bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prospective Evaluation of Circulating Tumor Cells and Cell-Free DNA in EGFR-Mutant Non–Small Cell Lung Cancer Patients Treated with Erlotinib on a Phase II Trial
Authors: Yanagita Masahiko , Redig Amanda J. , Paweletz Cloud P. , Dahlberg Suzanne E. , O'Connell Allison , Feeney Nora , Taibi Myriam , Boucher David , Oxnard Geoffrey R. , Johnson Bruce E. , Costa Daniel B. , Jackman David M. , Jänne Pasi A. 
Published: June 2016

Abstract
Purpose: Genotype-directed therapy is the standard of care for advanced non–small cell lung cancer (NSCLC), but obtaining tumor tissue for genotyping remains a challenge. Circulating tumor cell (CTC) or cell-free DNA (cfDNA) analysis may allow for noninvasive evaluation. This prospective trial evaluated CTCs and cfDNA in EGFR-mutant NSCLC patients treated with erlotinib until progression.
Experimental Design: EGFR-mutant NSCLC patients were enrolled in a phase II trial of erlotinib. Blood was collected at baseline, every 2 months on study, and at disease progression. Plasma genotyping was performed by droplet digital PCR for EGFR19del, L858R, and T790M. CTCs were isolated by CellSave, enumerated, and analyzed by immunofluorescence for CD45 and pan-cytokeratin and EGFR and MET FISH were also performed. Rebiopsy was performed at disease progression.
Results: Sixty patients were enrolled; 44 patients discontinued therapy for disease progression. Rebiopsy occurred in 35 of 44 patients (80%), with paired CTC/cfDNA analysis in 41 of 44 samples at baseline and 36 of 44 samples at progression. T790M was identified in 23 of 35 (66%) tissue biopsies and 9 of 39 (23%) cfDNA samples. CTC analysis at progression identified MET amplification in 3 samples in which tissue analysis could not be performed. cfDNA analysis identified T790M in 2 samples in which rebiopsy was not possible. At diagnosis, high levels of cfDNA but not high levels of CTCs correlated with progression-free survival.
Conclusions: cfDNA and CTCs are complementary, noninvasive assays for evaluation of acquired resistance to first-line EGFR TKIs and may expand the number of patients in whom actionable genetic information can be obtained at acquired resistance. Serial cfDNA monitoring may offer greater clinical utility than serial monitoring of CTCs. Clin Cancer Res; 22(24); 6010–20. ©2016 AACR.
Downregulation of the Deiminase PADI2 Is an Early Event in Colorectal Carcinogenesis and Indicates Poor Prognosis
Authors: Cantariño Neus , Musulén Eva , Valero Vanesa , Peinado Miquel Angel , Perucho Manuel , Moreno Victor , Forcales Sònia-Vanina , Douet Julien , Buschbeck Marcus 
Published: June 2016

Abstract
Peptidyl arginine deiminases (PADI) are a family of enzymes that catalyze the poorly understood posttranslational modification converting arginine residues into citrullines. In this study, the role of PADIs in the pathogenesis of colorectal cancer was investigated. Specifically, RNA expression was analyzed and its association with survival in a cohort of 98 colorectal cancer patient specimens with matched adjacent mucosa and 50 controls from donors without cancer. Key results were validated in an independent collection of tumors with matched adjacent mucosa and by mining of a publicly available expression data set. Protein expression was analyzed by immunoblotting for cell lines or IHC for patient specimens that further included 24 cases of adenocarcinoma with adjacent dysplasia and 11 cases of active ulcerative colitis. The data indicate that PADI2 is the dominantly expressed PADI enzyme in colon mucosa and is upregulated during differentiation. PADI2 expression is low or absent in colorectal cancer. Frequently, this occurs already at the stage of low-grade dysplasia. Mucosal PADI2 expression is also low in ulcerative colitis. The expression level of PADI2 in tumor and adjacent mucosa correlates with differential survival: low levels associate with poor prognosis.
Implications: Downregulation of PADI2 is an early event in the pathogenesis of colorectal cancer associated with poor prognosis and points toward a possible role of citrullination in modulating tumor cells and their microenvironment. Mol Cancer Res; 14(9); 841–8. ©2016 AACR.
Effect of Gender on Outcomes After Cardiac Resynchronization Therapy in Patients With a Narrow QRS Complex
Authors: Steffel Jan , Varma Niraj , Robertson Michele , Singh Jagmeet P. , Bax Jeroen J. , Borer Jeffrey S. , Dickstein Kenneth , Ford Ian , Gorcsan John , Gras Daniel , Krum Henry , Sogaard Peter , Holzmeister Johannes , Brugada Josep , Abraham William T. , Ruschitzka Frank 
Published: June 2016

