bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of CD39 Enzymatic Function at the Surface of Tumor Cells Alleviates Their Immunosuppressive Activity
Authors: Bastid Jeremy , Regairaz Anne , Bonnefoy Nathalie , Déjou Cécile , Giustiniani Jérôme , Laheurte Caroline , Cochaud Stéphanie , Laprevotte Emilie , Funck-Brentano Elisa , Hemon Patrice , Gros Laurent , Bec Nicole , Larroque Christian , Alberici Gilles , Bensussan Armand , Eliaou Jean-François 
Published: November 2014

AbstractThe ectonucleotidases CD39 and CD73 hydrolyze extracellular adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to generate adenosine, which binds to adenosine receptors and inhibits T-cell and natural killer (NK)–cell responses, thereby suppressing the immune system. The generation of adenosine via the CD39/CD73 pathway is recognized as a major mechanism of regulatory T cell (Treg) immunosuppressive function. The number of CD39+ Tregs is increased in some human cancers, and the importance of CD39+ Tregs in promoting tumor growth and metastasis has been demonstrated using several in vivo models. Here, we addressed whether CD39 is expressed by tumor cells and whether CD39+ tumor cells mediate immunosuppression via the adenosine pathway. Immunohistochemical staining of normal and tumor tissues revealed that CD39 expression is significantly higher in several types of human cancer than in normal tissues. In cancer specimens, CD39 is expressed by infiltrating lymphocytes, the tumor stroma, and tumor cells. Furthermore, the expression of CD39 at the cell surface of tumor cells was directly demonstrated via flow cytometry of human cancer cell lines. CD39 in cancer cells displays ATPase activity and, together with CD73, generates adenosine. CD39+CD73+ cancer cells inhibited the proliferation of CD4 and CD8 T cells and the generation of cytotoxic effector CD8 T cells (CTL) in a CD39- and adenosine-dependent manner. Treatment with a CD39 inhibitor or blocking antibody alleviated the tumor-induced inhibition of CD4 and CD8 T-cell proliferation and increased CTL- and NK cell–mediated cytotoxicity. In conclusion, interfering with the CD39–adenosine pathway may represent a novel immunotherapeutic strategy for inhibiting tumor cell–mediated immunosuppression. Cancer Immunol Res; 3(3); 254–65. ©2014 AACR.
Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure
Authors: Packer Milton , McMurray John J.V. , Desai Akshay S. , Gong Jianjian , Lefkowitz Martin P. , Rizkala Adel R. , Rouleau Jean L. , Shi Victor C. , Solomon Scott D. , Swedberg Karl , Zile Michael , Andersen Karl , Arango Juan Luis , Arnold J. Malcolm , Bělohlávek Jan , Böhm Michael , Boytsov Sergey , Burgess Lesley J. , Cabrera Walter , Calvo Carlos , Chen Chen-Huan , Dukat Andrej , Duarte Yan Carlos , Erglis Andrejs , Fu Michael , Gomez Efrain , Gonzàlez-Medina Angel , Hagège Albert A. , Huang Jun , Katova Tzvetana , Kiatchoosakun Songsak , Kim Kee-Sik , Kozan Ömer , Llamas Edmundo Bayram , Martinez Felipe , Merkely Bela , Mendoza Iván , Mosterd Arend , Negrusz-Kawecka Marta , Peuhkurinen Keijo , Ramires Felix J.A. , Refsgaard Jens , Rosenthal Arvo , Senni Michele , Sibulo Antonio S. , Silva-Cardoso José , Squire Iain B. , Starling Randall C. , Teerlink John R. , Vanhaecke Johan , Vinereanu Dragos , Wong Raymond Ching-Chiew 
Published: November 2014

Background—
Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients.

Methods and Results—

We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74–0.94;
P
=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52–0.85;
P
=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079;
P
<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction,
P
=0.005), to receive intravenous positive inotropic agents (31% risk reduction,
P
<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction,
P
=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro–B-type natriuretic peptide and troponin) versus enalapril.

