bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Bromodomain BET Inhibitor JQ1 Suppresses Tumor Angiogenesis in Models of Childhood Sarcoma
Authors: Bid Hemant K. , Phelps Doris A. , Xaio Linlin , Guttridge Denis C. , Lin Jiayuh , London Cheryl , Baker Laurence H. , Mo Xiaokui , Houghton Peter J. 
Published: February 2016

Abstract
The bromodomain and extra-terminal domain inhibitor JQ1 has marked antitumor activity against several hematologic malignancies as well as solid tumor models. Here, we investigated its activity in vitro and in vivo against models of childhood rhabdomyosarcoma and Ewing sarcoma. In vitro, JQ1 (but not the inactive enantiomer JQ1R) inhibited cell proliferation and increased G1 fraction of cells, although there was no correlation between cell line sensitivity and suppression of c-MYC or MYCN. In vivo, xenografts showed significant inhibition of growth during the period of treatment, and rapid regrowth after treatment was stopped, activity typical of antiangiogenic agents. Furthermore, xenografts derived from cell lines intrinsically resistant or sensitive to JQ1 in vitro had similar sensitivity in vivo as xenografts. Further investigation showed that JQ1 reduced tumor vascularization. This was secondary to both drug-induced downregulation of tumor-derived growth factors and direct effects of JQ1 on vascular elements. JQ1 suppressed VEGF-stimulated vascularization of Matrigel plugs in mice, and in vitro suppressed differentiation, proliferation, and invasion of human umbilical cord vascular endothelial cells (HUVEC). In HUVECs, JQ1 partially suppressed c-MYC levels, but dramatically reduced AP-1 levels and activity through suppression of the AP-1–associated protein FOSL1. Our data suggest that the antitumor activity of JQ1 in these sarcoma models is largely a consequence of its antiangiogenic activity. Mol Cancer Ther; 15(5); 1018–28. ©2016 AACR.
The Effect of Atorvastatin on Breast Cancer Biomarkers in High-Risk Women
Authors: Ji YongLi , Rounds Tiffany , Crocker Abigail , Sussman Betsy , Hovey Russell C. , Kingsley Fonda , Muss Hyman B. , Garber Judy E. , Wood Marie E. 
Published: February 2016

AbstractStatins have the potential to reduce breast cancer incidence and recurrence as shown in both epidemiologic and laboratory studies. The purpose of this study was to evaluate the effect of a lipophilic statin, atorvastatin, on breast cancer biomarkers of risk [mammographic density (MD) and insulin growth factor 1 (IGF-1)] in high-risk premenopausal women.Premenopausal women at increased risk for breast cancer received either 40 mg of atorvastatin or placebo for 1 year. Biomarker assessment was performed prior to initiation and at completion of study medication. MD was determined using both Breast Imaging Reporting and Data System and the visual analogue scale. Serum IGF-1 was determined by ELISA assay at the end of the study.Sixty-three women were enrolled between December 2005 and May 2010. Sixteen (25%) women withdrew. The mean age of participants was 43 (range, 35–50), 100% were white, and the average body mass index (BMI) was 26.4. The statin group demonstrated a significant decrease in cholesterol and low-density lipoprotein (LDL), suggesting compliance with study medication. After accounting for BMI, there was no difference in change in MD between groups. There was a significant increase in serum IGF-1 in the statin group.In this multi-institutional randomized prospective clinical trial of premenopausal women at increased risk for breast cancer, we did not see an effect of atorvastatin on MD. Further investigation of statins may be warranted; however, design of prior trials and potential mechanism of action of the agent need to be considered in the design of future trials. Cancer Prev Res; 9(5); 379–84. ©2016 AACR.
Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice
Authors: Poulsen Christian Bo , Mortensen Martin Bødtker , Koechling Wolfgang , Sørensen Charlotte Brandt , Bentzon Jacob Fog 
Published: February 2016

Background

Treatment of prostate cancer often involves androgen deprivation therapy (ADT) by gonadotropin‐releasing hormone (GnRH) receptor agonists, GnRH receptor antagonists, or orchiectomy. ADT may increase the rate of cardiovascular disease events, but recent clinical studies suggested that not all means of ADT carry the same risk, raising the possibility of non–testosterone‐mediated effects of different forms of ADT on atherosclerosis. Here we compared effects of ADT on atherosclerosis in intact and orchiectomized
Apoe
‐deficient mice.