Background—
In EchoCRT, a randomized controlled trial evaluating the effect of cardiac resynchronization therapy (CRT) in patients with a QRS duration of <130 ms and echocardiographic evidence of left ventricular dyssynchrony, the primary outcome (death from any cause or first hospitalization for worsening heart failure) occurred more frequently in the CRT-ON when compared with the control group. In this prespecified subgroup analysis, we evaluated the effect of sex on clinical outcome in EchoCRT.

Methods and Results—

In EchoCRT, 585 (72%) of included patients were men. At baseline, male patients had a higher incidence of ischemic cardiomyopathy and longer QRS duration. On uni- and multivariable analysis, no significant interaction was observed regarding sex for the primary or any of the secondary end points. Numerically, a higher all-cause mortality was observed in male patients randomized to CRT-ON versus CRT-OFF on univariable analysis (hazard ratio, 1.83; 95% confidence interval, 1.08–3.12); however, no statistically significant interaction compared with females randomized to CRT-ON versus CRT-OFF was noted (hazard ratio, 0.99;
P
interaction, 0.56). There was no difference in the primary safety end point of system-related complications, including CRT system- and implantation-related events.

Conclusions—
The largest hazard for all-cause mortality in EchoCRT was observed in men randomized to CRT-ON; the comparison with women did not reach statistical significance, which may be because of the premature termination of the trial and the limited data. These results suggest that male sex may be a risk factor for harm by CRT in patients with narrow QRS width, an observation which deserves further investigation.

Clinical Trial Registration—

URL:
https://clinicaltrials.gov
. Unique identifier: NCT00683696.
Spatial Variability of the Background Diurnal Cycle of Deep Convection around the GoAmazon2014/5 Field Campaign Sites
Authors: Burleyson Casey D. , Feng Zhe , Hagos Samson M. , Fast Jerome , Machado Luiz A. T. , Martin Scot T. 
Published: June 2016

AbstractThe isolation of the Amazon rain forest makes it challenging to observe precipitation forming there, but it also creates a natural laboratory to study anthropogenic impacts on clouds and precipitation in an otherwise pristine environment. Observations were collected upwind and downwind of Manaus, Brazil, during the “Observations and Modeling of the Green Ocean Amazon 2014–2015” experiment (GoAmazon2014/5). Besides aircraft, most of the observations were point measurements made in a spatially heterogeneous environment, making it hard to distinguish anthropogenic signals from naturally occurring spatial variability. In this study, 15 years of satellite data are used to examine the spatial and temporal variability of deep convection around the GoAmazon2014/5 sites using cold cloud tops (infrared brightness temperatures colder than 240 K) as a proxy for deep convection. During the rainy season, convection associated with the inland propagation of the previous day’s sea-breeze front is in phase with the diurnal cycle of deep convection near Manaus but is out of phase a few hundred kilometers to the east and west. Convergence between the river breezes and the easterly trade winds generates afternoon convection up to 10% more frequently (on average ~4 mm day−1 more intense rainfall) at the GoAmazon2014/5 sites east of the Negro River (T0e, T0t/k, and T1) relative to the T3 site, which was located west of the river. In general, the annual and diurnal cycles of precipitation during 2014 were similar to climatological values that are based on satellite data from 2000 to 2013.
An Initial Laboratory Prototype Experiment for Sequestration of Atmospheric CO2
Authors: Agee Ernest M. , Orton Andrea 
Published: June 2016

