bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver-Specific Cholesteryl Ester Hydrolase Deficiency Attenuates Sterol Elimination in the Feces and Increases Atherosclerosis in
Ldlr
−/−
Mice
Authors: Bie Jinghua , Wang Jing , Marqueen Kathryn E. , Osborne Rachel , Kakiyama Genta , Korzun William , Ghosh Siddhartha S. , Ghosh Shobha 
Published: June 2013

Objective—
Liver is the major organ responsible for the final elimination of cholesterol from the body either as biliary cholesterol or as bile acids. Intracellular hydrolysis of lipoprotein-derived cholesteryl esters (CEs) is essential to generate the free cholesterol required for this process. Earlier, we demonstrated that overexpression of human CE hydrolase (Gene symbol CES1) increased bile acid synthesis in human hepatocytes and enhanced reverse cholesterol transport in mice. The objective of the present study was to demonstrate that liver-specific deletion of its murine ortholog, Ces3, would decrease cholesterol elimination from the body and increase atherosclerosis.

Approach and Results—

Liver-specific Ces3 knockout mice (Ces3-LKO) were generated, and Ces3 deficiency did not affect the expression of genes involved in cholesterol homeostasis and free cholesterol or bile acid transport. The effects of Ces3 deficiency on the development of Western diet–induced atherosclerosis were examined in low density lipoprotein receptor knock out
−/−
mice. Despite similar plasma lipoprotein profiles, there was increased lesion development in low density lipoprotein receptor knock out
−/−
Ces3-LKO mice along with a significant decrease in the bile acid content of bile. Ces3 deficiency significantly reduced the flux of cholesterol from [
3
H]-CE–labeled high-density lipoproteins to feces (as free cholesterol and bile acids) and decreased total fecal sterol elimination.

Conclusions—
Our results demonstrate that hepatic Ces3 modulates the hydrolysis of lipoprotein-delivered CEs and thereby regulates free cholesterol and bile acid secretion into the feces. Therefore, its deficiency results in reduced cholesterol elimination from the body, leading to significant increase in atherosclerosis. Collectively, these data establish the antiatherogenic role of hepatic CE hydrolysis.
Life’s Simple 7 and Risk of Incident Stroke
Authors: Kulshreshtha Ambar , Vaccarino Viola , Judd Suzanne E. , Howard Virginia J. , McClellan William M. , Muntner Paul , Hong Yuling , Safford Monika M. , Goyal Abhinav , Cushman Mary 
Published: June 2013

Background and Purpose—
The American Heart Association developed Life’s Simple 7 (LS7) as a metric defining cardiovascular health. We investigated the association between LS7 and incident stroke in black and white Americans.

Methods—
The Reasons for Geographic And Racial Differences in Stroke (REGARDS) is a national population-based cohort of 30 239 blacks and whites, aged ≥45 years, sampled from the US population from 2003 to 2007. Data were collected by telephone, self-administered questionnaires, and an in-home examination. Incident strokes were identified through biannual participant contact followed by adjudication of medical records. Levels of the LS7 components (blood pressure, cholesterol, glucose, body mass index, smoking, physical activity, and diet) were each coded as poor (0 point), intermediate (1 point), or ideal (2 points) health. An overall LS7 score was categorized as inadequate (0–4), average (5–9), or optimum (10–14) cardiovascular health.

Results—

Among 22 914 subjects with LS7 data and no previous cardiovascular disease, there were 432 incident strokes over 4.9 years of follow-up. After adjusting for demographics, socioeconomic status, and region of residence, each better health category of the LS7 score was associated with a 25% lower risk of stroke (hazard ratios, 0.75; 95% confidence interval, 0.63–0.90). The association was similar for blacks and whites (interaction
P
value=0.55). A 1-point higher LS7 score was associated with an 8% lower risk of stroke (hazard ratios, 0.92; 95% confidence interval, 0.88–0.95).

Conclusions—
In both blacks and whites, better cardiovascular health, on the basis of the LS7 score, is associated with lower risk of stroke, and a small difference in scores was an important stroke determinant.
Caffeine-Containing Medicines Increase the Risk of Hemorrhagic Stroke
Authors: Lee Seung-Mi , Choi Nam-Kyong , Lee Byung-Chul , Cho Ki-Hyun , Yoon Byung-Woo , Park Byung-Joo 
Published: June 2013

Background and Purpose—
Research on the relationship between caffeine-containing medicines (CCMs) and the risk of hemorrhagic stroke (HS) is sparse. The aim of this study is to evaluate the association between CCMs and the risk of HS.

