bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compartmentalized Protective and Detrimental Effects of Endogenous Macrophage Migration-Inhibitory Factor Mediated by CXCR2 in a Mouse Model of Myocardial Ischemia/Reperfusion
Authors: Liehn Elisa A. , Kanzler Isabella , Konschalla Simone , Kroh Andreas , Simsekyilmaz Sakine , Sönmez Tolga Taha , Bucala Richard , Bernhagen Jürgen , Weber Christian 
Published: July 2013

Objective—
Here, we aimed to clarify the role of CXC chemokine receptor (CXCR) 2 in macrophage migration-inhibitory factor (MIF)–mediated effects after myocardial ischemia and reperfusion. As a pleiotropic chemokine-like cytokine, MIF has been identified to activate multiple receptors, including CD74 and CXCR2. In models of myocardial infarction, MIF exerts both proinflammatory effects and protective effects in cardiomyocytes. Similarly, CXCR2 displays opposing effects in resident versus circulating cells.

Approach and Results—

Using bone marrow transplantation, we generated chimeric mice with Cxcr2
−/−
bone marrow–derived inflammatory cells and wild-type (wt) resident cells (wt/Cxcr2
−/−
), Cxcr2
−/−
cardiomyocytes and wt bone marrow–derived cells (Cxcr2
−/−
/wt), and wt controls reconstituted with wt bone marrow (wt/wt). All groups were treated with anti-MIF or isotype control antibody before they underwent myocardial ischemia and reperfusion. Blocking MIF increased infarction size and impaired cardiac function in wt/wt and wt/CXCR2
−/−
mice but ameliorated functional parameters in Cxcr2
−/−
/wt mice, as analyzed by echocardiography and Langendorff perfusion. Neutrophil infiltration and angiogenesis were unaltered by MIF blockade or Cxcr2 deficiency. Monocyte infiltration was blunted in wt/Cxcr2
−/−
mice and reduced by MIF blockade in wt/wt and Cxcr2
−/−
/wt mice. Furthermore, MIF blockade attenuated collagen content in all groups in a CXCR2-independent manner.

Conclusions—
The compartmentalized and opposing effects of MIF after myocardial ischemia and reperfusion are largely mediated by CXCR2. Although MIF confers protective effects by improving myocardial healing and function through CXCR2 in resident cells, thereby complementing paracrine effects through CD74/AMP-activated protein kinase, it exerts detrimental effects on CXCR2-bearing inflammatory cells by increasing monocyte infiltration and impairing heart function. These dichotomous findings should be considered when developing novel therapeutic strategies to treat myocardial infarction.
NOD2-Mediated Innate Immune Signaling Regulates the Eicosanoids in Atherosclerosis
Authors: Liu Hui-Qing , Zhang Xiao-Ying , Edfeldt Kristina , Nijhuis Manon Oude , Idborg Helena , Bäck Magnus , Roy Joy , Hedin Ulf , Jakobsson Per-Johan , Laman Jon D. , de Kleijn Dominique P. , Pasterkamp Gerard , Hansson Göran K. , Yan Zhong-Qun 
Published: July 2013

Objective—
The activity of eicosanoid pathways is critical to the inflammatory and immune responses that are associated with the progression of atherosclerosis. Yet, the signals that regulate these pathways are poorly understood. Here, we address whether the innate immune signals of nucleotide-binding oligomerization domain–containing protein (NOD) 2 affect eicosanoids metabolism in atherosclerosis.

Approach and Results—

Analysis of human carotid plaques revealed that NOD2 was abundantly expressed at both mRNA and protein levels by endothelial cells and macrophages. Stimulation of NOD2 in ex vivo–cultured carotid plaques by muramyl dipeptide, an extrinsic ligand of NOD2, led to release of prostaglandin E
2
, upregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1, and to downregulation of cyclooxygenase-1. NOD2 was coexpressed with cyclooxygenase-2 in lesional macrophages. NOD2-induced cyclooxygenase-2 expression in macrophages was dependent on p38 mitogen-activated protein kinase activation and was mediated by interleukin-1β and tumor necrosis factor-α. Selective lipidomic analysis of the eicosanoids released by the carotid plaques characterized the metabolites of 12-, 5-, and 15-lipoxygenase as the predominant eicosanoids that were produced by the atherosclerotic lesion in the absence of additional stimuli. Unlike the prostaglandin E
2
pathway, metabolic activity of the lipoxygenase pathways was not altered on the short-term activation of NOD2 in carotid plaques.