AbstractAn initial phase of laboratory investigation has been completed in pursuit of a global-scale methodology for reduction of CO2 in ambient air through direct air capture (DAC). The methodology presented previously by Agee, Orton, and Rogers provides the background for this study. The laboratory prototype experiment presented has been designed to assess the potential for removing CO2 from ambient air by snow deposition. The approach consists of refrigeration to achieve the required CO2 deposition temperature of 135 K at 1 bar of pressure. The refrigerant of choice is liquid nitrogen (LN2) with cooling (77 K) at the top of a cylindrical 26.5-L Pyrex glass sequestration chamber. A highly conductive aluminum base with 14 instrumentation ports rests at the interface between the LN2 reservoir and the sequestration chamber. The cooling and mixing through Rayleigh–Taylor instability achieves uniform deposition temperature. Insulation to maintain the cooling process is provided to sustain CO2 depletion phase change at 135 K. The coldest temperature achieved in experimentation was 125 K. The required cooling period was 4.5 h, with an additional hour to achieve uniform chamber temperatures ≤ 135 K through top-down convective mixing. Experimental measurements showed a reduction of CO2 in the chamber air from initial values of ~500 ppmv down to 35 ppmv. Discussion is given to the issue of chamber CO2 frost versus CO2 snowflake formation, as well as the overall relevance of the experiment to DAC through refrigeration and storage in Antarctica to reduce atmospheric CO2.
The Transit-Time Distribution from the Northern Hemisphere Midlatitude Surface
Authors: Orbe Clara , Waugh Darryn W. , Newman Paul A. , Steenrod Stephen 
Published: June 2016

Abstract
The distribution of transit times from the Northern Hemisphere (NH) midlatitude surface is a fundamental property of tropospheric transport. Here, the authors present an analysis of the transit-time distribution (TTD) since air last contacted the NH midlatitude surface, as simulated by the NASA Global Modeling Initiative Chemistry Transport Model. Throughout the troposphere, the TTD is characterized by young modes and long tails. This results in mean transit times or “mean ages” Γ that are significantly larger than their corresponding modal transit times or “modal ages” τmode, especially in the NH, where Γ ≈ 0.5 yr, while τmode &lt; 20 days. In addition, the shape of the TTD changes throughout the troposphere as the ratio of the spectral width Δ—the second temporal moment of the TTD—to the mean age decreases sharply in the NH from ~2.5 at NH high latitudes to ~0.7 in the Southern Hemisphere (SH). Decreases in Δ/Γ in the SH reflect a narrowing of the TTD relative to its mean and physically correspond to changes in the contributions of fast transport paths relative to slow eddy-diffusive recirculations. It is shown that fast transport paths control the patterns and seasonal cycles of idealized 5- and 50-day loss tracers in the Arctic and the tropics, respectively. The relationship between different TTD time scales and the idealized loss tracers, therefore, is conditional on the shape of the TTD.
Using Natural Variability as a Baseline to Evaluate the Performance of Bias Correction Methods in Hydrological Climate Change Impact Studies
Authors: Chen Jie , St-Denis Blaise Gauvin , Brissette François P. , Lucas-Picher Philippe 
Published: June 2016

Abstract
Postprocessing of climate model outputs is usually performed to remove biases prior to performing climate change impact studies. The evaluation of the performance of bias correction methods is routinely done by comparing postprocessed outputs to observed data. However, such an approach does not take into account the inherent uncertainty linked to natural climate variability and may end up recommending unnecessary complex postprocessing methods. This study evaluates the performance of bias correction methods using natural variability as a baseline. This baseline implies that any bias between model simulations and observations is only significant if it is larger than the natural climate variability. Four bias correction methods are evaluated with respect to reproducing a set of climatic and hydrological statistics. When using natural variability as a baseline, complex bias correction methods still outperform the simplest ones for precipitation and temperature time series, although the differences are much smaller than in all previous studies. However, after driving a hydrological model using the bias-corrected precipitation and temperature, all bias correction methods perform similarly with respect to reproducing 46 hydrological metrics over two watersheds in different climatic zones. The sophisticated distribution mapping correction methods show little advantage over the simplest scaling method. The main conclusion is that simple bias correction methods appear to be just as good as other more complex methods for hydrological climate change impact studies. While sophisticated methods may appear more theoretically sound, this additional complexity appears to be unjustified in hydrological impact studies when taking into account the uncertainty linked to natural climate variability.
Energy and Variance Budgets of a Diffusive Staircase with Implications for Heat Flux Scaling
Authors: Hieronymus Magnus , Carpenter Jeffrey R. 
Published: June 2016

