Exert Distinct Influences on Parkinson’s Disease-Specific Metabolic Networks
Authors: Schindlbeck Katharina A , Vo An , Nguyen Nha , Tang Chris C , Niethammer Martin , Dhawan Vijay , Brandt Vicky , Saunders-Pullman Rachel , Bressman Susan B , Eidelberg David 
Published: October 2019

Abstract
The natural history of idiopathic Parkinson’s disease (PD) varies considerably across patients. While PD is generally sporadic, there are known genetic influences: the two most common, mutations in the LRRK2 or GBA1 gene, are associated with slower and more aggressive progression, respectively. Here, we applied graph theory to metabolic brain imaging to understand the effects of genotype on the organization of previously established PD-specific networks. We found that closely matched PD patient groups with the LRRK2-G2019S mutation (PD-LRRK2) or GBA1 variants (PD-GBA) expressed the same disease networks as sporadic disease (sPD), but PD-LRRK2 and PD-GBA patients exhibited abnormal increases in network connectivity that were not present in sPD. Using a community detection strategy, we found that the location and modular distribution of these connections differed strikingly across genotypes. In PD-LRRK2, connections were gained within the network core, with the formation of distinct functional pathways linking the cerebellum and putamen. In PD-GBA, by contrast, the majority of functional connections were formed outside the core, involving corticocortical pathways at the network periphery. Strategically localized connections within the core in PD-LRRK2 may maintain PD network activity at lower levels than in PD-GBA, resulting in a less aggressive clinical course.
Efficacy and Safety of a Single Dose of Ivermectin, Diethylcarbamazine, and Albendazole for Treatment of Lymphatic Filariasis in Côte d’Ivoire: An Open-label Randomized Controlled Trial
Authors: Bjerum Catherine M , Ouattara Allassane F , Aboulaye Méité , Kouadio Olivier , Marius Vanga K , Andersen Britt J , Weil Gary J , Koudou Benjamin G , King Christopher L 
Published: October 2019

Abstract

Background
Improved drug regimens are needed to accelerate elimination of lymphatic filariasis in Africa. This study determined whether a single co-administered dose of ivermectin plus diethylcarbamazine plus albendazole [IDA] is noninferior to standard 3 annual doses of ivermectin plus albendazole (IA) used in many LF-endemic areas of Africa.

Methods
Treatment-naive adults with Wuchereria bancrofti microfilaremia in Côte d’Ivoire were randomized to receive a single dose of IDA (n = 43) or 3 annual doses of IA (n = 52) in an open-label, single-blinded trial. The primary endpoint was the proportion of participants who were microfilaria (Mf) negative at 36 months. Secondary endpoints were Mf clearance at 6, 12, and 24 months; inactivation of adult worm nests; and safety.

Results
At 36 months posttreatment with IDA, 18/33 (55%; 95% CI, 38–72%) cleared Mf versus 33/42 (79%; 67–91%) with IA (P = .045). At 6 and 12 months IDA was superior to IA in clearing Mf (89% [77–99%] and 71% [56–85%]), respectively, versus 34% (20–48%) and 26% (14–42%) (P &lt; .001). IDA was equivalent to IA at 24 months (61% [45–77%] vs 54% [38–72%]; P = .53). IDA was superior to IA for inactivating adult worms at all time points. Both treatments were well tolerated, and there were no serious adverse events.

Conclusions
A single dose of IDA was superior to 2 doses of IA in reducing the overall Mf burden by 24 months. Reinfection may have contributed to the lack of sustained clearance of Mf with IDA.