Methods—
We performed a multicenter case–control study in South Korea, from 2002 to 2004. A total of 940 patients with nontraumatic acute HS, aged 30 to 84 years without a history of stroke, 940 community, and 940 hospital controls, age and sex matched to each case, were included. We obtained information on all medications taken in the 14 days before the date (index date) and time of stroke onset (zero-time) for case subjects or matched zero-time for control subjects. Exposure to CCMs was defined by use on the index date before zero-time or during the preceding 3 days. The adjusted odds ratios and their 95% confidence intervals (CIs) were estimated by conditional logistic regression.

Results—
The adjusted odds ratio for the association between the use of CCM and risk for HS was 2.23 (95% CI, 1.41–3.69) for all HS, 2.24 (95% CI, 1.08–4.66) for subarachnoid hemorrhage, and 2.49 (95% CI, 1.29–4.80) for intracerebral hemorrhage. Stratified by daily coffee intake, adjusted odds ratio of CCMs for HS was 2.95 (95% CI, 1.45–5.98) for those who did not drink coffee on a daily basis.

Conclusions—
These results suggest that use of CCMs is associated with increased risk of HS, both subarachnoid hemorrhage and intracerebral hemorrhage.
Spatiotemporal Uptake Characteristics of [
18
]F-2-Fluoro-2-Deoxy-
d
-Glucose in a Rat Middle Cerebral Artery Occlusion Model
Authors: Yuan Hong , Frank Jonathan E. , Hong Yonglong , An Hongyu , Eldeniz Cihat , Nie Jingxin , Bunevicius Adomas , Shen Dinggang , Lin Weili 
Published: June 2013

Background and Purpose—

Alterations of cerebral glucose metabolism are well anticipated during cerebral ischemia. However, detailed spatiotemporal characteristics of disturbed cerebral glucose metabolism during acute ischemia remain largely elusive. This study aims to delineate spatiotemporal distributions of [
18
]F-2-fluoro-2-deoxy-
d
-glucose (FDG) uptake using positron emission tomography imaging, particularly at the peri-ischemic zone, and its correlation with tissue outcome.

Methods—
The intraluminal suture middle cerebral artery occlusion model was used to induce focal cerebral ischemia in rats (n=48). All animals underwent sequential MRI and FDG positron emission tomography imaging at different times (30–150 minutes) after middle cerebral artery occlusion. MR and positron emission tomography images were coregistered. FDG uptake in the peri-ischemic zone was assessed in relation to middle cerebral artery occlusion duration, cerebral blood flow, apparent diffusion coefficient, and 24-hour T2 lesions.

Results—
Elevated FDG uptake was consistently observed at the peri-ischemic zone surrounding the presumed ischemic core with low FDG uptake. Both the spatial volume and the uptake level of the hyper-uptake region were inversely correlated with the duration of middle cerebral artery occlusion. The hyper-uptake regions exhibited a mild reduction of cerebral blood flow (28.2±3.2%) and apparent diffusion coefficient (9.1±1.4%) when compared with that in the contralateral hemisphere. Colocalization analysis revealed that, with reperfusion, an average of 12.1±1.7% of the hyper-uptake volume was recruited into final infarction.

Conclusions—
Elevated FDG uptake at the peri-ischemic zone is consistently observed during acute cerebral ischemia. The region with elevated FDG uptake likely reflects viable tissues that can be salvaged with reperfusion. Therefore, acute FDG positron emission tomography imaging might hold promise in the management of patients with acute stroke.
Displacement of Sensory Maps and Disorganization of Motor Cortex After Targeted Stroke in Mice
Authors: Harrison Thomas C. , Silasi Gergely , Boyd Jamie D. , Murphy Timothy H. 
Published: June 2013

Background and Purpose—
Recovery from stroke is hypothesized to involve the reorganization of surviving cortical areas. To study the functional organization of sensorimotor cortex at multiple time points before and after stroke, we performed longitudinal light-based motor mapping of transgenic mice expressing light-sensitive channelrhodopsin-2 in layer 5 cortical neurons.

