bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tofacitinib versus methotrexate in rheumatoid arthritis: patient-reported outcomes from the randomised phase III ORAL Start trial
Authors: Strand Vibeke , Lee Eun Bong , Fleischmann Roy , Alten Rieke E , Koncz Tamas , Zwillich Samuel H , Gruben David , Wilkinson Bethanie , Krishnaswami Sriram , Wallenstein Gene 
Published: September 2016

ObjectivesTo compare patient-reported outcomes (PROs) in methotrexate (MTX)-naive patients (defined as no prior treatment or ≤3 doses) receiving tofacitinib versus MTX.MethodsIn the 24-month, phase III, randomised, controlled, ORAL Start trial (NCT01039688), patients were randomised 2:2:1 to receive tofacitinib 5 mg two times per day (n=373), tofacitinib 10 mg two times per day (n=397) or MTX (n=186). PROs assessed included Patient Global Assessment of disease (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and health-related quality of life (Short Form-36 [SF-36]).ResultsPROs improved following tofacitinib and MTX treatment: benefits were sustained over 24 months. Patients receiving tofacitinib reported earlier responses which were significantly different between each tofacitinib dose and MTX at month 3 through month 24. At month 6 (primary end point), significant improvements versus MTX were observed in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 5/8 domain scores and FACIT-F with tofacitinib 5 mg two times per day; all PROs, except SF-36 Mental Component Summary Score and Medical Outcomes Survey-Sleep, with tofacitinib 10 mg two times per day. At month 6, the proportion of patients reporting improvements ≥minimum clinically important difference were significant versus MTX with tofacitinib 5 mg two times per day in PtGA and 3/8 SF-36 domains; and with tofacitinib 10 mg two times per day in PtGA, pain, HAQ-DI, SF-36 PCS, 4/8 domains and FACIT-F.ConclusionsPatients with rheumatoid arthritis receiving tofacitinib 5 and 10 mg two times per day monotherapy versus MTX reported statistically significant and clinically meaningful improvements in multiple PROs over 24 months; onset of benefit with tofacitinib treatment occurred earlier.Trial registration numberNCT01039688.
Petrogenesis of mafic magmatic enclaves of the Bundelkhand granitoids near Orchha, Central Indian shield: evidence for rapid crystallization
Authors: Ramiz Mir Md , Mondal M. E. A. 
Published: September 2016

Abstract
An attempt has been made to understand the origin and emplacement of the widespread mafic magmatic enclaves (MMEs) in the Neoarchean–Palaeoproterozoic Bundelkhand granitoids in the central Indian shield. These MMEs are very fine grained in texture, elliptical and ovoidal in shape and have a very sharp contact with the host granitoids. The MMEs exhibit sub-ophitic texture, acicular apatite and overgrowth of orthopyroxene over olivine crystals pointing towards a rapid crystallization of the MMEs magma in the granitoid magma. The host granitoids are calc-alkaline while the MMEs are tholeiitic, indicating contrasting geochemical composition. Low concentration of Rb, Sr, Ba and K in MMEs points away from the magma mixing with the granitoid magma. Both MMEs and host granitoids are metaluminous and are formed in a subduction zone environment. Although both MMEs and the granitoids were formed at the same time as the mafic magma was injected into the granitoid magma which was still crystallizing (semimolten stage), negligible to no mixing took place between the two contrasting magmas. We propose that the MMEs in the Bundelkhand granitoids are the result of rapid crystallization of the mafic magma in the cooler felsic one.
Doxorubicin-Induced Systemic Inflammation Is Driven by Upregulation of Toll-Like Receptor TLR4 and Endotoxin Leakage
Authors: Wang Lintao , Chen Qian , Qi Haixia , Wang Chunming , Wang Cheng , Zhang Junfeng , Dong Lei 
Published: September 2016

