bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liquid Biopsies Using Plasma Exosomal Nucleic Acids and Plasma Cell-Free DNA Compared with Clinical Outcomes of Patients with Advanced Cancers
Authors: Möhrmann Lino , Huang Helen J. , Hong David S. , Tsimberidou Apostolia M. , Fu Siqing , Piha-Paul Sarina A. , Subbiah Vivek , Karp Daniel D. , Naing Aung , Krug Anne , Enderle Daniel , Priewasser Tina , Noerholm Mikkel , Eitan Erez , Coticchia Christine , Stoll Georg , Jordan Lisa-Marie , Eng Cathy , Kopetz E. Scott , Skog Johan , Meric-Bernstam Funda , Janku Filip 
Published: October 2017

Abstract
Purpose: Blood-based liquid biopsies offer easy access to genomic material for molecular diagnostics in cancer. Commonly used cell-free DNA (cfDNA) originates from dying cells. Exosomal nucleic acids (exoNAs) originate from living cells, which can better reflect underlying cancer biology.
Experimental Design: Next-generation sequencing (NGS) was used to test exoNA, and droplet digital PCR (ddPCR) and BEAMing PCR were used to test cfDNA for BRAFV600, KRASG12/G13, and EGFRexon19del/L858R mutations in 43 patients with progressing advanced cancers. Results were compared with clinical testing of archival tumor tissue and clinical outcomes.
Results: Forty-one patients had BRAF, KRAS, or EGFR mutations in tumor tissue. These mutations were detected by NGS in 95% of plasma exoNA samples, by ddPCR in 92% of cfDNA samples, and by BEAMing in 97% cfDNA samples. NGS of exoNA did not detect any mutations not present in tumor, whereas ddPCR and BEAMing detected one and two such mutations, respectively. Compared with patients with high exoNA mutation allelic frequency (MAF), patients with low MAF had longer median survival (11.8 vs. 5.9 months; P = 0.006) and time to treatment failure (7.4 vs. 2.3 months; P = 0.009). A low amount of exoNA was associated with partial response and stable disease ≥6 months (P = 0.006).
Conclusions: NGS of plasma exoNA for common BRAF, KRAS, and EGFR mutations has high sensitivity compared with clinical testing of archival tumor and testing of plasma cfDNA. Low exoNA MAF is an independent prognostic factor for longer survival. Clin Cancer Res; 24(1); 181–8. ©2017 AACR.
Radiation-Induced DNA Damage in Operators Performing Endovascular Aortic Repair
Authors: El-Sayed Tamer , Patel Ashish S. , Cho Jun S. , Kelly James A. , Ludwinski Francesca E. , Saha Prakash , Lyons Oliver T. , Smith Alberto , Modarai Bijan , Tyrrell M , Gkoutzios P , Abisi S , Black S , Zayed H , Bell RE , Sallam M , Biasi L , Patel SD , Donati T , Dialynas M , Sandford B , Redwood S , Perera S , Pavlidis A , Prendergast B , Gill J 
Published: October 2017

Background:
Radiation exposure during fluoroscopically guided interventions such as endovascular aortic repair (EVAR) is a growing concern for operators. This study aimed to measure DNA damage/repair markers in operators perfoming EVAR.

Methods:
Expression of the DNA damage/repair marker, γ-H2AX and DNA damage response marker, phosphorylated ataxia telangiectasia mutated (pATM), were quantified in circulating lymphocytes in operators during the peri-operative period of endovascular (infrarenal, branched, and fenestrated) and open aortic repair using flow cytometry. These markers were separately measured in the same operators but this time wearing leg lead shielding in addition to upper body protection and compared with those operating with unprotected legs. Susceptibility to radiation damage was determined by irradiating operators’ blood in vitro.

Results:

γ-H2AX and pATM levels increased significantly in operators immediately after branched endovascular aortic repair/fenestrated endovascular aortic repair (
P
<0.0003 for both). Only pATM levels increased after infrarenal endovascular aortic repair (
P
<0.04). Expression of both markers fell to baseline in operators after 24 hours (
P
<0.003 for both). There was no change in γ-H2AX or pATM expression after open repair. Leg protection abrogated γ-H2AX and pATM response after branched endovascular aortic repair/fenestrated endovascular aortic repair. The expression of γ-H2AX varied significantly when operators’ blood was exposed to the same radiation dose in vitro (
P
<0.0001).

