bluuebunny/crossref_metadata_2025_split huggingface dataset:
Follicle-Stimulating Hormone Receptor as a Target in the Redirected T-cell Therapy for Cancer
Authors: Urbanska Katarzyna , Stashwick Caitlin , Poussin Mathilde , Powell Daniel J. 
Published: June 2015

AbstractAdoptive transfer of T cells engineered to express chimeric immunoreceptors is an effective strategy to treat hematologic cancers; however, the use of this type of therapy for solid cancers, such as ovarian cancer, remains challenging because a safe and effective immunotherapeutic target has not yet been identified. Here, we constructed and evaluated a novel redirected T-cell–based immunotherapy targeting human follicle-stimulating hormone receptor (FSHR), a highly conserved molecule in vertebrate animals with expression limited to gonadal tissues, ovarian cancer, and cancer-associated vasculature. Receptor ligand–based anti-FSHR immunoreceptors were constructed that contained small binding fragments from the ligand for FSHR, FSH, fused to T-cell transmembrane and T-cell signaling domains. Human T cells transduced to express anti-FSHR immunoreceptors were specifically immunoreactive against FSHR-expressing human and mouse ovarian cancer cell lines in an MHC-nonrestricted manner and mediated effective lysis of FHSR-expressing tumor cells, but not FSHR-deficient targets, in vitro. Similarly, the outgrowth of human ovarian cancer xenografts in immunodeficient mice was significantly inhibited by the adoptive transfer of FSHR-redirected T cells. Our experimental observations show that FSHR is a promising immunotherapeutic target for ovarian cancer and support further exploration of FSHR-targeted immune therapy approaches for patients with cancer. Cancer Immunol Res; 3(10); 1130–7. ©2015 AACR.
Both MC
1
and MC
3
Receptors Provide Protection From Cerebral Ischemia-Reperfusion–Induced Neutrophil Recruitment
Authors: Holloway Paul M. , Durrenberger Pascal F. , Trutschl Marjan , Cvek Urska , Cooper Dianne , Orr A. Wayne , Perretti Mauro , Getting Stephen J. , Gavins Felicity N.E. 
Published: June 2015

Objective—

Neutrophil recruitment is a key process in the pathogenesis of stroke, and may provide a valuable therapeutic target. Targeting the melanocortin (MC) receptors has previously shown to inhibit leukocyte recruitment in peripheral inflammation, however, it is not known whether treatments are effective in the unique cerebral microvascular environment. Here, we provide novel research highlighting the effects of the MC peptides on cerebral neutrophil recruitment, demonstrating important yet discrete roles for both MC
1
and MC
3
.

Approach and Results—

Using intravital microscopy, in 2 distinct murine models of cerebral ischemia-reperfusion (I/R) injury, we have investigated MC control for neutrophil recruitment. After global I/R, pharmacological treatments suppressed pathological neutrophil recruitment. MC
1
selective treatment rapidly inhibited neutrophil recruitment while a nonselective MC agonist provided protection even when coadministered with an MC
3/4
antagonist, suggesting the importance of early MC
1
signaling. However, by 2-hour reperfusion, MC
1
-mediated effects were reduced, and MC
3
anti-inflammatory circuits predominated. Mice bearing a nonfunctional MC
1
displayed a transient exacerbation of neutrophil recruitment after global I/R, which diminished by 2 hours. However importantly, enhanced inflammatory responses in both MC
1
mutant and MC
3
−/−
mice resulted in increased infarct size and poor functional outcome after focal I/R. Furthermore, we used an in vitro model of leukocyte recruitment to demonstrate these anti-inflammatory actions are also effective in human cells.

Conclusions—
These studies reveal for the first time MC control for neutrophil recruitment in the unique pathophysiological context of cerebral I/R, while also demonstrating the potential therapeutic value of targeting multiple MCs in developing effective therapeutics.
Increased High-Density Lipoprotein Cholesterol Levels in Mice With XX Versus XY Sex Chromosomes
Authors: Link Jenny C. , Chen Xuqi , Prien Christopher , Borja Mark S. , Hammerson Bradley , Oda Michael N. , Arnold Arthur P. , Reue Karen 
Published: June 2015

Objective—
The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels.

Approach and Results—
We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male–female gonadal sex and XX–XY chromosome complement. Gonadectomy of adult mice revealed that the male–female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male–female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration.