Abstract
Doxorubicin is one of the most effective chemotherapeutic agents used for cancer treatment, but it causes systemic inflammation and serious multiorgan side effects in many patients. In this study, we report that upregulation of the proinflammatory Toll-like receptor TLR4 in macrophages by doxorubicin is an important step in generating its toxic side effects. In patient serum, doxorubicin treatment resulted in leakage of endotoxin and inflammatory cytokines into circulation. In mice, doxorubicin damaged the intestinal epithelium, which also resulted in leakage of endotoxin from the gut flora into circulation. Concurrently, doxorubicin increased TLR4 expression in macrophages both in vitro and in vivo, which further enhanced the sensitivity of these cells to endotoxin. Either depletion of gut microorganisms or blockage of TLR4 signaling effectively decreased doxorubicin-induced toxicity. Taken together, our findings suggest that doxorubicin-triggered leakage of endotoxin into the circulation, in tandem with enhanced TLR4 signaling, is a candidate mechanism underlying doxorubicin-induced systemic inflammation. Our study provides new insights for devising relevant strategies to minimize the adverse effects of chemotherapeutic agents such as doxorubicin, which may extend its clinical uses to eradicate cancer cells. Cancer Res; 76(22); 6631–42. ©2016 AACR.
Somatic and Germline TP53 Alterations in Second Malignant Neoplasms from Pediatric Cancer Survivors
Authors: Sherborne Amy L. , Lavergne Vincent , Yu Katharine , Lee Leah , Davidson Philip R. , Mazor Tali , Smirnoff Ivan V. , Horvai Andrew E. , Loh Mignon , DuBois Steven G. , Goldsby Robert E. , Neglia Joseph P. , Hammond Sue , Robison Leslie L. , Wustrack Rosanna , Costello Joseph F. , Nakamura Alice O. , Shannon Kevin M. , Bhatia Smita , Nakamura Jean L. 
Published: September 2016

Abstract
Purpose: Second malignant neoplasms (SMNs) are severe late complications that occur in pediatric cancer survivors exposed to radiotherapy and other genotoxic treatments. To characterize the mutational landscape of treatment-induced sarcomas and to identify candidate SMN-predisposing variants, we analyzed germline and SMN samples from pediatric cancer survivors.
Experimental Design: We performed whole-exome sequencing (WES) and RNA sequencing on radiation-induced sarcomas arising from two pediatric cancer survivors. To assess the frequency of germline TP53 variants in SMNs, Sanger sequencing was performed to analyze germline TP53 in 37 pediatric cancer survivors from the Childhood Cancer Survivor Study (CCSS) without any history of a familial cancer predisposition syndrome but known to have developed SMNs.
Results: WES revealed TP53 mutations involving p53′s DNA-binding domain in both index cases, one of which was also present in the germline. The germline and somatic TP53-mutant variants were enriched in the transcriptomes for both sarcomas. Analysis of TP53-coding exons in germline specimens from the CCSS survivor cohort identified a G215C variant encoding an R72P amino acid substitution in 6 patients and a synonymous SNP A639G in 4 others, resulting in 10 of 37 evaluable patients (27%) harboring a germline TP53 variant.
Conclusions: Currently, germline TP53 is not routinely assessed in patients with pediatric cancer. These data support the concept that identifying germline TP53 variants at the time a primary cancer is diagnosed may identify patients at high risk for SMN development, who could benefit from modified therapeutic strategies and/or intensive posttreatment monitoring. Clin Cancer Res; 23(7); 1852–61. ©2016 AACR.
Distribution of Estimated 10-Year Risk of Recurrent Vascular Events and Residual Risk in a Secondary Prevention Population
Authors: Kaasenbrood Lotte , Boekholdt S. Matthijs , van der Graaf Yolanda , Ray Kausik K. , Peters Ron J.G. , Kastelein John J.P. , Amarenco Pierre , LaRosa John C. , Cramer Maarten J.M. , Westerink Jan , Kappelle L. Jaap , de Borst Gert J. , Visseren Frank L.J. 
Published: September 2016

Background:
Among patients with clinically manifest vascular disease, the risk of recurrent vascular events is likely to vary. We assessed the distribution of estimated 10-year risk of recurrent vascular events in a secondary prevention population. We also estimated the potential risk reduction and residual risk that can be achieved if patients reach guideline-recommended risk factor targets.

