bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicellular Transcriptional Analysis of Mammalian Heart Regeneration
Authors: Quaife-Ryan Gregory A. , Sim Choon Boon , Ziemann Mark , Kaspi Antony , Rafehi Haloom , Ramialison Mirana , El-Osta Assam , Hudson James E. , Porrello Enzo R. 
Published: July 2017

Background:
The inability of the adult mammalian heart to regenerate following injury represents a major barrier in cardiovascular medicine. In contrast, the neonatal mammalian heart retains a transient capacity for regeneration, which is lost shortly after birth. Defining the molecular mechanisms that govern regenerative capacity in the neonatal period remains a central goal in cardiac biology. Here, we assemble a transcriptomic framework of multiple cardiac cell populations during postnatal development and following injury, which enables comparative analyses of the regenerative (neonatal) versus nonregenerative (adult) state for the first time.

Methods:
Cardiomyocytes, fibroblasts, leukocytes, and endothelial cells from infarcted and noninfarcted neonatal (P1) and adult (P56) mouse hearts were isolated by enzymatic dissociation and fluorescence-activated cell sorting at day 3 following surgery. RNA sequencing was performed on these cell populations to generate the transcriptome of the major cardiac cell populations during cardiac development, repair, and regeneration. To complement our transcriptomic data, we also surveyed the epigenetic landscape of cardiomyocytes during postnatal maturation by performing deep sequencing of accessible chromatin regions by using the Assay for Transposase-Accessible Chromatin from purified mouse cardiomyocyte nuclei (P1, P14, and P56).

Results:
Profiling of cardiomyocyte and nonmyocyte transcriptional programs uncovered several injury-responsive genes across regenerative and nonregenerative time points. However, the majority of transcriptional changes in all cardiac cell types resulted from developmental maturation from neonatal stages to adulthood rather than activation of a distinct regeneration-specific gene program. Furthermore, adult leukocytes and fibroblasts were characterized by the expression of a proliferative gene expression network following infarction, which mirrored the neonatal state. In contrast, cardiomyocytes failed to reactivate the neonatal proliferative network following infarction, which was associated with loss of chromatin accessibility around cell cycle genes during postnatal maturation.

Conclusions:
This work provides a comprehensive framework and transcriptional resource of multiple cardiac cell populations during cardiac development, repair, and regeneration. Our findings define a regulatory program underpinning the neonatal regenerative state and identify alterations in the chromatin landscape that could limit reinduction of the regenerative program in adult cardiomyocytes.
Addition of 24‐Hour Heart Rate Variability Parameters to the Cardiovascular Health Study Stroke Risk Score and Prediction of Incident Stroke: The Cardiovascular Health Study
Authors: Bodapati Rohan K. , Kizer Jorge R. , Kop Willem J. , Kamel Hooman , Stein Phyllis K. 
Published: July 2017

Background

Heart rate variability (
HRV
) characterizes cardiac autonomic functioning. The association of
HRV
with stroke is uncertain. We examined whether 24‐hour
HRV
added predictive value to the Cardiovascular Health Study clinical stroke risk score (
CHS
‐
SCORE
), previously developed at the baseline examination.

Methods and Results

N=884 stroke‐free
CHS
participants (age 75.3±4.6), with 24‐hour Holters adequate for
HRV
analysis at the 1994–1995 examination, had 68 strokes over ≤8 year follow‐up (median 7.3 [interquartile range 7.1–7.6] years). The value of adding
HRV
to the
CHS
‐
SCORE
was assessed with stepwise Cox regression analysis. The
CHS
‐
SCORE
predicted incident stroke (
HR
=1.06 per unit increment,
P
=0.005). Two
HRV
parameters, decreased coefficient of variance of
NN
intervals (
CV
%,
P
=0.031) and decreased power law slope (
SLOPE
,
P
=0.033) also entered the model, but these did not significantly improve the c‐statistic (
P
=0.47). In a secondary analysis, dichotomization of
CV
% (
LOWCV
% ≤12.8%) was found to maximally stratify higher‐risk participants after adjustment for
CHS
‐
SCORE
. Similarly, dichotomizing
SLOPE
(
LOWSLOPE
<−1.4) maximally stratified higher‐risk participants. When these
HRV
categories were combined (eg,
HIGHCV
% with
HIGHSLOPE
), the c‐statistic for the model with the
CHS
‐
SCORE
and combined
HRV
categories was 0.68, significantly higher than 0.61 for the
CHS
‐
SCORE
alone (
P
=0.02).

