bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Arctic geopotential stress field and implications for geodynamic evolution
Authors: Schiffer Christian , Tegner Christian , Schaeffer Andrew J. , Pease Victoria , Nielsen Søren B. 
Published: April 2017

Abstract
We use new models of crustal structure and the depth of the lithosphere–asthenosphere boundary to calculate the geopotential energy and its corresponding geopotential stress field for the High Arctic. Palaeostress indicators such as dykes and rifts of known age are used to compare the present day and palaeostress fields. When both stress fields coincide, a minimum age for the configuration of the lithospheric stress field may be defined. We identify three regions in which this is observed. In north Greenland and the eastern Amerasia Basin, the stress field is probably the same as that present during the Late Cretaceous. In western Siberia, the stress field is similar to that in the Triassic. The stress directions on the eastern Russian Arctic Shelf and the Amerasia Basin are similar to that in the Cretaceous. The persistent misfit of the present stress field and Early Cretaceous dyke swarms associated with the High Arctic Large Igneous Province indicates a short-lived transient change in the stress field at the time of dyke emplacement. Most Early Cretaceous rifts in the Amerasia Basin coincide with the stress field, suggesting that dyking and rifting were unrelated. We present new evidence for dykes and a graben structure of Early Cretaceous age on Bennett Island.
Effect of exercise timing on elevated postprandial glucose levels
Authors: Hatamoto Yoichi , Goya Ryoma , Yamada Yosuke , Yoshimura Eichi , Nishimura Sena , Higaki Yasuki , Tanaka Hiroaki 
Published: April 2017

There is no consensus regarding optimal exercise timing for reducing postprandial glucose (PPG). The purpose of the present study was to determine the most effective exercise timing. Eleven participants completed four different exercise patterns 1) no exercise; 2) preprandial exercise (jogging); 3) postprandial exercise; and 4) brief periodic exercise intervention (three sets of 1-min jogging + 30 s of rest, every 30 min, 20 times total) in a random order separated by a minimum of 5 days. Preprandial and postprandial exercise consisted of 20 sets of intermittent exercise (1 min of jogging + 30 s rest per set) repeated 3 times per day. Total daily exercise volume was identical for all three exercise patterns. Exercise intensities were 62.4 ± 12.9% V̇o2peak. Blood glucose concentrations were measured continuously throughout each trial for 24 h. After breakfast, peak blood glucose concentrations were lower with brief periodic exercise (99 ± 6 mg/dl) than those with preprandial and postprandial exercise (109 ± 10 and 115 ± 14 mg/dl, respectively, P < 0.05, effect size = 0.517). After lunch, peak glucose concentrations were lower with brief periodic exercise than those with postprandial exercise (97 ± 5 and 108 ± 8 mg/dl, P < 0.05, effect size = 0.484). After dinner, peak glucose concentrations did not significantly differ among exercise patterns. Areas under the curve over 24 h and 2 h postprandially did not differ among exercise patterns. These findings suggest that brief periodic exercise may be more effective than preprandial and postprandial exercise at attenuating PPG in young active individuals. NEW & NOTEWORTHY This was the first study to investigate the effect of different exercise timing (brief periodic vs. preprandial vs. postprandial exercise) on postprandial glucose (PPG) attenuation in active healthy men. We demonstrated that brief periodic exercise attenuated peak PPG levels more than preprandial and postprandial exercise, particularly in the morning. Additionally, PPG rebounded soon after discontinuing postprandial exercise. Thus, brief periodic exercise may be better than preprandial and postprandial exercise at attenuating PPG levels.
Combined effect of Bacillus coagulans GBI-30, 6086 and HMB supplementation on muscle integrity and cytokine response during intense military training
Authors: Gepner Yftach , Hoffman Jay R. , Shemesh Elad , Stout Jeffrey R. , Church David D. , Varanoske Alyssa N. , Zelicha Hila , Shelef Ilan , Chen Yacov , Frankel Hagai , Ostfeld Ishay 
Published: April 2017

