bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of NT5C2 Germline Variants on 6‐Mecaptopurine Metabolism in Children With Acute Lymphoblastic Leukemia
Authors: Jiang Chuang , Yang Wenjian , Moriyama Takaya , Liu Chengcheng , Smith Colton , Yang Wentao , Qian Maoxiang , Li Ziping , Tulstrup Morten , Schmiegelow Kjeld , Crews Kristine R. , Zhang Hui , Pui Ching‐Hon , Evans William , Relling Mary , Bhatia Smita , Yang Jun J. 
Published: October 2020

6‐mercaptopurine (6‐MP) is widely used in the treatment of acute lymphoblastic leukemia (ALL), and its cytotoxicity is primarily mediated by thioguanine nucleotide (TGN) metabolites. A recent genomewide association study has identified germline polymorphisms (e.g., rs72846714) in the NT5C2 gene associated with 6‐MP metabolism in patients with ALL. However, the full spectrum of genetic variation in NT5C2 is unclear and its impact on 6‐MP drug activation has not been comprehensively examined. To this end, we performed targeted sequencing of NT5C2 in 588 children with ALL and identified 121 single nucleotide polymorphisms nominally associated with erythrocyte TGN during 6‐MP treatment (P < 0.05). Of these, 61 variants were validated in a replication cohort of 372 children with ALL. After considering linkage disequilibrium and multivariate analysis, we confirmed two clusters of variants, represented by rs72846714 and rs58700372, that independently affected 6‐MP metabolism. Functional studies showed that rs58700372 directly altered the activity of an intronic enhancer, with the variant allele linked to higher transcription activity and reduced 6‐MP metabolism (lower TGN). By contrast, rs72846714 was not located in a regulatory element and instead its association signal was explained by linkage disequilibrium with a proximal functional variant rs12256506 that activated NT5C2 transcription in‐cis. Our results indicated that NT5C2 germline variation significantly contributes to interpatient variability in thiopurine drug disposition.
Preliminary data on the potential for unintentional antidoping rule violations by permitted cannabidiol (CBD) use
Authors: Mareck Ute , Fusshöller Gregor , Geyer Hans , Huestis Marilyn A. , Scheiff Anja B. , Thevis Mario 
Published: October 2020

AbstractAccording to the World Anti‐Doping Agency (WADA) regulations, cannabinoids use is prohibited in competition except for cannabidiol (CBD) use. For an adverse analytical finding (AAF) in doping control, cannabinoid misuse is based on identification of the pharmacologically inactive metabolite 11‐nor‐delta‐9‐carboxy‐tetrahydrocannabinol‐9‐carboxylic acid (carboxy‐THC) in urine at a concentration greater than 180 ng/ml. All other (minor) cannabinoids are reported as AAF when identified, except for CBD that has been explicitly excluded from the class of cannabinoids on WADA's Prohibited List since 2018. However, due to the fact that CBD isolated from cannabis plants may contain additional minor cannabinoids, the permissible use of CBD can lead to unintentional violations of antidoping regulations. An assay for the detection of 16 cannabinoids in human urine was established. The sample preparation consisted of enzymatic hydrolysis of glucuronide conjugates, liquid–liquid extraction, trimethylsilylation, and analysis by gas chromatography/tandem mass spectrometry (GC–MS/MS). Spot urine samples from CBD users, as well as specimens obtained from CBD administration studies conducted with 15 commercially available CBD products, were analyzed, and assay characteristics such as selectivity, reproducibility of detection at the minimum required performance level, limit of detection, and limit of identification were determined. An ethical committee approved controlled single dose commercially available CBD products administration study was conducted to identify 16 cannabinoids in urine samples collected after ingestion or application of the CBD products as well as their presence in spot urine samples of habitual CBD users. Variable patterns of cannabinoids or their metabolites were observed in the urine samples, especially when full spectrum CBD products were consumed. The presence of minor cannabinoids or their metabolites in an athlete's in‐competition urine sample represents a substantial risk of an antidoping rule violation.
Landscape‐dependent effects of varietal mixtures on insect pest control and implications for farmer profits
Authors: Snyder Lauren D. , Gómez Miguel I. , Mudrak Erika L. , Power Alison G. 
Published: October 2020

