bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted Sequencing Reveals Low-Frequency Variants in EPHA Genes as Markers of Paclitaxel-Induced Peripheral Neuropathy
Authors: Apellániz-Ruiz María , Tejero Héctor , Inglada-Pérez Lucía , Sánchez-Barroso Lara , Gutiérrez-Gutiérrez Gerardo , Calvo Isabel , Castelo Beatriz , Redondo Andrés , García-Donás Jesús , Romero-Laorden Nuria , Sereno María , Merino María , Currás-Freixes María , Montero-Conde Cristina , Mancikova Veronika , Åvall-Lundqvist Elisabeth , Green Henrik , Al-Shahrour Fátima , Cascón Alberto , Robledo Mercedes , Rodríguez-Antona Cristina 
Published: September 2016

Abstract
Purpose: Neuropathy is the dose-limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for interindividual differences remain unexplained. In this study, we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes.
Experimental Design: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics, and 30 Charcot–Marie–Tooth genes, in 228 cancer patients with no/low neuropathy or high-grade neuropathy during paclitaxel treatment. An independent validation series included 202 paclitaxel-treated patients. Variation-/gene-based analyses were used to compare variant frequencies among neuropathy groups, and Cox regression models were used to analyze neuropathy along treatment.
Results: Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy. Low-frequency nonsynonymous variants in EPHA6 were present exclusively in patients with high neuropathy, and all affected the ligand-binding domain of the protein. Accumulated dose analysis in the discovery series showed a significantly higher neuropathy risk for EPHA5/6/8 low-frequency nonsynonymous variant carriers [HR, 14.60; 95% confidence interval (CI), 2.33–91.62; P = 0.0042], and an independent cohort confirmed an increased neuropathy risk (HR, 2.07; 95% CI, 1.14–3.77; P = 0.017). Combining the series gave an estimated 2.5-fold higher risk of neuropathy (95% CI, 1.46–4.31; P = 9.1 × 10−4).
Conclusions: This first study sequencing EPHA genes revealed that low-frequency variants in EPHA6, EPHA5, and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy. Furthermore, EPHA's neuronal injury repair function suggests that these genes might constitute important neuropathy markers for many neurotoxic drugs. Clin Cancer Res; 23(5); 1227–35. ©2016 AACR.
Complementing T-cell Function: An Inhibitory Role of the Complement System in T-cell–Mediated Antitumor Immunity
Authors: Peng Weiyi , McKenzie Jodi A. , Hwu Patrick 
Published: September 2016

AbstractSummary: New data from Wang and colleagues show that complement C3 suppresses the function of CD8+ tumor-infiltrating T cells by inhibiting IL10 production, and targeting the complement receptors C3aR and C5aR enhances the antitumor activity of immune checkpoint blockade. Their results not only define a new role of complement receptors as T-cell coinhibitory receptors, but also are useful in the development of novel strategies to improve the effectiveness of cancer immunotherapy. Cancer Discov; 6(9); 953–5. ©2016 AACR.See related article by Wang et al., p. 1022.
Clinical presentation and course of bleeding events in patients with venous thromboembolism, treated with apixaban or enoxaparin and warfarin
Authors: Cohen Alexander T. , Büller Harry R. , Agnelli Giancarlo , Gallus Alexander S. , Raskob Gary E. , Weitz Jeffrey I. , Curto Madelyn , Sisson Melanie , Middeldorp Saskia , Bleker Suzanne M. 
Published: September 2016

SummaryApixaban, a direct acting oral anticoagulant (DOAC), was found to be non-inferior to and safer as enoxaparin followed by warfarin for treatment of venous thromboembolism (VTE) in the AMPLIFY trial. Information is needed on how bleeding events with DOACs present and develop. In this post-hoc analysis, the clinical presentation and course of all major and clinically relevant non major (CRNM) bleeding events in the AMPLIFY trial were blindly classified by three investigators, using predesigned classification schemes containing four categories. Odds ratios (OR) for classifying as category three or four (representing a more severe clinical presentation and course) were calculated between apixaban and enoxaparin/warfarin. In total, 63 major and 311 CRNM bleeding events were classified. Of the major bleeds, a more severe clinical presentation occurred in 28.5% of apixaban versus 44.9% of enoxaparin/warfarin related recipients (OR 0.49, 95% confidence interval [CI] 0.14–1.78). A severe clinical course was observed in 14.3% and in 12.2%, respectively (OR 1.19, 95%CI 0.21–6.69). Of the CRNM bleeding events, a more severe clinical presentation and extent of clinical care was found in 25% of apixaban recipients compared to 22.7% in the enoxaparin/warfarin group (OR 1.13, 95%CI 0.65–1.97). The clinical presentation and course of major and CRNM bleeds were similar in apixaban and enoxaparin/warfarin treated patients. This finding should reassure physicians and patients that even in the absence of a specific reversal agent, apixaban is a convenient and safe choice for VTE.
Risk of myocardial infarction and death in patients with atrial fibrillation treated with dabigatran or vitamin K antagonists
Authors: Darwiche Walid , Bejan-Angoulvant Theodora , Angoulvant Denis , Babuty Dominique , Fauchier Laurent 
Published: September 2016