Conclusions:
This is the first study to detect an acute DNA damage response in operators performing fluoroscopically guided aortic procedures and highlights the protective effect of leg shielding. Defining the relationship between this response and cancer risk may better inform safe levels of chronic low-dose radiation exposure.
Management of Persistent Angina After Myocardial Infarction Treated With Percutaneous Coronary Intervention: Insights From the TRANSLATE‐ACS Study
Authors: Fanaroff Alexander C. , Kaltenbach Lisa A. , Peterson Eric D. , Hess Connie N. , Cohen David J. , Fonarow Gregg C. , Wang Tracy Y. 
Published: October 2017

Background

Angina has important implications for patients’ quality of life and healthcare utilization. Angina management after acute myocardial infarction (
MI
) treated with percutaneous coronary intervention (PCI) is unknown.

Methods and Results

TRANSLATE
‐
ACS
(Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) was a longitudinal study of
MI
patients treated with percutaneous coronary intervention at 233
US
hospitals from 2010 to 2012. Among patients with self‐reported angina at 6 weeks post‐
MI
, we described patterns of angina and antianginal medication use through 1 year postdischarge. Of 10 870 percutaneous coronary intervention–treated
MI
patients, 3190 (29.3%) reported angina symptoms at 6 weeks post‐
MI
; of these, 658 (20.6%) had daily/weekly angina while 2532 (79.4%) had monthly angina. Among patients with 6‐week angina, 2936 (92.0%) received β‐blockers during the 1 year post‐
MI
, yet only 743 (23.3%) were treated with other antianginal medications. At 1 year, 1056 patients (33.1%) with 6‐week angina reported persistent angina symptoms. Of these, only 31.2% had been prescribed non–β‐blocker antianginal medications at any time in the past year. Among patients undergoing revascularization during follow‐up, only 25.9% were on ≥1 non–β‐blocker anti‐anginal medication at the time of the procedure.

Conclusions

Angina is present in one third of percutaneous coronary intervention–treated
MI
patients as early as 6 weeks after discharge, and many of these patients have persistent angina at 1 year. Non–β‐blocker antianginal medications are infrequently used in these patients, even among those with persistent angina and those undergoing revascularization.
Investigating the effectiveness of webinars in the adoption of proven school wellness strategies
Authors: Hoke Alicia M , Francis Erica B , Hivner Elizabeth A , Lipsett Simpson Alison J , Hogentogler R Ellen , Kraschnewski Jennifer L 
Published: October 2017

Objective: Recent federal legislation in the USA highlights the role schools play in student health by requiring the utilisation of wellness councils for policy development and oversight. One barrier to developing good-quality wellness policies and wellness culture is limited knowledge of resources among school professionals. This article describes an approach to webinar delivery to improve school wellness efforts. Design: Eight webinars, 30–60 minutes in length, were delivered on topics designed to enhance school wellness environments. Setting: Webinars were delivered using an online meeting software platform to school professionals, who participated from their respective school buildings remotely. Method: Webinars featured content experts for the selected topics and were promoted to school professionals and wellness organisations. Attendees were invited to participate in a post-webinar questionnaire regarding satisfaction with the session and intent to act on knowledge gained from participation. Results: Webinars reached 280 school and wellness professionals (teachers, administrators, nurses, etc.). Participants who completed post-webinar surveys ( n = 78) rated the webinar’s ability to enhance their knowledge in the respective topic area with an average score of 4.3 out of 5.0 (1 = poor, 5 = excellent). Most respondents ( n = 69) intended to share the information gained with a colleague. Conclusion: Webinars provide a viable method of instruction and education for school personnel interested in strategies for improving a school’s wellness environment. Further investigation is necessary to determine the best strategies for promoting webinar engagement. Future research should also explore the link between webinar participation and positive changes in school wellness environments.
Pregnancy-related venous thromboembolism and risk of occult cancer
Authors: Hansen Anette Tarp , Veres Katalin , Horváth-Puhó Erzsébet , Ehrenstein Vera , Prandoni Paolo , Sørensen Henrik Toft 
Published: October 2017