AbstractIntraspecific plant diversity can significantly impact insect herbivore populations in natural systems. Yet, its role as an insect pest control strategy in agriculture has received less attention, and little is known about which crop traits are important to herbivores in different landscape contexts. Moreover, empirical economic analyses on the cost‐effectiveness of varietal mixtures are lacking. We used varietal mixtures ofBrassica oleraceacrops on working farms to examine how two metrics of intraspecific crop diversity, varietal richness and number of plant colors (color richness), affect crop damage and the incidence and abundance of two insect pest species:Pieris rapaeandPhyllotretaspp. We evaluated the context‐dependency of varietal mixtures by sampling early‐ and late‐season plantings ofB. oleraceacrops in farms across a gradient of landscape composition. We developed crop budgets and used a net present value analysis to assess the impact of varietal mixtures on input and labor costs, crop revenues, and profit. We found context‐dependent effects of varietal mixtures on both pests. In early‐season plantings, color richness did not affectPhyllotretaspp. populations. However, increasing varietal richness reducedPhyllotretaspp. incidence in simple landscapes dominated by cropland, but this trend was reversed in complex landscapes dominated by natural habitats. In late‐season plantings, color richness reduced the incidence and abundance ofP. rapaelarvae, but only in complex landscapes where their populations were highest. Varietal richness had the same effect onP. rapaelarvae as color richness. Unexpectedly, we consistently found lower pest pressure and reduced crop damage in simple landscapes. Although varietal mixtures did not affect crop damage, increasing color richness corresponded with increased profits, due to increased revenue and a marginal reduction in labor and input costs. We demonstrate varietal mixtures can significantly impact pest populations, and this effect can be mediated by intraspecific variation in crop color. However, the strength and direction of these effects vary by season, landscape composition, and pest species. The association between varietal color richness and profitability indicates farmers could design mixtures to enhance economic returns. We recommend additional research on the benefits of intraspecific trait variation for farmers.
Comparative patterns in taxonomic and functional spider diversities between tropical vs. temperate forests
Authors: Privet Kaïna , Pétillon Julien 
Published: October 2020

AbstractHigh diversity in tropical compared to temperate regions has long intrigued ecologists, especially for highly speciose taxa like terrestrial arthropods in tropical rainforests. Previous studies showed that arthropod herbivores account for much tropical diversity, yet differences in the diversity of predatory arthropods between tropical and temperate systems have not been properly quantified. Here, we present the first standardized tropical–temperate forest quantification of spider diversities, a dominant and mega‐diverse taxon of generalist predators. Spider assemblages were collected using a spatially replicated protocol including two standardized sampling methods (vegetation sweep netting and beating). Fieldwork took place between 2010 and 2015 in metropolitan (Brittany) and overseas (French Guiana) French territories. We found no significant difference in functional diversity based on hunting guilds between temperate and tropical forests, while species richness was 13–82 times higher in tropical versus temperate forests. Evenness was also higher, with tropical assemblages up to 55 times more even than assemblages in temperate forests. These differences in diversity far surpass previous estimates and exceed tropical–temperate ratios for herbivorous taxa.
Tricky partners: native plants show stronger interaction preferences than their exotic counterparts
Authors: Coux Camille , Donoso Isabel , Tylianakis Jason M. , García Daniel , Martínez Daniel , Dehling D. Matthias , Stouffer Daniel B. 
Published: October 2020

AbstractIn ecological networks, neutral predictions suggest that species’ interaction frequencies are proportional to their relative abundances. Deviations from neutral predictions thus correspond to interaction preferences (when positive) or avoidances (when negative), driven by nonneutral (e.g., niche‐based) processes. Exotic species interact with many partners with which they have not coevolved, and it remains unclear whether this systematically influences the strength of neutral processes on interactions, and how these interaction‐level differences scale up to entire networks. To fill this gap, we compared interactions between plants and frugivorous birds at nine forest sites in New Zealand varying in the relative abundance and composition of native and exotic species, with independently sampled data on bird and plant abundances from the same sites. We tested if the strength and direction of interaction preferences differed between native and exotic species. We further evaluated whether the performance of neutral predictions at the site level was predicted by the proportion of exotic interactions in each network from both bird and plant perspectives, and the species composition in each site. We found that interactions involving native plants deviated more strongly from neutral predictions than did interactions involving exotics. This “pickiness” of native plants could be detrimental in a context of global biotic homogenization where they could be increasingly exposed to novel interactions with neutrally interacting mutualists. However, the realization of only a subset of interactions in different sites compensated for the neutrality of interactions involving exotics, so that neutral predictions for whole networks did not change systematically with the proportion of exotic species or species composition. Therefore, the neutral and niche processes that underpin individual interactions may not scale up to entire networks. This shows that seemingly simplistic neutral assumptions entail complex processes and can provide valuable understanding of community assembly or invasion dynamics.
Voltammetric and Impedimetric Detection of Norfloxacin at Co Nanoparticle Modified Polymer Composite Electrodes
Authors: J. Louw Clementine , Hamnca Siyabulela , G. L. Baker Priscilla 
Published: October 2020