Methods and Results

Chow‐fed
Apoe‐
deficient mice were allocated to orchiectomy and/or monthly injections with the GnRH receptor agonist leuprolide or the GnRH receptor antagonist degarelix. Atherosclerosis was quantified at 26 weeks of age in the aortic arch by en face examination and in the aortic root by histology. In intact
Apoe‐
deficient mice, all types of ADT reduced testosterone production to castration levels. Although hypercholesterolemia was accentuated in leuprolide‐treated mice, the amount and composition of atherosclerosis was not different between the different types of ADT. In orchiectomized
Apoe‐
deficient mice, leuprolide, but not degarelix, augmented hypercholesterolemia, changed body, thymus, and spleen weights, and increased atherosclerosis in the aortic root. No direct effects of the drugs were detectable on cytokine secretion from murine bone marrow–derived macrophages or on splenocyte proliferation.

Conclusions

No differences in the development of atherosclerosis were detected among groups of intact
Apoe‐
deficient mice treated with different types of ADT. A pro‐atherogenic, possibly cholesterol‐mediated, effect of leuprolide was seen in orchiectomized mice that might be relevant for understanding the potential cardiovascular risk associated with GnRH agonist‐based ADT.
Early Endovascular Treatment in Intravenous Tissue Plasminogen Activator–Ineligible Patients
Authors: Rebello Letícia C. , Haussen Diogo C. , Grossberg Jonathan A. , Belagaje Samir , Lima Andrey , Anderson Aaron , Frankel Michael R. , Nogueira Raul G. 
Published: February 2016

Background and Purpose—
Intravenous tissue-type plasminogen activator (tPA) treatment in acute stroke has many exclusion criteria. We aimed to assess the safety and efficacy of endovascular therapy (ET) in intravenous (IV) tPA-ineligible patients.

Methods—
Retrospective analysis of a prospectively collected database of consecutive patients treated with ET within 6 hours of stroke onset between September 2010 and April 2015. Patients treated with IV-tPA followed by ET were compared with those treated with ET alone because of IV-tPA ineligibility. Efficacy and safety end points included the rates of good outcome (90-day modified Rankin scale score ≤2), successful reperfusion (modified Treatment in Cerebral Ischemia 2b-3), parenchymal hematoma (PH-1 and PH-2), and 90-day mortality. Univariate and logistic regression were performed to identify the predictors of outcomes.

Results—

A total of 422 patients were included. Two hundred and fifty-three (59%) patients received IV-tPA+ET, and 169 (41%), ET alone. Combined IV-tPA+ET patients were slightly younger (64.9±15.2 versus 67.9±14.9 years;
P
=0.05), more often males (56% versus 44%;
P
=0.01), and had less hypertension (70% versus 81%;
P
=0.02) and vertebrobasilar occlusions (3% versus 8%;
P
=0.02). The remaining baseline characteristics, including National Institutes of Health Stroke Scale score (20 [15–23] versus 19 [15–24];
P
=0.85), Alberta Stroke Program Early CT Score (ASPECTS; 8 [7–9] versus 8 [7–9];
P
=0.24), and stroke onset to puncture times (235±70 versus 240±81 minutes;
P
=0.27), were similar across both groups. There were no significant differences in the rates of modified Treatment in Cerebral Ischemia 2b-3 (83% versus 80%;
P
=0.52), 90-day modified Rankin scale score ≤2 (45% versus 38%;
P
=0.21), or any PH (3% versus 5%;
P
=0.21). Unadjusted 90-day mortality was higher with ET alone (21% versus 34%;
P
<0.01); however, IV-tPA ineligibility was not associated with modified Treatment in Cerebral Ischemia 2b-3, any PH, good outcome, or 90-day mortality on logistic regression.

