bluuebunny/crossref_metadata_2025_split huggingface dataset:
Administrative coordination capacity; does the wickedness of policy areas matter?
Authors: Christensen Tom , Lægreid Ole Martin , Lægreid Per 
Published: March 2019

Abstract
Based on a survey of civil servants in the Norwegian central government, this article describes perceptions of coordination capacity and examines to what degree the variations in perceived coordinating capacity can be explained by structural and cultural features. In particular, it focuses on the significance of wicked policy areas. Overall the coordination capacity is weaker in wicked policy areas than in other policy areas. Controlling for other features the coordination capacity is primarily related to cultural factors, such as mutual trust, level of conflict, and identification with the central government. Some structural features, such as administrative level, also have an effect.
Proteomic analysis reveals procoagulant properties of cigarette smoke‐induced extracellular vesicles
Authors: Benedikter Birke J. , Bouwman Freek G. , Heinzmann Alexandra C. A. , Vajen Tanja , Mariman Edwin C. , Wouters Emiel F. M. , Savelkoul Paul H. M. , Koenen Rory R. , Rohde Gernot G. U. , van Oerle Rene , Spronk Henri M. , Stassen Frank R. M. 
Published: March 2019

ABSTRACTAirway epithelial cells secrete extracellular vesicles (EVs) under basal conditions and when exposed to cigarette smoke extract (CSE). Getting insights into the composition of these EVs will help unravel their functions in homeostasis and smoking‐induced pathology. Here, we characterized the proteomic composition of basal and CSE‐induced airway epithelial EVs. BEAS‐2B cells were left unexposed or exposed to 1% CSE for 24 h, followed by EV isolation using ultrafiltration and size exclusion chromatography. Isolated EVs were labelled with tandem mass tags and their proteomic composition was determined using nano‐LC‐MS/MS. Tissue factor (TF) activity was determined by a factor Xa generation assay, phosphatidylserine (PS) content by prothrombinase assay and thrombin generation using calibrated automated thrombogram (CAT). Nano‐LC‐MS/MS identified 585 EV‐associated proteins with high confidence. Of these, 201 were differentially expressed in the CSE‐EVs according to the moderated t‐test, followed by false discovery rate (FDR) adjustment with the FDR threshold set to 0.1. Functional enrichment analysis revealed that 24 proteins of the pathway haemostasis were significantly up‐regulated in CSE‐EVs, including TF. Increased TF expression on CSE‐EVs was confirmed by bead‐based flow cytometry and was associated with increased TF activity. CSE‐EVs caused faster and more thrombin generation in normal human plasma than control‐EVs, which was partly TF‐, but also PS‐dependent. In conclusion, proteomic analysis allowed us to predict procoagulant properties of CSE‐EVs which were confirmed in vitro. Cigarette smoke‐induced EVs may contribute to the increased cardiovascular and respiratory risk observed in smokers.
The El Niño impact on maize yields is amplified in lower income teleconnected countries
Authors: Ubilava David , Abdolrahimi Maryam 
Published: March 2019

Abstract
We use a multiple-regime panel smooth transition regression to examine the economic and climatic sources of the nonuniform relationship between El Niño Southern Oscillation (ENSO) and maize yields around the globe. While the yield effect is predominantly observed in strongly teleconnected countries, it is amplified in lower income countries, which we attribute to possible lack of resilience to ENSO—induced weather shocks. Both El Niño-like and La Niña-like conditions result in maize yield reduction, but it is during El Niño events when maize yields drop by up to 20% in most affected countries. Because in many of these countries maize is an important agricultural crop, the presented results are of interest to researchers and policy makers in the areas of world nutrition and international aid. Moreover, because larger share of maize is produced by high income weakly teleconnected countries, the observed geographic heterogeneity of the El Niño impact offers possible benefits from global risk sharing. These findings also offer insights to climate change economics, as possible increased frequency of the ENSO cycle may negatively impact maize production in strongly teleconnected low income countries.
Deforestation displaced: trade in forest-risk commodities and the prospects for a global forest transition
Authors: Pendrill Florence , Persson U Martin , Godar Javier , Kastner Thomas 
Published: March 2019