Conclusions—
Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01035255.
Peripheral Arterial Disease and Risk of Atrial Fibrillation and Stroke: The Multi‐Ethnic Study of Atherosclerosis
Authors: O'Neal Wesley T. , Efird Jimmy T. , Nazarian Saman , Alonso Alvaro , Heckbert Susan R. , Soliman Elsayed Z. 
Published: November 2014

Background

Peripheral arterial disease (
PAD
) shares several risk factors with atrial fibrillation (
AF
), and persons with
PAD
have an increased risk of stroke. It is unclear if
PAD
is associated with an increased risk for
AF
and whether this potential association explains the increased risk of stroke observed in those with
PAD
.

Methods and Results

We examined the association between
PAD
, measured by ankle‐brachial index (
ABI
), and incident
AF
and incident stroke, separately, in 6568 participants (mean age 62±10 years, 53% women, 62% nonwhite) from the Multi‐Ethnic Study of Atherosclerosis (
MESA
).
ABI
values <1.0 or >1.4 defined
PAD
.
AF
was ascertained through review of hospital discharge records and from Medicare claims data until December 31, 2010. An independent adjudication committee ascertained stroke events. Cox regression was used to estimate hazard ratios and 95%
CI
s for the association between
PAD
and
AF
and stroke. Over a median follow‐up of 8.5 years, 301 (4.6%) participants developed
AF
and 140 (2.1%) developed stroke. In a model adjusted for sociodemographics, cardiovascular risk factors, and potential confounders,
PAD
was associated with an increased risk of
AF
(hazard ratio 1.5, 95%
CI
1.1 to 2.0). In a similar model,
PAD
was associated with incident stroke (hazard ratio 1.7, 95%
CI
1.1 to 2.5), and the magnitude of risk was not different after inclusion of
AF
as a time‐dependent covariate (hazard ratio 1.7, 95%
CI
1.1 to 2.5).

Conclusions

PAD
is associated with an increased risk of
AF
and stroke in
MESA
. Potentially, the relationship between
PAD
and stroke is not mediated by
AF
.
Effects of Cinacalcet on Atherosclerotic and Nonatherosclerotic Cardiovascular Events in Patients Receiving Hemodialysis: The EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial
Authors: Wheeler David C. , London Gerard M. , Parfrey Patrick S. , Block Geoffrey A. , Correa‐Rotter Ricardo , Dehmel Bastian , Drüeke Tilman B. , Floege Jürgen , Kubo Yumi , Mahaffey Kenneth W. , Goodman William G. , Moe Sharon M. , Trotman Marie‐Louise , Abdalla Safa , Chertow Glenn M. , Herzog Charles A. ,   the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial Investigators
Published: November 2014

Background

Premature cardiovascular disease limits the duration and quality of life on long‐term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet
HC
l Therapy to Lower CardioVascular Events (
EVOLVE
) Trial.

Methods and Results

EVOLVE
was a randomized, double‐blind, placebo‐controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95%
CI
0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance.

Conclusions
Accepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes.

Clinical Trials Registration

Unique identifier: NCT00345839. URL:
ClinicalTrials.gov
.
Cluster Analysis of Downscaled and Explicitly Simulated North Atlantic Tropical Cyclone Tracks
Authors: Daloz Anne S. , Camargo S. J. , Kossin J. P. , Emanuel K. , Horn M. , Jonas J. A. , Kim D. , LaRow T. , Lim Y.-K. , Patricola C. M. , Roberts M. , Scoccimarro E. , Shaevitz D. , Vidale P. L. , Wang H. , Wehner M. , Zhao M. 
Published: November 2014

