bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional adaptation of the human β‐cells after frequent exposure to noradrenaline
Authors: Dela Flemming 
Published: May 2015

Key points
Trained people produce less insulin than untrained; there is an adaptation of the insulin‐producing cells to the trained state.
The mechanism behind this adaptation is not known, but some sort of memory must be introduced into the insulin‐producing cells.
Here it is shown that this memory is introduced by 10 daily intravenous infusions of noradrenaline, mimicking the increases that occur during a 10 day training programme.
Thus, after the infusion period, the subjects produced less insulin in response to the same stimulus.
It is concluded that exercise‐induced increases in noradrenaline is most likely the stimulus that introduces a memory in the insulin‐producing cells.
AbstractPhysical training decreases glucose‐ and arginine‐stimulated insulin secretion. The mechanism by which the pancreatic β‐cells adapt to the training status of the individual is not known. We hypothesized that the adaptation is mediated via the frequent exercise‐induced increases in sympathetic activity. Simulation of exercise‐induced increases in plasma noradrenaline (NA) concentrations was carried out in nine untrained men (age: 25 ± 1 years (mean ± SEM); BMI: 24 ± 1 kg m−2), who received infusions of NA (0.2 μg kg−1 min−1) for 45 min every day for 10 days. The insulin response to glucose was measured during hyperglycaemic (20 mmol l−1) clampsbefore and after the NA infusion period. During NA infusions mean arterial blood pressure increased (from 89 ± 2 to 110 ± 5 mmHg, P < 0.05) and heart rate decreased (from 78 ± 7 to 69 ± 12 beats min−1, P < 0.05). During NA infusions plasma insulin concentrations decreased to nadir by 68% (P < 0.05). Fasting plasma glucose and insulin were not different at the two clamps (5.3 ± 0.1 and 5.3 ± 0.3 mmol l−1; 47 ± 15 and 31 ± 4 pmol l−1, respectively). Plasma glucose concentrations during the hyperglycaemic clamps were similar (P > 0.05) and averaged 19.9 ± 0.1 mmol l−1 with a coefficient of variation of 3.8 ± 0.3%, while the insulin response decreased (P < 0.05) by 26 ± 2% after the 10 days of NA infusions. It is concluded that NA mediates the adaptation of the β‐cells seen in trained people.
Multiplex single-cell profiling of chromatin accessibility by combinatorial cellular indexing
Authors: Cusanovich Darren A. , Daza Riza , Adey Andrew , Pliner Hannah A. , Christiansen Lena , Gunderson Kevin L. , Steemers Frank J. , Trapnell Cole , Shendure Jay 
Published: May 2015

Chromatin state and the single cellIdentifying the chromatin state of any single cell, which may or may not have a different function or represent different stages relative to others collected within any single culture, experiment, or tissue, has been challenging. Cusanovitchet al.skirted previously identified technological limitations to identify regions of accessible chromatin at single-cell resolution. Combinatorial cellular indexing, a strategy for multiplex barcoding of thousands of single cells per experiment, was successfully used to investigate the genome-wide chromatin accessibility landscape in each of over 15,000 single cells.Science, this issue p.910
Coach development programmes to improve interpersonal coach behaviours: a systematic review using the re-aim framework
Authors: Evans M Blair , McGuckin Matthew , Gainforth Heather L , Bruner Mark W , Côté Jean 
Published: May 2015

ObjectiveAlthough evidence supports the effectiveness of interpersonal Coach Development Programmes (CDPs), which are designed to foster coach–athlete relationships, an intervention's impact is shaped by numerous factors over and above effectiveness. The purpose of this systematic review was to examine the extent that published articles describing interpersonal CDP trials reported on indicators of internal and external validity, as conceptualised in the RE-AIM framework (ie, Reach, Effectiveness, Adoption, Implementation and Maintenance).MethodsThe search strategy was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, involving a database search and supplemental manual search of key articles and journals. After initial screening, the full-text search strategy involved identifying articles describing CDP trials and then selecting a specific subgroup of articles involving interpersonal CDP trials and excluding ineligible articles. Resulting trials were coded using a 47-item sport coaching adaptation of the RE-AIM coding sheet.Results17 published articles met eligibility criteria, representing 10 distinct CDP trials. After attaining coder agreement, global ratings of RE-AIM indicators within interpersonal CDP trials ranged from the low to moderate quality. Whereas indicators of effectiveness and implementation were reported to some extent across all studies, maintenance within sport organisations and a number of specific indicators from across dimensions were rarely reported.ConclusionsThese findings inform the future design and evaluation of CDPs that have the potential to be adopted in numerous settings and reach athletes and coaches who can most benefit.
Welfare generosity and population health among Canadian provinces: a time-series cross-sectional analysis, 1989–2009
Authors: Ng Edwin , Muntaner Carles 
Published: May 2015