Clinical Trials Registration
NCT02974049.
Diabetes mellitus: a single cardiorenal syndrome umbrella
Authors: Rodríguez Eva , Arias-Cabrales Carlos , Pascual Julio 
Published: October 2019

Abstract
Diabetes and chronic kidney disease are among the fastest-growing causes of death worldwide. An optimized conceptual framework on the pathogenesis of diabetic kidney disease and its interplay with cardiovascular disease will facilitate the development of monitoring and therapeutic strategies to decrease the risk for severe clinical events and early mortality. In this issue of ckj, Pinier et al. provide data supporting the existence in diabetic patients of a single cardiorenal syndrome umbrella, rather than separate cardiorenal or renocardiac entities (e.g. acute cardiorenal syndrome or chronic renocardiac syndromes).
‘For Time is / nothing if not amenable’ — exemplarity, time, reception
Authors: Güthenke Constanze 
Published: October 2019

AbstractThis article revisits exemplarity as a strategy of approaching, reading, and using the past. By going beyond treating it mostly as a historical phenomenon, in terms of its use as a purely pre-modern rhetorical trope connected to historical and ethical writings in the Greek and Roman world, I suggest that exemplarity has critical potential to make us reconsider its ability to break through temporalities in a calculated and sceptical way. As such, it offers a provocation to Reception Studies to engage with exemplarity both in and as a more deliberate and strategic manner.
3040Plaque burden, but not the severity of carotid stenosis, predicts adverse cardiovascular events in patients at high and very high cardiovascular risk
Authors: Genkel V , Salashenko A , Shaposhnik I 
Published: October 2019

Abstract

Introduction
According to the current guidelines the visualization of atherosclerotic plaques in the carotid arteries is the only option that carotid ultrasound provides for the assessment of cardiovascular risk (CVR). The direction devoted to the development and implementation of markers based on the quantification of atheroma, is promising.

Purpose
The aim of the study was to evaluate the prognostic value of various markers of carotid atherosclerosis (plaque, carotid total plaque area (cTPA) and carotid stenosis) in patients at high and very high CVR.

Methods
The study included patients aged 40–75 years at high and very high CVR. All patients underwent carotid duplex ultrasound. The presence of carotid plaque was assessed according to Mannheim consensus. The percentage of stenosis was measured planimetrically in the B-mode by the diameter in the cross section of the vessel.
cTPA was estimated in the longitudinal position, which allows to achieve the best visualization of plaque, the area of plaque was measured in the manual trace mode. These measurements were performed for each rendered plaque, followed by the calculation of the total value.
The combined endpoint was cardiovascular death, non-fatal myocardial infarction or unstable angina (which required hospitalization), non-fatal stroke, and coronary revascularization.

Results
The study included 100 patients at high and very high risk. The duration of the follow-up period was 24.4 (14.1–34.3) months. The events constituting the combined endpoint occurred in 34 (34%) patients: cardiovascular death was recorded in 7 (7%) patients; non-fatal myocardial infarction or stroke in 3 (3%) patients; unstable angina, which required hospitalization in 24 (24%) patients, while emergency coronary angiography was performed in 8 (8%) patients, coronary artery stenting was performed in 3 (3%) cases.
The presence of carotid plaque in accordance with Cox regression after adjusting for factors such as sex, age, smoking, hypertension, BMI, eGFR, LDL-c and HbA1c, RR of adverse cardiovascular events was 10.5 (95% CI 1.27–86.5; p=0.008; see Figure 1).
The optimal cut-off values of cTPA and carotid stenosis were determined by ROC-analysis.
An increase in cTPA ≥69 mm2 corrected for sex, age, smoking, hypertension, BMI, eGFR, LDL-c, HbA1c, and the presence of carotid plaque was associated with an increase in the RR of adverse cardiovascular events by 5.86 times (95% CI 2.09–16.4; p=0.001; see Figure 1).
Also, there were no statistically significant associations between carotid arteries stenosis and adverse cardiovascular events (RR 1.29; 95% CI 0.61–2.76; p=0.504).
Kaplan–Meier curves for cTPA, stenosis

Conclusion
In patients at high and very high cardiovascular risk among carotid ultrasound parameters the presence of carotid plaque and cTPA, but not the degree of stenosis, had an independent predictive value regarding the development of adverse cardiovascular events.
3043Endotrophin, a fragment of collagen type VI, is correlated to IMT and associated with cardiovascular events in patients with atherosclerosis and diabetes: the IMI-SUMMIT cohort
Authors: Holm Nielsen S , Goncalves I , Shore A , Natali A , Khan F , Genovese F , Karsdal M , Nilsson J 
Published: October 2019