Abstract
A realistic representation of the North Atlantic tropical cyclone tracks is crucial as it allows, for example, explaining potential changes in U.S. landfalling systems. Here, the authors present a tentative study that examines the ability of recent climate models to represent North Atlantic tropical cyclone tracks. Tracks from two types of climate models are evaluated: explicit tracks are obtained from tropical cyclones simulated in regional or global climate models with moderate to high horizontal resolution (1°–0.25°), and downscaled tracks are obtained using a downscaling technique with large-scale environmental fields from a subset of these models. For both configurations, tracks are objectively separated into four groups using a cluster technique, leading to a zonal and a meridional separation of the tracks. The meridional separation largely captures the separation between deep tropical and subtropical, hybrid or baroclinic cyclones, while the zonal separation segregates Gulf of Mexico and Cape Verde storms. The properties of the tracks’ seasonality, intensity, and power dissipation index in each cluster are documented for both configurations. The authors’ results show that, except for the seasonality, the downscaled tracks better capture the observed characteristics of the clusters. The authors also use three different idealized scenarios to examine the possible future changes of tropical cyclone tracks under 1) warming sea surface temperature, 2) increasing carbon dioxide, and 3) a combination of the two. The response to each scenario is highly variable depending on the simulation considered. Finally, the authors examine the role of each cluster in these future changes and find no preponderant contribution of any single cluster over the others.
Asian Summer Monsoon in CMIP5 Projections: A Link between the Change in Extreme Precipitation and Monsoon Dynamics
Authors: Freychet Nicolas , Hsu Huang-Hsiung , Chou Chia , Wu Chi-Hua 
Published: November 2014

Abstract
Change in extreme events in climate projections is a major concern. If the frequency of dry events is expected to increase in a warmer climate (thus, the overall number of wet days will decrease), heavy and extreme precipitation are also expected to increase because of a shift of the precipitation spectrum. However, the forecasts exhibit numerous uncertainties.
This study focuses on the Asian region, separated into the following three subregions: the East Asian region, the Indian region, and western North Pacific region, where the summer monsoon can bring heavy rainfall. Particularly emphasized herein is the reliability of the projection, using data from a large ensemble of 30 models from phase 5 of the Coupled Model Intercomparison Project. The scattering of the ensemble enables obtaining an optimal estimate of the uncertainties, and it is used to compute the correlation between projected changes of extreme events and circulation changes.
The results show clear spatial and temporal variations in the confidence of changes, with results being more reliable during the wet season (i.e., the summer monsoon). The ensemble predicts changes in atmospheric circulation with favorable confidence, especially in the low-level moisture flux convergence (MFC). However, the correlation between this mean change and the modification of extreme events is nonsignificant. Also analyzed herein are the correlation and change of MFC exclusively during these events. The horizontal MFC exerts a nonnegligible influence on the change in the intensity of extremes. However, it is mostly the change in vertical circulation and moisture advection that is correlated with the change in frequency and intensity of extreme events.
Surface Water and Energy Budgets for the Mississippi River Basin in Three NCEP Reanalyses
Authors: Yang Rongqian , Ek Michael , Meng Jesse 
Published: November 2014

Abstract
Surface water and energy budgets from the National Centers for Environmental Prediction–U.S. Department of Energy (NCEP–DOE) Atmospheric Model Intercomparison Project (AMIP-II) Global Reanalysis 2 (GR2), the North American Regional Reanalysis (NARR), and the NCEP Climate Forecast System Reanalysis (CFSR) are compared here with each other and with available observations over the Mississippi River basin. The comparisons in seasonal cycle, interannual variation, and annual mean over a 31-yr period show that there are a number of noticeable differences and similarities in the large-scale basin averages. Warm season precipitation and runoff in the GR2 are too large compared to the observations, and seasonal surface water variation is small. By contrast, the precipitation in both NARR and CFSR is more reasonable and in better agreement with the observation, although the corresponding seasonal runoff is very small. The main causes of the differences in both surface parameterization and approach used in assimilating the observed precipitation datasets and snow analyses are then discussed. Despite the discrepancies in seasonal water budget components, seasonal energy budget terms in the three reanalyses are close to each other and to available observations. The interannual variations in both water and energy budgets are comparable. This study shows that the CFSR achieves a large improvement over the GR2, indicating that the CFSR dataset can be used in climate variability studies. Nonetheless, improved land surface parameterization schemes and data assimilation techniques are needed to depict the surface water and energy climates better, in particular, the variation in seasonal runoff.
Correction of ADCP Compass Errors Resulting from Iron in the Instrument’s Vicinity*
Authors: Appen Wilken-Jon von 
Published: November 2014