Conclusions—

These results suggest that atherosclerosis may involve enhanced NOD2-mediated innate immunity. Activation of NOD2 preferentially upregulates the prostaglandin E
2
pathway. Nevertheless, lipoxygenase pathways, such as 12-lipoxygenase, predominate the basal synthesis and metabolism of eicosanoids in atherosclerotic plaques. These findings provide new insights into the regulation of eicosanoids in atherosclerosis.
LRP1 Protects the Vasculature by Regulating Levels of Connective Tissue Growth Factor and HtrA1
Authors: Muratoglu Selen C. , Belgrave Shani , Hampton Brian , Migliorini Mary , Coksaygan Turhan , Chen Ling , Mikhailenko Irina , Strickland Dudley K. 
Published: July 2013

Objective—

Low-density lipoprotein receptor–related protein 1 (LRP1) is a large endocytic and signaling receptor that is abundant in vascular smooth muscle cells. Mice in which the
lrp1
gene is deleted in smooth muscle cells (smLRP1
−/−
) on a low-density lipoprotein receptor–deficient background display excessive platelet derived growth factor-signaling, smooth muscle cell proliferation, aneurysm formation, and increased susceptibility to atherosclerosis. The objectives of the current study were to examine the potential of LRP1 to modulate vascular physiology under nonatherogenic conditions.

Approach and Results—

We found smLRP1
−/−
mice to have extensive in vivo aortic dilatation accompanied by disorganized and degraded elastic lamina along with medial thickening of the arterial vessels resulting from excess matrix deposition. Surprisingly, this was not attributable to excessive platelet derived growth factor-signaling. Rather, quantitative differential proteomic analysis revealed that smLRP1
−/−
vessels contain a 4-fold increase in protein levels of high-temperature requirement factor A1 (HtrA1), which is a secreted serine protease that is known to degrade matrix components and to impair elastogenesis, resulting in fragmentation of elastic fibers. Importantly, our study discovered that HtrA1 is a novel LRP1 ligand. Proteomics analysis also identified excessive accumulation of connective tissue growth factor, an LRP1 ligand and a key mediator of fibrosis.

Conclusions—
Our findings suggest a critical role for LRP1 in maintaining the integrity of vessels by regulating protease activity as well as matrix deposition by modulating HtrA1 and connective tissue growth factor protein levels. This study highlights 2 new molecules, connective tissue growth factor and HtrA1, which contribute to detrimental changes in the vasculature and, therefore, represent new target molecules for potential therapeutic intervention to maintain vessel wall homeostasis.
Novel Formulation of a Reconstituted High-Density Lipoprotein (CSL112) Dramatically Enhances ABCA1-Dependent Cholesterol Efflux
Authors: Diditchenko Svetlana , Gille Andreas , Pragst Ingo , Stadler Dominik , Waelchli Marcel , Hamilton Ross , Leis Andrew , Wright Samuel D. 
Published: July 2013

Objective—
The ability of high-density lipoprotein (HDL) to remove cholesterol from atherosclerotic plaque is thought to underlie its inverse correlation with cardiovascular risk. Our objective was to produce and characterize a human apolipoprotein AI (apoA-I) product optimized to treat clinical atherosclerotic disease.

Approach and Results—
A new formulation of full length, plasma-derived human apoA-I termed CSL112 was designed to maximize the cholesterol efflux from cells and exhibit favorable pharmacological properties. CSL112 is a disc-shaped particle that strongly elevates cholesterol esterification and shows good pharmacokinetics in rabbits. Infusion of CSL112 into rabbits caused a strong and immediate increase in the ATP binding cassette transporter A1 (ABCA1)-dependent efflux capacity of plasma, an increase in plasma unesterified cholesterol and rapid subsequent cholesterol esterification. In the presence of human plasma, CSL112 was significantly more potent than native HDL at enhancing cholesterol efflux from macrophages, and the efflux elevation was predominantly via the ABCA1 transporter. Consistent with this observation, addition of CSL112 to plasma led to generation of high levels of HDL-VS, a favorable substrate for ABCA1. The lipid profile of plasma did not affect these behaviors. In studies with whole human blood, CSL112 reduced expression of intercellular adhesion molecule 1 and cytokine secretion, and as with cholesterol efflux, these activities were substantially greater than those of native HDL assayed in parallel.

