bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Receiving Predictive Genetic Information about Lynch Syndrome on Individual Colonoscopy and Smoking Behaviors
Authors: Kim Joanne Soo-Min , Coyte Peter C. , Cotterchio Michelle , Keogh Louise A. , Flander Louisa B. , Gaff Clara , Laporte Audrey 
Published: August 2016

Abstract
Background: This study investigated whether receiving the results of predictive genetic testing for Lynch syndrome, indicating the presence or absence of an inherited predisposition to various cancers, including colorectal cancer, was associated with change in individual colonoscopy and smoking behaviors, which could prevent colorectal cancer.
Methods: The study population included individuals with no previous diagnosis of colorectal cancer, whose families had already identified deleterious mutations in the mismatch repair or EPCAM genes. Hypotheses were generated from a simple health economics model and tested against individual-level panel data from the Australasian Colorectal Cancer Family Registry.
Results: The empirical analysis revealed evidence consistent with some of the hypotheses, with a higher likelihood of undergoing colonoscopy in those who discovered their genetic predisposition to colorectal cancer and a lower likelihood of quitting smoking in those who discovered their lack thereof.
Conclusions: Predictive genetic information about Lynch syndrome was associated with change in individual colonoscopy and smoking behaviors but not necessarily in ways to improve population health.
Impact: The study findings suggest that the impact of personalized medicine on disease prevention is intricate, warranting further analyses to determine the net benefits and costs. Cancer Epidemiol Biomarkers Prev; 25(11); 1524–33. ©2016 AACR.
Recurrent TRIO Fusion in Nontranslocation–Related Sarcomas
Authors: Delespaul Lucile , Lesluyes Tom , Pérot Gaëlle , Brulard Céline , Lartigue Lydia , Baud Jessica , Lagarde Pauline , Le Guellec Sophie , Neuville Agnès , Terrier Philippe , Vince-Ranchère Dominique , Schmidt Susanne , Debant Anne , Coindre Jean-Michel , Chibon Frédéric 
Published: August 2016

Abstract
Purpose: Despite various differences, nontranslocation-related sarcomas (e.g., comprising undifferentiated pleomorphic sarcoma, leiomyosarcoma, myxofibrosarcoma) are unified by their complex genetics. Extensive analysis of the tumor genome using molecular cytogenetic approaches showed many chromosomal gains, losses, and translocations per cell. Genomic quantitative alterations and expression variations have been extensively studied by adapted high-throughput approaches, yet translocations still remained unscreened. We therefore analyzed 117 nontranslocation-related sarcomas by RNA sequencing to identify fusion genes.
Experimental design: We performed RNA sequencing and applied a bioinformatics pipeline dedicated to the detection of fusion transcripts. RT-PCR and Sanger sequencing were then applied to validate predictions and to search for recurrence and specificity.
Results: Among the 6,772 predicted fusion genes, 420 were in-frame. One recurrent rearrangement, consistently involving TRIO with various partners, was identified in 5.1% of cases. TRIO translocations are either intrachromosomal with TERT or interchromosomal with LINC01504 or ZNF558. Our results suggest that all translocations led to a truncated TRIO protein either directly or indirectly by alternative splicing. TRIO rearrangement is associated with a modified transcriptomic program to immunity/inflammation, proliferation and migration, and an increase in proliferation.
Conclusions: TRIO fusions have been identified in four different sarcoma histotypes, likely meaning that they are not related to a primary oncogenic event but rather to a secondary one implicated in tumor progression. Moreover, they appear to be specific to nontranslocation-related sarcomas, as no such rearrangement was identified in sarcomas with simple genetics. More cases could lead to a significant association of these fusions to a specific clinical behavior. Clin Cancer Res; 23(3); 857–67. ©2016 AACR.
Development of a RSK Inhibitor as a Novel Therapy for Triple-Negative Breast Cancer
Authors: Ludwik Katarzyna A. , Campbell J. Preston , Li Mingzong , Li Yu , Sandusky Zachary M. , Pasic Lejla , Sowder Miranda E. , Brenin David R. , Pietenpol Jennifer A. , O'Doherty George A. , Lannigan Deborah A. 
Published: August 2016