Methods—

Pulses of light stimulation were targeted to an array of cortical points, whereas evoked forelimb motor activity was recorded using noninvasive motion sensors. Intrinsic optical signal imaging produced maps of the forelimb somatosensory cortex. The resulting motor and sensory maps were repeatedly generated for weeks before and after small (0.2 mm
3
) photothrombotic infarcts were targeted to forelimb motor or sensory cortex.

Results—
Infarcts targeted to forelimb sensory or motor areas caused decreased motor output in the infarct area and spatial displacement of sensory and motor maps. Strokes in sensory cortex caused the sensory map to move into motor cortex, which adopted a more diffuse structure. Stroke in motor cortex caused a compensatory increase in peri-infarct motor output, but did not affect the position or excitability of sensory maps.

Conclusions—
After stroke in motor cortex, decreased motor output from the infarcted area was offset by peri-infarct excitability. Sensory stroke caused a new sensory map to form in motor cortex, which maintained its center position, despite becoming more diffuse. These data suggest that surviving regions of cortex are able to assume functions from stroke-damaged areas, although this may come at the cost of alterations in map structure.
Lipoprotein Receptor–Related Protein-6 Protects the Brain From Ischemic Injury
Authors: Abe Takato , Zhou Ping , Jackman Katherine , Capone Carmen , Casolla Barbara , Hochrainer Karin , Kahles Timo , Ross Margaret Elizabeth , Anrather Josef , Iadecola Costantino 
Published: June 2013

Background and Purpose—

Loss-of-function mutations of the lipoprotein receptor–related protein-6 (LRP6), a coreceptor in the Wingless-related integration site-β−catenin prosurvival pathway, have been implicated in myocardial ischemia and neurodegeneration. However, it remains to be established whether LRP6 is also involved in ischemic brain injury. We used LRP6
+/−
mice to examine the role of this receptor in the mechanisms of focal cerebral ischemia.

Methods—

Focal cerebral ischemia was induced by transient occlusion of the middle cerebral artery. Motor deficits and infarct volume were assessed 3 days later. Glycogen-synthase-kinase-3β (GSK-3β) phosphorylation was examined by Western blotting with phosphospecific antibodies, and the mitochondrial membrane potential changes induced by Ca
2+
were also assessed.

Results—

LRP6
+/−
mice have larger stroke and more severe motor deficits, effects that were independent of intraischemic cerebral blood flow, vascular factors, or cytosolic β-catenin levels. Rather, LRP6 haploinsufficiency increased the activating phosphorylation and decreased the inhibitory phosphorylation of GSK-3β, a kinase involved in proinflammatory signaling and mitochondrial dysfunction. Accordingly, postischemic inflammatory gene expression was enhanced in LRP6
+/−
mice. Furthermore, the association of mitochondria with activated GSK-3β was increased in LRP6
+/−
mice, resulting in a reduction in the Ca
2+
handling ability of mitochondria. The mitochondrial dysfunction was reversed by pharmacological inhibition of GSK-3β.

Conclusions—
LRP6 activates an endogenous neuroprotective pathway that acts independently of β-catenin by controlling GSK-3β activity and preventing its deleterious mitochondrial and proinflammatory effects. The findings raise the possibility that emerging treatment strategies for diseases attributable to LRP6 loss-of-function mutations could also lead to new therapeutic avenues for ischemic stroke.
Effects of Microvascular Permeability Changes on Contrast-Enhanced T1 and Pharmacokinetic MR Imagings After Ischemia
Authors: Liu Hua-Shan , Chung Hsiao-Wen , Chou Ming-Chung , Liou Michelle , Wang Chao-Ying , Kao Hung-Wen , Chiang Shih-Wei , Juan Chun-Jung , Huang Guo-Shu , Chen Cheng-Yu 
Published: June 2013

Background and Purpose—

Brain enhancement on contrast-enhanced T1-weighted imaging (CET1-WI) after ischemic stroke is generally accepted as an indicator of the blood–brain barrier disruption. However, this phenomenon usually starts to become visible at the subacute phase. The purpose of this study was to evaluate the time-course profiles of
K

trans

, cerebral blood volume (
v
p
), and CET1-WI with early detection of blood–brain barrier changes on
K

trans

maps and their role for prediction of subsequent hemorrhagic transformation in acute middle cerebral arterial infarct.