Conclusions—
CSL112 has favorable pharmacological properties and strongly elevates the ability of plasma to withdraw cholesterol from cells. Preferential elevation of ABCA1-dependent efflux may target atherosclerotic plaque for cholesterol removal and this property makes CSL112 a promising candidate therapy for acute coronary syndrome.
Noninvasive Assessment of Pulmonary Hemodynamics in Patients With Chronic Thromboembolic Pulmonary Hypertension by High Temporal Resolution Phase-Contrast MRI
Authors: Kreitner Karl-Friedrich , Wirth Gesine Maria , Krummenauer Frank , Weber Stefan , Pitton Michael Bernhard , Schneider Jens , Mayer Eckhard , Dueber Christoph 
Published: July 2013

Background—
Right heart catheterization is the gold standard for assessment of pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension. To date, MRI has not been able to produce precise measurements of mean pulmonary arterial pressure (mPAP). The purpose of the study was to create a model for estimating mPAP and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension by high temporal resolution phase-contrast MRI (PC-MRI) and to correlate the results with simultaneously acquired, invasive catheter-based measurements (simultaneously measured mPAP) and with right heart catheterization measurements.

Methods and Results—

A total of 19 patients with chronic thromboembolic pulmonary hypertension underwent right heart catheterization and—after digital subtraction angiography of the pulmonary arteries—subsequent PC-MRI at 1.5 T with simultaneous recording of mPAP. Velocity– and flow–time curves of PC-MRI were used to calculate absolute acceleration time (Ata), maximum of mean velocities (MV), volume of acceleration (AV), and maximum flow acceleration (dQ/dt). On the basis of these parameters, multiple linear regression analysis revealed maximum achievable model fit (B=0.902) for the following linear combination equation to calculate mPAP (mPAP_cal): mPAP_cal=69.446−(0.521×Ata)−(0.570×MV)+(1.507×AV)+(0.002×dQ/dt). There was a statistically significant equivalence of mPAP_cal and simultaneously measured mPAP with a goodness of fit of 0.892. Pulmonary vascular resistance was overestimated by calculated pulmonary vascular resistance on the basis of PC-MRI in comparison with right heart catheterization–based measurements by a median of −112 dyn·s·cm
−5
, the pairwise regression formula revealed a goodness of fit of 0.792.

Conclusions—
PC-MRI–derived parameters enable noninvasive assessment of pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension.
Provider Specialty and Atrial Fibrillation Treatment Strategies in United States Community Practice: Findings From the ORBIT‐AF Registry
Authors: Fosbol Emil L. , Holmes DaJuanicia N. , Piccini Jonathan P. , Thomas Laine , Reiffel James A. , Mills Roger M. , Kowey Peter , Mahaffey Kenneth , Gersh Bernard J. , Peterson Eric D. ,   the ORBIT‐AF Investigators and Patients
Published: July 2013

Background

The prevalence of atrial fibrillation (
AF
) continues to increase; however, there are limited data describing the division of care among practitioners in the community and whether care differs depending on provider specialty.

Methods and Results

Using the Outcomes Registry for Better Informed Treatment of
AF
(
ORBIT
‐
AF
) Registry, we described patient characteristics and
AF
management strategies in ambulatory clinic practice settings, including electrophysiology (
EP
), general cardiology, and primary care. A total of 10 097 patients were included; of these, 1544 (15.3%) were cared for by an
EP
provider, 6584 (65.2%) by a cardiology provider, and 1969 (19.5%) by an internal medicine/primary care provider. Compared with those patients who were cared for by cardiologists or internal medicine/primary care providers, patients cared for by
EP
providers were younger (median age, 73 years [interquartile range,
IQR
, 64, 80 years, Q1, Q3] versus 75 years [
IQR
, 67, 82 years] for cardiology and versus 76 years [
IQR
, 68, 82 years] for primary care). Compared with cardiology and internal medicine/primary care providers,
EP
providers used rhythm control (versus rate control) management more often (44.2% versus 29.7% and 28.8%, respectively,
P
<0.0001; adjusted odds ratio [
OR
]
EP
versus cardiology, 1.66 [95% confidence interval,
CI
, 1.05 to 2.61]; adjusted
OR
for internal medicine/primary care versus cardiology, 0.91 [95%
CI
, 0.65 to 1.26]). Use of oral anticoagulant therapy was high across all providers, although it was higher for cardiology and
EP
providers (overall, 76.1%;
P
=0.02 for difference between groups).