Methods:
The SMART score (Second Manifestations of Arterial Disease) for 10-year risk of myocardial infarction, stroke, or vascular death was applied to 6904 patients with vascular disease. The risk score was externally validated in 18 436 patients with various manifestations of vascular disease from the TNT (Treating to New Targets), IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), and CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trials. The residual risk at guideline-recommended targets was estimated by applying relative risk reductions from meta-analyses to the estimated risk for targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, and use of antithrombotic agents.

Results:
The external performance of the SMART risk score was reasonable, apart from overestimation of risk in patients with 10-year risk >40%. In patients with various manifestations of vascular disease, median 10-year risk of a recurrent major vascular event was 17% (interquartile range, 11%–28%), varying from <10% in 18% to >30% in 22% of the patients. If risk factors were at guideline-recommended targets, the residual 10-year risk would be <10% in 47% and >30% in 9% of the patients (median, 11%; interquartile range, 7%–17%).

Conclusions:
Among patients with vascular disease, there is very substantial variation in estimated 10-year risk of recurrent vascular events. If all modifiable risk factors were at guideline-recommended targets, half of the patients would have a 10-year risk <10%. These data suggest that even with optimal treatment, many patients with vascular disease will remain at >20% and even >30% 10-year risk, clearly delineating an area of substantial unmet medical need.
Retinal Vessel Calibers in Predicting Long-Term Cardiovascular Outcomes
Authors: Seidelmann Sara B. , Claggett Brian , Bravo Paco E. , Gupta Ankur , Farhad Hoshang , Klein Barbara E. , Klein Ronald , Di Carli Marcelo , Solomon Scott D. 
Published: September 2016

Background:
Narrower retinal arterioles and wider retinal venules have been associated with negative cardiovascular outcomes. We investigated whether retinal vessel calibers are associated with cardiovascular outcomes in long-term follow-up and provide incremental value over the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations in predicting atherosclerotic cardiovascular disease events.

Methods:
A total of 10 470 men and women without prior atherosclerotic cardiovascular disease events or heart failure in the ARIC Study (Atherosclerosis Risk in Communities) underwent retinal photography at visit 3 (1993–1995).

Results:

During a mean follow-up of 16 years, there were 1779 incident coronary heart disease events, 548 ischemic strokes, 1395 heart failure events, and 2793 deaths. Rates of all outcomes were higher in those with wider retinal venules and narrower retinal arterioles. Subjects with wider retinal venules (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.08–1.18; HR, 1.18; 95% CI, 1.07–1.31; and HR, 1.10; 95% CI, 1.00–1.20 per 1-SD increase) and narrower retinal arterioles (HR, 1.06; 95% CI, 1.01–1.11; HR, 1.14; 95% CI, 1.03–1.26; and HR, 1.13; 95% CI, 1.03–1.24 per 1-SD decrease) had a higher risk of death and stroke in both sexes and incident coronary heart disease in women but not men (interaction
P
=0.02) after adjustment for the Pooled Cohort Equations risk score variables. The association between retinal vessel caliber and heart failure was nonsignificant after adjustment for systolic blood pressure. Among women with Pooled Cohort Equations–predicted 10-year atherosclerotic cardiovascular disease event risk <5% (overall risk, 3.9%), women in the narrowest arteriolar quartile had a 10-year event rate of 5.6% compared with 2.8% for women in the widest quartile (5.0% versus 3.4% for wider versus narrower venules). Retinal vessel caliber reclassified 21% of low-risk women (11% of all women) as intermediate risk (>5%).