AbstractMetastatic breast cancer is an incurable disease and identification of novel therapeutic opportunities is vital. Triple-negative breast cancer (TNBC) frequently metastasizes and high levels of activated p90RSK (RSK), a downstream MEK-ERK1/2 effector, are found in TNBC. We demonstrate, using direct pharmacologic and genetic inhibition of RSK1/2, that these kinases contribute to the TNBC metastatic process in vivo. Kinase profiling showed that RSK1 and RSK2 are the predominant kinases targeted by the new inhibitor, which is based on the natural product SL0101. Further evidence for selectivity was provided by the observations that silencing RSK1 and RSK2 eliminated the ability of the analogue to further inhibit survival or proliferation of a TNBC cell line. In vivo, the new derivative was as effective as the FDA-approved MEK inhibitor trametinib in reducing the establishment of metastatic foci. Importantly, inhibition of RSK1/2 did not result in activation of AKT, which is known to limit the efficacy of MEK inhibitors in the clinic. Our results demonstrate that RSK is a major contributor to the TNBC metastatic program and provide preclinical proof-of-concept for the efficacy of the novel SL0101 analogue in vivo. Mol Cancer Ther; 15(11); 2598–608. ©2016 AACR.
A New Chromatin–Cytoskeleton Link in Cancer
Authors: Giaccia Amato J. 
Published: August 2016

Abstract
The set domain containing 2 (SETD2) histone methyltransferase, located at 3p2, specifically trimethylates lysine 36 of histone H3 (H3K36me3). H3K36me3 is an active mark involved in transcriptional elongation and RNA processing and a key regulator of DNA repair. In fact, SETD2 is the only methyltransferase that “writes” the H3K36me3 mark. Recent results from Park and colleagues have found a new role for SETD2 in the methylation of K40 of α-tubulin. Loss of SETD2 abolishes methylation of K40 of α-tubulin and results in a dysfunctional mitotic spindle and abnormalities in cytokinesis. Thus, SETD2 links chromatin and cytoskeleton homeostasis through its methyltransferase activity. These studies have important implications on the role of SETD2 mutations in promoting genomic instability and tumor progression. Mol Cancer Res; 14(12); 1173–5. ©2016 AACR.
The burden of inhibitors in haemophilia patients
Authors: Walsh Christopher , Auerswald Guenter , Grancha Salvador , Jiménez-Yuste Victor 
Published: August 2016

SummaryThe burden of disease in haemophilia patients has wide ranging implications for the family and to society. There is evidence that having a current inhibitor increases the risk of morbidity and mortality. Morbidity is increased by the inability to treat adequately and its consequent disabilities, which then equates to a poor quality of life compared with non-inhibitor patients. The societal cost of care, or `burden of inhibitors’, increases with the ongoing presence of an inhibitor. Therefore, it is clear that successful eradication of inhibitors by immune tolerance induction (ITI) is the single most important milestone one can achieve in an inhibitor patient. The type of factor VIII (FVIII) product used in ITI regimens varies worldwide. Despite ongoing debate, there is in vitro and retrospective clinical evidence to support the use of plasma-derived VWF-containing FVIII concentrates in ITI regimens in order to achieve early and high inhibitor eradication success rates.
Prescription of Guideline-Based Medical Therapies at Discharge After Carotid Artery Stenting and Endarterectomy
Authors: Aronow Herbert D. , Kennedy Kevin F. , Wayangankar Siddharth A. , Katzen Barry T. , Schneider Peter A. , Abou-Chebl Alex , Rosenfield Kenneth A. 
Published: August 2016

Background and Purpose—
Carotid artery revascularization was previously found to incrementally reduce stroke risk among patients with carotid stenosis treated with medical therapy. However, the frequency with which optimal medical therapies are used at discharge after carotid endarterectomy (CEA) and carotid artery stenting (CAS) is not known, and the influence of patient, operator, and hospital characteristics on the likelihood of prescription is poorly understood.

Methods—
In a retrospective cohort study of 23 112 patients undergoing CAS or CEA between January 2007 and June 2012 at US hospitals participating in the CARE registry (Carotid Artery Revascularization and Endarterectomy), we examined antiplatelet therapy and statin utilization at discharge. Hierarchical multivariable logistic regression was used in adjusted analyses.