SummaryThe safety of dabigatran versus adjusted-dose vitamin K antagonist (VKA) treatment is the subject of debate. We evaluated the risk of myocardial infarction (MI) or mortality in patients with atrial fibrillation (AF) treated in clinical practice with dabigatran or a VKA. We performed a meta-analysis of observational studies that included an adjusted or matched analysis and reported MI, or death in AF patients treated with dabigatran or a VKA. Ten published analyses met the inclusion criteria. Of the 539,559 patients, 17,365 (3%) patients were on dabigatran 110 mg twice daily (bid), 150,948 (28%) were on dabigatran 150 mg bid, and 371,246 (69%) were on VKA. Adjusted risk for MI versus VKA was 0.71 (0.47–1.07; p=0.10) in patients starting oral anticoagulant (OAC) treatment with dabigatran 110 mg, 0.82 (0.71–0.96; p=0.01) in patients starting dabigatran 150 mg, 1.40 (1.04–1.88; p=0.03) in patients switching OAC treatment to dabigatran 110 mg, and 1.28 (0.88–1.87; p=0.19) in patients switching OAC treatment to dabigatran 150 mg, with statistical homogeneity in each subgroup. Risk of death was consistently lower in patients treated with dabigatran 110 mg (HR 0.79; 0.65–0.96; p=0.02) or 150 mg (HR 0.65; 0.57–0.73; p<0.00001) versus VKA. In conclusion, dabigatran use, as currently prescribed in routine practice for AF patients, was associated with a lower risk of MI in OAC-naïve patients treated with dabigatran 150 mg compared with VKA, and a higher risk of MI in patients switching from VKA to dabigatran 110 mg. Risk of death was lower in AF patients treated with either dose of dabigatran versus VKA.
Efficacy of Intravenous Magnesium in Facilitating Cardioversion of Atrial Fibrillation
Authors: Rajagopalan Bharath , Shah Zubair , Narasimha Deepika , Bhatia Ashish , Kim Chee H. , Switzer Donald F. , Gudleski Gregory H. , Curtis Anne B. 
Published: September 2016

Background—
Low serum magnesium (Mg) levels are associated with an increased risk of atrial fibrillation. Some studies have shown a benefit of Mg in facilitating pharmacological cardioversion. The role of an intravenous infusion of Mg alone in facilitating electric cardioversion is not clear.

Methods and Results—

In a prospective, randomized, double-blind, placebo-controlled trial, we enrolled patients with atrial fibrillation who were scheduled for electric cardioversion. Patients were randomized to receive Mg or placebo before cardioversion using a step-up protocol with 75, 100, 150, and 200 J biphasic shocks. Patients with hypokalemia, hypermagnesemia, or postcardiac surgery atrial fibrillation were excluded. Patients on antiarrhythmic drugs were included as long as they were at steady state. All patients were monitored for 1 hour post procedure for the maintenance of sinus rhythm. A total of 261 patients (69% male, mean age 65.5±11.1 years) were randomized (132 and 129 patients receiving Mg and placebo, respectively). Baseline characteristics were similar between both the groups. There was no statistically significant difference in the success rate of cardioversion between the 2 groups (86.4% versus 86.0%;
P
=0.94), cumulative amount of energy required for successful cardioversion (123.3±55.5 versus 129.5±52.6 J;
P
=0.40), or the number of shocks required to convert to sinus rhythm (2.25±1.24 versus 2.41±1.22,
P
=0.31). No adverse events were noted in either group.

Conclusions—
In patients undergoing electric cardioversion for persistent atrial fibrillation, Mg infusion does not increase the rate of successful cardioversion.