Conclusions:
Narrower retinal arterioles and wider retinal venules conferred long-term risk of mortality and ischemic stroke in both sexes and coronary heart disease in women. These measures serve as an inexpensive, reproducible biomarker that added incremental value to current practice guidelines in atherosclerotic cardiovascular disease event risk prediction in low-risk women.
Automatic Model Calibration: A New Way to Improve Numerical Weather Forecasting
Authors: Gan Y. , Ye A. , Miao C. , Miao S. , Liang X. , Fan S. 
Published: September 2016

AbstractWeather forecasting skill has been improved over recent years owing to advances in the representation of physical processes by numerical weather prediction (NWP) models, observational systems, data assimilation and postprocessing, new computational capability, and effective communications and training. There is an area that has received less attention so far but can bring significant improvement to weather forecasting—the calibration of NWP models, a process in which model parameters are tuned using certain mathematical methods to minimize the difference between predictions and observations. Model calibration of the NWP models is difficult because 1) there are a formidable number of model parameters and meteorological variables to tune, and 2) a typical NWP model is very expensive to run, and conventional model calibration methods require many model runs (up to tens of thousands) or cannot handle the high dimensionality of NWP models. This study demonstrates that a newly developed automatic model calibration platform can overcome these difficulties and improve weather forecasting through parameter optimization. We illustrate how this is done with a case study involving 5-day weather forecasting during the summer monsoon in the greater Beijing region using the Weather Research and Forecasting Model. The keys to automatic model calibration are to use global sensitivity analysis to screen out the most important parameters influencing model performance and to employ surrogate models to reduce the need for a large number of model runs. Through several optimization and validation studies, we have shown that automatic model calibration can improve precipitation and temperature forecasting significantly according to a number of performance measures.
Identifying Dynamically Induced Variability in Glacier Mass-Balance Records
Authors: Christian John Erich , Siler Nicholas , Koutnik Michelle , Roe Gerard 
Published: September 2016

Abstract
Glacier mass balance provides a direct indicator of a glacier’s relationship with local climate, but internally generated variability in atmospheric circulation adds a significant degree of noise to mass-balance time series, making it difficult to correctly identify and interpret trends. This study applies “dynamical adjustment” to seasonal mass-balance records to identify and remove the component of variance in these time series that is associated with large-scale circulation fluctuations (dynamical adjustment refers here to a statistical method and not a glacier’s dynamical response to climate). Mass-balance records are investigated for three glaciers: Wolverine and Gulkana in Alaska and South Cascade in Washington. North Pacific sea level pressure and sea surface temperature fields perform comparably as predictors, each explaining 50%–60% of variance in winter balance and 25%–35% in summer balance for South Cascade and Wolverine Glaciers. Gulkana Glacier, located farther inland, is less closely linked to North Pacific climate variability, with the predictors explaining roughly 30% of variance in winter and summer balance. To investigate the degree to which this variability affects trends, adjusted mass-balance time series are compared to those in the raw data, with common results for all three glaciers; winter balance trends are not significant initially and do not gain robust significance after adjustment despite the large amount of circulation-related variability. However, the raw summer balance data have statistically significant negative trends that remain after dynamical adjustment. This indicates that these trends of increasing ablation in recent decades are not due to circulation anomalies and are consistent with anthropogenic warming.
Improvements to the Geostationary Visible Imager Ray-Matching Calibration Algorithm for CERES Edition 4
Authors: Doelling David R. , Haney Conor O. , Scarino Benjamin R. , Gopalan Arun , Bhatt Rajendra 
Published: September 2016

AbstractThe Clouds and the Earth’s Radiant Energy System (CERES) project relies on geostationary imager–derived TOA broadband fluxes and cloud properties to account for the regional diurnal fluctuations between the Terra and Aqua CERES and MODIS measurements. The CERES project employs a ray-matching calibration algorithm in order to transfer the Aqua MODIS calibration to the geostationary (GEO) imagers, thereby allowing the derivation of consistent fluxes and cloud retrievals across the 16 GEO imagers utilized in the CERES record. The CERES Edition 4 processing scheme grants the opportunity to recalibrate the GEO record using an improved GEO/MODIS all-sky ocean ray-matching algorithm. Using a graduated angle matching method, which is most restrictive for anisotropic clear-sky ocean radiances and least restrictive for isotropic bright cloud radiances, reduces the bidirectional bias while preserving the dynamic range. Furthermore, SCIAMACHY hyperspectral radiances are used to account for both the solar incoming and Earth-reflected spectra in order to correct spectral band differences. As a result, the difference between the linear regression offset and the maintained GEO space count was reduced, and the calibration slopes computed from the linear fit and the regression through the space count agreed to within 0.4%. A deep convective cloud (DCC) ray-matching algorithm is also presented. The all-sky ocean and DCC ray-matching timeline gains are within 0.7% of one another. Because DCC are isotropic and the brightest, Earth targets with near-uniform visible spectra, the temporal standard error of GEO imager gains, are reduced by up to 60% from that of all-sky ocean targets.
Simulation of Polarimetric Radar Variables from 2013 CAPS Spring Experiment Storm-Scale Ensemble Forecasts and Evaluation of Microphysics Schemes
Authors: Putnam Bryan J. , Xue Ming , Jung Youngsun , Zhang Guifu , Kong Fanyou 
Published: September 2016

