bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human and Mouse VEGFA-Amplified Hepatocellular Carcinomas Are Highly Sensitive to Sorafenib Treatment
Authors: Horwitz Elad , Stein Ilan , Andreozzi Mariacarla , Nemeth Julia , Shoham Avivit , Pappo Orit , Schweitzer Nora , Tornillo Luigi , Kanarek Naama , Quagliata Luca , Zreik Farid , Porat Rinnat M. , Finkelstein Rutie , Reuter Hendrik , Koschny Ronald , Ganten Tom , Mogler Carolin , Shibolet Oren , Hess Jochen , Breuhahn Kai , Grunewald Myriam , Schirmacher Peter , Vogel Arndt , Terracciano Luigi , Angel Peter , Ben-Neriah Yinon , Pikarsky Eli 
Published: April 2014

Abstract
Death rates from hepatocellular carcinoma (HCC) are steadily increasing, yet therapeutic options for advanced HCC are limited. We identify a subset of mouse and human HCCs harboring VEGFA genomic amplification, displaying distinct biologic characteristics. Unlike common tumor amplifications, this one seems to work via heterotypic paracrine interactions; stromal VEGF receptors (VEGFR), responding to tumor VEGF-A, produce hepatocyte growth factor (HGF) that reciprocally affects tumor cells. VEGF-A inhibition results in HGF downregulation and reduced proliferation, specifically in amplicon-positive mouse HCCs. Sorafenib—the first-line drug in advanced HCC—targets multiple kinases, including VEGFRs, but has only an overall mild beneficial effect. We found that VEGFA amplification specifies mouse and human HCCs that are distinctly sensitive to sorafenib. FISH analysis of a retrospective patient cohort showed markedly improved survival of sorafenib-treated patients with VEGFA-amplified HCCs, suggesting that VEGFA amplification is a potential biomarker for HCC response to VEGF-A–blocking drugs.
Significance: Using a mouse model of inflammation-driven cancer, we identified a subclass of HCC carrying VEGFA amplification, which is particularly sensitive to VEGF-A inhibition. We found that a similar amplification in human HCC identifies patients who favorably responded to sorafenib—the first-line treatment of advanced HCC—which has an overall moderate therapeutic efficacy. Cancer Discov; 4(6); 730–43. ©2014 AACR.
See related commentary by Luo and Feng, p. 640
This article is highlighted in the In This Issue feature, p. 621
Low Yield of Stress Imaging in a Population-Based Study of Asymptomatic Patients After Percutaneous Coronary Intervention
Authors: Peterson Tyler , Askew J. Wells , Bell Malcolm , Crusan Daniel , Hodge David , Gibbons Raymond J. 
Published: April 2014

Background—
Little is known about the clinical value of stress imaging studies in asymptomatic patients after percutaneous coronary intervention (PCI).

Methods and Results—

Residents of Olmsted County, MN, who underwent PCI were followed up for the occurrence of stress imaging (stress nuclear or stress echocardiography), coronary angiography, or coronary artery bypass grafting (without angiography) as initial procedures after PCI. Patients whose first follow-up procedure was a stress imaging test were evaluated for their symptom status at the time of the study and whether they underwent angiography or revascularization (PCI or coronary artery bypass grafting) within 90 days. Of 1848 patients who underwent PCI during the study period, 710 (38%) had stress imaging as their initial procedure after PCI, and 241 (13% of the entire cohort) were asymptomatic at the time of testing. The majority (86%) of these 241 patients underwent PCI for acute myocardial infarction or unstable angina. Within 90 days of stress imaging, 16 of the 241 asymptomatic patients underwent angiography, and 2 patients were revascularized. Stratified by timing after PCI, none of 138 asymptomatic patients tested within 2 years of PCI underwent revascularization. Two of 103 asymptomatic patients tested after 2 years from PCI underwent revascularization. Compared with patients who were asymptomatic at the time of stress imaging, patients who did not undergo any follow-up procedures (stress imaging, angiography, or coronary artery bypass grafting) after the index PCI were older, were more likely to have comorbidities, and had significantly greater all-cause mortality (
P
<0.001).