Clinical Trial Information—

URL:
https://clinicaltrials.gov
. Unique identifier: NCT01597557.
Long-Term Outcomes of Carotid Artery Stenting in Clinical Practice
Authors: Mudra Harald , Staubach Stephan , Hein-Rothweiler Ralph , Segerer Manuela , Strohm Henning , Weber Hannes , Ledwoch Jakob 
Published: September 2016

Background—
There is a lack of long-term data and data outside of controlled clinical trials in carotid artery stenting. Thus, we sought to evaluate the long-term effectiveness in stroke prevention by carotid artery stenting in a large number of patients in a real-world setting.

Methods and Results—

The present work represents an all-comer registry with a strict, prospectively designed, follow-up protocol, including an independent pre- and postprocedural neurological assessment. Between November 1999 and March 2015, 1000 procedures in 901 patients were consecutively performed in a single center. Mean age was 71±9 years, and symptomatic stenosis was present in 262 patients (29.1%). The population was also characterized by a high comorbidity: 289 patients (32.1%) would have been excluded according to the CREST protocol (Carotid Revascularization Endarterectomy Versus Stent Trial). The median length of follow-up was 5.5 (interquartile range, 2.6–7.9) years and complete in 93% of the patients. The rate of the primary end point (composite of stroke, death, and myocardial infarction [major adverse cardiac or cerebrovascular event] by day 30 plus ipsilateral stroke beyond 30 days) was 6.9% (9.9% in symptomatic versus 5.7% in asymptomatic patients;
P
=0.03). The rate was higher in CREST ineligible than in CREST eligible patients (11.4% versus 4.9%;
P
=0.001).

Conclusions—
Long-term stroke prevention by carotid artery stenting is effective in experienced centers. A high percentage of patients who would have been excluded from controlled clinical trials undergoes carotid artery stenting in daily clinical practice. However, these patients have a substantially higher risk for an acute major adverse cardiac or cerebrovascular event.
Arterial Stiffness Impairment in Sickle Cell Disease Associated With Chronic Vascular Complications
Authors: Ranque Brigitte , Menet Aymeric , Boutouyrie Pierre , Diop Ibrahima Bara , Kingue Samuel , Diarra Mamadou , N’Guetta Roland , Diallo Dapa , Diop Saliou , Diagne Ibrahima , Sanogo Ibrahima , Tolo Aissata , Chelo David , Wamba Guillaume , Gonzalez Jean Paul , Abough’elie Cochise , Diakite Cheick Oumar , Traore Youssouf , Legueun Gaëlle , Deme-Ly Indou , Faye Blaise Felix , Seck Moussa , Kouakou Boidy , Kamara Ismael , Le Jeune Sylvain , Jouven Xavier 
Published: September 2016

Background:
Although a blood genetic disease, sickle cell disease (SCD) leads to a chronic vasculopathy with multiple organ involvement. We assessed arterial stiffness in SCD patients and looked for associations between arterial stiffness and SCD-related vascular complications.

Methods:
The CADRE (Coeur Artères et Drepanocytose, ie, Heart Arteries and Sickle Cell Disease) study prospectively recruited pediatric and adult SCD patients and healthy controls in Cameroon, Ivory Coast, Gabon, Mali, and Senegal. Patients underwent clinical examination, routine laboratory tests (complete blood count, serum creatinine level), urine albumin/creatinine ratio measure, and a measure of carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AI) at a steady state. The clinical and biological correlates of cf-PWV and AI were investigated by using a multivariable multilevel linear regression analysis with individuals nested in families further nested in countries.

Results:

Included were 3627 patients with SCD and 943 controls. Mean cf-PWV was lower in SCD patients (7.5±2.0 m/s) than in controls (9.1±2.4 m/s,
P
<0.0001), and lower in SS-Sβ
0
than in SC-Sβ
+
phenotypes. AI, corrected for heart rate, increased more rapidly with age in SCD patients and was higher in SCD than in control adults. cf-PWV and AI were independently associated with age, sex, height, heart rate, mean blood pressure, hemoglobin level, country, and hemoglobin phenotype. After adjustment for these correlates, cf-PWV and AI were associated with the glomerular filtration rate and osteonecrosis. AI was also associated with stroke, pulmonary hypertension, and priapism, and cf-PWV was associated with microalbuminuria.