Conclusions

In this sample of older adults, 2
HRV
parameters,
CV
% and power law slope, emerged as significantly associated with incident stroke when added to a validated clinical risk score. After each parameter was dichotomized based on its optimal cut point in this sample, their composite significantly improved prediction of incident stroke during ≤8‐year follow‐up. These findings will require validation in separate, larger cohorts.
Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low‐Density Lipoprotein Cholesterol
Authors: Lawler Patrick R. , Akinkuolie Akintunde O. , Chu Audrey Y. , Shah Svati H. , Kraus William E. , Craig Damian , Padmanabhan Latha , Glynn Robert J. , Ridker Paul M , Chasman Daniel I. , Mora Samia 
Published: July 2017

Background

Levels of LDL (low‐density lipoprotein) cholesterol in the population are declining, and increasing attention is being focused on residual lipid‐related pathways of atherosclerotic cardiovascular disease risk beyond
LDL
cholesterol. Among individuals with low (<130 mg/dL)
LDL
cholesterol, we undertook detailed profiling of circulating atherogenic lipoproteins in relation to incident cardiovascular disease in 2 populations.

Methods and Results

We performed proton nuclear magnetic resonance spectroscopy to quantify concentrations of
LDL
and VLDL (very low‐density lipoprotein) particle subclasses in 11 984
JUPITER
trial participants (
NCT
00239681). Adjusted Cox models examined cardiovascular disease risk associated with lipoprotein measures according to treatment allocation. Risk (adjusted hazard ratio [95%
CI
] per
SD
increment) among placebo‐allocated participants was associated with total
LDL
particles (1.19 [1.02, 1.38]) and total
VLDL
particles (1.21 [1.04, 1.41]), as well as apolipoprotein B, non–high‐density lipoprotein cholesterol, and triglycerides, but not LDL‐c. Rosuvastatin reduced
LDL
measures but had variable effects on triglyceride and
VLDL
measures. On‐statin levels of the smallest
VLDL
particle subclass were associated with a 68% per‐
SD
(adjusted hazard ratio 1.68 [1.28, 2.22]) increase in residual risk—this risk was related to
VLDL
cholesterol and not triglyceride or larger
VLDL
particles. There was evidence that residual risk prediction during statin therapy could be significantly improved through the inclusion of key
VLDL
measures (Harrell C‐index 0.780 versus 0.712;
P
<0.0001). In an independent, prospective cohort of 4721 individuals referred for cardiac catheterization (
CATHGEN
), similar patterns of lipoprotein‐related risk were observed.

Conclusions

Atherogenic lipoprotein particle concentrations were associated with cardiovascular disease risk when
LDL
cholesterol was low.
VLDL
lipoproteins, particularly the smallest remnant subclass, may represent unused targets for risk prediction and potential therapeutic intervention for reducing residual risk.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00239681.
Should Bilateral Internal Thoracic Artery Grafting Be Used in Patients After Recent Myocardial Infarction?
Authors: Loberman Dan , Pevni Dmitry , Mohr Rephael , Paz Yosef , Nesher Nahum , Midlij Mohamad Khaled , Ben‐Gal Yanai 
Published: July 2017

Background

Bilateral internal thoracic artery grafting (
BITA
) is associated with improved survival. However, surgeons do not commonly use
BITA
in patients after myocardial infarction (
MI
) because survival is good with single
internal thoracic artery grafting
(
SITA
). We aimed to compare the outcomes of
BITA
with those of
SITA
and other approaches in patients with multivessel disease after recent
MI
.

Methods and Results

In total, 938 patients with recent
MI
(<3 months) who underwent
BITA
between 1996 and 2011 were compared with 682 who underwent
SITA
.
SITA
patients were older and more likely to have comorbidities (diabetes mellitus, chronic obstructive pulmonary disease, chronic renal failure, peripheral vascular disease), to be female, and to have had a previous
MI
. Acute
MI
and 3‐vessel disease were more prevalent in the
BITA
group. Operative mortality of
BITA
patients was lower (3.0% versus 5.8%,
P
=0.01), and sternal infections and strokes were similar. Median follow‐up was 15.21 years (range: 0–21.25 years). Survival of
BITA
patients was better (70.3% versus 52.5%,
P
<0.001). Propensity score matching was used to account for differences in preoperative characteristics between groups. Overall, 551 matched pairs had similar preoperative characteristics.
BITA
was a predictor of better survival in the matched groups (hazard ratio: 0.679;
P
=0.002; Cox model). Adjusted survival of emergency
BITA
and
SITA
patients was similar (
hazard ratio:
0.883;
P
=0.447); however, in the nonemergency group,
BITA
was a predictor of better survival (hazard ratio: 0.790;
P
=0.009; Cox model).