Key PointsThe cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected. An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk.
Management and long-term outcomes of sarcoidosis-associated pulmonary hypertension
Authors: Boucly Athénaïs , Cottin Vincent , Nunes Hilario , Jaïs Xavier , Tazi Abdelatif , Prévôt Grégoire , Reynaud-Gaubert Martine , Dromer Claire , Viacroze Catherine , Horeau-Langlard Delphine , Pison Christophe , Bergot Emmanuel , Traclet Julie , Weatherald Jason , Simonneau Gérald , Valeyre Dominique , Montani David , Humbert Marc , Sitbon Olivier , Savale Laurent 
Published: October 2017

Studies reporting the effects of modern strategies with pulmonary arterial hypertension (PAH)-targeted therapies in sarcoidosis-associated pulmonary hypertension (S-APH) are limited.Clinical and haemodynamic data from newly diagnosed patients with severe S-APH (mean pulmonary artery pressure (mPAP) >35 mmHg or mPAP 25–35 mmHg with cardiac index <2.5 L·min−1·m−2) were collected from the French Pulmonary Hypertension Registry between 2004 and 2015.Data from 126 patients with severe S-APH were analysed (mean±sdage 57.5±11.6 years, 74% radiological stage IV). 97 patients (77%) received PAH-targeted therapy and immunosuppressive therapy was initiated or escalated in 33 patients at the time of pulmonary hypertension diagnosis. Four months after PAH-targeted therapy initiation, mean±sdpulmonary vascular resistance decreased from 9.7±4.4 to 6.9±3.0 Wood units (p<0.001), without significant improvement in exercise capacity. Among the 11 patients treated only with immunosuppressive therapy, a haemodynamic improvement was observed in four patients, including two with compressive lymph nodes. After a median follow-up of 28 months, 39 patients needed PAH-targeted therapy escalation, nine underwent lung transplantation and 42 had died. Survival at 1, 3 and 5 years was 93%, 74% and 55%, respectively.PAH-targeted therapy improved short-term pulmonary haemodynamics in severe S-APH without change in exercise capacity. Immunosuppressive therapy improved haemodynamics in selected patients. Pulmonary hypertension in sarcoidosis remains associated with a poor prognosis.
Optimal cutoff for the evaluation of insulin resistance through triglyceride-glucose index: A cross-sectional study in a Venezuelan population
Authors: Salazar Juan , Bermúdez Valmore , Calvo María , Olivar Luis Carlos , Luzardo Eliana , Navarro Carla , Mencia Heysa , Martínez María , Rivas-Ríos José , Wilches-Durán Sandra , Cerda Marcos , Graterol Modesto , Graterol Rosemily , Garicano Carlos , Hernández Juan , Rojas Joselyn 
Published: October 2017

Background: Insulin resistance (IR) evaluation is a fundamental goal in clinical and epidemiological research. However, the most widely used methods are difficult to apply to populations with low incomes. The triglyceride-glucose index (TGI) emerges as an alternative to use in daily clinical practice. Therefore the objective of this study was to determine an optimal cutoff point for the TGI in an adult population from Maracaibo, Venezuela. Methods: This is a sub-study of Maracaibo City Metabolic Syndrome Prevalence Study, a descriptive, cross-sectional study with random and multi-stage sampling. For this analysis, 2004 individuals of both genders ≥18 years old with basal insulin determination and triglycerides < 500 mg/dl were evaluated.. A reference population was selected according to clinical and metabolic criteria to plot ROC Curves specific for gender and age groups to determine the optimal cutoff point according to sensitivity and specificity.The TGI was calculated according to the equation: ln [Fasting triglyceride (mg / dl) x Fasting glucose (mg / dl)] / 2. Results: The TGI in the general population was 4.6±0.3 (male: 4.66±0.34 vs. female: 4.56±0.33, p=8.93x10-10). The optimal cutoff point was 4.49, with a sensitivity of 82.6% and specificity of 82.1% (AUC=0.889, 95% CI: 0.854-0.924). There were no significant differences in the predictive capacity of the index when evaluated according to gender and age groups. Those individuals with TGI≥4.5 had higher HOMA2-IR averages than those with TGI <4.5 (2.48 vs 1.74, respectively, p<0.001). Conclusions: The TGI is a measure of interest to identify IR in the general population. We propose a single cutoff point of 4.5 to classify individuals with IR. Future studies should evaluate the predictive capacity of this index to determine atypical metabolic phenotypes, type 2 diabetes mellitus and even cardiovascular risk in our population.
Educação Básica na América Latina: uma análise dos últimos dez anos a partir dos dados do programa internacional de avaliação de estudantes (PISA)
Authors: Dias Bruno Francisco Batista , Mariano Sandra Regina Holanda , Cunha Robson Moreira 
Published: October 2017