Results—
Antiplatelet agents and statins were prescribed at discharge in 99% and 78%, respectively, after CAS and 93% and 75%, respectively, after CEA. After adjustment, antiplatelet therapy was more often prescribed after CAS than CEA (odds ratio 2.4 [95% confidence interval 1.68–3.45]), but statin prescription was equally likely (odds ratio 1.11 [95% confidence interval 0.84–1.49]). Operator specialty (medical>radiology/surgery) and hospital community setting (suburban>urban>rural) independently predicted antiplatelet and statin agent use at discharge, whereas hospital geographic location (Northeast>Midwest/South>West) predicted use of statins but not antiplatelet therapy at discharge.

Conclusions—
US antiplatelet agent and statin discharge prescription rates were suboptimal after both CAS and CEA and varied by revascularization modality, operating physician specialty, and hospital characteristics. Improved and more uniform utilization after these procedures will be critical to the success of comprehensive stroke risk reduction efforts.
Cerebral Microbleeds and Cortical Superficial Siderosis in Patients Presenting With Minor Cerebrovascular Events
Authors: Zerna Charlotte , Modi Jayesh , Bilston Lisa , Shoamanesh Ashkan , Coutts Shelagh B. , Smith Eric E. 
Published: August 2016

Background and Purpose—
Transient focal neurological episodes occur in cerebral amyloid angiopathy (CAA) and can mimic transient ischemic attack (TIA). Risk factors and outcomes of minor ischemic stroke or TIA might differ in patients with and without cerebral microbleeds (CMBs), including CAA-consistent lobar CMB.

Methods—
Baseline magnetic resonance imaging (MRI) was analyzed for CMBs and cortical superficial siderosis in 416 patients in the prospective computed tomography and MRI in the CATCH study (Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients). Clinical symptoms, baseline characteristics, recurrence, and 90-day modified Rankin Scale were prospectively collected. MRI white-matter hyperintensity was measured using the Fazekas scale.

Results—

CMBs were detected in 65 (15.6%) and cortical superficial siderosis in 11 patients (2.6%). Lobar CMBs were present in 49 (11.8%). In multivariable logistic regression adjusted for risk factors and age, subcortical Fazekas score was associated with lobar CMB (odds ratio, 2.07; 95% confidence interval, 1.23–3.48;
P
=0.006). Forty-two patients (10.1%) had lobar-only CMBs with or without cortical superficial siderosis consistent with modified Boston criteria for possible/probable CAA. The possible/probable CAA pattern was not predictive of recurrent TIA (odds ratio, 0.42; 95% confidence interval, 0.05–3.31;
P
=0.41), stroke (odds ratio, 1.24; 95% confidence interval, 0.26–5.99;
P
=0.79), or 90-day modified Rankin Scale score ≥2 (odds ratio, 1.38; 95% confidence interval, 0.62–3.07;
P
=0.42).

Conclusions—
CMBs in TIA and minor stroke are moderately common but do not predict recurrence or 90-day outcome. CAA-related transient focal neurological episodes and TIA have overlapping clinical symptoms, suggesting that MRI may be needed for differentiation.
Impact of Initial Diffusion-Weighted Imaging Lesion Growth Rate on the Success of Endovascular Reperfusion Therapy
Authors: Olivot Jean-Marc , Sissani Leila , Meseguer Elena , Inoue Manabu , Labreuche Julien , Mlynash Michael , Amarenco Pierre , Mazighi Mikael 
Published: August 2016

Background and Purpose—
Initial diffusion-weighted imaging lesion growth rate (IGR) assessed by diffusion-weighted imaging lesion volume divided by the delay from onset to magnetic resonance imaging offers an estimate of early brain infarction progression. We investigated the impact of IGR on the rate of favorable outcome according to the occurrence of a successful endovascular revascularization within 6 hours after onset in patients experiencing an acute brain infarction complicating internal carotid artery terminus/middle cerebral artery M1 occlusion.

Methods—
The primary study end point was a favorable outcome defined by a modified Rankin Scale score of ≤2, 90 days after onset. A Thrombolysis in Cerebral Infarction score 2b/3 defined a successful recanalization.