Conclusions

This study suggests that survival is better with
BITA
compared with SITA in nonemergency cases after recent
MI,
with proper patient selection.
Intensive Exercise Training Improves Cardiac Electrical Stability in Myocardial‐Infarcted Rats
Authors: Dor‐Haim Horesh , Lotan Chaim , Horowitz Michal , Swissa Moshe 
Published: July 2017

Background
Moderate exercise training has been shown to decrease sudden cardiac death post myocardial infarction. However, the effects of intensive exercise are still controversial.

Methods and Results

Fourteen myocardial‐infarcted rats were divided into sedentary (n=8) and intensive training groups (n=6) and 18 sham control rats to sedentary (n=10) and intensive training groups (n=8). Heart rate variability was obtained at weeks 1 and 8. The inducibility of ventricular tachycardia/fibrillation was assessed in a Langendorff system. Fast Fourier transforms were applied on the recorded ventricular tachycardia/fibrillations. Training reduces low to high frequency ratio of heart rate variability at week 8 compared with that at week 1 (
P
<0.05). In isolated hearts, the probability for ventricular tachycardia/fibrillation was decreased from 4.5±0.8% in sedentary controls to 1.56±0.2% in intensive training controls (
P
<0.05) and from 13.5±2.1% in the sedentary group to 5.4±1.2% in the intensive training group (
P
<0.01). Moreover, the pacing current required for ventricular fibrillation induction in the trained groups was increased following exercise (
P
<0.05). Fast Fourier transform analysis of
ECG
findings revealed an exercise‐induced ventricular fibrillation transition from a narrow, single‐peak spectrum at 17 Hz in sedentary controls to a broader range of peaks ranging from 13 to 22 Hz in the intensive training controls.

Conclusions
Intensive exercise in infarcted rats leads to reduced ventricular fibrillation propensity and is associated with normalization of refractoriness and intrinsic spatiotemporal electrical variations.
Focal Cerebral Arteriopathy
Authors: Steinlin Maja , Bigi Sandra , Stojanovski Belinda , Gajera Jay , Regényi Maria , El-Koussy Marwan , Mackay Mark T. 
Published: July 2017

Background and Purpose—
Focal cerebral arteriopathy accounts for up to 35% of arterial ischemic stroke (AIS) in children and is the most important predictor of stroke recurrence. The study objective was to compare outcomes for children with focal cerebral arteriopathy treated with combined corticosteroid antithrombotic treatment (CAT) to those receiving antithrombotic treatment (AT) alone.

Methods—
This multicenter retrospective Swiss/Australian cohort study analyzed consecutive children, aged 1 month to 18 years, presenting with first AIS because of a focal cerebral arteriopathy from 2000 to 2014. Children with CAT were compared with those treated with AT. Primary outcome was the presence of neurological deficits at 6 months post–AIS as measured by the Pediatric Stroke Outcome Measure. Secondary outcomes included resolution of stenosis and stroke recurrence. Analysis of covariance was used to adjust for potential confounders (baseline pediatric National Institute of Health Stroke Scale and concomitant acyclovir use).

Results—

A total of 73 children (51% males) were identified, 21 (29%) of whom received CAT. Mean (SD) age at stroke for the entire group was 7.9 years (4.7). Median (interquartile range) pediatric National Institute of Health Stroke Scale was 3 (2.0–8.0) in the CAT group and 5 (3.0–9.0) in the AT group (
P
=0.098). Median (interquartile range) Pediatric Stroke Outcome Measure 6 months post-AIS was 0.5 (0–1.5) in the CAT group compared with 1.0 (0.5–2.0) in the AT group (
P
=0.035), the finding was sustained after adjusting for potential confounders. Complete resolution of stenosis at last MRI was noted in 17 (81%) in the CAT group compared with 24 (59%) in the AT group (
P
=0.197). Stroke recurrence occurred in 1 patient in each group.