A Diretoria de Educação da OCDE formulou, em 1997, o Programa Internacional de Avaliação de Alunos (Programme for International Student Assessment – PISA), com o objetivo de contribuir para a elevação do capital humano dos países, definido pelas “habilidades de conhecimento, competências e atributos incorporados em indivíduos que facilitem a criação de bem-estar pessoal, social e econômico". Os resultados dos páises da America Latina nesse exame apresenta resultados proximos a de países de extrema pobreza, como os do Norte da Áfrical, sendo baixo nível de desempenho dos estudantes dessa região fatores determinantes para crescimentos econômicos inferiores aos demais países do mundo nas últimas quatro décadas. Diante dessa problematica, este estudo se propõe a conhecer a realidade da educação pública básica dos sete países da américa latina que participam do PISA na última década, compara-la com os resultados obtidos no exame, e identificar possíveis fatores que se relacionam, tanto com o baixo, quanto ao alto desempenho observados em algumas dessas regiões. Sendo o foco deste artigo prover informações que permita comparar a realidade da educação dessas nações.
Competitive Price Targeting with Smartphone Coupons
Authors: Dubé Jean-Pierre , Fang Zheng , Fong Nathan , Luo Xueming 
Published: October 2017

With the cooperation of a large mobile service provider, we conduct a novel field experiment that simultaneously randomizes the prices of two competing movie theaters using mobile coupons. Unlike studies that vary only one firm’s prices, our experiment allows us to account for competitor response. We test mobile targeting based on consumers’ real-time and historic locations, allowing us to evaluate popular mobile coupon strategies in a competitive market. The experiment reveals substantial profit gains from mobile discounts during an off-peak period. Both firms could create incremental profits by targeting their competitor’s location. However, the returns to such “geoconquesting” are reduced when the competitor also launches its own targeting campaign. We combine our experimentally generated data with a demand model to analyze optimal pricing in a static Bertrand–Nash equilibrium. Interestingly, competitive responses raise the profitability of behavioral targeting where symmetric pricing incentives soften price competition. By contrast, competitive responses lower the profitability of geographic targeting, where asymmetric pricing incentives toughen price competition. If we endogenize targeting choice, both firms would choose behavioral targeting in equilibrium, even though more granular geobehavioral targeting combining both real-time and historic locations is possible. These findings demonstrate the importance of considering competitor response when piloting novel price-targeting mechanisms. Data are available at https://doi.org/10.1287/mksc.2017.1042 .
Hormonal Contraceptives Do Not Impact Economic Preferences: Evidence from a Randomized Trial
Authors: Ranehill Eva , Zethraeus Niklas , Blomberg Liselott , von Schoultz Bo , Hirschberg Angelica Lindén , Johannesson Magnus , Dreber Anna 
Published: October 2017

A growing body of correlational studies suggests that sex hormones such as those contained in, or affected by, oral contraceptives (OCs) may impact economic behavior. However, despite widespread use of OCs among women in Western countries, little is known about their potential behavioral effects. The present study investigates whether OCs causally influence economic preferences. We randomly allocate 340 women aged 18–35 to three months of a widely used OC or placebo treatment. At the end of treatment, we conduct an economic experiment measuring altruism, financial risk taking, and willingness to compete. The statistical power is 80% to detect an effect size equal to a Cohen’s d of 0.30 at the 5% level. We find no significant effects of OCs on any of the measured preferences, indicating that this widely used OC treatment, commonly used throughout the world, does not significantly affect the measured economic preferences. Further, we find no relation between menstrual cycle phase and economic preferences in the placebo group. Data are available at https://doi.org/10.1287/mnsc.2017.2844 . This paper was accepted by Uri Gneezy, behavioral economics.
Robust Postdonation Blood Screening Under Prevalence Rate Uncertainty
Authors: El-Amine Hadi , Bish Ebru K. , Bish Douglas R. 
Published: October 2017

