bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilayer network analysis of oil linkages
Authors: Casarin Roberto , Iacopini Matteo , Molina German , ter Horst Enrique , Espinasa Ramon , Sucre Carlos , Rigobon Roberto 
Published: January 2020

SummaryThis manuscript proposes a new approach for unveiling existing linkages within the international oil market across multiple driving factors beyond production. A multilayer, multicountry network is extracted through a novel Bayesian graphical vector autoregressive model, which allows for a more comprehensive, dynamic representation of the network linkages than do traditional or static pairwise Granger-causal inference approaches. Building on previous work, the layers of the network include country- and region-specific oil production levels and rigs, both through simultaneous and lagged temporal dependences among key factors, while controlling for oil prices and a world economic activity index. The proposed approach extracts relationships across all variables through a dynamic, cross-regional network. This approach is highly scalable and adjusts for time-evolving linkages. The model outcome is a set of time-varying graphical networks that unveil both static representations of world oil linkages and variations in microeconomic relationships both within and between oil producers. An example is provided, illustrating the evolution of intra- and inter-regional relationships for two major interconnected oil producers: the United States, with a regional decomposition of its production and rig deployment, and the Arabian Peninsula and key Middle Eastern producers, with a country-based decomposition of production and rig deployment, while controlling for oil prices and global economic indices. Production is less affected by concurrent changes in oil prices and the overall economy than rigs. However, production is a lagged driver for prices, rather than rigs, which indicates that the linkage between rigs and production may not be fully accounted for in the markets.
Three-dimensional changes in the craniofacial complex associated with soft-diet feeding
Authors: Kono Kana , Tanikawa Chihiro , Murata Yuka , Yanagita Takeshi , Kamioka Hiroshi , Yamashiro Takashi 
Published: January 2020

Summary

Background and objectives
The masticatory force affects craniofacial development. We aimed to quantify the topological deviation of the growing craniofacial structure due to soft-food diet feeding and to map the region where the phenotypes appeared on three-dimensional (3D) images.

Material and methods
Mice were fed a powdered soft diet (SD) or conventional hard diet (HD) of regular rodent pellets at 3 weeks of age until 9 weeks of age. The heads, excluding the mandibles, were scanned by micro-computed tomography. The topographic deviation of the bony surface was quantitatively assessed by a wire mesh fitting analysis. The actual displacement and significant differences were mapped and visualized in each x-, y-, and z-axis on the 3D craniofacial image. On these reconstructed images, two-dimensional linear measurements between the landmark points confirmed the 3D skeletal displacement.

Results
In the transverse direction, the zygomatic arches and the region in which the temporal muscle attaches to the parietal and temporal bones were narrow in the SD group. The temporal muscle attachment regions significantly shifted anteriorly, and consequently, the sagittal zygomatic arch shortened. Although the cranial sagittal length was not affected, the vertical height was also reduced in the SD group compared to the HD group.

Conclusions
Our 3D surface-based analysis demonstrated that SD feeding resulted in reduced 3D bony development at the region where the chewing muscles attach to the zygomatic arches and the temporal and parietal bones. Interestingly, SD feeding induced an anterior shift in the temporal and parietal bone regions, which can affect the skeletal inter-jaw relationship.
Population-Specific Genetic and Expression Differentiation in Europeans
Authors: Jiang Xueyuan , Assis Raquel 
Published: January 2020

AbstractMuch of the enormous phenotypic variation observed across human populations is thought to have arisen from events experienced as our ancestors peopled different regions of the world. However, little is known about the genes involved in these population-specific adaptations. Here, we explore this problem by simultaneously examining population-specific genetic and expression differentiation in four human populations. In particular, we derive a branch-based estimator of population-specific differentiation in four populations, and apply this statistic to single-nucleotide polymorphism and RNA-seq data from Italian, British, Finish, and Yoruban populations. As expected, genome-wide estimates of genetic and expression differentiation each independently recapitulate the known relationships among these four human populations, highlighting the utility of our statistic for identifying putative targets of population-specific adaptations. Moreover, genes with large copy number variations display elevated levels of population-specific genetic and expression differentiation, consistent with the hypothesis that gene duplication and deletion events are key reservoirs of adaptive variation. Further, many top-scoring genes are well-known targets of adaptation in Europeans, including those involved in lactase persistence and vitamin D absorption, and a handful of novel candidates represent promising avenues for future research. Together, these analyses reveal that our statistic can aid in uncovering genes involved in population-specific genetic and expression differentiation, and that such genes often play important roles in a diversity of adaptive and disease-related phenotypes in humans.
Genome-wide analysis of the H3K27me3 epigenome and transcriptome in Brassica rapa
Authors: Payá-Milans Miriam , Poza-Viejo Laura , Martín-Uriz Patxi San , Lara-Astiaso David , Wilkinson Mark D , Crevillén Pedro 
Published: January 2020