Methods—

Twenty-six patients with acute middle cerebral arterial stroke and early spontaneous reperfusion, whose MR images were obtained at predetermined stroke stages, were included. T2*-based MR perfusion-weighted images were acquired using the first-pass pharmacokinetic model to derive
K

trans

and
v
p
. Parenchymal enhancement observed on maps of
K

trans

,
v
p
, and CET1-WI at each stage was compared. Association among these measurements and hemorrhagic transformation was analyzed.

Results—

K
trans

map showed significantly higher parenchymal enhancement in ischemic parenchyma as compared with that of
v
p
map and CET1-WI at early stroke stages (
P
<0.05). The increased
K

trans

at acute stage was not associated with parenchymal enhancement in CET1-WI at the same stage. Parenchymal enhancement in CET1-WI started to occur at the late subacute stage and tended to be luxury reperfusion–dependent. Patients with hemorrhagic transformation showed higher mean
K

trans

values as compared with patients without hemorrhagic transformation (
P
=0.02).

Conclusions—
Postischemic brain enhancement on routine CET1-WI seems to be closely related to the luxury reperfusion at the late subacute stage and is not dependent on microvascular permeability changes at the acute stage.
ETEA: A Euclidean Minimum Spanning Tree-Based Evolutionary Algorithm for Multi-Objective Optimization
Authors: Li Miqing , Yang Shengxiang , Zheng Jinhua , Liu Xiaohui 
Published: June 2013

The Euclidean minimum spanning tree (EMST), widely used in a variety of domains, is a minimum spanning tree of a set of points in space where the edge weight between each pair of points is their Euclidean distance. Since the generation of an EMST is entirely determined by the Euclidean distance between solutions (points), the properties of EMSTs have a close relation with the distribution and position information of solutions. This paper explores the properties of EMSTs and proposes an EMST-based evolutionary algorithm (ETEA) to solve multi-objective optimization problems (MOPs). Unlike most EMO algorithms that focus on the Pareto dominance relation, the proposed algorithm mainly considers distance-based measures to evaluate and compare individuals during the evolutionary search. Specifically, in ETEA, four strategies are introduced: (1) An EMST-based crowding distance (ETCD) is presented to estimate the density of individuals in the population; (2) A distance comparison approach incorporating ETCD is used to assign the fitness value for individuals; (3) A fitness adjustment technique is designed to avoid the partial overcrowding in environmental selection; (4) Three diversity indicators—the minimum edge, degree, and ETCD—with regard to EMSTs are applied to determine the survival of individuals in archive truncation. From a series of extensive experiments on 32 test instances with different characteristics, ETEA is found to be competitive against five state-of-the-art algorithms and its predecessor in providing a good balance among convergence, uniformity, and spread.
The Geospatial and Temporal Distributions of Severe Thunderstorms from High-Resolution Dynamical Downscaling
Authors: Robinson Eric D. , Trapp Robert J. , Baldwin Michael E. 
Published: June 2013

AbstractTrends in severe thunderstorms and the associated phenomena of tornadoes, hail, and damaging winds have been difficult to determine because of the many uncertainties in the historical eyewitness-report-based record. The authors demonstrate how a synthetic record that is based on high-resolution numerical modeling may be immune to these uncertainties. Specifically, a synthetic record is produced through dynamical downscaling of global reanalysis data over the period of 1990–2009 for the months of April–June using the Weather Research and Forecasting model. An artificial neural network (ANN) is trained and then utilized to identify occurrences of severe thunderstorms in the model output. The model-downscaled precipitation was determined to have a high degree of correlation with precipitation observations. However, the model significantly overpredicted the amount of rainfall in many locations. The downscaling methodology and ANN generated a realistic temporal evolution of the geospatial severe-thunderstorm activity, with a geographical shift of the activity to the north and east as the warm season progresses. Regional time series of modeled severe-thunderstorm occurrences showed no significant trends over the 20-yr period of consideration, in contrast to trends seen in the observational record. Consistently, no significant trend was found over the same 20-yr period in the environmental conditions that support the development of severe thunderstorms.
What Do Rain Gauges Tell Us about the Limits of Precipitation Predictability?*
Authors: Gianotti Dan , Anderson Bruce T. , Salvucci Guido D. 
Published: June 2013