Blood products are essential components of any healthcare system, and their safety, in terms of being free of transfusion-transmittable infections, is crucial. While the Food and Drug Administration (FDA) in the United States requires all blood donations to be tested for certain infection types, it does not dictate which particular tests should be used by blood centers. Multiple FDA-licensed blood screening tests are available for each infection type, and screening tests are imperfectly reliable and have different costs. In addition, infection prevalence rates within the donor population are uncertain for both emerging and established infection types. In this setting, the budget-constrained blood center’s objective is to devise a “robust” postdonation bloodscreening scheme that minimizes the risk of an infectious donation being released into the blood supply. Toward this goal, we study the minimization of the transfusion-transmittable infection risk considering regret- and expectation-based objectives, and we characterize structural properties of their optimal solutions. This allows us to gain insight, derive the price of robustness, and develop efficient algorithms. The proposed robust solution lowers the expected infection risk over various FDA-compliant testing schemes as well as the expectation-based scheme under forecast error. These findings have important public policy implications. The e-companion is available at https://doi.org/10.1287/opre.2017.1658 .
Protein Turnover Measurements in Human Serum by Serial Immunoaffinity LC-MS/MS
Authors: Farrokhi Vahid , Chen Xiaoying , Neubert Hendrik 
Published: October 2017

AbstractBACKGROUNDThe half-life of target proteins is frequently an important parameter in mechanistic pharmacokinetic and pharmacodynamic (PK/PD) modeling of biotherapeutics. Clinical studies for accurate measurement of physiologically relevant protein turnover can reduce the uncertainty in PK/PD model-based predictions, for example, of the therapeutic dose and dosing regimen in first-in-human clinical trials.METHODSWe used a targeted mass spectrometry work flow based on serial immunoaffinity enrichment ofmultiple human serum proteins from a [5,5,5-2H3]-L-leucine tracer pulse-chase study in healthy volunteers. To confirm the reproducibility of turnover measurements from serial immunoaffinity enrichment, multiple aliquots from the same sample set were subjected to protein turnover analysis in varying order. Tracer incorporation was measured by multiple–reaction-monitoring mass spectrometry and target turnover was calculated using a four-compartment pharmacokinetic model.RESULTSFive proteins of clinical or therapeutic relevance including soluble tumor necrosis factor receptor superfamily member 12A, tissue factor pathway inhibitor, soluble interleukin 1 receptor like 1, soluble mucosal addressin cell adhesion molecule 1, and muscle-specific creatine kinase were sequentially subjected to turnover analysis from the same human serum sample. Calculated half-lives ranged from 5–15 h; however, no tracer incorporation was observed for mucosal addressin cell adhesion molecule 1.CONCLUSIONSThe utility of clinical pulse-chase studies to investigate protein turnover can be extended by serial immunoaffinity enrichment of target proteins. Turnover analysis from serum and subsequently from remaining supernatants provided analytical sensitivity and reproducibility for multiple human target proteins in the same sample set, irrespective of the order of analysis.
The Effect of Audit Opinion, Financial Distress, Client Size, Management Turn and KAP Size on Auditor Switching
Authors: Darmayanti Novi 
Published: October 2017

The issue of Auditor Independence, the most frequently, makes the debate of auditor rotation. This auditor rotation is related to the company activity for doing auditor switching. Some previous studies showed that switching auditors leads to the various result and it needs to hold rediscovery and to verify the theory of auditor switching. The study Aimed to test empirically the Â auditor opinion, financial distress, the client company size, management turnover, and KAP size toward auditor switching onÂ manufacturing companies listed on the Indonesian Stock Exchange (BEI) in 2010 until 2014. The study is an explanatory quantitative research with purposive sampling technique for the collection of data. The 39 manufacturing companies used as a sample. The study used SPSS Application with 18 version and regression logistics to test the hypothesis because the independent variable is the combination between metric and non-metric. The result of the study Showed that the independent variable has an effect on auditor switching and auditorâ€™s opinion. Financial distress, the client company size, management turnover and the firm size do not affect the auditor switching.Â