Conclusions—
We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels.
Acute Hyperglycemia Impairs Vascular Function in Healthy and Cardiometabolic Diseased Subjects
Authors: Loader Jordan , Montero David , Lorenzen Christian , Watts Rani , Méziat Cindy , Reboul Cyril , Stewart Simon , Walther Guillaume 
Published: June 2015

Objectives—
Controversy exists over the effect of acute hyperglycemia on vascular function. In this systematic review, we compared the effect of acute hyperglycemia on endothelial and vascular smooth muscle functions across healthy and cardiometabolic diseased subjects.

Approach and Results—

A systematic search of MEDLINE, EMBASE, and Web of Science from inception until July 2014 identified articles evaluating endothelial or vascular smooth muscle function during acute hyperglycemia and normoglycemia. Meta-analyses compared the standardized mean difference (SMD) in endothelial and vascular smooth muscle functions between acute hyperglycemia and normoglycemia. Subgroup analyses and metaregression identified sources of heterogeneity. Thirty-nine articles (525 healthy and 540 cardiometabolic subjects) were analyzed. Endothelial function was decreased (39 studies; n=1065; SMD, −1.25; 95% confidence interval, −1.52 to −0.98;
P
<0.01), whereas vascular smooth muscle function was preserved (6 studies; n=144; SMD, −0.07; 95% confidence interval, −0.30 to 0.16;
P
=0.55) during acute hyperglycemia compared with normoglycemia. Significant heterogeneity was detected among endothelial function studies (
P
<0.01). A subgroup analysis revealed that endothelial function was decreased in the macrocirculation (30 studies; n=884; SMD, −1.40; 95% confidence interval, −1.68 to −1.12;
P
<0.01) but not in the microcirculation (9 studies; n=181; SMD, −0.63; 95% confidence interval, −1.36 to 0.11;
P
=0.09). Similar results were observed according to health status. Macrovascular endothelial function was inversely associated with age, blood pressure, and low-density lipoprotein cholesterol and was positively associated with the postocclusion interval of vascular assessment.

Conclusions—
To our knowledge, this is the first systematic review and meta-analysis of its kind. In healthy and diseased subjects, we found evidence for macrovascular but not microvascular endothelial dysfunction during acute hyperglycemia.
Foamy Monocytes Form Early and Contribute to Nascent Atherosclerosis in Mice With Hypercholesterolemia
Authors: Xu Lu , Dai Perrard Xiaoyuan , Perrard Jerry L. , Yang Donglin , Xiao Xinhua , Teng Ba-Bie , Simon Scott I. , Ballantyne Christie M. , Wu Huaizhu 
Published: June 2015

Objective—
To examine infiltration of blood foamy monocytes, containing intracellular lipid droplets, into early atherosclerotic lesions and its contribution to development of nascent atherosclerosis.

Approach and Results—

In apoE
–/–
mice fed Western high-fat diet (WD), >10% of circulating monocytes became foamy monocytes at 3 days on WD and >20% of monocytes at 1 week. Foamy monocytes also formed early in blood of Ldlr
–/–
Apobec1
–/–
(LDb) mice on WD. Based on CD11c and CD36, mouse monocytes were categorized as CD11c
–
CD36
–
, CD11c
–
CD36
+
, and CD11c
+
CD36
+
. The majority of foamy monocytes were CD11c
+
CD36
+
, whereas most nonfoamy monocytes were CD11c
–
CD36
–
or CD11c
–
CD36
+
in apoE
–/–
mice on WD. In wild-type mice, CD11c
+
CD36
+
and CD11c
–
CD36
+
, but few CD11c
–
CD36
–
, monocytes took up cholesteryl ester–rich very low-density lipoproteins (CE-VLDLs) isolated from apoE
–/–
mice on WD, and CE-VLDL uptake accelerated CD11c
–
CD36
+
to CD11c
+
CD36
+
monocyte differentiation. Ablation of CD36 decreased monocyte uptake of CE-VLDLs. Intravenous injection of DiI-CE-VLDLs in apoE
–/–
mice on WD specifically labeled CD11c
+
CD36
+
foamy monocytes, which infiltrated into nascent atherosclerotic lesions and became CD11c
+
cells that were selectively localized in atherosclerotic lesions. CD11c deficiency reduced foamy monocyte infiltration into atherosclerotic lesions. Specific and consistent depletion of foamy monocytes (for 3 weeks) by daily intravenous injections of low-dose clodrosome reduced development of nascent atherosclerosis.