Abstract

Background/Introduction
Patients with micro- and macrovascular diseases, including atherosclerosis, have increased risk of cardiovascular events and early mortality. The atherosclerotic disease is characterised by accumulation of lipids, cells and proteins in the arterial wall, which includes remodelling of the extracellular matrix (ECM). Collagen type VI (COL6) is known to be over-expressed in patients with atherosclerosis. The biomarker PRO-C6, known as endotrophin, is a COL6 fragment that reflects formation of collagen type VI, and possess pro-inflammatory and pro-fibrotic activities.

Purpose
We explored whether increased endotrophin levels, measured by PRO-C6, were associated with intima-media thickness (IMT) and mortality in the IMI-SUMMIT cohort.

Methods
Circulating protein levels of PRO-C6 were measured in EDTA plasma from 1500 patients enrolled at four European University Hospitals, using an enzyme-linked immunosorbent assay. Follow-up data were available up to three years after sample collection. Associations between PRO-C6 and incidence of cardiovascular (CV) events and all-cause mortality were assessed by Kaplan-Meier curves and Cox proportional hazard regression analyses. Pearson correlation was performed to explore the association of PRO-C6, IMT and clinical variables. Known confounders defined by the Framingham Heart study (age, gender and diabetes) were included in the Cox proportional hazard regression analysis.

Results
Plasma PRO-C6 was significantly correlated with IMT in both the common carotid artery and the carotid bulb (r=0.09, p=0.002 and r=0.11, p=0.0003, respectively), HbA1c (r=0.11, p<0.0001) and C-reactive protein (r=0.14, p<0.0001). A total of 145 patients suffered from fatal or non-fatal cardiovascular events during the three-year follow-up period. Patients in the highest PRO-C6 tertile had a two-fold increased risk of experiencing a CV event during follow-up (p=0.002), independently of age, presence of CVD at baseline, type 2 diabetes, smoking and statin treatment in a regression model.

Conclusion
The present findings demonstrate that circulating levels of PRO-C6 are associated with atherosclerosis severity and increased incidence of cardiovascular events. Since PRO-C6 detects the signaling molecule endotrophin, the results may indicate that endotrophin is not only a biomarker of atherosclerotic disease, but may have a role in promoting disease progression.

Acknowledgement/Funding
This work was supported by the Danish Research Foundation, The Danish innovation foundation and the IMI-SUMMIT participants
3053High mortality in atrial fibrillation patients suffering ischemic stroke, intracranial hemorrhage or a gastrointestinal bleed and associations with the preceding antithrombotic treatment
Authors: Komen J J , Forslund T , Mantel - Teeuwisse A K , Klungel O H , Wettermark B , Von Euler M , Braunschweig F , Wallen H , Hjemdahl P 
Published: October 2019

Abstract

Background
Anticoagulation treatment reduces the risk of stroke but increases the risk of bleeding in atrial fibrillation (AF) patients. There is little data on survival after a stroke or a severe bleed.

Objective
To analyze 90-day mortality in AF patients after an ischemic stroke, an intracranial hemorrhage (ICH) or a gastrointestinal bleed (GIB) and assess associations with the type of antithrombotic treatment preceding the event.

Methods
From the Stockholm Healthcare database (n=2.3 million inhabitants) we selected all AF patients suffering from an ischemic stroke, an intracranial bleed, or a severe GIB requiring acute hospital care between July 2011 and August 2018 and assessed 90-day mortality rates. We assessed current use of warfarin, non-vitamin K oral anticoagulants (NOAC), or antiplatelet agents at the time of the event. We used a Cox regression to calculate adjusted hazard ratios (aHRs), adjusting for components of the Charlson Comorbidity Index, the CHADsVASc score, the HAS-BLED score, comedication, and year of inclusion, for the association between treatment preceding the event and mortality. In addition, we performed log-rank tests in propensity score matched cohorts.