Abstract
Polarimetric radar variables are simulated from members of the 2013 Center for Analysis and Prediction of Storms (CAPS) Storm-Scale Ensemble Forecasts (SSEF) with varying microphysics (MP) schemes and compared with observations. The polarimetric variables provide information on hydrometeor types and particle size distributions (PSDs), neither of which can be obtained through reflectivity (Z) alone. The polarimetric radar simulator pays close attention to how each MP scheme [including single- (SM) and double-moment (DM) schemes] treats hydrometeor types and PSDs. The recent dual-polarization upgrade to the entire WSR-88D network provides nationwide polarimetric observations, allowing for direct evaluation of the simulated polarimetric variables.
Simulations for a mesoscale convective system (MCS) and supercell cases are examined. Five different MP schemes—Thompson, DM Milbrandt and Yau (MY), DM Morrison, WRF DM 6-category (WDM6), and WRF SM 6-category (WSM6)—are used in the ensemble forecasts. Forecasts using the partially DM Thompson and fully DM MY and Morrison schemes better replicate the MCS structure and stratiform precipitation coverage, as well as supercell structure compared to WDM6 and WSM6. Forecasts using the MY and Morrison schemes better replicate observed polarimetric signatures associated with size sorting than those using the Thompson, WDM6, and WSM6 schemes, in which such signatures are either absent or occur at abnormal locations. Several biases are suggested in these schemes, including too much wet graupel in MY, Morrison, and WDM6; a small raindrop bias in WDM6 and WSM6; and the underforecast of liquid water content in regions of pure rain for all schemes.
Aspirating and Nonaspirating Swallow Sounds in Children
Authors: Frakking Thuy , Chang Anne , O’Grady Kerry , David Michael , Weir Kelly 
Published: September 2016

Background: Cervical auscultation (CA) may be used to complement feeding/swallowing evaluations when assessing for aspiration. There are no published pediatric studies that compare the properties of sounds between aspirating and nonaspirating swallows. Aim: To establish acoustic and perceptual profiles of aspirating and nonaspirating swallow sounds and determine if a difference exists between these 2 swallowing types. Methods: Aspiration sound clips were obtained from recordings using CA simultaneously undertaken with videofluoroscopic swallow study. Aspiration was determined using the Penetration-Aspiration Scale. The presence of perceptual swallow/breath parameters was rated by 2 speech pathologists who were blinded to the type of swallow. Acoustic data between groups were compared using Mann Whitney U-tests, while perceptual differences were determined by a test of 2 proportions. Combinations of perceptual parameters of 50 swallows (27 aspiration, 23 no aspiration) from 47 children (57% male) were statistically analyzed using area under a receiver operating characteristic (aROC), sensitivity, specificity, and positive and negative predictive values to determine predictors of aspirating swallows. Results: The combination of post-swallow presence of wet breathing and wheeze and absence of GRS and normal breathing was the best predictor of aspiration (aROC = 0.82, 95% CI, 0.70-0.94). There were no significant differences between these 2 swallow types for peak frequency, duration, and peak amplitude. Conclusion: Our pilot study has shown that certain characteristics of swallow obtained using CA may be useful in the prediction of aspiration. However, further research comparing the acoustic swallowing sound profiles of normal children to children with dysphagia (who are aspirating) on a larger scale is required.