Conclusions—
Foamy monocytes, which form early in blood of mice with hypercholesterolemia, infiltrate into early atherosclerotic lesions in a CD11c-dependent manner and play crucial roles in nascent atherosclerosis development.
Fibroblast Growth Factor 23 Is Associated With Carotid Plaque Presence and Area
Authors: Shah Nirav H. , Dong Chuanhui , Elkind Mitchell S.V. , Sacco Ralph L. , Mendez Armando J. , Hudson Barry I. , Silverberg Shonni , Wolf Myles , Rundek Tatjana , Wright Clinton B. 
Published: June 2015

Objective—
Elevated fibroblast growth factor 23 (FGF23), a hormone that regulates phosphate homeostasis, has been associated with mortality, cardiovascular events, and stroke, and to arterial calcification in chronic kidney disease, but its role in atherosclerosis is unclear and population-based studies are lacking. We hypothesized that elevated FGF23 would associate with carotid plaque presence, area, and echogenicity in the race/ethnically diverse community-based Northern Manhattan Study (NOMAS) sample.

Approach and Results—

There were 1512 stroke-free NOMAS participants with FGF23 and 2-dimensional carotid ultrasound data (mean age, 68±9 years; 61% women; 62% Hispanic, 18% black, and 18% white). We used multivariable linear and logistic regression to evaluate FGF23, continuously and by quintiles, as a correlate of carotid plaque, plaque area (cubic root transformed), and echogenicity adjusting for sociodemographic and vascular risk factors. Participants with FGF23 levels in the top quintile were more likely to have carotid plaque (odds ratio, 1.49; 95% confidence interval, 1.02–2.19;
P
=0.04) and larger plaque area (β=0.32 mm
2
, 95% confidence interval, 0.10–0.53 mm
2
;
P
=0.004) than those in the lowest quintile, adjusting for estimated glomerular filtration rate, demographics, and vascular risk factors. Linear regression models also showed that log transformed FGF23 (LnFGF23) associated with greater odds of plaque presence (odds ratio, 1.26 per LnFGF23; 95% confidence interval, 1.01–1.58;
P
=0.04), and plaque area (β=0.19 mm
2
per LnFGF23; 95% confidence interval, 0.07–0.31 mm
2
;
P
=0.002).

Conclusions—
Higher FGF23 associated with greater likelihood and burden of carotid atherosclerosis independent of CKD. Atherosclerosis may be a mechanism through which FGF23 increases cardiovascular events and stroke.
Loss-of-Function
SCN5A
Mutations Associated With Sinus Node Dysfunction, Atrial Arrhythmias, and Poor Pacemaker Capture
Authors: Chiang David Y. , Kim Jeffrey J. , Valdes Santiago O. , de la Uz Caridad , Fan Yuxin , Orcutt Jeffrey , Domino Melissa , Smith Melissa , Wehrens Xander H.T. , Miyake Christina Y. 
Published: June 2015

Background—
Cardiac device implantation can be complicated by inability to adequately place leads because of significant lead capture issues. This study sought to determine whether there are genetic bases that underlie poor lead capture.

Methods and Results—

Retrospective review of all patients with structurally normal hearts who underwent new device implantation at Texas Children’s Hospital between 2009 and 2014 was performed. Patients with inability to capture at 10 V or a final capture threshold ≥3 V at 0.4 ms during implant were analyzed. Among a total of 136 patients (median age, 13 years; range, 3 days to 46 years), 11 patients (8.1%) who underwent dual chamber device implantation had elevated thresholds in the atria (4), ventricle (3), or both chambers (4; atrial-lead threshold, 4.7±4.3 versus 0.7±0.3 V; ventricular-lead, 3.0±3.3 versus 0.7±0.3 V). All 11 patients presented with sinus node dysfunction and 10 had atrial arrhythmias. At implant, inability to find atrial capture was seen in 4 patients. Three demonstrated intermittent complete loss of ventricular capture after implantation: 1 has recurrent syncope, 2 eventually died. Genetic testing performed in 10 demonstrated 7 patients with 6 distinct
SCN5A
mutations, all predicted to be severe loss-of-function mutations by bioinformatic analyses. In the remaining patients, although putative pathogenic mutations were not found, multiple
SCN5A
polymorphisms were identified in 2 and a desmin mutation in 1.