AbstractThe steady-state energy and thermal variance budgets form the basis for most current methods for evaluating turbulent fluxes of buoyancy, heat, and salinity. This study derives these budgets for a double-diffusive staircase and quantifies them using direct numerical simulations; 10 runs with different Rayleigh numbers are considered. The energy budget is found to be well approximated by a simple three-term balance, while the thermal variance budget consists of only two terms. The two budgets are also combined to give an expression for the ratio of the heat and salt fluxes. The heat flux scaling is also studied and found to agree well with earlier estimates based on laboratory experiments and numerical simulations at high Rayleigh numbers. At low Rayleigh numbers, however, the authors find large deviations from earlier scaling laws. Last, the scaling theory of Grossman and Lohse, which was developed for Rayleigh–Bénard convection and is based on the partitioning of the kinetic energy and tracer variance dissipation, is adapted to the diffusive regime of double-diffusive convection. The predicted heat flux scalings are compared to the results from the numerical simulations and earlier estimates.
Response of a Preexisting Cyclonic Ocean Eddy to a Typhoon
Authors: Lu Zhumin , Wang Guihua , Shang Xiaodong 
Published: June 2016

AbstractThe three-dimensional responses of a cyclonic ocean eddy (COE) for 1–2 months following a typhoon were investigated using altimeter data and numerical experiments. Two significant features were found: 1) the cyclonic eddy was enhanced, and the three-dimensional structure was changed, and 2) the cyclonic eddy underwent two processes: elliptical deformation and reaxisymmetrization in the horizontal plane. These two features are generally associated with typhoon-induced upwelling and the dynamic processes of eddy adjustment. These results imply that the local ocean processes can be affected by a typhoon through low-frequency response.
Cloud Discrimination from Sky Images Using a Clear-Sky Index
Authors: Saito Masanori , Iwabuchi Hironobu 
Published: June 2016

AbstractCloud fraction mainly affects the incoming solar irradiance at the surface and is measured with ground-based sky imagers. Although several methods enable cloud discrimination from digital sky images, cloud discrimination methods are still being developed to improve the classification accuracy. This study presents two methods for effective cloud discrimination from digital sky images using a newly defined clear-sky index (CSI). The CSI represents the degree of similarity of the spectral distribution to that expected for clear sky. In the advanced method (AM), the CSI is obtained from red–green–blue (RGB) signals in RAW format by linear transformation by taking into account the solar spectrum at the top of the atmosphere, the ozone transmittance, and the spectral response of the RGB channels. The simplified method (SM) uses digital signals in a JPEG format assuming prescribed color matching functions and atmospheric states. The AM can correctly classify broken gray clouds as cloud and aureole as clear sky in most cases, and it discriminates clear sky and clouds with a correct classification rate of 93.6% based on a comparison with the zenith-pointing lidar measurements. The SM demonstrates accurate cloud discrimination performance as well as the red-to-blue ratio method does. The use of RAW format data allows for more accurate image-based cloud discrimination.
Stratospheric Temperature Climate Data Record from Merged SSU and AMSU-A Observations
Authors: Zou Cheng-Zhi , Qian Haifeng 
Published: June 2016