Conclusions:
PWV and AI are deeply modified in SCD patients in comparison with healthy controls. These changes are independently associated with a lower blood pressure and a higher heart rate but also with the hemoglobin phenotype. Moreover, PWV and AI are associated with several SCD clinical complications. Their prognostic value will be assessed at follow-up of the patients.
Information Technology and Lifestyle: A Systematic Evaluation of Internet and Mobile Interventions for Improving Diet, Physical Activity, Obesity, Tobacco, and Alcohol Use
Authors: Afshin Ashkan , Babalola Damilola , Mclean Mireille , Yu Zhi , Ma Wenjie , Chen Cheng‐Yu , Arabi Mandana , Mozaffarian Dariush 
Published: September 2016

Background

Novel interventions are needed to improve lifestyle and prevent noncommunicable diseases, the leading cause of death and disability globally. This study aimed to systematically review, synthesize, and grade scientific evidence on effectiveness of novel information and communication technology to reduce
noncommunicable disease
risk.

Methods and Results

We systematically searched PubMed for studies evaluating the effect of Internet, mobile phone, personal sensors, or stand‐alone computer software on diet, physical activity, adiposity, tobacco, or alcohol use. We included all interventional and prospective observational studies conducted among generally healthy adults published between January 1990 and November 2013. American Heart Association criteria were used to evaluate and grade the strength of evidence. From 8654 abstracts, 224 relevant reports were identified. Internet and mobile interventions were most common. Internet interventions improved diet (N=20 studies) (Class
II
a A), physical activity (N=33), adiposity (N=35), tobacco (N=22), and excess alcohol (N=47) (Class I A each). Mobile interventions improved physical activity (N=6) and adiposity (N=3) (Class I A each). Evidence limitations included relatively brief durations (generally <6 months, nearly always <1 year), heterogeneity in intervention content and intensity, and limited representation from middle/low‐income countries.

Conclusions
Internet and mobile interventions improve important lifestyle behaviors up to 1 year. This systematic review supports the need for long‐term interventions to evaluate sustainability.
Bastardierung von Testudo horsfieldii (Gray) und Testudo h. h erman ni Gmelin.
Authors: Kirsche W. 
Published: September 2016

Abstract. The egglaying (4 eggs) of a Testudo horsfieldii (1570g), which lives in a large outdoor enclosure since 1968, was observed. In a special breeding apparatus two hybrids hatched, the two other ones died in the shell. The parent's mating had not been observed. Fertile males of Testudo h. hermanni (7), Testudo horsfieldii (2) and Testudo graeca ibera (1) are living together in the enclosure with female tortoises. An analysis of the phenotype demonstrated the two hatchlings to be hybrids between T. horsfieldii and T. hermanni. The inauguration of a separate genus Agrionemys is critically discussed.
Zusammenfassung. Von einer beobachteten Eiablage (4 Eier) einer Testudo horsfieldii (1570g), die seit 1968 in einer grossen Freiland-Anlage lebt, schlüpften in einem speziellen Brutapparat zwei Bastarde, während 2 Embryonen abstarben. Die vorangegangene Paarung konnte nicht beobachtet werden. In der Anlage Ieben fertile ♂♂ von Testudo h. hermanni (7), Testudo horsfieldii (2) und Testudo graeca ibera (1) . Durch Merkmalsanalyse der Bas tarde konnte eine Kreuzung zwischen Testudo horsfieldii und Testudo h. hermanni nachgewiesen werden . Die Berechtigung einer eigenen Gattung Agrionemys fiir die Art h orsfieldii wird kritisch diskutiert.
Testing Atmospheric Oxidation in an Alabama Forest
Authors: Feiner Philip A. , Brune William H. , Miller David O. , Zhang Li , Cohen Ronald C. , Romer Paul S. , Goldstein Allen H. , Keutsch Frank N. , Skog Kate M. , Wennberg Paul O. , Nguyen Tran B. , Teng Alex P. , DeGouw Joost , Koss Abigail , Wild Robert J. , Brown Steven S. , Guenther Alex , Edgerton Eric , Baumann Karsten , Fry Juliane L. 
Published: September 2016