Conclusions—

This study suggests that significant capture issues at implant may be because of loss-of-function
SCN5A
mutations, providing new insights into
SCN5A
function. Recognition of this association may be critical for planning device implantation strategies and patient follow-up.
Association of Interstage Home Monitoring With Mortality, Readmissions, and Weight Gain
Authors: Oster Matthew E. , Ehrlich Alexandra , King Eileen , Petit Christopher J. , Clabby Martha , Smith Sherry , Glanville Michelle , Anderson Jeffrey , Darbie Lynn , Beekman Robert H. 
Published: June 2015

Background—
Daily home monitoring of oxygen saturation and weight has been reported to improve outcomes for patients with single-ventricle heart disease during the period between stage I palliation and stage II palliation. However, these studies have been limited to single institutions and used historical control subjects. Our objective was to determine the association of various interstage home monitoring strategies with outcomes using a multicenter cohort with contemporary control subjects.

Methods and Results—

We performed a retrospective cohort study using prospectively collected data from the National Pediatric Cardiology Quality Improvement Collaborative from 2008 to 2012. We compared interstage mortality, unscheduled readmissions, and change in weight-for-age
Z
score for various home monitoring strategies of oxygen saturation (n=494) or weight (n=472), adjusting for sex, syndrome, tricuspid regurgitation, arch obstruction, and shunt type. Overall interstage mortality was 8.1%, and 47% had ≥1 unscheduled readmission. We did not find any associations of home oxygen saturation or weight monitoring with mortality or readmission. Although there was no difference in weight-for-age
Z
score for daily (0.33±0.12) versus weekly (0.34±0.18,
P
=0.98) weight monitoring, daily home weight monitoring was superior to no home weight monitoring (−0.15±0.18;
P
<0.01).

Conclusions—
Home weight monitoring is associated with improved weight gain during the interstage period, but we did not find any benefits in other clinical outcomes for either home oxygen saturation monitoring or home weight monitoring.
New Ocean Winds Satellite Mission to Probe Hurricanes and Tropical Convection
Authors: Ruf Christopher S. , Atlas Robert , Chang Paul S. , Clarizia Maria Paola , Garrison James L. , Gleason Scott , Katzberg Stephen J. , Jelenak Zorana , Johnson Joel T. , Majumdar Sharanya J. , O’brien Andrew , Posselt Derek J. , Ridley Aaron J. , Rose Randall J. , Zavorotny Valery U. 
Published: June 2015

Abstract
The Cyclone Global Navigation Satellite System (CYGNSS) is a new NASA earth science mission scheduled to be launched in 2016 that focuses on tropical cyclones (TCs) and tropical convection. The mission’s two primary objectives are the measurement of ocean surface wind speed with sufficient temporal resolution to resolve short-time-scale processes such as the rapid intensification phase of TC development and the ability of the surface measurements to penetrate through the extremely high precipitation rates typically encountered in the TC inner core. The mission’s goal is to support significant improvements in our ability to forecast TC track, intensity, and storm surge through better observations and, ultimately, better understanding of inner-core processes. CYGNSS meets its temporal sampling objective by deploying a constellation of eight satellites. Its ability to see through heavy precipitation is enabled by its operation as a bistatic radar using low-frequency GPS signals. The mission will deploy an eight-spacecraft constellation in a low-inclination (35°) circular orbit to maximize coverage and sampling in the tropics. Each CYGNSS spacecraft carries a four-channel radar receiver that measures GPS navigation signals scattered by the ocean surface. The mission will measure inner-core surface winds with high temporal resolution and spatial coverage, under all precipitating conditions, and over the full dynamic range of TC wind speeds.
An Experiment on Risk-Based Decision-Making in Water Management Using Monthly Probabilistic Forecasts
Authors: Crochemore Louise , Ramos Maria-Helena , Pappenberger Florian , Andel Schalk Jan van , Wood Andrew W. 
Published: June 2015