Abstract
A generalizable method is presented for establishing the potential predictability for seasonal precipitation occurrence using rain gauge data. This method provides an observationally based upper limit for potential predictability for 774 weather stations in the contiguous United States. It is found that the potentially predictable fraction varies seasonally and spatially, and that on average 30% of year-to-year seasonal variability is potentially explained by predictable climate processes. Potential predictability is generally highest in winter, appears to be enhanced by orography and land surface coupling, and is lowest (stochastic variance is highest) along the Pacific coast. These results depict “hot” spots of climate variability, for use in guiding regional climate forecasting and in uncovering processes driving climate. Identified “cold” spots are equally useful in guiding future studies as predictable climate signals in these areas will likely be undetectable.
Differences in laboratory requesting patterns in emergency department in Spain
Authors: Salinas Maria , López-Garrigós Maite , Uris Joaquín ,   on behalf of the Pilot Group of the Appropriate Utilization of Laboratory Tests (REDCONLAB) Working Group
Published: June 2013

Background It is necessary to achieve a reduction in the number of requests for laboratory tests by improving the appropriateness of testing behaviour. The aim of the study was, first, to compare laboratory requiring patterns for emergency department (ED) patients in clinical laboratories of different institutions in Spain; second, to design an appropriateness pre-pre-analytical quality control report based on appropriateness indicators. Methods A call for data was posted on a website. We obtained production statistics for the year 2010 from emergency laboratories at 36 hospitals. Two types of appropriateness indicators were calculated: test request per 1000 ED admissions or related test requesting ratios. In order to explore the inter-practice variability in tests requests, the ‘index of variability’ was calculated. A pre-pre-analytical quality control report was designed, prepared and sent to each participating laboratory. The savings generated, if each Health-care Department would have achieved the appropriate indicator standard, were calculated. Results The rate of request of the stat tests ranged from 44 to 412 per 1000 ED patient admissions. There was a high and peculiar dispersion of related test requesting ratio results. If every single laboratory would have achieved the appropriate indicator, we would have saved 1,019,230 urea, 302,511 AST and 316,161 CK unnecessary tests. Conclusions There are large variations of test requesting in the emergency setting. An appropriateness pre-pre-analytical quality control report was useful for comparing requesting patterns. The study shows the need to unify demand. The key to achieve this goal will be interdepartmental cooperation between ED clinicians and laboratory professionals.
Development of scales to assess mental health literacy relating to recognition of and interventions for depression, anxiety disorders and schizophrenia/psychosis
Authors: Reavley Nicola J , Morgan Amy J , Jorm Anthony F 
Published: June 2013

Objective: The aim of this study was to develop scales to assess mental health literacy relating to affective disorders, anxiety disorders and schizophrenia/psychosis. Method: Scales were created to assess mental health literacy in relation to depression, depression with suicidal thoughts, early schizophrenia, chronic schizophrenia, social phobia and post-traumatic stress disorder using data from a survey of 1536 health professionals (general practitioners, clinical psychologists and psychiatrists), assessing recognition of these disorders and beliefs about the helpfulness of interventions. This was done by using the consensus of experts about the helpfulness and harmfulness of treatments for each disorder as a criterion. Data from a general population survey of 6019 Australians aged ≥ 15 was used to examine associations between scale scores, exposure to mental disorders and sociodemographic variables, to assess scale validity. Results: Those with a close friend or family member with a mental disorder had significantly higher mean scores on all mental health literacy scales, providing support for scale validity. Personal experience of the problem and working with people with a similar problem was linked to higher scores on some scales. Male sex, a lower level of education and age > 60 were linked to lower levels of mental health literacy. Higher scores were also linked to a greater belief that people with mental disorders are sick rather than weak. Conclusions: The scales developed in this study allow for the assessment of mental health literacy in relation to depression, depression with suicidal thoughts, early schizophrenia, chronic schizophrenia, social phobia and PTSD. Those with exposure to mental disorders had higher scores on the scales, and analyses of the links between scale scores and sociodemographic variables of age, gender and level of education were in line with those seen in other studies, providing support for scale validity.