Results
Of 105 313 patients with AF, 6 017 were included after an ischemic stroke, 3 006 after an ICH, and 4 291 after a GIB. 90-day mortality rates were 25.1%, 31.6% and 16.2%, respectively. Patients suffering from an ischemic stroke were the oldest at 81.6±9.8 (S.D:) years of age followed by patients suffering from an ICH (80.2±9.8 years) or a GIB (78.7±10.5 years). A large proportion of patients suffering ischemic stroke (72%) had no anticoagulant treatment preceding the event. After ICH, there was a significantly increased risk of mortality in warfarin compared to NOAC treated patients after adjusting for confounders (aHR: 1.36 CI: 1.04–1.78). Patients receiving antiplatelets or no treatment had significantly higher mortality rates than patients on NOAC treatment, both after an ischemic stroke and a GIB, but there was no significant difference between warfarin and NOACs (aHR 0.84 CI: 0.63–1.12 after ischemic stroke, aHR 0.91 CI: 0.66–1.25 after GIB). Propensity score matched analyses yielded similar results.
Survival curves after event

Conclusion
Mortality rates are high in AF patients suffering from an ischemic stroke, an ICH, or a GIB. NOAC treatment was associated with a lower 90-day mortality after ICH than warfarin, but no such difference was found after ischemic stroke or GIB. After ischemic stroke and GIB, mortality rates were higher in antiplatelet treated and untreated patients compared to NOAC treated patients.

Acknowledgement/Funding
Swedish Heart Lung Foundation
3069Epigenetic changes in heart failure cohorts: novel insights into methylation changes of protein and RNA coding genes in human cardiac tissue
Authors: Glezeva N , Moran B , Collier P , Moravec C , Phelan D , Donnellan E , Russell-Hallinan A , O'connor D , Gallagher W , Gallagher J , McDonald K , Ledwidge M , Baugh J , Das S , Watson C 
Published: October 2019

Abstract

Background
Limited knowledge exists of the extent of epigenetic alterations, such as DNA methylation, in Heart Failure (HF). We conducted targeted DNA methylation sequencing to identify DNA methylation alterations in coding and non-coding RNA across different etiological sub-types of HF.

Methods and results
A targeted bisulfite sequence capture sequencing platform was applied to DNA extracted from cardiac interventricular septal tissue of 30 male HF patients encompassing etiologies including Hypertrophic Obstructive Cardiomyopathy (HOCM, n=12), Ischemic Cardiomyopathy (ISCM, n=9), Dilated Cardiomyopathy (DCM, n=9), and 9 control patients with non-failing hearts (NF). We detected 62,678 differentially methylated regions (DMR) in the studied HF cohort. By comparing each HF sub-group to the NF control group we identified 195 unique DMRs: 5 in HOCM, 151 in DCM, and 55 in ISCM. These translated to 4 genes/1 non-coding RNA (ncRNA) in HOCM, 131 genes/17 ncRNA in DCM, and 51 genes/5 ncRNA in ISCM. Subsequent gene/ncRNA expression analysis was assessed using qRT-PCR and revealed 6 genes: 4 hypermethylated (HEY2, MSR1, MYOM3, COX17), 2 hypomethylated (CTGF, MMP2); and 2 microRNA: 1 hypermethylated (miR-24–1), 1 hypomethylated (miR-155) with significantly up- or down-regulated expression levels consistent with the direction of methylation in the particular HF sub-group.

Conclusions
For the first time DNA methylation alterations and associated gene expression changes were identified in etiologically-variant pathological heart failure tissue. The methylation-sensitive and disease-associated genes/non-coding RNA identified from this study represent a unique cohort of loci that demonstrate a plausible potential as a novel diagnostic and/or therapeutic target in HF and warrant further investigation.