Abstract

Background
Genome-wide maps of histone modifications have been obtained for several plant species. However, most studies focus on model systems and do not enforce FAIR data management principles. Here we study the H3K27me3 epigenome and associated transcriptome of Brassica rapa, an important vegetable cultivated worldwide.

Findings
We performed H3K27me3 chromatin immunoprecipitation followed by high-throughput sequencing and transcriptomic analysis by 3′-end RNA sequencing from B. rapa leaves and inflorescences. To analyze these data we developed a Reproducible Epigenomic Analysis pipeline using Galaxy and Jupyter, packaged into Docker images to facilitate transparency and reuse. We found that H3K27me3 covers roughly one-third of all B. rapa protein-coding genes and its presence correlates with low transcript levels. The comparative analysis between leaves and inflorescences suggested that the expression of various floral regulatory genes during development depends on H3K27me3. To demonstrate the importance of H3K27me3 for B. rapa development, we characterized a mutant line deficient in the H3K27 methyltransferase activity. We found that braA.clf mutant plants presented pleiotropic alterations, e.g., curly leaves due to increased expression and reduced H3K27me3 levels at AGAMOUS-like loci.

Conclusions
We characterized the epigenetic mark H3K27me3 at genome-wide levels and provide genetic evidence for its relevance in B. rapa development. Our work reveals the epigenomic landscape of H3K27me3 in B. rapa and provides novel genomics datasets and bioinformatics analytical resources. We anticipate that this work will lead the way to further epigenomic studies in the complex genome of Brassica crops.
The impact of pill counting on resource-limited health facilities: a thematic qualitative analysis in eSwatini
Authors: Krezanoski Joseph D , Matshotyana Kidwell , Nxumalo Nkosinathi , Comfort Alison B , Khumalo Phinda , Krezanoski Paul J 
Published: January 2020

Abstract
Research on health systems in resource-limited settings has garnered considerable attention, but the dispensing of individual prescriptions has not been thoroughly explored as a specific bottleneck to effective delivery of care. The rise of human immunodeficiency virus/tuberculosis prevalence and non-communicable diseases in the Kingdom of eSwatini has introduced significant pressures on health facilities to meet patient demands for lifelong medications. Because automated pill counting methods are impracticable and expensive, most prescriptions are made by means of manually counting individual prescriptions using a plastic dish and spatula. The aim of this work was to examine the perceptions of health providers of causes for pill counting errors, and pill counting’s impact on clinic workflow. Our study took place in 13 randomly selected public health facilities in eSwatini, stratified by three groups based on monthly patient volumes. Thirty-one participants who count pills regularly and 13 clinic supervisors were interviewed with semi-structured materials and were audio-recorded for later transcription. Interviews were thematically analysed with inductive coding and three major themes emerged: workflow, counting error causes and effect on clinic function. Findings demonstrate large variety in how facilities manage pill counting for prescription making. Due to patient demands, most facilities utilize all available personnel, from cleaners to nurses, to partake in prescription making. Major causes for pill counting errors were distractions, exhaustion and being hurried. Participants mentioned that patients said that they had initially received the wrong quantity of pills and this affected medication adherence measurements based off pill counts. Most participants described how efforts put into pill counting detracted from their work performance, wasted valuable time and increased patient wait times. Future research is needed to quantify prescription accuracy, but our data suggest that interventions directly alleviating the burden of pill counting could lead to improved clinic quality and possibly improve patient outcomes.
Risk of Venous Thromboembolism After Hospital Discharge in Patients With Inflammatory Bowel Disease: A Population-based Study
Authors: McCurdy Jeffrey D , Kuenzig M Ellen , Smith Glenys , Spruin Sarah , Murthy Sanjay K , Carrier Marc , Nguyen Geoffrey C , Benchimol Eric I 
Published: January 2020

Abstract

Background
Inflammatory bowel disease (IBD) is associated with a high risk of venous thromboembolism (VTE) during hospitalization. It is unclear if this association persists after discharge. We aimed to assess the incidence of postdischarge VTE in IBD patients and to determine if IBD is associated with increased VTE risk.