BackgroundRecent work in comparative social epidemiology uses an expenditures approach to examine the link between welfare states and population health. More work is needed that examines the impact of disaggregated expenditures within nations. This study takes advantage of provincial differences within Canada to examine the effects of subnational expenditures and a provincial welfare generosity index on population health.MethodsTime-series cross-sectional data are retrieved from the Canadian Socio-Economic Information Management System II Tables for 1989–2009 (10 provinces and 21 years=210 cases). Expenditures are measured using 20 disaggregated indicators, total expenditures and a provincial welfare generosity index, a ombined measure of significant predictors. Health is measured as total, male and female age-standardised mortality rates per 1000 deaths. Estimation techniques include the Prais-Winsten regressions with panel-corrected SEs, a first-order autocorrelation correction model, and fixed-unit effects, adjusted for alternative factors.ResultsAnalyses reveal that four expenditures effectively reduce mortality rates: medical care, preventive care, other social services and postsecondary education. The provincial welfare generosity index has even larger effects. For an SD increase in the provincial welfare generosity index, total mortality rates are expected to decline by 0.44 SDs. Standardised effects are larger for women (β=−0.57, z(19)=−5.70, p<0.01) than for men (β=−0.38, z(19)=−5.59, p<0.01).ConclusionsFindings show that the expenditures approach can be effectively applied within the context of Canadian provinces, and that targeted spending on health, social services and education has salutary effects.
Hepatocellular Shuttling and Recirculation of Sorafenib-Glucuronide Is Dependent on Abcc2, Abcc3, and Oatp1a/1b
Authors: Vasilyeva Aksana , Durmus Selvi , Li Lie , Wagenaar Els , Hu Shuiying , Gibson Alice A. , Panetta John C. , Mani Sridhar , Sparreboom Alex , Baker Sharyn D. , Schinkel Alfred H. 
Published: May 2015

Abstract
Recently, an efficient liver detoxification process dubbed “hepatocyte hopping” was proposed on the basis of findings with the endogenous compound, bilirubin glucuronide. According to this model, hepatocytic bilirubin glucuronide can follow a liver-to-blood shuttling loop via Abcc3 transporter-mediated efflux and subsequent Oatp1a/1b-mediated liver uptake. We hypothesized that glucuronide conjugates of xenobiotics, such as the anticancer drug sorafenib, can also undergo hepatocyte hopping. Using transporter-deficient mouse models, we show here that sorafenib-glucuronide can be extruded from hepatocytes into the bile by Abcc2 or back into the systemic circulation by Abcc3, and that it can be taken up efficiently again into neighboring hepatocytes by Oatp1a/1b. We further demonstrate that sorafenib-glucuronide excreted into the gut lumen can be cleaved by microbial enzymes to sorafenib, which is then reabsorbed, supporting its persistence in the systemic circulation. Our results suggest broad relevance of a hepatocyte shuttling process known as “hepatocyte hopping”—a novel concept in clinical pharmacology—for detoxification of targeted cancer drugs that undergo hepatic glucuronidation, such as sorafenib. Cancer Res; 75(13); 2729–36. ©2015 AACR.
Cholesterol Levels in Blood and the Risk of Prostate Cancer: A Meta-analysis of 14 Prospective Studies
Authors: YuPeng Liu , YuXue Zhang , PengFei Li , Cheng Cheng , YaShuang Zhao , DaPeng Li , Chen Du 
Published: May 2015