AbstractThe measurement of antibiotics in environmental water systems is increasingly becoming a top priority for global environmental watchdog organisations, as the looming threat of emerging contaminants moves to centre stage. A novel chemical sensor based on polyamic acid (PAA) semiconducting polymer and cobalt nanoparticles (CoNP) was developed and used to demonstrate proof of concept evidence for measurement of norfloxacin at trace concentrations in aqueous systems. Polyamic acid and cobalt nanoparticles were both chemically synthesised and characterised using Fourier transform infrared spectroscopy, transmission electron microscopy, cyclic voltammetry and small angle x‐ray scattering. The polyamic acid and cobalt nanoparticles were electrodeposited onto screen printed carbon electrodes to produce novel composite sensors (SPCE/PAA/CoNP). The polymer composite chemical sensors were applied to the detection of norfloxacin in the micromolar concentration using square wave voltammetry, with a sensitivity of 18.0±6.59 μA/mM, calculated from the slope of the calibration curve and a limit of detection (LOD) of 0.979 ±0.419 mM, with LOD=3.3(Sy/S). The SPCE/PAA/CoNP sensor response to norfloxacin as measured by electrochemical impedance spectroscopy, yielded a sensitivity of 17.6±8.72 Ω/mM as and a limit of detection (LOD) of 0.228±0.0935 mM.
Validation of (not‐historical) large‐event near‐fault ground‐motion simulations for use in civil engineering applications
Authors: Petrone Floriana , Abrahamson Norman , McCallen David , Miah Mamun 
Published: October 2020

AbstractGround‐motion simulations generated from physics‐based wave propagation models are gaining increasing interest in the engineering community for their potential to inform the performance‐based design and assessment of infrastructure residing in active seismic areas. A key prerequisite before the ground‐motion simulations can be used with confidence for application in engineering domains is their comprehensive and rigorous investigation and validation. This article provides a four‐step methodology and acceptance criteria to assess the reliability of simulated ground motions of not historical events, which includes (1) the selection of a population of real records consistent with the simulated scenarios, (2) the comparison of the distribution of Intensity Measures (IMs) from the simulated records, real records, and Ground‐Motion Prediction Equations (GMPEs), (3) the comparison of the distribution of simple proxies for building response, and (4) the comparison of the distribution of Engineering Demand Parameters (EDPs) for a realistic model of a structure. Specific focus is laid on near‐field ground motions (<10km) from large earthquakes (Mw7), for which the database of real records for potential use in engineering applications is severely limited. The methodology is demonstrated through comparison of (2490) near‐field synthetic records with 5 Hz resolution generated from the Pitarka et al (2019) kinematic rupture model with a population of (38) pulse‐like near‐field real records from multiple events and, when applicable, with NGA‐W2 GMPEs. The proposed procedure provides an effective method for informing and advancing the science needed to generate realistic ground‐motion simulations, and for building confidence in their use in engineering domains.
Earthquake ground motion modeling of induced seismicity in the Groningen gas field
Authors: Paolucci R. , Mazzieri I. , Piunno G. , Smerzini C. , Vanini M. , Özcebe A.G. 
Published: October 2020