Conclusions—
IV-tPA-eligible and -ineligible patients seem to have similar outcomes after early ET.
Changes in the Seoul Metropolitan Area Urban Heat Environment with Residential Redevelopment
Authors: Hong Je-Woo , Hong Jinkyu 
Published: February 2016

AbstractSince the Industrial Revolution, the geographical extent of cities has increased around the world. In particular, following three decades of rapid regional economic growth, many Asian megacities have emerged and continue to expand, resulting in inevitable short-term urban redevelopment. In this region, the microclimatic impacts of urban redevelopment have not been extensively investigated using long-term in situ observations. In this study, changes in surface sensible heat exchange, heat storage, and anthropogenic heat emissions that are due to urban residential redevelopment were quantified and analyzed on the basis of a 3-yr micrometeorological record from the Seoul, South Korea, metropolitan area. The results show that, following urban redevelopment of compact high-rise residential buildings, 1) the daily minimum air temperature near the ground surface increased by ~0.6 K; 2) the ratio between surface sensible heat and net radiation increased by from ~9% (summer) to 31% (winter), anthropogenic heat emissions increased by from 7.6 (summer) to 23.6 (spring) W m−2, and daily maximum heat storage ranged from 35.1 (spring) to 54.5 (summer) W m−2; and 3) there was a transition of local circulation with changes in the surface properties of heat sources and roughness.
Early-Warning Signals for the Onsets of Greenland Interstadials and the Younger Dryas–Preboreal Transition
Authors: Rypdal Martin 
Published: February 2016

AbstractThe climate system approaches a tipping point if the prevailing climate state loses stability, making a transition to a different state possible. A result from the theory of randomly driven dynamical systems is that the reduced stability in the vicinity of a tipping point is accompanied by increasing fluctuation levels and longer correlation times (critical slowing down) and can in principle serve as early-warning signals of an upcoming tipping point. This study demonstrates that the high-frequency band of the δ18O variations in the North Greenland Ice Core Project displays fluctuation levels that increase as one approaches the onset of an interstadial (warm) period. Similar results are found for the locally estimated Hurst exponent for the high-frequency fluctuations, signaling longer correlation times. The observed slowing down is found to be even stronger in the Younger Dryas, suggesting that both the Younger Dryas–Preboreal transition and the onsets of the Greenland interstadials are preceded by decreasing stability of the climate state. It is also verified that the temperature fluctuations during the stadial periods can be approximately modeled as a scale-invariant persistent noise, which can be approximated as an aggregation of processes that respond to perturbations on certain characteristic time scales. The results are consistent with the hypothesis that both the onsets of the Greenland interstadials and the Younger Dryas–Preboreal transition are caused by tipping points in dynamical processes with characteristic time scales on the order of decades and that the variability of other processes on longer time scales masks the early-warning signatures in the δ18O signal.
Orographic Precipitation in Coastal Southern Chile: Mean Distribution, Temporal Variability, and Linear Contribution
Authors: Garreaud R. , Falvey M. , Montecinos A. 
Published: February 2016

AbstractThe Nahuelbuta Mountains (NM) are a semielliptical massif 1300 m high in coastal southern Chile (37°–38°S) facing frontal storms that move from the Pacific. Mean precipitation between 900 and 1200 mm yr−1 is observed in the surrounding lowland, but river flow measurements suggest values ≥3000 mm yr−1 atop the mountains. To verify and characterize such marked orographic enhancement, 15 rain gauges were deployed around and over the NM. The observations were supplemented by a high-resolution WRF simulation and linear theory (LT) modeling during the winter of 2011. The estimated mean precipitation increases gradually from offshore (~1000 mm yr−1) to the north-facing foothills (2000 mm yr−1). The precipitation rapidly increases in the upslope sector to reach ~4000 mm yr−1 over the northern half of the NM elevated plateau, and decreases farther south to reach background values 20–30 km downstream of the mountains. The upstream (downstream) orographic enhancement (suppression) was relatively uniform among storms when considering event accumulations but varied substantially within each storm, with larger modifications during pre- and postfrontal stages and minor modifications during the brief but intense frontal passage. WRF results are in good agreement with observations in terms of seasonal and daily mean rainfall distributions, as well as temporal variability. Given its linear, steady-state formulation, the LT model cannot resolve rainfall variability at short (hourly) time scales, which in WRF is at least characterized by transient, mesoscale rainbands. Nonetheless, the rainbands are mobile so the accumulation field at monthly or longer time scales produced by the linear model is remarkably similar to its WRF counterpart.
On the Use of X-Band Weather Radar for Wind Field Retrieval in Coastal Zone
Authors: Forget P. , Saillard M. , Guérin C.-A. , Testud J. , Le Bouar E. 
Published: February 2016