Acknowledgement/Funding
Enterprise Ireland; European Regional Development Fund under Ireland's European Structural and Investment Funds Programmes 2014-2020
3152Right ventricular function and long-term outcomes in cardiac resynchronization therapy patients enrolled in MADIT-CRT
Authors: Nagy V K , Merkely B , Geller L , Kosztin A , Solomon S , McNitt S , Goldenberg I , Kutyifa V 
Published: October 2019

Abstract

Background
Long-term predictive value of baseline right ventricular (RV) function and CRT-induced changes of RV function for the clinical outcomes, mortality or heart failure are not well understood, especially in mild HF patients implanted with CRT-D.

Methods
MADIT-CRT enrolled 1,820 patients at 110 centers worldwide, with either ischemic cardiomyopathy (New York Heart Association [NYHA] functional class I or II), or non-ischemic cardiomyopathy (NYHA functional class II only), sinus rhythm, ejection fraction of 30% or less, and a QRS duration of 130 ms or more. We assessed right ventricular function (RVF) as RV fractional area change by echocardiography at baseline and after 1 year of therapy in patients with LBBB assigned to CRT arm (n=633). Kaplan-Meier survival analyses and multivariate Cox models were utilized to identify RV parameters predicting long-term outcomes of HF or death events.

Results
During the median follow up of 5.6 years 192 (30.3%) patients had heart failure or death. CRT-D LBBB patients with below or above median RV end-systolic area (RVS) had lower cumulative probabilities of HF/death (p=0.02). Lower, than the median value of both RVS and RVF were associated with higher risk of HF events alone (p=0.004; p=0.01 respectively). In multivariate analysis, after adjustment of relevant clinical covariates more RV reverse remodeling in the terms of RV end-diastolic area (RVD) decrease proved to be an independent predictor for 5-year all-cause mortality (HR: 0.4; p=0.03).
Kaplan-Meier analysis of baseline RVF

Conclusions
Based on our results RV geometry and function before CRT implant and also significant RV reverse remodeling at 12 months follow up are significant predictors of long-term outcomes.
3260Prognostic value of cardiac power reserve in patients with normal left ventricular ejection fraction undergoing exercise stress echocardiography
Authors: Anand V , Kane G , Pislaru S , Adigun R , McCully R , Pellikka P , Pislaru C 
Published: October 2019

Abstract

Background
Cardiac power output-to-mass (CPOM) ratio is a measure of myocardial performance that incorporates both pressure and flow output, normalized to left ventricular (LV) mass generating that cardiac work. Prior small studies have shown that CPOM predicts outcomes in patients with ischemic cardiomyopathy and reduced LV ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise CPOM and power reserve (increase from rest to peak exercise) in patients with normal EF.

Methods and results
Retrospective study in 24,783 patients (age 59±13 years, 45% females) with EF≥50% and no significant valve disease or right ventricular (RV) dysfunction, undergoing exercise stress echocardiography between 2004–2018. CPOM was calculated as previously described (0.222 x cardiac output x mean blood pressure / LV mass) and expressed in Watts/100g myocardium. Power reserve was calculated as difference in CPOM between peak stress and rest. All-cause mortality was the primary endpoint. Patients were divided into quartiles of power reserve. Patients with higher power reserve were younger, had higher blood pressure and heart rate, lower LV mass, and lower prevalence of prior myocardial infarction. (Table). During follow-up (median (IQR) 3.9 (0.6–8.3) years), 931 (3.8%) patients died. Progressively lower power reserve was associated with increasing mortality (Figure A). Compared to patients with abnormal stress test, patients with the lowest power reserve but otherwise normal stress test had the same survival as those with infarction/cardiomyopathy or ischemia on stress test (Figure B). Resting CPOM had lower predictive value. After adjusting for age, sex, METs achieved, ischemia/infarction on stress test results, and diastolic function grade, both peak exercise CPOM and power reserve were independent predictors of mortality (p<0.0001), incremental to conventional measures.

Conclusion
Cardiac power output and reserve measured during exercise stress echo provides independent prognostic information in patients with normal resting EF and no significant valve disease or RV dysfunction. The survival of patients with low power reserve but normal stress test was similar to patients with prior infarction/ cardiomyopathy or ischemia on stress test.