Abstract
The chemical species emitted by forests create complex atmospheric oxidation chemistry and influence global atmospheric oxidation capacity and climate. The Southern Oxidant and Aerosol Study (SOAS) provided an opportunity to test the oxidation chemistry in a forest where isoprene is the dominant biogenic volatile organic compound. Hydroxyl (OH) and hydroperoxyl (HO2) radicals were two of the hundreds of atmospheric chemical species measured, as was OH reactivity (the inverse of the OH lifetime). OH was measured by laser-induced fluorescence (LIF) and by taking the difference in signals without and with an OH scavenger that was added just outside the instrument’s pinhole inlet. To test whether the chemistry at SOAS can be simulated by current model mechanisms, OH and HO2 were evaluated with a box model using two chemical mechanisms: Master Chemical Mechanism, version 3.2 (MCMv3.2), augmented with explicit isoprene chemistry and MCMv3.3.1. Measured and modeled OH peak at about 106 cm−3 and agree well within combined uncertainties. Measured and modeled HO2 peak at about 27 pptv and also agree well within combined uncertainties. Median OH reactivity cycled between about 11 s−1 at dawn and about 26 s−1 during midafternoon. A good test of the oxidation chemistry is the balance between OH production and loss rates using measurements; this balance was observed to within uncertainties. These SOAS results provide strong evidence that the current isoprene mechanisms are consistent with measured OH and HO2 and, thus, capture significant aspects of the atmospheric oxidation chemistry in this isoprene-rich forest.
The Influence of Wind Direction on Campbell Scientific CSAT3 and Gill R3-50 Sonic Anemometer Measurements
Authors: Grare Laurent , Lenain Luc , Melville W. Kendall 
Published: September 2016

AbstractMeasurements from the Campbell CSAT3 and Gill R3-50 anemometers were conducted in four different experiments, in laboratory and field environments. Consistent differences between these two sonic anemometers were observed. The data have revealed that the differences were strongly correlated with the wind direction. According to the datasets used, the CSAT3 was the anemometer whose measurements were more sensitive to the instrument’s orientation relative to the wind direction. While the mean wind speed and direction remained within the manufacturers’ specifications (a few percent for the wind speed and a few degrees for the wind direction), the estimates of the friction velocity from the CSAT3 differed from the R3-50 by up to 20%.
The Role of Topographically Induced Vortices in Tropical Cyclone Formation over the Indian Ocean
Authors: Fine Caitlin M. , Johnson Richard H. , Ciesielski Paul E. , Taft Richard K. 
Published: September 2016

AbstractThe role of Sumatra and adjacent topographic features in tropical cyclone (TC) formation over the Indian Ocean (IO) is investigated. Sumatra, as well as the Malay Peninsula and Java, have mountainous terrain that partially blocks low-level flow under typical environmental stratification. For easterly low-level flow, these terrain features often produce lee vortices, some of which subsequently shed and move westward from the northern and southern tips of Sumatra and thence downstream over the IO. Since Sumatra straddles the equator, extending in a northwest–southeast direction from approximately 6°N to 6°S, the lee vortices, while counter-rotating, are both cyclonic. Hence, they can serve as initial disturbances that eventually contribute to TC formation over the IO. In addition, low-level, equatorial westerly flow impinging on Sumatra is also typically blocked and diverges, at times contributing to cyclonic circulations over the IO, primarily near the southern end of the island.Data from two recent tropical campaigns, the 2008–10 Year of Tropical Convection (YOTC) and the 2011 Dynamics of the Madden–Julian Oscillation (DYNAMO), are used to study these phenomena. These datasets reveal the frequent occurrence of shed and nonshed terrain-induced cyclonic circulations over the IO, the majority of which occur during boreal fall and winter. During the 2.5 yr of the two campaigns, 13 wake vortices (13% of the shed circulations identified) were tracked and observed to subsequently develop into TCs over the northern and southern IO, accounting for 25% of the total TCs forming in the IO during that period.
Preserving Nonnegativity in Discontinuous Galerkin Approximations to Scalar Transport via Truncation and Mass Aware Rescaling (TMAR)
Authors: Light Devin , Durran Dale 
Published: September 2016

AbstractAn accurate nonnegativity preserving limiter is presented for use with discontinuous Galerkin (DG) discretizations of scalar advection equations. The nonnegativity of the tracer field is preserved through the application of a mass conservative limiter that truncates negatives within each element and linearly rescales the resulting DG polynomials to preserve element-mean mass. As a preliminary step, the DG fluxes through each side of the element are limited in a manner similar to flux-corrected transport to ensure that the element-mean mass remains nonnegative during each individual stage of the time integration. In this paper, it is proven that such a truncation and mass aware rescaling (TMAR) does not change the order of accuracy of the underlying unlimited DG approximation. Numerical tests with two-dimensional deforming flows confirm that the method remains accurate and efficient while preserving nonnegativity. In comparison to some popular previous approaches, TMAR limiting is particularly well suited to approximations that use high-degree polynomial expansions (quartics or higher) to capture features that are only moderately well resolved.