Abstract
While many developed countries are increasing their forest cover, deforestation is still rife in the tropics and subtropics. With international trade in forest-risk commodities on the rise, it is becoming increasingly important to consider between-country trade linkages in assessing the drivers of—and possible connections between—forest loss and gain across countries. Previous studies have shown that countries that have undergone a forest transition (and are now increasing their forest cover) tend to displace land use outside their borders. However, lack of comprehensive data on deforestation drivers imply that it has not been possible to ascertain whether this has accelerated forest loss in sourcing countries. To remedy this, we present a land-balance model that quantifies deforestation embodied in production of agricultural and forestry commodities at country level across the tropics and subtropics, subsequently tracing embodied deforestation to countries of apparent consumption using a physical, country-to-country trade model. We find that in the period 2005–2013, 62% (5.5 Mha yr−1) of forest loss could be attributed to expanding commercial cropland, pastures and tree plantations. The commodity groups most commonly associated with deforestation were cattle meat, forestry products, oil palm, cereals and soybeans, though variation between countries and regions was large. A large (26%) and slightly increasing share of deforestation was attributed to international demand, the bulk of which (87%) was exported to countries that either exhibit decreasing deforestation rates or increasing forest cover (late- or post-forest transition countries), particularly in Europe and Asia (China, India, and Russia). About a third of the net forest gains in post-forest transition countries was in this way offset by imports of commodities causing deforestation elsewhere, suggesting that achieving a global forest transition will be substantially more challenging than achieving national or regional ones.
Post–Modern Epidemiology: When Methods Meet Matter
Authors: Davey Smith George 
Published: March 2019

Abstract
In the last third of the 20th century, etiological epidemiology within academia in high-income countries shifted its primary concern from attempting to tackle the apparent epidemic of noncommunicable diseases to an increasing focus on developing statistical and causal inference methodologies. This move was mutually constitutive with the failure of applied epidemiology to make major progress, with many of the advances in understanding the causes of noncommunicable diseases coming from outside the discipline, while ironically revealing the infectious origins of several major conditions. Conversely, there were many examples of epidemiologic studies promoting ineffective interventions and little evident attempt to account for such failure. Major advances in concrete understanding of disease etiology have been driven by a willingness to learn about and incorporate into epidemiology developments in biology and cognate data science disciplines. If fundamental epidemiologic principles regarding the rooting of disease risk within populations are retained, recent methodological developments combined with increased biological understanding and data sciences capability should herald a fruitful post–Modern Epidemiology world.
Dr.VAE: improving drug response prediction via modeling of drug perturbation effects
Authors: Rampášek Ladislav , Hidru Daniel , Smirnov Petr , Haibe-Kains Benjamin , Goldenberg Anna 
Published: March 2019

Abstract

Motivation
Individualized drug response prediction is a fundamental part of personalized medicine for cancer. Great effort has been made to discover biomarkers or to develop machine learning methods for accurate drug response prediction in cancers. Incorporating prior knowledge of biological systems into these methods is a promising avenue to improve prediction performance. High-throughput cell line assays of drug-induced transcriptomic perturbation effects are a prior knowledge that has not been fully incorporated into a drug response prediction model yet.

Results
We introduce a unified probabilistic approach, Drug Response Variational Autoencoder (Dr.VAE), that simultaneously models both drug response in terms of viability and transcriptomic perturbations. Dr.VAE is a deep generative model based on variational autoencoders. Our experimental results showed Dr.VAE to do as well or outperform standard classification methods for 23 out of 26 tested Food and Drug Administration-approved drugs. In a series of ablation experiments we showed that the observed improvement of Dr.VAE can be credited to the incorporation of drug-induced perturbation effects with joint modeling of treatment sensitivity.

Availability and implementation
Processed data and software implementation using PyTorch (Paszke et al., 2017) are available at: https://github.com/rampasek/DrVAE.