Conclusions

Our data demonstrate important differences between provider specialties, the demographics of the
AF
patient population treated, and treatment strategies—particularly for rhythm control and anticoagulation therapy.
Spatiotemporal Variability of Summer Precipitation in Southeastern Arizona
Authors: Stillman Susan , Zeng Xubin , Shuttleworth William J. , Goodrich David C. , Unkrich Carl L. , Zreda Marek 
Published: July 2013

Abstract
The Walnut Gulch Experimental Watershed (WGEW) in southeastern Arizona covers ~150 km2 and receives the majority of its annual precipitation from highly variable and intermittent summer storms during the North American monsoon. In this study, the patterns of precipitation in the U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) 88-rain-gauge network are analyzed for July through September from 1956 to 2011. Because small-scale convective systems generate most of this summer rainfall, the total (T), intensity (I), and frequency (F) exhibit high spatial and temporal variability. Although subsidiary periods may have apparent trends, no significant trends in T, I, and F were found for the study period as a whole. Observed trends in the spatial coverage of storms change sign in the late 1970s, and the multidecadal variation in I and spatial coverage of storms have statistically significant correlation with the Pacific decadal oscillation and the Atlantic multidecadal oscillation indices. Precipitation has a pronounced diurnal cycle with the highest T and F occurring between 1500 and 2200 LT, and its average fractional coverage over 2- and 12-h periods is less than 40% and 60% of the gauges, respectively. Although more gauges are needed to estimate area-averaged daily precipitation, 5–11 gauges can provide a reasonable estimate of the area-averaged monthly total precipitation during the period from July through September.
Resolution and Accuracy of an Airborne Scanning Laser System for Beach Surveys
Authors: Middleton J. H. , Cooke C. G. , Kearney E. T. , Mumford P. J. , Mole M. A. , Nippard G. J. , Rizos C. , Splinter K. D. , Turner I. L. 
Published: July 2013

Abstract
Airborne scanning laser technology provides an effective method to systematically survey surface topography and changes in that topography with time. In this paper, the authors describe the capability of a rapid-response lidar system in which airborne observations are utilized to describe results from a set of surveys of Narrabeen–Collaroy Beach, Sydney, New South Wales, Australia, over a short period of time during which significant erosion and deposition of the subaerial beach occurred. The airborne lidar data were obtained using a Riegl Q240i lidar coupled with a NovAtel SPAN-CPT integrated Global Navigation Satellite System (GNSS) and inertial unit and flown at various altitudes. A set of the airborne lidar data is compared with ground-truth data acquired from the beach using a GNSS/real-time kinematic (RTK) system mounted on an all-terrain vehicle. The comparison shows consistency between systems, with the airborne lidar data being less than 0.02 m different from the ground-truth data when four surveys are undertaken, provided a method of removing outliers—developed here and designated as “weaving”—is used. The combination of airborne lidar data with ground-truth data provides an excellent method of obtaining high-quality topographic data. Using the results from this analysis, it is shown that airborne lidar data alone produce results that can be used for ongoing large-scale surveys of beaches with reliable accuracy, and that the enhanced accuracy resulting from multiple airborne surveys can be assessed quantitatively.
An Observational Study of Tropical Cyclone Spinup in Supertyphoon Jangmi (2008) from 24 to 27 September
Authors: Sanger Neil T. , Montgomery Michael T. , Smith Roger K. , Bell Michael M. 
Published: July 2013