Conclusions—
Corticosteroid treatment may provide additional benefit over AT for improved neurological outcome in childhood AIS because of focal cerebral arteriopathy. Larger prospective studies are warranted to further investigate these differences and understand mechanisms by which steroids modify outcome.
Risk Factors of Sudden Death From Subarachnoid Hemorrhage
Authors: Lindbohm Joni Valdemar , Kaprio Jaakko , Jousilahti Pekka , Salomaa Veikko , Korja Miikka 
Published: July 2017

Background and Purpose—
One in every 4 subarachnoid hemorrhage (SAH) patients dies suddenly outside hospital, but most SAH risk factor studies focus on hospitalized patients. We studied the differences in risk factors between hospitalized SAH and sudden-death SAH patients.

Methods—
The population-based FINRISK study cohort of 65 521 individuals was followed up for 1.52 million person-years. The Cox proportional hazards model calculated hazard ratios (HRs), with all analyses adjusted for known SAH risk factors, marital status, and socioeconomic status. A competing risks model analyzed differences in risk factors between hospitalized SAHs and sudden-death SAHs.

Results—

We identified 98 sudden-death SAHs and 445 hospitalized SAHs confirmed by autopsy or by standard SAH diagnostics. Increase by 5 cigarettes smoked per day elevated sudden-death SAH risk (HR, 1.28; 95% confidence interval [CI], 1.17–1.39) more than hospitalized SAH risk (HR, 1.19; 95% CI, 1.13–1.24;
P
=0.05 for difference). Per SD (21.4 mm Hg) increase, systolic blood pressure elevated risk of sudden-death SAH (HR, 1.34; 95% CI, 1.09–1.65) more than risk for hospitalized SAH (HR, 1.25; (95% CI, 1.12–1.38;
P
=0.05 for difference). Participants living without a partner were at elevated risk of sudden-death SAH (HR, 2.09; 95% CI, 1.33–3.28) but not of hospitalized SAH. No sudden-death SAHs occurred in normotensive never smokers aged <50 years.

Conclusions—
Sudden-death SAH risk seems to be highest among those individuals with the most adverse risk factor profiles and among those who live without a partner, whereas it is rare among normotensive never smokers aged <50 years.
Skeptical but Adapting: What Midwestern Farmers Say about Climate Change
Authors: Doll Julie E. , Petersen Brian , Bode Claire 
Published: July 2017

Abstract
Farmers stand to be greatly affected by changes in the climate, necessitating adaptive responses, yet little is documented on how U.S. Midwestern farmers understand and perceive climate change adaptation. Eight focus groups with 53 Michigan farmers were conducted in 2011–12 to better understand the following: 1) what do farmers think about the relationship between climate change and agriculture, 2) what differentiates normal weather-related management from climate change adaptation actions, and 3) how do farmers understand the term “climate change adaptation.” Farmers expressed skepticism at global climate change yet conveyed specific details about the local changes in climate they are experiencing on their farms. They were not able to clearly define the term “climate change adaptation” but did note specific adaptive actions they have already implemented. The farmers explained that nonclimate factors were of more concern to them when making management decisions, and they showed reactive (not proactive) actions toward adaptation. Farmers noted that any action they take has to address their specific situation, suggesting that generalized adaptation actions and language might not resonate with them. Building on quantitative surveys conducted by others, the findings in this paper contribute to ongoing efforts to more effectively assess farmers’ perceptions related to climate change adaptation and to use that understanding to promote education, outreach, research, and public policies to more proactively address the consequences posed by climate change.
A Storm in a Teacup? Hurricanes and Sugar Prices in the First Half of the Nineteenth Century
Authors: Bensassi Sami , Mohan Preeya , Strobl Eric 
Published: July 2017

Abstract
This paper investigates the impact of hurricanes in the Caribbean on sugar prices in Britain between 1815 and 1841. The authors expect the news of hurricanes arriving at British harbors to drive up sugar prices mainly because the market anticipated that the supply of sugar from the Caribbean colonies would drop dramatically in the near future. The econometric results suggest a significant rise in prices due to hurricanes. Moreover this study finds that the lag between the hurricane strike and its transmission into sugar prices on the London market decreased over the sample period. This latter result might be explained by the technological innovations marking this era, where technological progress in transport reduced the time required for information to cross the Atlantic, making markets more reactive to the news of supply shocks.
The Burden and Visit Prevalence of Pediatric Chronic Rhinosinusitis
Authors: Gilani Sapideh , Shin Jennifer J. 
Published: July 2017

