bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the Mechanism and Therapeutic Potential of PTC-028, a Novel Inhibitor of BMI-1 Function in Ovarian Cancer
Authors: Dey Anindya , Xiong Xunhao , Crim Aleia , Dwivedi Shailendra Kumar Dhar , Mustafi Soumyajit Banerjee , Mukherjee Priyabrata , Cao Liangxian , Sydorenko Nadiya , Baiazitov Ramil , Moon Young-Choon , Dumble Melissa , Davis Thomas , Bhattacharya Resham 
Published: November 2017

Abstract
BMI-1, also known as a stem cell factor, is frequently upregulated in several malignancies. Elevated expression of BMI-1 correlates with poor prognosis and is therefore considered a viable therapeutic target in a number of malignancies including ovarian cancer. Realizing the immense pathologic significance of BMI-1, small-molecule inhibitors against BMI-1 are recently being developed. In this study, we functionally characterize PTC-028, an orally bioavailable compound that decreases BMI-1 levels by posttranslational modification. We report that PTC-028 treatment selectively inhibits cancer cells in clonal growth and viability assays, whereas normal cells remain unaffected. Mechanistically, hyperphosphorylation-mediated depletion of cellular BMI-1 by PTC-028 coupled with a concurrent temporal decrease in ATP and a compromised mitochondrial redox balance potentiates caspase-dependent apoptosis. In vivo, orally administered PTC-028, as a single agent, exhibits significant antitumor activity comparable with the standard cisplatin/paclitaxel therapy in an orthotopic mouse model of ovarian cancer. Thus, PTC-028 has the potential to be used as an effective therapeutic agent in patients with epithelial ovarian cancer, where treatment options are limited. Mol Cancer Ther; 17(1); 39–49. ©2017 AACR.
Favorable Effects of Endoscopic Ligation Combined with Drugs on Rebleeding and Mortality in Cirrhotic Patients: A Network Meta-Analysis
Authors: Shi Liang , Zhang Xueping , Li Jianye , Bai Xibo 
Published: November 2017

<b><i>Background:</i></b> To assess the effects of combination therapies (endoscopic plus drug[s], drug combinations) on variceal/any-cause rebleeding and mortality among cirrhotic patients with one previous episode of variceal hemorrhage. <b><i>Summary:</i></b> We searched PubMed, Embase, Cochrane Library, and Web of Science for eligible studies. We included 26 randomized controlled trials involving 2,536 adults using OR to measure the effects. Endoscopic variceal ligation (EVL) plus nadolol ranked first for reducing recurrent bleeds. Both EVL + nadolol and EVL + drugs (nadolol, sucralfate) decreased the risk of any-cause rebleeding than EVL alone (OR 0.34, 95% CI 0.12–0.97; OR 0.40, 95% CI 0.18–0.88, respectively). Meanwhile, EVL + drugs ranked first lowering mortality rates (P-score &#x3e;0.85) with a marginal superiority over EVL alone (OR 0.52, 95% CI 0.26–1.01). Beta-blockers with isosorbide mononitrate (ISMN) also reached a marginal superiority (OR 0.78, 95% CI 0.56–1.09) for improving mortality. <b><i>Key Messages:</i></b> Our findings indicated that EVL + nadolol might be the preferred choice to cirrhotic patients with one previous episode of variceal hemorrhage for preventing rebleeding. EVL + nadolol + sucralfate and beta-blockers + ISMN may be potential alternatives to improve mortality. Further, well-controlled studies are warranted to compare the promising combination therapies.
Rosuvastatin Reduces Aortic Sinus and Coronary Artery Atherosclerosis in SR-B1 (Scavenger Receptor Class B Type 1)/ApoE (Apolipoprotein E) Double Knockout Mice Independently of Plasma Cholesterol Lowering
Authors: Yu Pei , Xiong Ting , Tenedero Christine B. , Lebeau Paul , Ni Ran , MacDonald Melissa E. , Gross Peter L. , Austin Richard C. , Trigatti Bernardo L. 
Published: November 2017

Objective—
Rosuvastatin has been widely used in the primary and secondary prevention of coronary heart disease. However, its antiatherosclerotic properties have not been tested in a mouse model that could mimic human coronary heart disease. The present study was designed to test the effects of rosuvastatin on coronary artery atherosclerosis and myocardial fibrosis in SR-B1 (scavenger receptor class B type 1) and apoE (apolipoprotein E) double knockout mice.