AbstractObservations from the Stratospheric Sounding Unit (SSU) on board historical NOAA polar-orbiting satellites have played a vital role in investigations of long-term trends and variability in the middle- and upper-stratospheric temperatures during 1979–2006. The successor to SSU is the Advanced Microwave Sounding Unit-A (AMSU-A) starting from 1998 until the present. Unfortunately, the two observations came from different sets of atmospheric layers, and the SSU weighting functions varied with time and location, posing a challenge to merge them with sufficient accuracy for development of an extended SSU climate data record. This study proposes a variational approach for the merging problem, matching in both temperatures and weighting functions. The approach yields zero means with a small standard deviation and a negligible drift over time in the temperature differences between SSU and its extension to AMSU-A. These features made the approach appealing for reliable detection of long-term climate trends. The approach also matches weighting functions with high accuracy for SSU channels 1 and 2 and reasonable accuracy for channel 3. The total decreases in global mean temperatures found from the merged dataset were from 1.8 K in the middle stratosphere to 2.4 K in the upper stratosphere during 1979–2015. These temperature drops were associated with two segments of piecewise linear cooling trends, with those during the first period (1979–97) being much larger than those of the second period (1998–2015). These differences in temperature trends corresponded well to changes of the atmospheric ozone amount from depletion to recovery during the respective time periods, showing the influence of human decisions on climate change.
A Comparative Study of the 3 June 2015 Great Plains Low-Level Jet
Authors: Parish Thomas R. 
Published: June 2016

Abstract
Detailed ground-based and airborne measurements were conducted of the summertime Great Plains low-level jet (LLJ) in central Kansas during the Plains Elevated Convection at Night (PECAN) campaign. Airborne measurements using the University of Wyoming King Air were made to document the vertical wind profile and the forcing of the jet during the nighttime hours on 3 June 2015. Two flights were conducted that document the evolution of the LLJ from sunset to dawn. Each flight included a series of vertical sawtooth and isobaric legs along a fixed track at 38.7°N between longitudes 98.9° and 100°W.
Comparison of the 3 June 2015 LLJ was made with a composite LLJ case obtained from gridded output from the North American Mesoscale Forecast System for June and July of 2008 and 2009. Forcing of the LLJ was detected using cross sections of D values that allow measurement of the vertical profile of the horizontal pressure gradient force and the thermal wind. Combined with observations of the actual wind, ageostrophic components normal to the flight track can be detected. Observations show that the 3 June 2015 LLJ displayed classic features of the LLJ, including an inertial oscillation of the ageostrophic wind. Oscillations in the geostrophic wind as a result of diurnal heating and cooling of the sloping terrain are not responsible for the nocturnal wind maximum. Net daytime heating of the sloping Great Plains, however, is responsible for the development of a strong background geostrophic wind that is critical to formation of the LLJ.
Lay and professional stakeholder involvement in scoping palliative care issues: Methods used in seven European countries
Authors: Brereton Louise , Ingleton Christine , Gardiner Clare , Goyder Elizabeth , Mozygemba Kati , Lysdahl Kristin Bakke , Tummers Marcia , Sacchini Dario , Leppert Wojciech , Blaževičienė Aurelija , van der Wilt Gert Jan , Refolo Pietro , De Nicola Martina , Chilcott James , Oortwijn Wija 
Published: June 2016

Background: Stakeholders are people with an interest in a topic. Internationally, stakeholder involvement in palliative care research and health technology assessment requires development. Stakeholder involvement adds value throughout research (from prioritising topics to disseminating findings). Philosophies and understandings about the best ways to involve stakeholders in research differ internationally. Stakeholder involvement took place in seven countries (England, Germany, Italy, Lithuania, the Netherlands, Norway and Poland). Findings informed a project that developed concepts and methods for health technology assessment and applied these to evaluate models of palliative care service delivery. Aims: To report on stakeholder involvement in the INTEGRATE-HTA project and how issues identified informed project development. Design: Using stakeholder consultation or a qualitative research design, as appropriate locally, stakeholders in seven countries acted as ‘advisors’ to aid researchers’ decision making. Thematic analysis was used to identify key issues across countries. Setting/participants: A total of 132 stakeholders (82 professionals and 50 ‘lay’ people) aged ⩾18 participated in individual face-to-face or telephone interviews, consultation meetings or focus groups. Results: Different stakeholder involvement methods were used successfully to identify key issues in palliative care. A total of 23 issues common to three or more countries informed decisions about the intervention and comparator of interest, sub questions and specific assessments within the health technology assessment. Conclusion: Stakeholders, including patients and families undergoing palliative care, can inform project decision making using various involvement methods according to the local context. Researchers should consider local understandings about stakeholder involvement as views of appropriate and feasible methods vary. Methods for stakeholder involvement, especially consultation, need further development.