Conclusions—
In a population-based sample of patients undergoing PCI primarily for acute coronary syndromes, 1 in 8 had subsequent stress imaging when they were asymptomatic. These stress imaging tests resulted in further revascularization in <1% of patients. The low rate of downstream revascularization suggests that stress imaging in asymptomatic patients after PCI has low value.
“World, Solitude, Finitude”: Derrida’s Final Seminar
Authors: Naas Michael 
Published: April 2014

Abstract
In his final seminar, The Beast and the Sovereign, vol. 2 (2002–2003), Jacques Derrida spends the entire year reading just two texts, Daniel Defoe’s Robinson Crusoe and Martin Heidegger’s Fundamental Concepts of Metaphysics. This essay looks in detail at Derrida’s treatment of this latter and, in particular, at Derrida’s emphasis on the Heideggerian notion of Walten (as sovereign power or originary violence) in this work. The essay begins by considering several of Derrida’s prior engagements with Heidegger, especially in Of Spirit and the “Geschlecht” essays, and their analyses of such themes as Geist or spirit, sexual and species difference, violence, and ontotheology. The essay then develops the relationship between what Derrida considered to be the hyper-sovereignty of Walten and Derrida’s own notions of autoimmunity and différance, before concluding with the question of why Derrida would think it necessary to devote so much of his final seminar to this Heideggerian notion.
A Regression Model for Smoke Plume Rise of Prescribed Fires Using Meteorological Conditions
Authors: Liu Yongqiang 
Published: April 2014

AbstractSmoke plume rise is an important factor for smoke transport and air quality impact modeling. This study provides a practical tool for estimating plume rise of prescribed fires. A regression model was developed on the basis of observed smoke plume rise for 20 prescribed fires in the southeastern United States. The independent variables include surface wind, air temperature, fuel moisture, and atmospheric planetary boundary layer (PBL) height. The first three variables were obtained from the Remote Automatic Weather Stations, most of which are installed in locations where they can monitor local fire danger and are easily accessed by fire managers. The PBL height was simulated with the Weather Research and Forecasting Model. The confidence and validation analyses indicate that the regression model is significant at the 95% confidence level and able to predict hourly values and the average smoke plume rise during a burn, respectively. The prediction of the average smoke plume rise shows larger skills. The model also shows improved skills over two extensively used empirical models for the prescribed burn cases examined in this study, suggesting that it may have the potential to improve smoke plume rise and air quality modeling for prescribed burns. The regression model, however, tends to underestimate large plume rise values and overestimate small ones. A suite of alternative regression models was also provided, one of which can be used when no PBL information is available.
A Global Land Cover Climatology Using MODIS Data
Authors: Broxton Patrick D. , Zeng Xubin , Sulla-Menashe Damien , Troch Peter A. 
Published: April 2014

AbstractGlobal land cover data are widely used in weather, climate, and hydrometeorological models. The Collection 5.1 Moderate Resolution Imaging Spectroradiometer (MODIS) Land Cover Type (MCD12Q1) product is found to have a substantial amount of interannual variability, with 40% of land pixels showing land cover change one or more times during 2001–10. This affects the global distribution of vegetation if any one year or many years of data are used, for example, to parameterize land processes in regional and global models. In this paper, a value-added global 0.5-km land cover climatology (a single representative map for 2001–10) is developed by weighting each land cover type by its corresponding confidence score for each year and using the highest-weighted land cover type in each pixel in the 2001–10 MODIS data. The climatology is validated by comparing it with the System for Terrestrial Ecosystem Parameterization database as well as additional pixels that are identified from the Google Earth proprietary software database. When compared with the data of any individual year, this climatology does not substantially alter the overall global frequencies of most land cover classes but does affect the global distribution of many land cover classes. In addition, it is validated as well as or better than the MODIS data for individual years. Also, it is based on higher-quality data and is validated better than the Global Land Cover Characteristics database, which is based on 1 year of Advanced Very High Resolution Radiometer data and represents a widely used first-generation global product.
A Dual-Polarization Radar Hydrometeor Classification Algorithm for Winter Precipitation
Authors: Thompson Elizabeth J. , Rutledge Steven A. , Dolan Brenda , Chandrasekar V. , Cheong Boon Leng 
Published: April 2014