AbstractIron in the vicinity of compasses results in compass deviations. ADCPs mounted on steel buoyancy devices and deployed on seven moorings on the East Greenland outer shelf and upper slope from 2007 to 2008 suffered from severe compass deviations as large as 90°, rendering the ADCP data useless without a compass correction. The effects on the measured velocities, which may also be present in other oceanic velocity measurements, are explained. On each of the moorings, velocity measurements from a different instrument are overlapping in space and time with the compromised measurements. The iron was not in the vicinity of this second instrument, and the instrument is therefore assumed not to be affected by compass deviations. A method is described to determine the compass deviation from the compromised and uncompromised velocity measurements, and the compromised compass headings. The method depends on the assumptions that at least one instrument per mooring is not compromised and that the change in flow direction over the vertical distance from the compromised to the uncompromised velocity measurement is zero on average. With this method, the compromised headings and the compromised velocity records can be corrected. The method is described in detail and a MATLAB function implementing the method is supplied. The success of the method is demonstrated for a mooring with a minor compass deviation and for one with a large amplitude deviation.
Investigation of anti-oxidative stress in vitro and water apparent diffusion coefficient in MRI on rat after spinal cord injury in vivo with Tithonia diversifolia ethanolic extracts treatment
Authors: Juang Chi-Long , Yang Fei Shish , Hsieh Ming Shuang , Tseng Hu-Yi , Chen Su-Chiu , Wen Hsiao-Chuan 
Published: November 2014

Abstract

Background
Spinal cord injury (SCI)-induced secondary oxidative stress associates with a clinical complication and high mortality. Treatments to improve the neurological outcome of secondary injury are considered as important issues. The objective of the current study is to evaluate the anti-oxidative effect of Tithonia diversifolia ethanolic extracts (TDE) on cells and apply the pharmacological effect to SCI model using a MRI imaging algorism.

Methods
The anti-oxidation properties were tested in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Rat liver cells (clone-9) were treated with various doses of TDE (0 ~ 50 μg/ml) before exposed to 250 μM H2O2 and cell survival was determined by MTT and LDH assays. We performed water apparent diffusion coefficient (ADC) map in MR techniques to investigate the efficacy of TDE treatment on SCI animal model. We performed T5 laminectomy and compression (50 g, 1 min) to induce SCI. PHILIP 3.0 T MRI was used to image 24 male Sprague–Dawley rats weighing 280–320 g. Rats were randomly divided into three groups: sham group, SCI group, SCI treated with TDE group. The MRI images were taken and ADC were acquired before and after of treatment of TDE (50 mg/kg B. W. orally, 5 days) in SCI model.

Results
TDE protected clone-9 cells against H2O2-induced toxicity through DPPH scavenging mechanism. In addition, SCI induced the increase in ADC after 6 hours. TDE treatment slightly decreased the ADC level after 1-week SCI compared with control animals.

Conclusion
Our studies have proved that the cytoprotection effect of TDE, at least in part, is through scavenging ROS to eliminate intracellular oxidative stress and highlight a potential therapeutic consideration of TDE in alternative and complementary medicine.
Dual active layer a-IGZO TFT via homogeneous conductive layer formation by photochemical H-doping
Authors: Jeong Seung-Ki , Kim Myeong-Ho , Lee Sang-Yeon , Seo Hyungtak , Choi Duck-Kyun 
Published: November 2014