Approach and Results—

Three-week-old SR-B1
−/−
/apoE
−/−
mice were injected daily with 10 mg/kg of rosuvastatin for 2 weeks. Compared with saline-treated mice, rosuvastatin-treated mice showed increased levels of hepatic PCSK9 (proprotein convertase subtilisin/kexin type-9) and LDLR (low-density lipoprotein receptor) message, increased plasma PCSK9 protein but decreased levels of hepatic LDLR protein and increased plasma total cholesterol associated with apoB (apolipoprotein B) 48-containing lipoproteins. In spite of this, rosuvastatin treatment was associated with decreased atherosclerosis in both the aortic sinus and coronary arteries and reduced platelet accumulation in atherosclerotic coronary arteries. Cardiac fibrosis and cardiomegaly were also attenuated in rosuvastatin-treated SR-B1
−/−
/apoE
−/−
mice. Two-week treatment with rosuvastatin resulted in significant decreases in markers of oxidized phospholipids in atherosclerotic plaques. In vitro analysis showed that incubation of bone marrow-derived macrophages with rosuvastatin substantially downregulated cluster of differentiation (CD)36 and inhibited oxidized LDL-induced foam cell formation.

Conclusions—

Rosuvastatin protected SR-B1
−/−
/apoE
−/−
mice against atherosclerosis and platelet accumulation in coronary arteries and attenuated myocardial fibrosis and cardiomegaly, despite increased plasma total cholesterol. The ability of rosuvastatin to reduce oxidized phospholipids in atherosclerotic plaques and inhibit macrophage foam cell formation may have contributed to this protection.
Changes in High-Density Lipoprotein Cholesterol Efflux Capacity After Bariatric Surgery Are Procedure Dependent
Authors: Heffron Sean P. , Lin Bing-Xue , Parikh Manish , Scolaro Bianca , Adelman Steven J. , Collins Heidi L. , Berger Jeffrey S. , Fisher Edward A. 
Published: November 2017

Objective—
High-density lipoprotein cholesterol efflux capacity (CEC) is inversely associated with incident cardiovascular events, independent of high-density lipoprotein cholesterol. Obesity is often characterized by impaired high-density lipoprotein function. However, the effects of different bariatric surgical techniques on CEC have not been compared. This study sought to determine the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on CEC.

Approach and Results—

We prospectively studied severely obese, nondiabetic, premenopausal Hispanic women not using lipid medications undergoing RYGB (n=31) or SG (n=36). Subjects were examined before and at 6 and 12 months after surgery. There were no differences in baseline characteristics between surgical groups. Preoperative CEC correlated most strongly with Apo A1 (apolipoprotein A1) concentration but did not correlate with body mass index, waist:hip, high-sensitivity C-reactive protein, or measures of insulin resistance. After 6 months, SG produced superior response in high-density lipoprotein cholesterol and Apo A1 quantity, as well as global and non-ABCA1 (ATP-binding cassette transporter A1)–mediated CEC (
P
=0.048,
P
=0.018, respectively) versus RYGB. In multivariable regression models, only procedure type was predictive of changes in CEC (
P
=0.05). At 12 months after SG, CEC was equivalent to that of normal body mass index control subjects, whereas it remained impaired after RYGB.

Conclusions—
SG and RYGB produce similar weight loss, but contrasting effects on CEC. These findings may be relevant in discussions about the type of procedure that is most appropriate for a particular obese patient. Further study of the mechanisms underlying these changes may lead to improved understanding of the factors governing CEC and potential therapeutic interventions to maximally reduce cardiovascular disease risk in both obese and nonobese patients.
Exogenous Insulin Infusion Can Decrease Atherosclerosis in Diabetic Rodents by Improving Lipids, Inflammation, and Endothelial Function
Authors: Park Kyoungmin , Li Qian , Evcimen Net Daş , Rask-Madsen Christian , Maeda Yasutaka , Maddaloni Ernesto , Yokomizo Hisashi , Shinjo Takanori , St-Louis Ronald , Fu Jialin , Gordin Daniel , Khamaisi Mogher , Pober David , Keenan Hillary , King George L. 
Published: November 2017

Objective—
The objective of this study is to evaluate whether exogenously induced hyperinsulinemia may increase the development of atherosclerosis.