AbstractThis paper documents the study of the radar signature of the sea surface on the images collected by an X-band weather radar and its application to remote sensing of the coastal zone. The main radar parameters considered here are the reflectivity factor [which was converted into a normalized radar cross section (NRCS)], the differential reflectivity, and the mean radial velocity. Measurements of the NRCS in the vicinity of an instrumented offshore buoy allowed for identifying its variations with wind speed and relative direction, which are found to be consistent with the Georgia Institute of Technology (GIT) model and other measurements. A more accurate empirical model for the NRCS is developed. For moderate to strong winds, the mean radial velocity is linearly related to the radial component of the wind speed, showing the potentiality of weather radars to map the radial surface wind speed at the scale of a basin. The influence of surface currents is weak here but should be likely taken into account in other places with stronger currents. Measurements of the differential reflectivity are also consistent with other measurements made elsewhere for the polarization ratio. The analysis of radar data over the entire coverage could also be performed using surface wind estimates from a meteorological model. Similar but less accurate results are obtained for the NRCS and the mean radial velocity. The extra spatial variability not due to wind speed variations is identified. An inversion procedure is proposed to recover the wind vector field from radar measurements after calibration of the NRCS values. Results are promising and pave the way to the concept of weather radar for ocean remote sensing.
Sensitivity to the Representation of Microphysical Processes in Numerical Simulations during Tropical Storm Formation
Authors: Penny Andrew B. , Harr Patrick A. , Doyle James D. 
Published: February 2016

AbstractAn analysis of in situ observations from the nondeveloping tropical disturbance named TCS025 revealed that a combination of unfavorable system-scale and environmental factors limited further development. In this study, a multiphysics ensemble of high-resolution simulations of TCS025 are analyzed and compared. A simulation that overdeveloped the TCS025 disturbance is compared with one that correctly simulated nondevelopment and reveals that convection was stronger and diabatic heating rates were larger in the developing simulation. This led to continued spinup of the low-level circulation primarily through vorticity stretching. In contrast, convection was much weaker in the nondeveloping simulation, and after an initial period of deep convection, average vorticity tendencies from stretching became weakly negative, which allowed for the frictional spindown of the low-level circulation.Convective-scale differences identified early in the simulations appear to have resulted from the explicit representation of graupel in the developing simulation. The net impacts resulting from these differences in convection are manifest in the average diabatic heating profiles that are important for determining the developmental outcome. Additional simulations are conducted whereby the diabatic heating rates are artificially adjusted. Relatively small changes in the diabatic heating rate led to significantly different outcomes with respect to storm development, and the degree of overdevelopment is largely dictated by the diabatic heating rate. These findings suggest the correct representation of convective processes and associated diabatic heating are necessary to adequately forecast tropical cyclogenesis, especially for systems near a threshold of development like TCS025.
Sinonasal Tract Inflammation as a Precursor to Nasopharyngeal Carcinoma
Authors: Riley Charles A. , Marino Michael J. , Hawkey Nathan , Lawlor Claire M. , McCoul Edward D. 
Published: February 2016