AbstractA physics‐based numerical approach is used to characterize earthquake ground motion due to induced seismicity in the Groningen gas field and to improve empirical ground motion models for seismic hazard and risk assessment. To this end, a large‐scale (20 km × 20 km) heterogeneous 3D seismic wave propagation model for the Groningen area is constructed, based on the significant bulk of available geological, geophysical, geotechnical, and seismological data. Results of physics‐based numerical simulations are validated against the ground motion recordings of the January 8, 2018, ML 3.4 Zeerijp earthquake. Taking advantage of suitable models of slip time functions at the seismic source and of the detailed geophysical model, the numerical simulations are found to reproduce accurately the observed features of ground motions at epicentral distances less than 10 km, in a broad frequency range, up to about 8 Hz. A sensitivity analysis is also addressed to discuss the impact of 3D underground geological features, the stochastic variability of seismic velocities and the frequency dependence of the quality factor. Amongst others, results point out some key features related to 3D seismic wave propagation, such as the magnitude and distance dependence of site amplification functions, that may be relevant to the improvement of the empirical models for earthquake ground motion prediction.
Research status and analysis of stabilization mechanisms and demulsification methods of heavy oil emulsions
Authors: Fajun Zhao , Zhexi Tian , Zhongqi Yu , Hongzhi Shang , Yanping Wu , Yufei Zhang 
Published: October 2020

AbstractOne major challenge often encountered during the production and transportation of crude oil in petroleum industries is the formation of extremely stable emulsions. This problem is particularly present during the production of heavy oils where steam is used to reduce the viscosity of heavy oil or where submersible pumps are used to artificially lift the produced fluids. This review elaborates on the mechanism of the formation and stability of heavy oil emulsions, discusses the effect of natural surfactants (resins, asphaltenes, solid particles, etc) on the stability of heavy oil emulsions, and summarizes the prominent and sustainable technological and methodological developments in the demulsification of heavy oil emulsions from an economical and environmental perspective. Ionic liquids have been reported as efficient and environmental demulsifiers, and the latest research results on this topic are discussed. Microwave and ultrasonic demulsification methods have been reported to be effective in treating heavy oil emulsions and are also recommended as substitutes in the further development of demulsification technology for treating heavy oil emulsions.
A novel hybrid scale for the assessment of cognitive and executive function: The Free‐Cog
Authors: Burns Alistair , Harrison Judith R. , Symonds Catherine , Morris Julie 
Published: October 2020

AbstractBackgroundScales measuring cognitive and executive functions are integral to the assessment and management of patients with suspected cognitive impairment. Some of the most commonly used cognitive tests are now subject to copyright restrictions. Furthermore, no existing scale assesses both executive and cognitive abilities.AimsWe aimed to develop and validate a novel hybrid scale for use in clinical practice which integrate measures of cognition and executive abilities (‘Free‐Cog’).MethodsThe instrument was devised through a national collaboration including health professionals, those with lived experience of dementia and researchers. Following ethics committee approval, the Free‐Cog was assessed in 25 real‐world clinical settings across England, Wales and Scotland. It was compared to three other cognitive tests routinely administered in clinical practice: the Mini‐Mental State Examination (MMSE), the Montreal Cognitive Assessment (MOCA), and the Addenbrooke's Cognitive Examination (ACE).ResultsThe Free‐Cog was tested in 960 patients with clinical diagnoses of dementia, Mild Cognitive Impairment (MCI), and normal controls. Similar to the MMSE, MOCA and ACE, it discriminated well between the three groups (p < 0.001). It correlated well with the other instruments. Using a receiver operating characteristic curve analysis, Free‐Cog achieved an Area Under Curve of 0.94 for dementia versus controls, 0.80 for MCI versus controls and 0.77 for dementia versus MCI. A version of the tool adapted for telephone consultation, the Tele Free‐Cog, also discriminated well between patient groups.ConclusionsFree‐Cog is a non‐proprietary, empirically derived, concise assessment. Uniquely, it combines cognitive and executive function questions in the one instrument. It could be used to inform the assessment of people presenting with cognitive impairment and is available to anyone interested in trialling it.
Hepatic Fibrosis Associates With Multiple Cardiometabolic Disease Risk Factors: The Framingham Heart Study
Authors: Long Michelle T. , Zhang Xiaoyu , Xu Hanfei , Liu Ching‐Ti , Corey Kathleen E. , Chung Raymond T. , Loomba Rohit , Benjamin Emelia J. 
Published: October 2020

Background and Aims
NAFLD is increasing in prevalence and will soon be the most common chronic liver disease. Liver stiffness, as assessed by vibration‐controlled transient elastography (VCTE), correlates with hepatic fibrosis, an important predictor of liver‐related and all‐cause mortality. Although liver fat is associated with cardiovascular risk factors, the association between hepatic fibrosis and cardiovascular risk factors is less clear.