Abstract
The purpose of this study is to demonstrate the use of polarimetric observations in a radar-based winter hydrometeor classification algorithm. This is accomplished by deriving bulk electromagnetic scattering properties of stratiform, cold-season rain, freezing rain, sleet, dry aggregated snowflakes, dendritic snow crystals, and platelike snow crystals at X-, C-, and S-band wavelengths based on microphysical theory and previous observational studies. These results are then used to define the expected value ranges, or membership beta functions, of a simple fuzzy-logic hydrometeor classification algorithm. To test the algorithm’s validity and robustness, polarimetric radar data and algorithm output from four unique winter storms are investigated alongside surface observations and thermodynamic soundings. This analysis supports that the algorithm is able to realistically discern regions dominated by wet snow, aggregates, plates, dendrites, and other small ice crystals based solely on polarimetric data, with guidance from a melting-level detection algorithm but without external temperature information. Temperature is still used to distinguish rain from freezing rain or sleet below the radar-detected melting level. After appropriate data quality control, little modification of the algorithm was required to produce physically reasonable results on four different radar platforms at X, C, and S bands. However, classification seemed more robust at shorter wavelengths because the specific differential phase is heavily weighted in ice crystal classification decisions. It is suggested that parts, or all, of this algorithm could be applicable in both operational and research settings.
Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for Advanced Stage Oropharyngeal Squamous Cell Carcinoma With HPV and P16 Testing
Authors: Flavill Eric , Fang Yisheng V. , Miles Brett , Truelson John , Perkins Steve 
Published: April 2014

Objective: The objective was to report our experience with advanced stage oropharyngeal squamous cell carcinoma treated sequentially with induction chemotherapy followed by concurrent chemoradiotherapy. Methods: Retrospective chart review identified 49 eligible patients with advanced stage oropharyngeal squamous cell carcinoma treated with induction chemotherapy followed by concurrent chemoradiotherapy. HPV and p16INK4A testing was performed on pathology specimens. Follow-up of over 11 months was required unless a death or treatment failure occurred before that time. Results: Treatment with induction chemotherapy followed by concurrent chemoradiotherapy resulted in 44/48 (90%) complete durable response. One death occurred from pulmonary embolism. Toxicity profiles were comparable to other published data. Average follow-up was 3.9 years. Oncologic failure rates among subgroups showed 5.7% failure for HPV+/p16+ cancer, 9.1% failure for HPV-/p16+ cancer, 100% failure for HPV-/p16- cancer, 0% failure for nonsmokers, and 17.9% failure for smokers. Conclusions: This study showed favorable outcomes in terms of durable oncologic response and acceptable toxicity profiles. It is notable that 36/49 patients were HPV+/p16+ and 11/49 were HPV-/p16+. Only 2 patients were HPV-/p16-, and both died as a result of oncologic failures. This highlights the importance of obtaining HPV and p16 testing in studies evaluating the efficacy of treatments for oropharyngeal squamous cell carcinoma.
Effects of Input Shaping on Manual Control of Flexible and Time-Delayed Systems
Authors: Potter James J. , Singhose William E. 
Published: April 2014