Abstract
Background: As a neutral lipid and prominent component of the Western diet, cholesterol levels might be a risk factor for prostate cancer. However, current evidence has been inconsistent. This meta-analysis aimed to evaluate the association between blood cholesterol levels and the risk of prostate cancer.
Methods: An extensive search was performed in MEDLINE and EMBASE for prospective studies that have reported the association between total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) levels in blood and risk of prostate cancer. Random-effects models were used to summarize the study-specific results.
Results: Fourteen studies were included in this meta-analysis. In the meta-analysis, the summarized risk ratios (RR) for the highest to lowest cholesterol levels were as follows: 1.05 [95% confidence interval (CI), 0.97–1.14; P = 0.21] for TC, 0.93 (95% CI, 0.80–1.10; P = 0.40) for HDL, and 1.17 (95% CI, 0.88–1.55; P = 0.51) for LDL. When restricting to high-grade prostate cancer, the pooled RR was 1.32 (95% CI, 0.93–1.87; P = 0.13) for TC. In dose–response analyses, a 1 mmol/L increment in blood TC, HDL, and LDL level conferred an RR of 1.01 (95% CI, 0.99–1.02; P = 0.38), 0.98 (95% CI, 0.91–1.07; P = 0.72), and 1.04 (95% CI, 0.98–1.10; P = 0.24), respectively.
Conclusion: In this meta-analysis of 14 large prospective studies, blood TC, HDL, and LDL levels were not associated with the risk of either overall prostate cancer or high-grade prostate cancer.
Impact: Our findings did not appear to support the hypothesis that hypercholesterolemia increases the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev; 24(7); 1086–93. ©2015 AACR.
Heritability of Biomarkers of Oxidized Lipoproteins
Authors: Rao Fangwen , Schork Andrew J. , Maihofer Adam X. , Nievergelt Caroline M. , Marcovina Santica M. , Miller Elizabeth R. , Witztum Joseph L. , O’Connor Daniel T. , Tsimikas Sotirios 
Published: May 2015

Objective—
To determine whether biomarkers of oxidized lipoproteins are genetically determined. Lipoprotein(a) (Lp[a]) is a heritable risk factor and carrier of oxidized phospholipids (OxPL).

Approach and Results—

We measured oxidized phospholipids on apolipoprotein B–containing lipoproteins (OxPL-apoB), Lp(a), IgG, and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes in 386 monozygotic and dizygotic twins to estimate trait heritability (
h
2
) and determine specific genetic effects among traits. A genome-wide linkage study followed by genetic association was performed. The
h
2
(scale: 0–1) for Lp(a) was 0.91±0.01 and for OxPL-apoB 0.87±0.02, which were higher than physiological, inflammatory, or lipid traits.
h
2
of IgM malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes were 0.69±0.04, 0.67±0.05, and 0.80±0.03, respectively, and for IgG malondialdehyde-modified low-density lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes 0.62±0.05, 0.52±0.06, and 0.53±0.06, respectively. There was an inverse correlation between the major apo(a) isoform and OxPL-apoB (
R
=−0.49;
P
<0.001) and Lp(a) (
R
=−0.48;
P
<0.001) and OxPL-apoB was modestly correlated with Lp(a) (ρ=0.57;
P
<0.0001). The correlation in major apo(a) isoform size was concordant (
R
=1.0;
P
<0.001) among monozygotic twins but not dizygotic twins (
R
=0.40;
P
=0.055). Lp(a) and OxPL-apoB shared genetic codetermination (genetic covariance, ρG=0.774±0.032;
P
=1.09×10
−38
), although not environmental determination (environmental covariance, ρE=0.081±0.15;
P
=0.15). In contrast, Lp(a) shared environmental but not genetic codetermination with autoantibodies to malondialdehyde-modified low-density lipoprotein and copper oxidized low-density lipoprotein, and apoB-immune complexes. Sib-pair genetic linkage of the Lp(a) trait revealed that single nucleotide polymorphism rs10455872 was significantly associated with OxPL-apoB after adjusting for Lp(a).

Conclusions—
OxPL-apoB and other biomarkers of oxidized lipoproteins are highly heritable cardiovascular risk factors that suggest novel genetic origins of atherothrombosis.
Systolic Blood Pressure Response During Exercise Stress Testing: The Henry Ford ExercIse Testing (FIT) Project
Authors: O'Neal Wesley T. , Qureshi Waqas T. , Blaha Michael J. , Keteyian Steven J. , Brawner Clinton A. , Al‐Mallah Mouaz H. 
Published: May 2015

Background
The prognostic significance of modest elevations in exercise systolic blood pressure response has not been extensively examined.