AbstractAn observational study of tropical cyclone intensification is performed using dropsondes, in situ flight-level data, satellite imagery, and Electra Doppler Radar (ELDORA) during the spinup of Tropical Storm Jangmi (2008) in the western North Pacific. This event was observed with research aircraft during the Tropical Cyclone Structure 2008 (TCS08) field experiment over the course of 3 days as Jangmi intensified rapidly from a tropical storm to a supertyphoon. The dropsonde analysis indicates that the peak azimuthally averaged storm-relative tangential wind speed occurs persistently within the boundary layer throughout the spinup period and suggests that significant supergradient winds are present near and just within the radius of maximum tangential winds. An examination of the ELDORA data in Tropical Storm Jangmi reveals multiple rotating updrafts near the developing eye beneath cold cloud top temperatures ≤−65°C. In particular, there is a 12-km-wide, upright updraft with a peak velocity of 9 m s−1 with collocated strong low-level (z &lt; 2 km) convergence of 2 × 10−3 s−1 and intense relative vorticity of 4 × 10−3 s−1. The analysis of the corresponding infrared satellite imagery suggests that vortical updrafts are common before and during rapid intensification. The findings of this study support a recent paradigm of tropical cyclone intensification in which rotating convective clouds are important elements in the spinup process. In a system-scale view of this process, the maximum tangential wind is found within the boundary layer, where the tangential wind becomes supergradient before the air ascends into the eyewall updraft.
Airborne Measurements of Terrain-Induced Pressure Perturbations
Authors: Parish Thomas R. , Geerts Bart 
Published: July 2013

Abstract
Airborne measurement of the horizontal pressure field using differential GPS technology has been established during the last few years. Accurate aircraft measurement of the horizontal pressure gradient force requires an independent determination of the height of the airborne platform above some reference level. Here the authors demonstrate a differential GPS technique that uses data from a fixed reference station to refine the vertical position of the aircraft. A series of research flight legs by the University of Wyoming King Air research aircraft (UWKA) were conducted during the winter seasons of 2008 and 2009 over the Medicine Bow Mountains in southern Wyoming. Flight patterns consisted of a series of geographically fixed, parallel legs along a quasi-isobaric surface above the mountainous terrain, allowing the finescale mapping of the horizontal pressure (or geopotential height) field. The removal of the large-scale gradient and tendency isolates the terrain-induced pressure perturbation field. Results obtained using differential GPS measurements of aircraft height show that the Medicine Bow Range induces pronounced horizontal pressure perturbations, with a leeside region of low pressure downwind of the crest, in two cases: on 11 February 2008 and 20 February 2009. A wind maximum is found downwind of the elevated terrain consistent with this pressure gradient. Simulations of these two cases were performed using the Weather Research and Forecasting Model (WRF). The WRF height patterns for the time of the UWKA flight matched the general isobaric height patterns observed. Simulations and observations consistently show that the cross-mountain acceleration is stronger when the perturbation pressure gradient is larger.
Total artificial heart in the pediatric patient with biventricular heart failure
Authors: Park SS , Sanders DB , Smith BP , Ryan J , Plasencia J , Osborn MB , Wellnitz CM , Southard RN , Pierce CN , Arabia FA , Lane J , Frakes D , Velez DA , Pophal SG , Nigro JJ 
Published: July 2013

Mechanical circulatory support emerged for the pediatric population in the late 1980s as a bridge to cardiac transplantation. The Total Artificial Heart (TAH-t) (SynCardia Systems Inc., Tuscon, AZ) has been approved for compassionate use by the Food and Drug Administration for patients with end-stage biventricular heart failure as a bridge to heart transplantation since 1985 and has had FDA approval since 2004. However, of the 1,061 patients placed on the TAH-t, only 21 (2%) were under the age 18. SynCardia Systems, Inc. recommends a minimum patient body surface area (BSA) of 1.7 m2, thus, limiting pediatric application of this device. This unique case report shares this pediatric institution’s first experience with the TAH-t. A 14-year-old male was admitted with dilated cardiomyopathy and severe biventricular heart failure. The patient rapidly decompensated, requiring extracorporeal life support. An echocardiogram revealed severe biventricular dysfunction and diffuse clot formation in the left ventricle and outflow tract. The decision was made to transition to biventricular assist device. The biventricular failure and clot formation helped guide the team to the TAH-t, in spite of a BSA (1.5 m2) below the recommendation of 1.7m2. A computed tomography (CT) scan of the thorax, in conjunction with a novel three-dimensional (3D) modeling system and team, assisted in determining appropriate fit. Chest CT and 3D modeling following implantation were utilized to determine all major vascular structures were unobstructed and the bronchi were open. The virtual 3D model confirmed appropriate device fit with no evidence of compression to the left pulmonary veins. The postoperative course was complicated by a left lung opacification. The left lung anomalies proved to be atelectasis and improved with aggressive recruitment maneuvers. The patient was supported for 11 days prior to transplantation. Chest CT and 3D modeling were crucial in assessing whether the device would fit, as well as postoperative complications in this smaller pediatric patient.