The purpose of this study was to compare the coadministration of the probiotic Bacillus coagulans GBI-30, 6086 (BC30) with β-hydroxy-β-methylbutyrate (HMB) calcium (CaHMB) to CaHMB alone on inflammatory response and muscle integrity during 40 days of intense military training. Soldiers were randomly assigned to one of two groups: CaHMB with BC30 (CaHMBBC30; n = 9) or CaHMB with placebo (CaHMBPL, n = 9). A third group of participants served as a control (CTL; n = 8). During the first 28 days soldiers were garrisoned on base and participated in the same training tasks. During the final 2 wk soldiers navigated 25–30 km per night in difficult terrain carrying ~35 kg of equipment. All assessments (blood draws and diffusion tensor imaging to assess muscle integrity) were conducted before and ~12 h after final supplement consumption. Analysis of covariance was used to analyze all blood and muscle measures. Significant attenuations were noted in IL-1β, IL-2, IL-6, CX3CL1, and TNF-α for both CaHMBBC30 and CaHMBPL compared with CTL. Plasma IL-10 concentrations were significantly attenuated for CaHMBBC30 compared with CTL only. A significant decrease in apparent diffusion coefficients was also observed for CaHMBBC30 compared with CaHMBPL. Results provide further evidence that HMB supplementation may attenuate the inflammatory response to intense training and that the combination of the probiotic BC30 with CaHMB may be more beneficial than CaHMB alone in maintaining muscle integrity during intense military training. NEW & NOTEWORTHY β-Hydroxy-β-methylbutyrate (HMB) in its free acid form was reported to attenuate inflammation and maintain muscle integrity during military training. However, this formulation was difficult to maintain in the field. In this investigation, soldiers ingested HMB calcium (CaHMB) with Bacillus coagulans (BC30) or CaHMB alone during 40 days of training. Results indicated that CaHMB attenuated the inflammatory response and that BC30 combined with CaHMB may be more beneficial than CaHMB alone in maintaining muscle integrity during intense military training.
“Obesity-Associated” Breast Cancer in Lean Women: Metabolism and Inflammation as Critical Modifiers of Risk
Authors: Denis Gerald V. , Palmer Julie R. 
Published: April 2017

Abstract
Why is obesity only weakly associated with certain “obesity-driven” cancers? Recent population studies identify cohorts of high body mass index (BMI) subjects with unexpectedly reduced risk for breast and colon cancer, and normal BMI subjects with unexpectedly elevated risk for breast cancer, provoking hard thinking about cellular and molecular mechanisms that most strongly couple obesity to cancer occurrence or progression. Emerging work suggests that abnormal metabolism and its associated chronic inflammation make the difference. Type II diabetes, for example, is a chronic inflammatory disease with specific imbalances in T-cell and myeloid-origin cytokines. Inflammation is elevated systemically, measured through blood biomarkers, and locally in adipose tissue. Here, cytokines and chemokines likely modify tumor microenvironments in dangerous ways. High BMI subjects with low inflammation and less disturbed metabolism appear to have reduced risk for certain obesity-associated cancers, whereas lean or slightly overweight subjects with high inflammation and metabolic abnormalities have elevated risk. This latter phenotype is prevalent among South Asian adults and suggests we are not monitoring certain normal weight adults sufficiently for risks of “obesity-associated” cancers. Profiling of patient metabolism and inflammation should accompany measures of body composition when considering cancer risk; the evidence base for these refinements must be extended through new, prospective observational studies. Cancer Prev Res; 10(5); 267–9. ©2017 AACR.
See related article by Iyengar et al., Cancer Prev Res 2017;10(4):235–43.
Glucagon-like peptide 1-related peptides increase nitric oxide effects to reduce platelet activation
Authors: Barale Cristina , Buracco Simona , Cavalot Franco , Frascaroli Chiara , Guerrasio Angelo , Russo Isabella 
Published: April 2017

SummaryGlucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only its metabolic effects but also the protective vascular actions. Since platelets exert a primary role in the pathogenesis of atherosclerosis, inflammation and vascular complications, we investigated whether GLP-1 directly influences platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute incubation with the native form GLP-1(7–36), the N-terminally truncated form GLP-1(9–36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation induced by collagen or arachidonic acid (AA); ii) platelet function under shear stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)-induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv) activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress. Experiments were repeated in the presence of the nitric oxide donor Na–nitroprusside. We found that platelets constitutively express GLP-1R and that, independently of GLP-1R, GLP-1(7–36), GLP-1(9–36) and Liraglutide exert platelet inhibitory effects as shown by: a) increased NO-antiaggregating effects, b) increased the activation of the cGMP/PKG/VASP pathway, c) reduced the activation of PI3-K/Akt and MAPK/ERK-2 pathways, d) reduced the AA-induced oxidative stress. When the experiments were repeated in the presence of the antagonist of GLP-1R Exendin(9–39), the platelet inhibitory effects were maintained, thus indicating a mechanism independent of GLP-1R. In conclusion, GLP-1(7–36), its degradation product GLP-1(9–36) and Liraglutide exert similar inhibitory effects on platelet activation, suggesting a potential protective effect on the cardiovascular system.
Leukocyte Overexpression of Intracellular NAMPT Attenuates Atherosclerosis by Regulating PPARγ-Dependent Monocyte Differentiation and Function
Authors: Bermudez Beatriz , Dahl Tuva Borresdatter , Medina Indira , Groeneweg Mathijs , Holm Sverre , Montserrat-de la Paz Sergio , Rousch Mat , Otten Jeroen , Herias Veronica , Varela Lourdes M. , Ranheim Trine , Yndestad Arne , Ortega-Gomez Almudena , Abia Rocio , Nagy Laszlo , Aukrust Pal , Muriana Francisco J.G. , Halvorsen Bente , Biessen Erik Anna Leonardus 
Published: April 2017

Objective—

Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) mediates inflammatory and potentially proatherogenic effects, whereas the role of intracellular NAMPT (iNAMPT), the rate limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD)
+
generation, in atherogenesis is largely unknown. Here we investigated the effects of iNAMPT overexpression in leukocytes on inflammation and atherosclerosis.

Approach and Results—

Low-density lipoprotein receptor–deficient mice with hematopoietic overexpression of human iNAMPT (iNAMPT
hi
), on a western type diet, showed attenuated plaque burden with features of lesion stabilization. This anti-atherogenic effect was caused by improved resistance of macrophages to apoptosis by attenuated chemokine (C–C motif) receptor 2-dependent monocyte chemotaxis and by skewing macrophage polarization toward an anti-inflammatory M2 phenotype. The iNAMPT
hi
phenotype was almost fully reversed by treatment with the NAMPT inhibitor FK866, indicating that iNAMPT catalytic activity is instrumental in the atheroprotection. Importantly, iNAMPT overexpression did not induce any increase in eNAMPT, and eNAMPT had no effect on chemokine (C–C motif) receptor 2 expression and promoted an inflammatory M1 phenotype in macrophages. The iNAMPT-mediated effects at least partly involved sirtuin 1–dependent molecular crosstalk of NAMPT and peroxisome proliferator–activated receptor γ. Finally, iNAMPT and peroxisome proliferator–activated receptor γ showed a strong correlation in human atherosclerotic, but not healthy arteries, hinting to a relevance of iNAMPT/peroxisome proliferator–activated receptor γ pathway also in human carotid atherosclerosis.

Conclusions—
This study highlights the functional dichotomy of intracellular versus extracellular NAMPT, and unveils a critical role for the iNAMPT–peroxisome proliferator–activated receptor γ axis in atherosclerosis.
Association of Air Pollution Exposures With High-Density Lipoprotein Cholesterol and Particle Number
Authors: Bell Griffith , Mora Samia , Greenland Philip , Tsai Michael , Gill Ed , Kaufman Joel D. 
Published: April 2017

Objective—
The relationship between air pollution and cardiovascular disease may be explained by changes in high-density lipoprotein (HDL).

Approach and Results—

We examined the cross-sectional relationship between air pollution and both HDL cholesterol and HDL particle number in the MESA Air study (Multi-Ethnic Study of Atherosclerosis Air Pollution). Study participants were 6654 white, black, Hispanic, and Chinese men and women aged 45 to 84 years. We estimated individual residential ambient fine particulate pollution exposure (PM
2.5
) and black carbon concentrations using a fine-scale likelihood-based spatiotemporal model and cohort-specific monitoring. Exposure periods were averaged to 12 months, 3 months, and 2 weeks prior to examination. HDL cholesterol and HDL particle number were measured in the year 2000 using the cholesterol oxidase method and nuclear magnetic resonance spectroscopy, respectively. We used multivariable linear regression to examine the relationship between air pollution exposure and HDL measures. A 0.7×10
−
6
m
−
1
higher exposure to black carbon (a marker of traffic-related pollution) averaged over a 1-year period was significantly associated with a lower HDL cholesterol (−1.68 mg/dL; 95% confidence interval, −2.86 to −0.50) and approached significance with HDL particle number (−0.55 mg/dL; 95% confidence interval, −1.13 to 0.03). In the 3-month averaging time period, a 5 μg/m
3
higher PM
2.5
was associated with lower HDL particle number (−0.64 μmol/L; 95% confidence interval, −1.01 to −0.26), but not HDL cholesterol (−0.05 mg/dL; 95% confidence interval, −0.82 to 0.71).