Methods and Results
We examined the association between systolic blood pressure response and all‐cause death and incident myocardial infarction (MI) in 44 089 (mean age 53±13 years, 45% female, 26% black) patients who underwent exercise treadmill stress testing from the Henry Ford ExercIse Testing (FIT) Project (1991–2010). Exercise systolic blood pressure response was examined as a categorical variable (>20 mm Hg: referent; 1 to 20 mm Hg, and ≤0 mm Hg) and per 1 SD decrease. Cox regression was used to compute hazard ratios (HR) and 95% CI for the association between systolic blood pressure response and all‐cause death and incident MI. Over a median follow‐up of 10 years, a total of 4782 (11%) deaths occurred and over 5.2 years, a total of 1188 (2.7%) MIs occurred. In a Cox regression analysis adjusted for demographics, physical fitness, and cardiovascular risk factors, an increased risk of death was observed with decreasing systolic blood pressure response (>20 mm Hg: HR=1.0, referent; 1 to 20 mm Hg: HR=1.13, 95% CI=1.05, 1.22; ≤0 mm Hg: HR=1.21, 95% CI=1.09, 1.34). A trend for increased MI risk was observed (>20 mm Hg: HR=1.0, referent; 1 to 20 mm Hg: HR=1.09, 95% CI=0.93, 1.27; ≤0 mm Hg: HR=1.19, 95% CI=0.95, 1.50). Decreases in systolic blood pressure response per 1 SD were associated with an increased risk for all‐cause death (HR=1.08, 95% CI=1.05, 1.11) and incident MI (HR=1.09, 95% CI=1.03, 1.16).

Conclusions
Our results suggest that modest increases in exercise systolic blood pressure response are associated with adverse outcomes.
Relative Influence of Capillary Index Score, Revascularization, and Time on Stroke Outcomes From the Interventional Management of Stroke III Trial
Authors: Al-Ali Firas , Elias John J. , Tomsick Thomas A. , Liebeskind David S. , Broderick Joseph P. 
Published: May 2015

Background and Purpose—
Until recently, acute ischemic stroke (AIS) trials have failed to show a benefit of endovascular therapy compared with standard therapy, leading some authors to recommend decreasing the time from ictus to revascularization to improve outcomes. We hypothesize that improving patient selection using the capillary index score (CIS) may also be a useful strategy.

Methods—

CIS was calculated, blinded to outcome, from pretreatment diagnostic cerebral angiograms for 78 subjects in the Interventional Management of Stroke III database with internal carotid artery and middle cerebral artery trunk occlusion. The CIS was dichotomized into favorable (
f
CIS=2 or 3) and poor (
p
CIS=0 or 1). Outcomes were categorized based on the modified Rankin Scale score at 90 days (0–2 considered a good outcome). Modified thrombolysis in cerebral infarction score 2b or 3 was considered good revascularization. Multivariable logistic regression was performed to relate CIS, time from ictus to revascularization, modified thrombolysis in cerebral infarction score, and National Institue of Health Stroke Scale score to good outcomes.

Results—

Only CIS and modified thrombolysis in cerebral infarction scores were correlated with good outcomes (
P
<0.01). Patients with
f
CIS and good revascularization achieved 71% modified Rankin Scale ≤2, compared with 13% for patients with
p
CIS and good revascularization.

Conclusions—
In this subset of patients from the Interventional Management of Stroke III Trial, CIS and modified thrombolysis in cerebral infarction were strong predictors of outcome after endovascular reperfusion. Using the CIS to improve patient selection could be a powerful strategy to improve rate of good outcomes in endovascular therapy. A randomized trial is needed.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00359424.
Is Blood Pressure Control for Stroke Prevention the Correct Goal?
Authors: Howard George , Banach Maciej , Cushman Mary , Goff David C. , Howard Virginia J. , Lackland Daniel T. , McVay Jim , Meschia James F. , Muntner Paul , Oparil Suzanne , Rightmyer Melanie , Taylor Herman A. 
Published: May 2015

Background and Purpose—
Although pharmacological treatment of hypertension has important health benefits, it does not capture the benefit of maintenance of ideal health through the prevention or delay of hypertension.

Methods—
A total of 26 875 black and white participants aged 45+ years were assessed and followed for incident stroke events. The association was assessed between incident stroke and: (1) systolic blood pressure (SBP)categorized as normal (<120 mm Hg), prehypertension (120–139 mm Hg), stage 1 hypertension (140–159 mm Hg), and stage 2 hypertension (160 mm Hg+), and (2) number of classes of antihypertensive medications, classified as none, 1, 2, or 3 or more.