Methods
We performed a population-based cohort study between 2002 and 2016 using Ontario health administrative data sets. Hospitalized (≥72 hours) adults with IBD were stratified into nonsurgical and surgical cohorts and matched on propensity score to non-IBD controls. Time to postdischarge VTE was assessed by Kaplan-Meier methods, and VTE risk was assessed by Cox proportional hazard models.

Results
A total of 81,900 IBD discharges (62,848 nonsurgical and 19,052 surgical) were matched to non-IBD controls. The cumulative incidence of VTE at 12 months after discharge was 2.3% for nonsurgical IBD patients and 1.6% for surgical IBD patients. The incidence increased in the nonsurgical IBD cohort by 4% per year (incidence rate ratio, 1.04; 95% CI, 1.02–1.05). In our propensity score-matched analysis, the risk of VTE at 1-month postdischarge was greater in nonsurgical IBD patients (hazard ratio [HR], 1.72; 95% CI, 1.51–1.96) and surgical patients with ulcerative colitis (HR, 1.68; 95% CI, 1.16–2.45) but not surgical patients with Crohn’s disease. These trends persisted through 12 months.

Conclusions
Nonsurgical IBD patients and surgical patients with ulcerative colitis are 1.7-fold more likely to develop postdischarge VTE than non-IBD patients. These findings support the need for increased vigilance and consideration of thromboprophylaxis in this population.
Clinical Validation of a 106-SNV MALDI-ToF MS Pharmacogenomic Panel
Authors: Williams Grace R , Cook Leanne , Lewis Lionel D , Tsongalis Gregory J , Nerenz Robert D 
Published: January 2020

AbstractBackgroundLaboratorians have the opportunity to help minimize the frequency of adverse drug reactions by implementing pharmacogenomic testing and alerting care providers to possible patient/drug incompatibilities before drug treatment is initiated. Methods combining PCR with MALDI-ToF MS have allowed for sensitive, economical, and multiplexed pharmacogenomic testing results to be delivered in a timely fashion.MethodThis study evaluated the analytical performance of the Agena Biosciences iPLEX® PGx 74 panel and a custom iPLEX panel on a MassARRAY MALDI-TOF MS instrument in a clinical laboratory setting. Collectively, these panels evaluate 112 SNVs across 34 genes implicated in drug response. Using commercially available samples (Coriell Biorepository) and in-house extracted DNA, we determined ideal reaction conditions and assessed accuracy, precision, and robustness.ResultsFollowing protocol optimization, the Agena PGx74 and custom panels demonstrated 100% concordance with the 1000 Genomes Project Database and clinically validated hydrolysis probe genotyping assays. 100% concordance was also observed in all assessments of assay precision when appropriate QC metrics were applied.ConclusionsSignificant development time was required to optimize sample preparation and instrumental analysis and 3 assays were removed due to inconsistent performance. Following modification of the manufacturer’s protocol and instituting manual review of each assay plate, the Agena PGx74 and custom panel constitute a cost-effective, robust, and accurate method for clinical identification of 106 SNVs involved in drug response.
Cannabinol (CBN) Cross-Reacts with Two Urine Immunoassays Designed to Detect Tetrahydrocannabinol (THC) Metabolite
Authors: Kroner Grace M , Johnson-Davis Kamisha L , Doyle Kelly , McMillin Gwendolyn A 
Published: January 2020