Approach and Results
We performed VCTE, assessing controlled attenuation parameter (CAP; measure of steatosis) and liver stiffness measurement (LSM) in 3,276 Framingham Heart Study adult participants (53.9% women, mean age 54.3 ± 9.1 years) presenting for a routine study visit. We performed multivariable‐adjusted logistic regression models to determine the association between LSM and obesity‐related, vascular‐related, glucose‐related, and cholesterol‐related cardiovascular risk factors. The prevalence of hepatic steatosis (CAP ≥ 290 dB/m) was 28.8%, and 8.8% had hepatic fibrosis (LSM ≥ 8.2 kPa). Hepatic fibrosis was associated with multiple cardiovascular risk factors, including increased odds of obesity (OR, 1.82; 95% CI, 1.35‐2.47), metabolic syndrome (OR, 1.49; 95% CI 1.10‐2.01), diabetes (OR, 2.67; 95% CI, 1.21‐3.75), hypertension (OR, 1.52; 95% CI, 1.15‐1.99), and low high‐density lipoprotein cholesterol (OR, 1.47; 95% CI, 1.09‐1.98), after adjustment for age, sex, smoking status, alcohol drinks/week, physical activity index, aminotransferases, and CAP.

Conclusions
In our community‐based cohort, VCTE‐defined hepatic fibrosis was associated with multiple cardiovascular risk factors, including obesity, metabolic syndrome, diabetes, hypertension, and high‐density lipoprotein cholesterol, even after accounting for covariates and CAP. Additional longitudinal studies are needed to determine if hepatic fibrosis contributes to incident cardiovascular disease risk factors or events.
Vinylbenziodoxol(on)es: Synthetic Methods and Applications
Authors: Declas Nina , Pisella Guillaume , Waser Jerome 
Published: October 2020

AbstractCyclic hypervalent iodine reagents are now frequently used in synthetic organic chemistry, either as oxidants or group‐transfer reagents. Vinylbenziodoxol(on)es (VBXs) bearing alkene substituents have been less investigated than the corresponding trifluoromethyl or alkynyl reagents. Nevertheless, since 2016 the development of new synthetic methods to access VBXs has awakened the interest of the synthetic community, leading to new transformations highlighting their unique reactivity as electrophilic alkene synthons. In this review, an overview of the synthesis and applications of VBX reagents will be presented. The review is organized according to the two main classes of VBX reagents reported so far – simple alkyl/aryl‐substituted VBXs and heteroatom (S, O, N, X)‐substituted VBXs – as they differ significantly from the point of view of synthetic access.
A systematic review and meta‐analysis of diagnostic accuracy of HPV tests for the screening of cervical cancer in low‐resource settings
Authors: Magdi Rana , Elshafeey Farida , Elshebiny Mohamed , Kamel Menna , Abuelnaga Yasmeen , Ghonim Mohanad , Nabhan Ashraf ,   ECEBM Working Group
Published: October 2020

AbstractBackgroundHPV tests for the screening of cervical cancer in low‐income countries (LICs) might improve early detection and preventive efforts.ObjectivesTo determine the diagnostic accuracy of HPV tests for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) in LICs.Search strategyThe Cochrane Library, MEDLINE, and CINAHL databases were searched on June 1, 2020. References of relevant studies were hand‐searched.Selection criteriaDiagnostic test accuracy studies were included if women had an HPV test for cervical cancer screening, followed by verification with colposcopy and colposcopy‐directed biopsy. The primary target was CIN2+.Data collection and analysisTwo authors independently screened studies, extracted data, and assessed methodological quality. Bivariate diagnostic random‐effects meta‐analysis was used.Main resultsEleven studies including 82 556 women were eligible, most of which were at low risk of bias. The pooled diagnostic odds ratio of hybrid capture test of samples collected from the cervix by healthcare providers for detecting CIN2+ and CIN3+ was 42.0 (95% confidence interval [CI] 20.7–76.3) and 97.1 (95% CI 35.3–215.0), respectively.ConclusionsEvidence indicates that hybrid capture tests can be used for screening of cervical cancer in LICs. Future studies are warranted for self‐sampling and for low‐cost HPV tests.