ObjectiveChronic inflammation has been described as a precursor to the development of malignancy in several disease states. However, the relationship of sinonasal tract inflammation to nasopharyngeal carcinoma (NPC) remains poorly defined.Data SourcesSystematic review of primary studies identified through PubMed, EMBASE, MEDLINE, and Cochrane.Methods ReviewSystematic review and meta‐analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines. MEDLINE, EMBASE, and Cochrane databases were queried for English‐language studies published between 1980 and 2015. Studies were excluded that did not provide quantitative data on sinonasal tract inflammation such as chronic rhinosinusitis (CRS), allergic rhinitis (AR), or human papillomavirus (HPV) status and NPC. An itemized assessment of the risk of bias was conducted for each included study.ResultsOf the 325 studies identified during systematic review, 5 met the criteria for analysis. The level of evidence of those studies was generally low. There was an increased risk of NPC in patients with a previous diagnosis of CRS or AR. Meta‐analysis demonstrated an odds ratio (95% confidence interval [CI]) of 2.35 (2.00‐2.76) for all studies. Subgroup analysis of patients with sinonasal inflammation had an odds ratio of 2.39 (95% CI, 2.20‐2.60). Patients with AR had an odds ratio of 2.29 (95% CI, 2.06‐2.54), while those with CRS had an odds ratio of 2.70 (95% CI, 1.98‐3.70).ConclusionsThis systematic review and meta‐analysis suggests an association between previous sinonasal inflammatory disease and subsequent NPC. Prospective studies are needed to further examine this relationship.
Safety of Ultrasound‐Guided Botulinum Toxin Injections for Sialorrhea as Performed by Pediatric Otolaryngologists
Authors: Shariat‐Madar Bahbak , Chun Robert H. , Sulman Cecille G. , Conley Stephen F. 
Published: February 2016

ObjectiveTo evaluate incidence of complications and hospital readmission as a result of ultrasound‐guided botulinum toxin injections to manage sialorrhea.Study DesignCase series with chart review.SettingChildren’s Hospital of Wisconsin.Subjects and MethodsA case series with chart review was performed of all cases of ultrasound‐guided injection of botulinum toxin by pediatric otolaryngologists from March 5, 2010, to September 26, 2014,. Primary outcomes included complications such as dysphagia, aspiration pneumonia, and motor paralysis. Secondary outcomes included hospitalization, intubation, and nasogastric tube placement.ResultsThere were 48 patients, 111 interventions, and 306 intraglandular injections identified. Botulinum toxin type A and type B were utilized in 4 and 107 operative interventions, respectively. Type A was injected into 4 parotid and 4 submandibular glands, utilizing doses of 20 U per parotid and 30 U per submandibular gland. Type B was injected into 98 parotid and 200 submandibular glands, with average dosing of 923 U per parotid and 1170 U per submandibular gland, respectively. There were 2 instances of subjectively worsening of baseline dysphagia that self‐resolved. No cases were complicated by aspiration pneumonia or motor paralysis. No patients required hospital readmission, intubation, or nasogastric tube placement.ConclusionPrior published data indicated 16% complication incidence with ultrasound‐guided injection of botulinum toxin. Our study found a low complication rate (0.6%) with ultrasound‐guided injections of botulinum toxin to manage sialorrhea, without cases of aspiration pneumonia or motor paralysis. Of 306 intraglandular injections, there were 2 cases of worsening baseline subjective dysphagia that self‐resolved.
ClariVein® – Early results from a large single-centre series of mechanochemical endovenous ablation for varicose veins
Authors: Tang TY , Kam JW , Gaunt ME 
Published: February 2016

Objectives This study assessed the effectiveness and patient experience of the ClariVein® endovenous occlusion catheter for varicose veins from a large single-centre series in the UK. Methods A total of 300 patients (371 legs) underwent ClariVein® treatment for their varicose veins; 184 for great saphenous vein (GSV) incompetence, 62 bilateral GSV, 23 short saphenous vein (SSV), 6 bilateral SSV and 25 combined unilateral great saphenous vein and SSV. Patients were reviewed at an interval of two months post procedure and underwent Duplex ultrasound assessment. Postoperative complications were recorded along with patient satisfaction. Results All 393 procedures were completed successfully under local anaesthetic. Complete occlusion of the treated vein was initially achieved in all the patients, but at eight weeks’ follow-up, there was only partial obliteration in 13/393 (3.3%) veins. These were all successfully treated with ultrasound-guided foam sclerotherapy. Procedures were well tolerated with a mean pain score of 0.8 (0–10). No significant complications were reported. Conclusions ClariVein® can be used to ablate long and short saphenous varicose veins on a walk-in–walk-out basis. Bilateral procedures can be successfully performed, and these are well tolerated as can multiple veins in the same leg. Early results are promising but further evaluation and longer term follow-up are required.