Approach and Results—

Hyperinsulinemia, induced by exogenous insulin implantation in high-fat fed (60% fat HFD) apolipoprotein E–deficient mice (ApoE
−/−
) mice, exhibited insulin resistance, hyperglycemia, and hyperinsulinemia. Atherosclerosis was measured by the accumulation of fat, macrophage, and extracellular matrix in the aorta. After 8 weeks on HFD, ApoE
−/−
mice were subcutaneously implanted with control (sham) or insulin pellet, and phlorizin, a sodium glucose cotransporters inhibitor (1/2)inhibitor, for additional 8 weeks. Intraperitoneal glucose tolerance test showed that plasma glucose levels were lower and insulin and IGF-1 (insulin-like growth factor-1) levels were 5.3- and 3.3-fold higher, respectively, in insulin-implanted compared with sham-treated ApoE
−/−
mice. Plasma triglyceride, cholesterol, and lipoprotein levels were decreased in mice with insulin implant, in parallel with increased lipoprotein lipase activities. Atherosclerotic plaque by en face and complexity staining showed significant reductions of fat deposits and expressions of vascular adhesion molecule-1, tumor necrosis factor-α, interleukin 6, and macrophages in arterial wall while exhibiting increased activation of pAKT and endothelial nitric oxide synthase (
P
<0.05) comparing insulin-implanted versus sham HFD ApoE
−/−
mice. No differences were observed in atherosclerotic plaques between phlorizin-treated and sham HFD ApoE
−/−
mice, except phlorizin significantly lowered plasma glucose and glycated hemoglobin levels while increased glucosuria. Endothelial function was improved only by insulin treatment through endothelial nitric oxide synthase/nitric oxide activations and reduced proinflammatory (M1) and increased anti-inflammatory (M2) macrophages, which were inhibited by endothelial nitric oxide synthase inhibitor.

Conclusions—

Exogenous insulin decreased atherosclerosis by lowering inflammatory cytokines, macrophages, and plasma lipids in HFD-induced hyperlipidemia, insulin resistant and mildly diabetic ApoE
−/−
mice.
Angiography Versus Hemodynamics to Predict the Natural History of Coronary Stenoses
Authors: Ciccarelli Giovanni , Barbato Emanuele , Toth Gabor G. , Gahl Brigitta , Xaplanteris Panagiotis , Fournier Stephane , Milkas Anastasios , Bartunek Jozef , Vanderheyden Marc , Pijls Nico , Tonino Pim , Fearon William F. , Jüni Peter , De Bruyne Bernard 
Published: November 2017

Background:
Among patients with documented stable coronary artery disease and in whom no revascularization was performed, we compared the respective values of angiographic diameter stenosis (DS) and fractional flow reserve (FFR) in predicting natural history.

Methods:
The present analysis included the 607 patients from the FAME 2 trial (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation 2) in whom no revascularization was performed. FFR varied from 0.20 to 1.00 (average 0.74±0.16), and DS (by quantitative coronary analysis) varied from 8% to 98% (average 53±15). The primary end point, defined as vessel-oriented clinical end point (VOCE) at 2 years, was a composite of prospectively adjudicated cardiac death, vessel-related myocardial infarction, vessel-related urgent, and not urgent revascularization. The stenoses were divided into 4 groups according to FFR and %DS values: positive concordance (FFR≤0.80; DS≥50%), negative concordance (FFR>0.80; DS<50%), positive mismatch (FFR≤0.80; DS<50%), and negative mismatch (FFR>0.80; DS≥50%).

Results:

The rate of VOCE was highest in the positive concordance group (log rank: X
2
=80.96;
P
=0.001) and lowest in the negative concordance group. The rate of VOCE was higher in the positive mismatch group than in the negative mismatch group (hazard ratio, 0.38; 95% confidence interval, 0.21–0.67;
P
=0.001). There was no significant difference in VOCE between the positive concordance and positive mismatch groups (FFR≤0.80; hazard ratio, 0.77; 95% confidence interval, 0.57–1.09;
P
=0.149) and no significant difference in rate of VOCE between the negative mismatch and negative concordance groups (FFR>0.80; hazard ratio, 1.89; 95% confidence interval, 0.96–3.74;
P
=0.067).

Conclusions:
In patients with stable coronary disease, physiology (FFR) is a more important determinant of the natural history of coronary stenoses than anatomy (DS).