Abstract
In this study, InGaZnO (IGZO) thin film transistors (TFTs) with a dual active layer (DAL) structure are fabricated by inserting a homogeneous embedded conductive layer (HECL) in an amorphous IGZO (a-IGZO) channel with the aim of enhancing the electrical characteristics of conventional bottom-gate-structure TFTs. A highly conductive HECL (carrier concentration at 1.6 × 1013 cm-2, resistivity at 4.6 × 10-3 Ω∙cm, and Hall mobility at 14.6 cm2/Vs at room temperature) is fabricated using photochemical H-doping by irradiating UV light on an a-IGZO film. The electrical properties of the fabricated DAL TFTs are evaluated by varying the HECL length. The results reveal that carrier mobility increased proportionally with the HECL length. Further, a DAL TFT with a 60-μm-long HECL embedded in an 80-μm-long channel exhibits comprehensive and outstanding improvements in its electrical properties: a saturation mobility of 60.2 cm2/Vs, threshold voltage of 2.7 V, and subthreshold slope of 0.25 V/decade against the initial values of 19.9 cm2/Vs, 4.7 V, and 0.45 V/decade, respectively, for a TFT without HECL. This result confirms that the photochemically H-doped HECL significantly improves the electrical properties of DAL IGZO TFTs.
Rice miR172 induces flowering by suppressing OsIDS1 and SNB, two AP2 genes that negatively regulate expression of Ehd1 and florigens
Authors: Lee Yang-Seok , Lee Dong-Yeon , Cho Lae-Hyeon , An Gynheung 
Published: November 2014

Abstract

Background
Rice is a facultative short-day plant that flowers under long days (LD) after a lengthy vegetative phase. Although several inhibitors that delay flowering have been identified, the process by which rice eventually flowers under non-permissive LD conditions is not well understood.

Results
Overexpression of miR172 reduced flowering time significantly, suggesting its role as an inducer. Levels of miR172 increased as plants aged, further supporting our findings. Transcripts of SNB and OsIDS1, two members of the AP2 family that have the miR172 target site, were reduced in older plants as the level of miR172 rose. Overexpression of those AP2 genes delayed flowering; overexpression of miR172-resistant forms of SNB or OsIDS1 further delayed this process. This demonstrated that the AP2 genes function downstream of miR172. Two florigen genes -- Hd3a and RFT1 -- and their immediate upstream regulator Ehd1 were suppressed in the AP2 overexpression plants. This suggested that the AP2 genes are upstream repressors of Ehd1. In phytochrome mutants, miR172d levels were increased whereas those of SNB and OsIDS1 were decreased. Thus, it appears that phytochromes inhibit miR172d, an AP2 suppresser.

Conclusions
We revealed that miR172d developmentally induced flowering via repressing OsIDS1 and SNB, which suppressed Ehd1. We also showed that phytochromes negatively regulated miR172.
Protein in nutritional support: the newborn hero for the critically ill?
Authors: Oshima Taku , Heidegger Claudia P , Pichard Claude 
Published: November 2014

AbstractIn their current review, Weijs and colleagues highlight the importance of protein and amino acid provision for improving clinical outcome in critically ill patients. The interdependence between energy and protein is highlighted. They call for urgent research to develop new methods to evaluate protein and amino acid requirements, accurately and conveniently, in order to optimize nutrition support for critically ill patients.Appropriate nutrition delivery for critically ill patients remains a highly debated issue. Energy, a critical factor for life, was until now the superstar of nutrition support. It now faces a rival or, more correctly, a partner in function, namely protein. This is a chance to take a close look at protein, the new hero in the field of critical care nutrition, and the struggles it encounters in becoming the true superstar.
Aging and the intramyocardial inflammatory response
Authors: Walley Keith R 
Published: November 2014

AbstractThe sepsis-induced intramyocardial inflammatory response results in decreased ventricular function and myocardial damage. Chemokines such as monocyte chemoattractant protein-1 causally contribute to retention of intramyocardial mononuclear leukocytes and subsequent ventricular dysfunction during endotoxemic shock in mice and, importantly, this effect is age dependent. It is therefore useful to consider where monocyte chemoattractant protein-1 fits in the complex pathway leading to ventricular dysfunction during sepsis, why this might be an age-dependent effect, and what this implies for care of older sepsis patients.