Objective: The objective was to study the performance of a manual tracking task with system flexibility and time delays in the input channel and to examine the effects of input shaping the human operator’s commands. Background: It has long been known that low-frequency, lightly damped vibration hinders performance of a manually controlled system. Recently, input shaping has been shown to improve the performance of such systems in a compensatory-display tracking task. It is unknown if similar improvements are seen with pursuit-display tasks, or how the improvement changes when time delays are added to the system. Method: A total of 18 novice participants performed a pursuit-view tracking experiment with a spring-centered joystick. Controlled elements included an integrator, an integrator with a lightly damped flexible mode, and an input-shaped integrator with a flexible mode. The input to these controlled elements was delayed between 0 and 1 s. Tracking performance was quantified by root mean square tracking error, and subjective difficulty was quantified by ratings on a Cooper–Harper scale. Results: Performance was best with the undelayed integrator. Both time delay and flexibility degraded performance. Input shaping improved control of the flexible element, with a diminishing benefit as the time delay increased. Tracking error and subjective rating were significantly related. Some operators used a pulsive control strategy. Conclusion: Input shaping can improve the performance of a manually controlled system with flexibility, even when time delays are present. Application: This study is useful to designers of human-controlled systems, especially those with problematic flexibility and/or time delays.
Supporting Attention Allocation in Multitask Environments
Authors: Wiczorek Rebecca , Manzey Dietrich 
Published: April 2014

Objective: The aim of the current study was to investigate potential benefits of likelihood alarm systems (LASs) over binary alarm systems (BASs) in a multitask environment. Background: Several problems are associated with the use of BASs, because most of them generate high numbers of false alarms. Operators lose trust in the systems and ignore alarms or cross-check all of them when other information is available. The first behavior harms safety, whereas the latter one reduces productivity. LASs represent an alternative, which is supposed to improve operators’ attention allocation. Method: We investigated LASs and BASs in a dual-task paradigm with and without the possibility to cross-check alerts with raw data information. Participants’ trust in the system, their behavior, and their performance in the alert and the concurrent task were assessed. Results: Reported trust, compliance with alarms, and performance in the alert and the concurrent task were higher for the LAS than for the BAS. The cross-check option led to an increase in alert task performance for both systems and a decrease in concurrent task performance for the BAS, which did not occur in the LAS condition. Conclusion: LASs improve participants’ attention allocation between two different tasks and therefore lead to an increase in alert task and concurrent task performance. The performance maximum is achieved when LAS is combined with a cross-check option for validating alerts with additional information. Application: The use of LASs instead of BASs in safety-related multitask environments has the potential to increase safety and productivity likewise.
Otitis Media and Caregiver Quality of Life: Psychometric Properties of the Modified Danish Version of the Caregiver Impact Questionnaire
Authors: Heidemann Christian Hamilton , Godballe Christian , Kjeldsen Anette Drøhse , Johansen Eva Charlotte Jung , Faber Christian Emil , Lauridsen Henrik Hein 
Published: April 2014

ObjectiveOtitis media in children may have a considerable impact on caregiver quality of life. The disease‐specific Caregiver Impact Questionnaire is designed to assess caregiver quality of life in relation to child otitis media. Assessment of the psychometric properties of this instrument is limited. This study assesses the psychometric properties of this instrument including validity, reproducibility, responsiveness, and interpretability.Study DesignLongitudinal validation study.SettingSecondary care units.MethodsAnalyses were based on data from 435 families. Validity was assessed using confirmatory factor analysis, internal consistency, and hypothesis testing. Test–retest reliability and measures of smallest detectable change were investigated in the assessment of reproducibility. Responsiveness was investigated by means of hypothesis testing and receiver operating characteristic analysis. An anchor‐based distribution method was applied for determining minimal important change as perceived by the respondent.ResultsFactor analysis confirmed the hypothesized 1‐factor structure with an acceptable fit. Cronbach's alpha was. 90. In the analysis of construct validity, 88.9% of the hypothesized correlations were correctly predicted. Intraclass correlation coefficient was 0.87 and smallest detectable change corresponded to approximately one‐fourth of the scale. Responsiveness was found to be good and a change score of 13.8 represented minimal important change.ConclusionThe modified Danish version of the Caregiver Impact Questionnaire is a valid and reproducible measurement tool that is also sensitive to measuring change in the current setting. A change score representing minimal important change as perceived by the respondent is proposed. Results of this study support the use of this instrument.
Endoscopic Repair of Nasal Septal Perforation with “Slide and Patch” Technique
Authors: Cassano Michele 
Published: April 2014