ObjectivesPediatric chronic rhinosinusitis has a substantial impact, but its epidemiology has yet to be elucidated. Our objectives were (1) to determine the associated national visit burden and (2) to assess its frequency relative to other frequent childhood otolaryngological illnesses.Study DesignAnalysis of national survey databases.SettingAmbulatory care settings in the United States, 2005 to 2012.Subjects and MethodsCases with a diagnosis of chronic rhinosinusitis were assessed in total and as a proportion of all visits reported in National Ambulatory Medical Care Surveys. To place these data into context, results for acute rhinosinusitis, allergic rhinitis, upper respiratory tract infection, and otitis media were also extracted and compared. Data specific to individual age group and calendar year were assessed.ResultsChronic rhinosinusitis accounted for 5.6 million visits per annum (range, 3.7‐7.5 million) among patients 0 to 20 years of age. Children in the >5‐ to 10‐year‐old and >10‐ to 15‐year‐old age groups were more likely to be affected (P <. 001). Among all visits, chronic rhinosinusitis was diagnosed in 2.1% (95% confidence interval [CI], 1.9%‐2.4%), acute rhinosinusitis in 0.6% (95% CI, 0.5%‐0.7%), allergic rhinitis in 2.6% (95% CI, 2.3%‐2.8%), upper respiratory tract infection in 8.0% (95% CI, 7.5%‐8.4%), and otitis media in 6.7% (95% CI, 6.5%‐7.1%). Chronic rhinosinusitis visits were significantly more prevalent than for acute rhinosinusitis (relative risk, 3.40; 95% CI, 2.70‐4.10; P <. 0001). Among those >15 to 20 years of age, chronic rhinosinusitis was 2.18‐fold (95% CI, 1.65‐2.70) more frequently diagnosed than otitis media.ConclusionsThe visit burden from pediatric chronic rhinosinusitis exceeds that of acute rhinosinusitis and equals the burden from allergic rhinitis.
Optimized tPA: A non-neurotoxic fibrinolytic agent for the drainage of intracerebral hemorrhages
Authors: Goulay Romain , Naveau Mikaël , Gaberel Thomas , Vivien Denis , Parcq Jérôme 
Published: July 2017

Intracerebral hemorrhage (ICH) is the most severe form of stroke. Catheter-delivered thrombolysis with recombinant tissue-type plasminogen activator (rtPA) for the drainage of ICH is currently under evaluation in a phase III clinical trial (MISTIE III). However, in a pig model of ICH, in situ fibrinolysis with rtPA was reported to increase peri-lesional edema by promoting N-methyl-D-aspartate (NMDA)-dependent excitotoxicity. In the present study, we engineered a non-neurotoxic tPA variant, OptPA, and investigated its safety and efficacy for in situ fibrinolysis in a rat model of ICH. Magnetic resonance imaging analyses of hematoma and edema volumes, behavioral tasks and histological analyses were performed to measure the effects of treatments. In vitro, OptPA was equally fibrinolytic as rtPA without promoting NMDA-dependent neurotoxicity. In vivo, in situ fibrinolysis using OptPA reduced hematoma volume, like rtPA, but it also reduced the evolution of peri-hematomal neuronal death and subsequent edema progression. Overall, this preclinical study demonstrates beneficial effects of OptPA compared to rtPA for the drainage of ICH.
Leaching behaviour of municipal solid waste incineration bottom ash: From granular material to monolithic concrete
Authors: Sorlini Sabrina , Collivignarelli Maria Cristina , Abbà Alessandro 
Published: July 2017

The aim of this work was to assess the leaching behaviour of the bottom ash derived from municipal solid waste incineration (MSWI) used in concrete production. In particular, the release of pollutants was evaluated by the application of different leaching tests, both on granular materials and monolithic samples (concrete mixtures cast with bottom ash). The results confirmed that, according to Italian regulations, unwashed bottom ashes present critical issues for the use as alternative aggregates in the construction sector due to the excessive release of pollutants; instead, the leachate from washed bottom ashes was similar to natural aggregates. The concentration of pollutants in the leachate from concrete mixtures was lower than regulation limits for reuse. The crushing process significantly influenced the release of pollutants: this behaviour was due both to the increase in surface area and the release of contaminants from cement. Moreover, the increase in contact time (up to 64 days) involved more heavy metals to be released.