Results—

A total of 166 patients were included. Median IGR was 7 mL/h (interquartile range, 2–26). Sixty-eight patients (41%) experienced a favorable outcome. After adjustment on age, systolic blood pressure, vessel site occlusion, National Institutes of Health Stroke Scale, and antithrombotic medication, increase in IGR was associated with a decreased occurrence of favorable outcome with an odds ratio per SD increase of 0.60 (95% confidence interval, 0.38–0.94;
P
=0.03). A successful recanalization was achieved among 56% of the patients after a median delay of 251 minutes (interquartile range, 211–291 minutes). Increasing IGR was associated with a decreased favorable outcome only when a successful recanalization was not achieved (adjusted odds ratio, 0.32; 95% confidence interval, 0.12–0.85;
P
=0.02).

Conclusions—
Proximal internal carotid artery/M1 occlusion did result into a wide range of IGR within 6 hours after onset. Increasing IGR was associated with a lower rate of favorable outcome after endovascular treatment overall and when a successful recanalization was not achieved.
Expectations versus Reality of Artificial Intelligence: Using Art to
Examine Ontological Issues
Authors: Torre Giuseppe 
Published: August 2016

ABSTRACT
The author presents three of his artworks that engage with issues surrounding artificial intelligence (AI) research. The artworks provide a means for discussing issues that are predominantly ontological rather than technical; while the author used a variety of computational methods in the development of the artworks, he did not make use of any AI techniques and tools. The discussion is carried on in a speculative manner that draws from concept art, academic research and sci-fi culture.
Most Americans Want to Learn More about Climate Change
Authors: Perkins David , Maibach Ed , Gardiner Ned , Witte Joe , Ward Bud , Placky Bernadette Woods , Seitter Keith , Cullen Heidi 
Published: August 2016

Abstract
As American Meteorological Society (AMS) members who study Americans’ understanding of climate change and who are engaged in programs to educate Americans about climate change, we want our AMS colleagues to realize their key role in public education. In this article we make the case that 1) AMS members are well positioned to play important leadership roles in educational outreach on climate change, 2) the public wants to learn more about climate change, 3) there is a need for more effective public engagement efforts, and 4) we have successful outreach and educational models that we can start using today.
On the Role of Tropical Ocean Forcing of the Persistent North American West Coast Ridge of Winter 2013/14a
Authors: Seager Richard , Henderson Naomi 
Published: August 2016

Abstract
The causes of the high pressure ridge at the North American west coast during winter 2013/14, the driest winter of the recent California drought, are examined. The ridge was part of an atmosphere–ocean state that included anomalies, defined relative to a 1979–2014 mean, of circulation across the Northern Hemisphere, warm sea surface temperatures (SSTs) in the tropical western and northeastern Pacific and the south Indian Ocean, and cool SSTs in the central tropical Pacific. The SST anomalies differ sufficiently between datasets that, when used to force atmosphere models, the simulated circulation anomalies vary notably in realism. Recognizing uncertainty in the SST field, the authors use idealized tropical SST anomaly experiments to identify an optimal combination of SST anomalies that forces a circulation response that best matches observations. The optimal SST pattern resembles that observed but the associated circulation pattern is much weaker than observed, suggesting an important but limited role for ocean forcing. Analysis of the equilibrium and transient upper-troposphere vorticity balance indicates that the SST-forced component of the ridge arose as a summed effect of Rossby waves forced by SST anomalies across the tropical Indo-Pacific oceans and drives upper-troposphere convergence and subsidence at the west coast. The ridge, in observations and model, is associated with northward and southward diversion of storms. The results suggest that tropical Indo-Pacific ocean SSTs helped force the west coast ridge and drought of winter 2013/14.
Regional Impacts of Irrigation in Mexico and the Southwestern United States on Hydrometeorological Fields in the North American Monsoon Region
Authors: Mahalov Alex , Li Jialun , Hyde Peter 
Published: August 2016