Abstract
The use of probabilistic forecasts is necessary to take into account uncertainties and allow for optimal risk-based decisions in streamflow forecasting at monthly to seasonal lead times. Such probabilistic forecasts have long been used by practitioners in the operation of water reservoirs, in water allocation and management, and more recently in drought preparedness activities. Various studies assert the potential value of hydrometeorological forecasting efforts, but few investigate how these forecasts are used in the decision-making process. Role-playing games can help scientists, managers, and decision-makers understand the extremely complex process behind risk-based decisions. In this paper, we present an experiment focusing on the use of probabilistic forecasts to make decisions on reservoir outflows. The setup was a risk-based decision-making game, during which participants acted as water managers. Participants determined monthly reservoir releases based on a sequence of probabilistic inflow forecasts, reservoir volume objectives, and release constraints. After each decision, consequences were evaluated based on the actual inflow. The analysis of 162 game sheets collected after eight applications of the game illustrates the importance of leveraging not only the probabilistic information in the forecasts but also predictions for a range of lead times. Winning strategies tended to gradually empty the reservoir in the months before the peak inflow period to accommodate its volume and avoid overtopping. Twenty percent of the participants managed to do so and finished the management period without having exceeded the maximum reservoir capacity or violating downstream release constraints. The role-playing approach successfully created an open atmosphere to discuss the challenges of using probabilistic forecasts in sequential decision-making.
Assessment of the Sources of Variation in Changes of Precipitation Characteristics over the Rhine Basin Using a Linear Mixed-Effects Model
Authors: Hanel Martin , Buishand T. Adri 
Published: June 2015

Abstract
A linear mixed-effects (LME) model is developed to discriminate the sources of variation in the changes of several precipitation characteristics over the Rhine basin as projected by an ensemble of 191 global climate model (GCM) simulations from phase 5 of the Coupled Model Intercomparison Project (CMIP5). The uncertainty in climate change projections originates from natural internal variability, imperfect climate models, and the unpredictability of future greenhouse gas forcing. The LME model allows for the quantification of the contribution of these sources of uncertainty as well as the interaction between greenhouse gas forcing and climate model. In addition, dependence between climate models can be accounted for by using a two-level LME model in which the GCMs are grouped according to their atmospheric circulation model. Statistical models of varied complexity are assessed by the Akaike information criterion. More than 60% of the variance of the changes in mean summer precipitation and various quantiles of 5-day summer precipitation at the end of the twenty-first century can be explained by the climate model. Differences between climate models are also the main source of uncertainty for the changes in three drought characteristics in the summer half-year. In winter, the differences between GCMs are smaller, and natural variability explains a large proportion of the variance of the changes. Natural variability is also the main source of uncertainty for the changes in two indices of extreme precipitation. The contribution of the forcing scenario to the variance of the changes is generally less than 25%.
Characteristics, Energetics, and Origins of Agulhas Current Meanders and Their Limited Influence on Ring Shedding
Authors: Elipot Shane , Beal Lisa M. 
Published: June 2015

AbstractThe Agulhas Current intermittently undergoes dramatic offshore excursions from its mean path because of the downstream passage of mesoscale solitary meanders or Natal pulses. New observations and analyses are presented of the variability of the current and its meanders using mooring observations from the Agulhas Current Time-Series Experiment (ACT) near 34°S. Using a new rotary EOF method, mesoscale meanders and smaller-scale meanders are differentiated and each captured in a single mode of variance. During mesoscale meanders, an onshore cyclonic circulation and an offshore anticyclonic circulation act together to displace the jet offshore, leading to sudden and strong positive conversion of kinetic energy from the mean flow to the meander via nonlinear interactions. Smaller meanders are principally represented by a single cyclonic circulation spanning the entire jet that acts to displace the jet without extracting kinetic energy from the mean flow. Synthesizing in situ observations with altimeter data leads to an account of the number of mesoscale meanders at 34°S: 1.6 yr−1 on average, in agreement with a recent analysis by Rouault and Penven (2011) and significantly less than previously understood. The links between meanders and the arrival of Mozambique Channel eddies or Madagascar dipoles at the western boundary upstream are found to be robust in the 20-yr altimeter record. Yet, only a small fraction of anomalies arriving at the western boundary result in meanders, and of those, two-thirds can be related to ring shedding. Most Agulhas rings are shed independently of meanders.