Supplementary information
Supplementary data are available at Bioinformatics online.
Integration of methylation QTL and enhancer–target gene maps with schizophrenia GWAS summary results identifies novel genes
Authors: Wu Chong , Pan Wei 
Published: March 2019

Abstract

Motivation
Most trait-associated genetic variants identified in genome-wide association studies (GWASs) are located in non-coding regions of the genome and thought to act through their regulatory roles.

Results
To account for enriched association signals in DNA regulatory elements, we propose a novel and general gene-based association testing strategy that integrates enhancer-target gene pairs and methylation quantitative trait locus data with GWAS summary results; it aims to both boost statistical power for new discoveries and enhance mechanistic interpretability of any new discovery. By reanalyzing two large-scale schizophrenia GWAS summary datasets, we demonstrate that the proposed method could identify some significant and novel genes (containing no genome-wide significant SNPs nearby) that would have been missed by other competing approaches, including the standard and some integrative gene-based association methods, such as one incorporating enhancer-target gene pairs and one integrating expression quantitative trait loci.

Availability and implementation
Software: wuchong.org/egmethyl.html

Supplementary information
Supplementary data are available at Bioinformatics online.
Genome-wide DNA methylation profile of early-onset endometrial cancer: its correlation with genetic aberrations and comparison with late-onset endometrial cancer
Authors: Makabe Takeshi , Arai Eri , Hirano Takuro , Ito Nanako , Fukamachi Yukihiro , Takahashi Yoriko , Hirasawa Akira , Yamagami Wataru , Susumu Nobuyuki , Aoki Daisuke , Kanai Yae 
Published: March 2019

Abstract
The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide DNA methylation analysis and targeted sequencing of tumor-related genes were performed using the Infinium MethylationEPIC BeadChip and the Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples of normal control endometrial tissue from patients without endometrial cancer and 81 samples of endometrial cancer tissue. Principal component analysis revealed that tumor samples had a DNA methylation profile distinct from that of control samples. Gene Ontology enrichment analysis revealed significant differences of DNA methylation at 1034 CpG sites between early-onset endometrioid endometrial cancer (EE) tissue (patients aged ≤40 years) and late-onset endometrioid endometrial cancer (LE) tissue, which were accumulated among ‘transcriptional factors’. Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs. Unsupervised hierarchical clustering grouped EE samples in Cluster EA (n = 22) and samples in Cluster EB (n = 12). Clinicopathologically less aggressive tumors tended to be accumulated in Cluster EB, and DNA methylation levels of 18 genes including HOXA9, HOXD10 and SOX11 were associated with differences in such aggressiveness between the two clusters. We identified 11 marker CpG sites that discriminated EB samples from EA samples with 100% sensitivity and specificity. These data indicate that genetically and epigenetically different pathways may participate in the development of EEs and LEs, and that DNA methylation profiling may help predict tumors that are less aggressive and amenable to fertility preservation treatment.
Human Papillomavirus Antibody Levels and Quadrivalent Vaccine Clinical Effectiveness in Perinatally Human Immunodeficiency Virus–infected and Exposed, Uninfected Youth
Authors: Moscicki Anna-Barbara , Karalius Brad , Tassiopoulos Katherine , Yao Tzy-Jyun , Jacobson Denise L , Patel Kunjal , Purswani Murli , Seage George R ,   Pediatric HIV/AIDS Cohort Study, Yogev Ram , Sanders Margaret Ann , Malee Kathleen , Hunter Scott , Shearer William , Paul Mary , Cooper Norma , Harris Lynnette , Purswani Murli , Baig Mahboobullah Mirza , Villegas Alma , Puga Ana , Navarro Sandra , Garvie Patricia A , Blood James , Burchett Sandra K , Karthas Nancy , Kammerer Betsy , Wiznia Andrew , Burey Marlene , Shaw Ray , Auguste Raphaelle , Dieudonne Arry , Bettica Linda , Johnson Juliette , Chen Janet S , Bulkley Maria Garcia , Ivey Latreaca , Grant Mitzie , Knapp Katherine , Allison Kim , Wilkins Megan , Russell-Bell Jamie , Acevedo-Flores Midnela , Rios Heida , Olivera Vivian , Silio Margarita , Gabriel Medea , Sirois Patricia , Spector Stephen A , Norris Kim , Nichols Sharon , McFarland Elizabeth , Cagwin Eric , Barr Emily , Katai Alisa , Scott Gwendolyn , Alvarez Grace , Fernandez Gabriel , Cuadra Anai 
Published: March 2019