Results—
During 6.3 years of follow-up, 823 stroke events occurred. Nearly half (46%) of the population were successfully treated (SBP<140 mm Hg) hypertensives. Within blood pressure strata, the risk of stroke increased with each additional class of required antihypertensive medication, with hazard ratio [HR], 1.33; 95% confidence interval, 1.16 to 1.52 for normotensive, HR, 1.15; 95% confidence interval, 1.05 to 1.26 for prehypertension, and HR, 1.22; 95% confidence interval, 1.06 to 1.39 for stage 1 hypertension. A successfully treated (SBP<120 mm Hg) hypertensive person on 3+ antihypertensive medication classes was at marginally higher stroke risk than a person with untreated stage 1 hypertension (HR, 2.48 versus HR=2.19; relative to those with SBP <120 on no antihypertensive medications).

Conclusions—
Maintaining the normotensive status solely through pharmacological treatment has a profound impact, as nearly half of this general population cohort were treated to guideline (SBP<140 mm Hg) but failed to return to risk levels similar to normotensive individuals. Even with successful treatment, there is a substantial potential gain by prevention or delay of hypertension.
A Regression-Based Approach for Cool-Season Storm Surge Predictions along the New York–New Jersey Coast
Authors: Roberts Keith J. , Colle Brian A. , Georgas Nickitas , Munch Stephan B. 
Published: May 2015

AbstractA multilinear regression (MLR) approach is developed to predict 3-hourly storm surge during the cool-season months (1 October–31 March 31) between 1979 and 2012 using two different atmospheric reanalysis datasets and water-level observations at three stations along the New York–New Jersey coast (Atlantic City, New Jersey; the Battery in New York City; and Montauk Point, New York). The predictors of the MLR are specified to represent prolonged surface wind stress and a surface sea level pressure minimum for a boxed region near each station. The regression underpredicts relatively large (≥95th percentile) storm maximum surge heights by 6.0%–38.0%. A bias-correction technique reduces the average mean absolute error by 10%–15% at the various stations for storm maximum surge predictions. Using the same forecast surface winds and pressures from the North American Mesoscale (NAM) model between October and March 2010–14, raw and bias-corrected surge predictions at the Battery are compared with raw output from a numerical hydrodynamic model’s [the Stevens Institute of Technology New York Harbor Observing and Prediction System (SIT-NYHOPS)] predictions. The accuracy of surge predictions between the SIT-NYHOPS output and bias-corrected MLR model at the Battery are similar for predictions that meet or exceed the 95th percentile of storm maximum surge heights.
Sea Surface Temperature Predictions in NCEP CFSv2 Using a Simple Ocean Initialization Scheme
Authors: Zhu Jieshun , Kumar Arun , Wang Hui , Huang Bohua 
Published: May 2015

Abstract
In contrast to operational climate predictions based on sophisticated ocean data assimilation schemes at the National Centers for Environmental Predictions (NCEP), this study applied a simple ocean initialization scheme to the NCEP latest seasonal prediction model, the Climate Forecast System, version 2 (CFSv2). In the scheme, sea surface temperature (SST) was the only observed information applied to derive ocean initial states. The physical basis for the method is that, through air–sea coupling, SST is capable of reproducing some observed features of ocean evolutions by forcing the atmospheric winds. SST predictions based on the scheme are compared against hindcasts from the National (lately North American) Multimodel Ensemble (NMME) project.
It was found that due to substantial biases in the tropical eastern Pacific in the ocean initial conditions produced by SST assimilation, ENSO SST predictions were not as good as those with sophisticated initialization schemes (e.g., hindcasts in the NMME project). However, in other basins, SST predictions based on a simple ocean initialization procedure were not worse (sometimes even better) than those with sophisticated initialization schemes. These comparisons indicate that it was helpful that subsurface ocean information be assimilated to improve the tropical Pacific SST predictions, while SST-based ocean assimilation was an effective way to enhance SST prediction capability in other ocean basins. By examining multimodel ensembles with the simple scheme-based hindcasts either included or excluded in NMME, it is also suggested that including the hindcast would generally benefit multimodel ensemble forecasts. In addition, possible ways to further improve ENSO SST predictions with the simple initialization scheme are also discussed.