AbstractBackgroundThe psychoactive component of cannabis, tetrahydrocannabinol (THC), is one of many cannabinoids present in the plant. Since cannabinoids have extensive structural similarity, it is important to be aware of potential cross-reactivity with immunoassays designed to detect THC metabolite. This is especially important as cannabinoid products are increasingly marketed as legal supplements. The objective of this study was to assess the cross-reactivity of 2 commercial immunoassays designed to detect THC metabolite with 4 cannabinoids: cannabidiol, cannabinol, cannabichromene, and cannabigerol.MethodsDeidentified residual patient urine samples that tested negative for THC metabolite on initial testing were pooled and fortified with the above compounds to detect cross-reactivity. We next tested a range of CBN concentrations to determine what concentration of CBN was required to trigger a positive immunoassay result. Finally, we tested whether CBN has an additive effect with THC in the immunoassay by adding CBN to 21 samples weakly positive for THC by a mass spectrometry method but negative by the EMIT II Plus immunoassay.ResultsBoth the EMIT II Plus assay and the Microgenics MultiGent assay demonstrated cross-reactivity with CBN. For the EMIT II Plus assay, about 5-fold more CBN than THC metabolite was required to produce an assay signal equivalent to the cutoff concentration, and CBN displayed an additive effect with THC metabolite. For the Microgenics assay, 20-fold more CBN than THC metabolite was required to cross the cutoff concentration.ConclusionsThese data may help guide the need for confirmatory testing when results of THC metabolite testing by immunoassay are inconsistent with expectations.
Determination of 5-MeO-DIPT in Human Urine Using Gas Chromatography Coupled with High-Resolution Orbitrap Mass Spectrometry
Authors: Yan Xiuying , Xiang Ping , Zhao Yunli , Yu Zhiguo , Yan Hui 
Published: January 2020

Abstract
5-Methoxy-N,N-Diisopropyltryptamine (5-MeO-DIPT) is a designer hallucinogen derived from tryptamine and its use has been banned by many countries. In this study, a qualitative and quantitative method was developed for determining 5-MeO-DIPT in urine by gas chromatography high-resolution mass spectrometry. 5-hydroxy-N,N-diisopropyltryptamine (5-OH-DIPT) and 5-methoxy-N-isopropyltryptamine (5-MeO-IPT) were identified as 5-MeO-DIPT metabolites in abusers’ urine. 5-MeO-DIPT was extracted from urine by liquid–liquid extraction with ethyl acetate under alkaline conditions. The extract was analyzed by GC-Orbitrap-MS in full scan mode with a resolution of 60,000 full width at half maxima (FWHM). The linear range of this method was 2–300 ng/mL with r &gt; 0.99, and the limit of detection was 1 ng/mL. The accuracy and precision were 93–108.7% and 3.1–10.3%, respectively. This method is simple and sensitive. It has been successfully used to detect 5-MeO-DIPT in drug abusers’ urine, which showed that the concentrations of 5-MeO-DIPT were between 1 and 2.8 ng/mL. 5-OH-DIPT and 5-MeO-IPT, two urinary major metabolites of 5-MeO-DIPT, were identified in urine samples from 5-MeO-DIPT users. Furthermore, the stability of 5-MeO-DIPT in human urine was investigated. It was discovered that the concentration of 5-MeO-DIPT in urine decreased by 22.8, 33.2 and 38.2% after samples were stored for 24 h at 25°C, 5 days at 4°C and 7 days at 4°C, respectively. And 5-MeO-DIPT in urine were stable after they were stored for 30 days at −20°C. Therefore, it is recommended that urine should be stored under freezing conditions before performing 5-MeO-DIPT analysis.
Detection of Chemical Weapon Nerve Agents in Bone by Liquid Chromatography–Mass Spectrometry
Authors: Rubin Katie M , Goldberger Bruce A , Garrett Timothy J 
Published: January 2020