Conclusions—
These data are consistent with the hypothesis that exposure to air pollution is adversely associated with measures of HDL.
External Arrhythmia Ablation Using Photon Beams
Authors: Lehmann H. Immo , Deisher Amanda J. , Takami Mitsuru , Kruse Jon J. , Song Limin , Anderson Sarah E. , Cusma Jack T. , Parker Kay D. , Johnson Susan B. , Asirvatham Samuel J. , Miller Robert C. , Herman Michael G. , Packer Douglas L. 
Published: April 2017

Background—
This study sought to investigate external photon beam radiation for catheter-free ablation of the atrioventricular junction in intact pigs.

Methods and Results—
Ten pigs were randomized to either sham irradiation or irradiation of the atrioventricular junction (55, 50, 40, and 25 Gy). Animals underwent baseline electrophysiological evaluation, cardiac gated multi-row computed tomographic imaging for beam delivery planning, and intensity-modulated radiation therapy. Doses to the coronary arteries were optimized. Invasive follow-up was conducted ≤4 months after the irradiation. A mean volume of 2.5±0.5 mL was irradiated with target dose. The mean follow-up length after irradiation was 124.8±30.8 days. Out of 7 irradiated animals, complete atrioventricular block was achieved in 6 animals of all 4 dose groups (86%). Using the same targeting margins, ablation lesion size notably increased with the delivered dose because of volumetric effects of isodose lines around the target volume. The mean macroscopically calculated atrial lesion volume for all 4 dose groups was 3.8±1.1 mL, lesions extended anteriorly into the interventricular septum. No short-term side effects were observed. No damage was observed in the tissues of the esophagus, phrenic nerves, or trachea. However, histology revealed in-field beam effects outside of the target volume.

Conclusions—
Single-fraction doses as low as 25 Gy caused a lesion with interruption of cardiac impulse propagation using this respective target volume. With doses of ≤55 Gy, maximal point-doses to coronary arteries could be kept <7Gy, but target conformity of lesions was not fully achieved using this approach.
Interpreting Incidentally Identified Variants in Genes Associated With Catecholaminergic Polymorphic Ventricular Tachycardia in a Large Cohort of Clinical Whole-Exome Genetic Test Referrals
Authors: Landstrom Andrew P. , Dailey-Schwartz Andrew L. , Rosenfeld Jill A. , Yang Yaping , McLean Margaret J. , Miyake Christina Y. , Valdes Santiago O. , Fan Yuxin , Allen Hugh D. , Penny Daniel J. , Kim Jeffrey J. 
Published: April 2017

Background—
The rapid expansion of genetic testing has led to increased utilization of clinical whole-exome sequencing (WES). Clinicians and genetic researchers are being faced with assessing risk of disease vulnerability from incidentally identified genetic variants which is typified by variants found in genes associated with sudden death-predisposing catecholaminergic polymorphic ventricular tachycardia (CPVT). We sought to determine whether incidentally identified variants in genes associated with CPVT from WES clinical testing represent disease-associated biomarkers.

Methods and Results—

CPVT-associated genes
RYR2
and
CASQ2
variants were identified in one of the world’s largest collections of clinical WES referral tests (N=6517, Baylor Miraca Genetics Laboratories) and compared with a control cohort of ostensibly healthy individuals (N=60 706) and a case cohort of CPVT cases (N=155). Within the WES cohort, the rate of rare variants in CPVT-associated genes was 8.8% compared with 6.0% among controls and 60.0% among cases. There was a predominance of variants of undetermined significance (97.7%). After protein topology mapping, WES variants colocalized more frequently to residues with variants found in controls compared with cases. Retrospective clinical evaluation of individuals referred to our institution with WES-positive variants demonstrated no evidence of clinical CPVT in individuals with a low pretest clinical suspicion for CPVT.