ObjectiveThe aim of this study is to report our new endoscopic technique for the repair of nasal septal perforations, called the “slide and patch” technique because it combines a mucoperiosteal free graft of the inferior turbinate with a mucosal rotational or advancement flap from the nasal septum.MethodsTwenty‐two patients with symptomatic septal nasal perforation of various sizes underwent our method of repair.ResultsAt the last follow‐up, 21 (95.4%) perforations were closed. There was a partial closure in only 1 patient with a large perforation (3.5 cm in diameter). After surgery, 19 (86.3%) patients were asymptomatic, 2 (9%) showed persistence of crusting, and 1 (4.5%) showed the appearance of nasal obstruction 1 month postoperatively.ConclusionThe method described herein has shown to be effective in nasal septal perforation repair and in nasal symptoms relief with the advantage of not requiring grafts from outside the nose.
Prevalence and Predictors of Poor Sleep Quality in Mild Cognitive Impairment
Authors: McKinnon Andrew , Terpening Zoe , Hickie Ian B. , Batchelor Jennifer , Grunstein Ron , Lewis Simon J. G. , Naismith Sharon L. 
Published: April 2014

Aims: To investigate the prevalence of and contributors to poor sleep quality in patients with mild cognitive impairment (MCI). Methods: Data were collected for 158 patients meeting the criteria for MCI. Measures included the Pittsburgh Sleep Quality Index, Geriatric Depression Scale, and Mini-Mental State Examination. Demographic, lifestyle, medication, and substance use data were also collected. Results: A total of 63% of patients with MCI demonstrated sleep disturbance, a significantly higher rate than that of the controls (44%; chi-square = 8.77; P = .003). Depressive symptoms, cognition, antidepressant usage, alcohol consumption, age, and education were identified as significant predictors of self-reported sleep quality in patients with MCI ( R2 = .327, F6,145 = 11.729, P < .0001). Conclusions: Sleep disturbance occurs in around two-thirds of patients with MCI. Interventions addressing depression, cognition, and substance and medication use may improve sleep quality in MCI.
Erythromycin, QTc interval prolongation, and torsade de pointes: Case reports, major risk factors and illness severity
Authors: Hancox Jules C. , Hasnain Mehrul , Vieweg W. Victor R. , Gysel Michael , Methot Michelle , Baranchuk Adrian 
Published: April 2014

Objectives: Erythromycin is a macrolide antibiotic that is widely used for various infections of the upper respiratory tract, skin, and soft tissue. Similar to other macrolides (clarithromycin, azithromycin), erythromycin has been linked to QTc interval prolongation and torsade de pointes ( TdP) arrhythmia. We sought to identify factors that link to erythromycin-induced/associated QTc interval prolongation and TdP. Methods and Results: In a critical evaluation of case reports, we found 29 cases: 22 women and 7 men (age range 18–95 years). With both oral and intravenous erythromycin administration, there was no significant relationship between dose and QTc interval duration in these cases. Notably, all patients had severe illness. Other risk factors included female sex, older age, presence of heart disease, concomitant administration of either other QTc prolonging drugs or agents that were substrates for or inhibitors of CYP3A4. Most patients had at least two risk factors. Conclusions: On the basis of case report evaluation, we believe that major risk factors for erythromycin-associated TdP are female sex, heart disease and old age, particularly against a background of severe illness. Coadministration of erythromycin with other drugs that inhibit or are metabolized by CYP3A4 or with QTc prolonging drugs should be avoided in this setting.