AbstractBackgroundPersons who are infected with human immunodeficiency virus (HIV) are at high risk of human papillomavirus (HPV)-associated cancers. The objectives are to compare antibody titers to HPV 6, 11, 16, and 18 and rate of abnormal cytology between perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth.MethodsThis is a prospective observational cohort study of HPV4 vaccinated youth performed as part of the multicenter Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol. Seroconversion and geometric mean titer (GMT) against HPV types 6, 11, 16, and 18 were calculated. Vaccine effectiveness included rates of abnormal cervical cytology and genital warts.ResultsSeroconversion to HPV 6, 11, 16, and 18 occurred in 83%, 84%, 90%, and 62% of 310 vaccinated PHIV youth compared to 94%, 96%, 99%, and 87% of 148 vaccinated PHEU youth, respectively (P &lt; .05 for all comparisons). GMTs were lower in the PHIV vs PHEU within each category of HPV4 doses received. Higher GMTs were associated with younger age, lower HIV type 1 RNA viral load, and higher CD4% at first HPV4 vaccination, as well as shorter duration between last vaccine dose and antibody specimen. Abnormal cytology occurred in 33 of 56 PHIV and 1 of 7 PHEU sexually active vaccinated females, yielding incidence rates per 100 person-years of 15.0 (10.9 to 20.6) and 2.9 (0.4 to 22.3), respectively.ConclusionAntibody titers to HPV4 were lower for all serotypes in PHIV compared to PHEU youth. Protection against abnormal cytology was also diminished in sexually active PHIV females.
Early Initiation of Anti-TNF is Associated with Favourable Long-term Outcome in Crohn’s Disease: 10-Year-Follow-up Data from the Swiss IBD Cohort Study
Authors: Frei Roy , Fournier Nicolas , Zeitz Jonas , Scharl Michael , Morell Bernhard , Greuter Thomas , Schreiner Philipp , Misselwitz Benjamin , Safroneeva Ekaterina , Schoepfer Alain M , Vavricka Stephan R , Rogler Gerhard , Biedermann Luc 
Published: March 2019

Abstract

Background and Aims
The optimal timing of treatment escalation in Crohn’s disease [CD] remains a challenging issue, and very little is known about its long-term development following early versus late administration of anti-TNF antibodies. The long-term outcome of Swiss CD patients was comparatively assessed in an up to 10-year follow-up, using patients participating in the Swiss Inflammatory Bowel Disease Cohort Study [SIBDCS].

Methods
Prospectively collected SIBDCS patient data, including disease history, baseline characteristics at enrolment, and course of disease, were analysed in patients with early versus late [<24 versus ≥24 months after diagnosis] and no anti-TNF treatment.

Results
A reduced risk of developing bowel stenosis was found in patients who received early anti-TNF treatment. This association was seen in patients overall and also in the subgroups of CD patients without pre-existing complications [Log-rank test: p < 0.001].
Furthermore, osteoporosis and anaemia were observed significantly less frequently in patients who received early anti-TNF treatment, compared with either patients who received treatment late [p < 0.001 and p = 0.046, respectively] or were never [p < 0.001 for both] treated with anti-TNF antibodies. Patients with early anti-TNF administration sought medical consultations significantly less often, including gastroenterologists in private practice [p = 0.017], ambulatory [outpatient] hospital visits [p = 0.038], and a composite of any medical visits [p = 0.001]. The percentage of patients unable to work was lowest for early-anti-TNF–treated patients, in comparison with patients who were treated late or never [3.6% vs 8.8% vs 3.7%, p = 0.016].