Abstract
In this study, the impacts of Mexican and southwestern U.S. agricultural and urban irrigation on North American monsoon (NAM) rainfall and other hydrometeorological fields are investigated using the Weather Research and Forecasting (WRF) Model by implementing an irrigation scheme into the WRF–land surface model. Taking the 2000–12 monsoon seasons as examples, multiple WRF simulations with irrigation are conducted by designing different crops’ maximum allowable water depletions (SWm). In comparison with gridded rainfall observations in urban and rural area, the WRF simulations with/without irrigation generally capture the observations very well, but with underestimation along the western slope of the Sierra Madre Occidental (SMO) and overestimation over southern Mexico. The simulations of WRF with irrigation are slightly improved over those without irrigation, compared with rainfall and sounding observations. Sensitivity studies reveal that the impact of irrigation on rainfall varies with location and NAM rainfall variability. Irrigation increases rainfall in eastern Arizona–western New Mexico and in northwestern Mexico because of the irrigation-induced increases of convective available potential energy (CAPE) and precipitable water. Overall, irrigation decreases rainfall in western Arizona, along the western slope of the SMO, and in central Mexico because of irrigation-induced increases of convective inhibition (CIN), decreases of CAPE, and/or large-scale water vapor divergence.
Assimilation of Flash Extent Data in the Variational Framework at Convection-Allowing Scales: Proof-of-Concept and Evaluation for the Short-Term Forecast of the 24 May 2011 Tornado Outbreak
Authors: Fierro Alexandre O. , Gao Jidong , Ziegler Conrad L. , Calhoun Kristin M. , Mansell Edward R. , MacGorman Donald R. 
Published: August 2016

AbstractThis work evaluates the performance of the assimilation of total lightning data within a three-dimensional variational (3DVAR) framework for the analysis and short-term forecast of the 24 May 2011 tornado outbreak using the Weather Research and Forecasting (WRF) Model at convection-allowing scales. Between the lifted condensation level and a fixed upper height, pseudo-observations for water vapor mass first are created based on either the flash extent densities derived from Oklahoma Lightning Mapping Array data or the lightning source densities derived from the Earth Networks pulse data, and then assimilated by the 3DVAR system. Assimilation of radar data with 3DVAR and a cloud analysis algorithm (RAD) also are performed as a baseline for comparison and in tandem with lightning to evaluate the added value of this lightning data assimilation (LDA) method.Given a scenario wherein the control experiment without radar or lightning data assimilation fails to accurately initiate and forecast the observed storms, the LDA and RAD yield comparable short-term forecast improvements. The RAD alone produces storms of similar strength to the observations during the first 30 min of forecast more rapidly than the LDA alone; however, the LDA is able to better depict individual supercellular features at 1-h forecast. When both the lightning and radar data are assimilated, the 30-min forecast showed noteworthy improvements over RAD in terms of the model’s ability to better resolve individual supercell structures and still maintained a 1-h forecast similar to that from the LDA. The results chiefly illustrate the potential value of assimilating total lightning data along with radar data.
Wave Probabilities Consistent with Official Tropical Cyclone Forecasts
Authors: Sampson Charles R. , Hansen James A. , Wittmann Paul A. , Knaff John A. , Schumacher Andrea 
Published: August 2016

Abstract
Development of a 12-ft-seas significant wave height ensemble consistent with the official tropical cyclone intensity, track, and wind structure forecasts and their errors from the operational U.S. tropical cyclone forecast centers is described. To generate the significant wave height ensemble, a Monte Carlo wind speed probability algorithm that produces forecast ensemble members is used. These forecast ensemble members, each created from the official forecast and randomly sampled errors from historical official forecast errors, are then created immediately after the official forecast is completed. Of 1000 forecast ensemble members produced by the wind speed algorithm, 128 of them are selected and processed to produce wind input for an ocean surface wave model. The wave model is then run once per realization to produce 128 possible forecasts of significant wave height. Probabilities of significant wave height at critical thresholds can then be computed from the ocean surface wave model–generated significant wave heights. Evaluations of the ensemble are provided in terms of maximum significant wave height and radius of 12-ft significant wave height—two parameters of interest to both U.S. Navy meteorologists and U.S. Navy operators. Ensemble mean errors and biases of maximum significant wave height and radius of 12-ft significant wave height are found to be similar to those of a deterministic version of the same algorithm. Ensemble spreads capture most verifying maximum and radii of 12-ft significant wave heights.