Abstract
A recently proposed model for the incorporation of xenobiotics of forensic interest into the human skeleton suggests nerve agent metabolites may incorporate into bone at relatively elevated concentrations based on their unique chemical properties. To test the hypothesis that nerve agent metabolites interact with bone, methods for the extraction, isolation and semi-quantitative detection of nerve agent metabolites (MPA, EMPA, IMPA, iBuMPA, CMPA and PMPA, corresponding to the nerve agents VX, Russian VX, sarin, cyclosarin and soman, respectively) from osseous tissue were developed using liquid chromatography–mass spectrometry with both quadrupole time-of-flight and triple quadrupole (QqQ) instruments. The optimized methods were validated on the QqQ instrument. Despite high ion suppression, the achieved limits of detection (5–20 pg/g for four analytes; 350 pg/g for the fifth analyte) were lower than many of those published for the same analytes in other biomatrices, including serum and urine. These methods were tested on the skeletal remains of minipigs exposed to the chemical weapon VX in vivo. The VX metabolite was detected in multiple minipig bone samples; to the authors’ knowledge, this is the first time in vivo nerve agent exposure has been detected from bone. Further, detected concentrations and diaphyseal-to-epiphyseal area count ratios reflect animal exposure history. Although the results are limited, they are promising, indicating that nerve agent metabolites may interact with bone as a pharmacokinetic compartment and can be extracted from bone postmortem. Additional studies, assessing the effects of different agents, exposure pathways and taphonomic variables, are needed; however, these results suggest the method may be used with human bone to detect use of chemical weapons from postmortem biomatrices even well after a suspected attack. More general implications for both nerve agent toxicology and skeletal toxicology are also discussed.
Designing an early failure indicator channel for an in-tank hydrogen valve via a fatigue-based approach
Authors: Cao Thanh Binh , Kedziora Slawomir , Sellen Stephan , Maas Stefan , Repplinger Christian 
Published: January 2020

Abstract
This study introduced a fatigue-based approach to design and implement an indicator channel into an in-tank hydrogen valve. It was aimed at providing a mean to point out multiple early valve's damages. To achieve the goal, the study was proposed to handle via three main phases. They included (i) the risk point determinations, (ii) the new valve design and the crack nucleation life estimations, as well as (iii) the simplified crack growth analyses. The obtained results firstly highlighted the construction of the test channel (TC), whose branches were located close to the predicted damage's sites. The damages could be identified either when a crack reaches the TC (then forms a leakage) or indirectly via the crack propagations’ correlation. The results also pointed out that the TC-implemented valve could perform as similarly as the non-TC one in the non-treated condition. More importantly, this new structure was proved to have a capacity of satisfying the required minimal life of 1.5E5 cycles, depending on the combined uses of the specific material and the pre-treatment, among those considered. In addition, the results emphasized the complexity of the TC that could not be formed by the traditional manufacturing process. Hence, direct metal laser sintering was proposed for the associated prototype and the final TC was issued based on the fundamental requirements of the technique. Finally, it was suggested that practical experiments should essentially be carried out to yield more evidence to support the demonstrated results.
Neuropathologic Changes in Sudden Unexplained Death in Childhood
Authors: McGuone Declan , Leitner Dominique , William Christopher , Faustin Arline , Leelatian Nalin , Reichard Ross , Shepherd Timothy M , Snuderl Matija , Crandall Laura , Wisniewski Thomas , Devinsky Orrin 
Published: January 2020

Abstract
Sudden unexplained death in childhood (SUDC) affects children &gt;1-year-old whose cause of death remains unexplained following comprehensive case investigation and is often associated with hippocampal abnormalities. We prospectively performed systematic neuropathologic investigation in 20 SUDC cases, including (i) autopsy data and comprehensive ancillary testing, including molecular studies, (ii) ex vivo 3T MRI and extensive histologic brain samples, and (iii) blinded neuropathology review by 2 board-certified neuropathologists. There were 12 girls and 8 boys; median age at death was 33.3 months. Twelve had a history of febrile seizures, 85% died during apparent sleep and 80% in prone position. Molecular testing possibly explained 3 deaths and identified genetic mutations in TNNI3, RYR2, and multiple chromosomal aberrations. Hippocampal abnormalities most often affected the dentate gyrus (altered thickness, irregular configuration, and focal lack of granule cells), and had highest concordance between reviewers. Findings were identified with similar frequencies in cases with and without molecular findings. Number of seizures did not correlate with hippocampal findings. Hippocampal alterations were the most common finding on histological review but were also found in possibly explained deaths. The significance and specificity of hippocampal findings is unclear as they may result from seizures, contribute to seizure pathogenesis, or be an unrelated phenomenon.