Clinical Trial Registration:

URL:
https://clinicaltrials.gov
. Unique identifier: NCT01132495.
High-Density Lipoprotein Subspecies Defined by Presence of Apolipoprotein C-III and Incident Coronary Heart Disease in Four Cohorts
Authors: Jensen Majken K. , Aroner Sarah A. , Mukamal Kenneth J. , Furtado Jeremy D. , Post Wendy S. , Tsai Michael Y. , Tjønneland Anne , Polak Joseph F. , Rimm Eric B. , Overvad Kim , McClelland Robyn L. , Sacks Frank M. 
Published: November 2017

Background:
The causal role of high-density lipoprotein (HDL) cholesterol in cardioprotection has been questioned by genetic and randomized studies. Novel measures that relate to HDL function may contribute new information to the prediction of cardiovascular risk. Apolipoprotein C-III (apoC-III) is a key regulator of lipoprotein metabolism. We investigated whether subspecies of HDL defined by apoC-III are associated with coronary heart disease (CHD).

Methods:
We used immunoaffinity chromatography to measure the apoA-I concentrations of HDL that contains and lacks apoC-III in 2 prospective studies of adults free of CHD. In MESA (Multi-Ethnic Study of Atherosclerosis), 5657 participants (52% women, 52–72 years of age) were followed for risk of CHD from 2000 to 2002 through 2013. In a case-cohort study nested within the DCH study (Danish Diet, Cancer, and Health), 3642 participants (47% women, 51–64 years of age) were followed from 1994 to 1997 through 2010. Subsequently, we conducted a meta-analysis that combined these results with the previously published findings from 2 cohort studies that used similar laboratory methodology to measure lipoproteins, totaling 2997 incident cases.

Results:

ApoC-III was found on 6% to 8% of apoA-I. The 2 HDL subspecies showed opposing associations, with risk of CHD in each of the individual cohorts and in the meta-analysis (
P
heterogeneity between the 2 subspecies <0.01). HDL that contains apoC-III was associated with a higher risk of CHD (pooled relative risk per standard deviation, 1.09; 95% confidence interval, 1.01–1.18), whereas HDL that lacks apoC-III was associated with lower risk (relative risk, 0.76; 95% confidence interval, 0.70–0.83). The relative risk for HDL lacking apoC-III was even more negative than the relative risk for total HDL (relative risk, 0.80; 95% confidence interval, 0.74–0.87).

Conclusions:
Our findings from 4 prospective studies support the hypothesis that apoC-III may mark a subfraction of HDL that is associated with higher risk of CHD. New measures reflecting HDL structure and function may provide novel insights for cardiovascular risk that extend beyond traditional plasma HDL cholesterol concentrations.
Atmospheric Overturning across Multiple Scales of an MJO Event during the CINDY/DYNAMO Campaign
Authors: Chen Xingchao , Pauluis Olivier M. , Zhang Fuqing 
Published: November 2017

Abstract
This study investigates the atmospheric overturning of the October 2011 MJO event observed during the Cooperative Indian Ocean Experiment on Intraseasonal Variability in the Year 2011 (CINDY)/DYNAMO field experiment using a cloud-permitting numerical model. The isentropic analysis is used to sort the vertical mass transport in terms of the equivalent potential temperature of the air parcels, which naturally decomposes the atmospheric overturning between ascending air with high entropy and subsiding air with low entropy. The circulation is further decomposed into contributions of four main scales: basinwide ascent, meridional overturning, regional overturning, and convection. Results show that the convective scale dominates the upward mass transport while larger scales play an important role both by allowing a deeper overturning and by modulating convective activity. There are substantial changes in the atmospheric overturning during different phases of this MJO event. Increased convective activity at low levels precedes the onset of the MJO by several days. The initiation of the MJO itself is associated with a substantial increase in the atmospheric overturning over the Indian Ocean. The subsequent eastward propagation of the MJO event can be clearly captured by the evolutions of convective-scale vertical mass fluxes at different altitudes. The equivalent potential temperatures of the rising and subsiding air parcels in the convective-scale overturning are also increased in the troposphere during the active phase of the MJO.
Potential Large-Scale Forcing Mechanisms Driving Enhanced North Atlantic Tropical Cyclone Activity since the Mid-1990s
Authors: Zhao Haikun , Duan Xingyi , Raga G. B. , Sun Fengpeng 
Published: November 2017