Conclusions—
The prevalence of incidentally identified CPVT-associated variants is ≈9% among WES tests. Variants of undetermined significances in CPVT-associated genes in WES genetic testing, in the absence of clinical suspicion for CPVT, are unlikely to represent markers of CPVT pathogenicity.
Admixture Mapping of Subclinical Atherosclerosis and Subsequent Clinical Events Among African Americans in 2 Large Cohort Studies
Authors: Shendre Aditi , Wiener Howard , Irvin Marguerite R. , Zhi Degui , Limdi Nita A. , Overton Edgar T. , Wassel Christina L. , Divers Jasmin , Rotter Jerome I. , Post Wendy S. , Shrestha Sadeep 
Published: April 2017

Background—
Local ancestry may contribute to the disproportionate burden of subclinical and clinical cardiovascular disease among admixed African Americans compared with other populations, suggesting a rationale for admixture mapping.

Methods and Results—

We estimated local European ancestry (LEA) using Local Ancestry inference in adMixed Populations using Linkage Disequilibrium method (LAMP-LD) and evaluated the association with common carotid artery intima–media thickness (cCIMT) using multivariable linear regression analysis among 1554 African Americans from MESA (Multi-Ethnic Study of Atherosclerosis). We conducted secondary analysis to examine the significant cCIMT–LEA associations with clinical cardiovascular disease events. We observed genome-wide significance in relation to cCIMT association with the
SERGEF
gene (secretion-regulating guanine nucleotide exchange factor; β=0.0137;
P
=2.98×10
−
4
), also associated with higher odds of stroke (odds ratio=1.71;
P
=0.02). Several regions, in particular
CADPS
gene (Ca
2+
-dependent secretion activator 1) region identified in MESA, were also replicated in the ARIC cohort (Atherosclerosis Risk in Communities). We observed other cCIMT–LEA regions associated with other clinical events, most notably the regions harboring
CKMT2
gene (creatine kinase, mitochondrial 2) and
RASGRF2
gene (Ras protein–specific guanine nucleotide–releasing factor 2) with all clinical events except stroke, the
LRRC3B
gene (leucine-rich repeat containing 3B) with myocardial infarction, the
PRMT3
gene (protein arginine methyltransferase 3) with stroke, and the
LHFPL2
gene (lipoma high mobility group protein I-C fusion partner-like 2) with hard and all coronary heart disease.

Conclusions—
We identified several novel LEA regions, in addition to previously identified genetic variations, associated with cCIMT and cardiovascular disease events among African Americans.
Adenosine Formed by CD73 on T Cells Inhibits Cardiac Inflammation and Fibrosis and Preserves Contractile Function in Transverse Aortic Constriction–Induced Heart Failure
Authors: Quast Christine , Alter Christina , Ding Zhaoping , Borg Nadine , Schrader Jürgen 
Published: April 2017

Background—

Structural damage during heart failure development leads to increased infiltration of leukocytes. Because purinergic signaling on immune cells may impact on the inflammatory response, we evaluated the role of ecto-5′-nucleotidase (CD73) on the development of heart failure after transverse aortic constriction (TAC) using global and T-cell–specific CD73
−
/−
mice.

Methods and Results—

Leukocytes infiltrating the failing heart were analyzed by a multistep enzymatic procedure over a period of 16 weeks using fluorescence-activated cell sorting. TAC significantly enhanced the infiltration of leukocytes, especially T cells. The fraction of CD73 expressing cells increased over time exclusively on cytotoxic T cells, T-helper cells, and regulatory T cells. Cardiac function significantly declined in T-cell–specific CD4-Cre
+/
−
CD73
flox/flox
mice identical to that observed in global CD73 mutants and was associated with enhanced fibrosis (collagen, laminin, vimentin, periostin). Expression analysis by quantitative reverse transcription polymerase chain reaction of extracellular purine degrading enzymes and P1 and P2 receptors on T cells isolated from the injured heart revealed profound upregulation of the enzymatic machinery for hydrolysis of extracellular adenosine triphosphate and nicotinamide adenine dinucleotide, both pathways converging in the formation of AMP and adenosine via CD73. Among the P1 receptors, only the A2a receptor was significantly upregulated after TAC. T cells isolated from TAC-treated hearts show enhanced production of proinflammatory cytokines (interleukin-3, interleukin-6, interleukin-13, interleukin-17, macrophage inflammatory proteins-1α, and macrophage inflammatory proteins-1β) when CD73 was lacking.

Conclusions—
Our data provide first evidence that CD73 on T cells plays an important anti-inflammatory role in TAC-induced heart failure, which is associated with antifibrotic activity and reduced production of proinflammatory cytokines most likely by activation of the adenosine A2a receptor.