Conclusions
In CD patients within the SIBDCS, early anti-TNF administration was found to be associated with several indicators of a more favourable long-term outcome.
Adolescent Mental Health Problems, Behaviour Penalties, and Distributional Variation in Educational Achievement
Authors: Evensen Miriam 
Published: March 2019

Abstract
Prior research shows that mental health problems are linked to worse student achievements in school, but few studies address whether the consequences of such problems vary by student achievement level and the role of teachers’ grading practices in these processes. In this study, I examine the relationship between mental health problems and grade achievement at the end of compulsory education using a population-based Norwegian health survey, the Young-HUNT study, matched with administrative data. The results show a robust negative influence of attention problems and conduct problems on average grade achievement, and a positive role of internalizing problems, in fixed-effects models controlling for unobserved characteristics of school context. Further, conduct problems are more strongly related with student achievement in the lower end of the grade distribution, indicating that low-achieving students are disproportionally affected by mental health problems. I also compare grades assigned by classroom teachers with anonymously graded exams, and find that part of the negative association between externalizing problems and achievement reflect a ‘behavioural penalty’ due to teacher-bias in grading practices.
Impact of large periprocedural myocardial infarction on mortality after percutaneous coronary intervention and coronary artery bypass grafting for left main disease: an analysis from the EXCEL trial
Authors: Ben-Yehuda Ori , Chen Shmuel , Redfors Björn , McAndrew Thomas , Crowley Aaron , Kosmidou Ioanna , Kandzari David E , Puskas John D , Morice Marie-Claude , Taggart David P , Leon Martin B , Lembo Nicholas J , Brown W Morris , Simonton Charles A , Dressler Ovidiu , Kappetein Arie Pieter , Sabik Joseph F , Serruys Patrick W , Stone Gregg W 
Published: March 2019

Abstract

Aims
The prognostic implications of periprocedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) remain controversial. We examined the 3-year rates of mortality among patients with and without PMI undergoing left main coronary artery intervention randomized to PCI with everolimus-eluting stents vs. CABG in the large-scale, multicentre, prospective, randomized EXCEL trial.

Methods and results
By protocol, PMI was defined using an identical threshold for PCI and CABG [creatinine kinase-MB (CK-MB) elevation &gt;10× the upper reference limit (URL) within 72 h post-procedure, or &gt;5× URL with new Q-waves, angiographic vessel occlusion, or loss of myocardium on imaging]. Cox proportional hazards modelling was performed controlling for age, sex, hypertension, diabetes mellitus, left ventricular ejection fraction, SYNTAX score, and chronic obstructive pulmonary disease (COPD). A total of 1858 patients were treated as assigned by randomization. Periprocedural MI occurred in 34/935 (3.6%) of patients in the PCI group and 56/923 (6.1%) of patients in the CABG group [odds ratio 0.61, 95% confidence interval (CI) 0.40–0.93; P = 0.02]. Periprocedural MI was associated with SYNTAX score, COPD, cross-clamp duration and total procedure duration, and not using antegrade cardioplegia. By multivariable analysis, PMI was associated with cardiovascular death and all-cause death at 3 years [adjusted hazard ratio (HR) 2.63, 95% CI 1.19–5.81; P = 0.02 and adjusted HR 2.28, 95% CI 1.22–4.29; P = 0.01, respectively]. The effect of PMI was consistent for PCI and CABG for cardiovascular death (P interaction = 0.56) and all-cause death (P interaction = 0.59). Peak post-procedure CK-MB ≥10× URL strongly predicted mortality, whereas lesser degrees of myonecrosis were not associated with prognosis.

Conclusion
In the EXCEL trial, PMI was more common after CABG than PCI, and was strongly associated with increased 3-year mortality after controlling for potential confounders. Only extensive myonecrosis (CK-MB ≥10× URL) was prognostically important.