AbstractA significant increase of tropical cyclone (TC) frequency is observed over the North Atlantic (NATL) basin during the recent decades (1995–2014). In this study, the changes in large-scale controls of the NATL TC activity are compared between two periods, one before and one since 1995, when a regime change is observed. The results herein suggest that the significantly enhanced NATL TC frequency is related mainly to the combined effect of changes in the magnitudes of large-scale atmospheric and oceanic factors and their association with TC frequency. Interdecadal changes in the role of vertical wind shear and local sea surface temperatures (SSTs) over the NATL appear to be two important contributors to the recent increase of NATL TC frequency. Low-level vorticity plays a relatively weak role in the recent increase of TC frequency. These changes in the role of large-scale factors largely depend on interdecadal changes of tropical SST anomalies (SSTAs). Enhanced low-level westerlies to the east of the positive SSTAs have been observed over the tropical Atlantic since 1995, with a pattern nearly opposite to that seen before 1995. Moreover, the large-scale contributors to the NATL TC frequency increase since 1995 are likely related to both local and remote SSTAs. Quantification of the impacts of local and remote SSTAs on the increase of TC frequency over the NATL basin and the physical mechanisms require numerical simulations and further observational analyses.
Evaluation of Downscaled CMIP5 Coupled with VIC Model for Flash Drought Simulation in a Humid Subtropical Basin, China
Authors: Zhang Yuqing , You Qinglong , Chen Changchun , Ge Jing , Adnan Muhammad 
Published: November 2017

Abstract
Compared to traditional drought events, flash droughts evolve rapidly during short-term extreme atmospheric conditions, with a lasting period of one pentad to several weeks. There are two main categories of flash droughts: the heat wave flash drought (HWFD), which is mainly caused by persistent high temperatures (heat waves), and the precipitation deficit flash drought (PDFD), which is mainly triggered by precipitation deficits. The authors’ previous research focused on the characteristics and causes of flash drought based on meteorological observations and Variable Infiltration Capacity (VIC) model simulations in a humid subtropical basin (Gan River basin, China). In this study, the authors evaluated the downscaled phase 5 of the Coupled Model Intercomparison Project (CMIP5) models’ simulations, coupled with the VIC model (CMIP5–VIC) in reproducing flash droughts in a humid subtropical basin in China. Most downscaled CMIP5–VIC simulations can reproduce the spatial patterns of flash droughts with respect to the benchmarks. The coupled models fail to readily replicate interannual variation (interannual pentad change), but most models can reflect the interannual variability (temporal standard deviation) and long-term average pentads of flash droughts. It is difficult to simultaneously depict both the spatial and temporal features of flash droughts within only one coupled model. The climatological patterns of the best multimodel ensemble mean are close to those of the all-model ensemble mean, but the best multimodel ensemble mean has a minimal bias range and relatively low computational burden.
Multiscale Variations of Precipitable Water over China Based on 1999–2015 Ground-Based GPS Observations and Evaluations of Reanalysis Products
Authors: Zhang Weixing , Lou Yidong , Huang Jinfang , Zheng Fu , Cao Yunchang , Liang Hong , Shi Chuang , Liu Jingnan 
Published: November 2017

Abstract
The dense ground-based GPS provides a good tool to study water vapor distribution and multiscale variations, especially for linear trends on the interannual scale and short-term variations on the diurnal scale. It can also serve as an independent data source to evaluate performances of reanalyses. In this study, the 6-hourly precipitable water (PW) products at more than 260 GPS stations over China from 1999 to 2015 were analyzed and eight commonly used reanalyses, including 20CR version 2 (20CRv2), CFSR, ERA-Interim, JRA-25, JRA-55, MERRA, NCEP–NCAR, and NCEP–DOE AMIP-II, were evaluated. The climatological annual mean GPS PW distribution over China roughly shows a decreasing trend from southeast to northwest, with the largest annual and semiannual amplitudes in the lower reaches of the Yangtze River and mideastern China, respectively, and the smallest values in the Tibetan Plateau and southwestern China. All reanalyses (except for 20CRv2) can generally reproduce well the climatological annual mean PW (within 20%), annual amplitudes (within 20%), and semiannual amplitudes (within 20% except in the tropical monsoon region), but they all show wet biases in the Tibetan Plateau. Diurnal variation amplitudes reproduced by all reanalysis products are smaller than amplitudes estimated from GPS observations over China as a whole, and none of the reanalyses can capture the diurnal phases correctly. PW linear trends at most GPS stations in the recent 16 years are insignificant or with absolute values smaller than 0.10 mm yr−1. However, because of the assimilation of the unhomogenized radiosonde humidity data, most reanalyses show artificial decreasing PW trends (except in 20CRv2 and CFSR).