bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients with paroxysmal nocturnal hemoglobinuria demonstrate a prothrombotic clotting phenotype which is improved by complement inhibition with eculizumab
Authors: Macrae Fraser L. , Peacock‐Young Barnaby , Bowman Polly , Baker Stephen R. , Quested Sam , Linton Emma , Hillmen Peter , Griffin Morag , Munir Talha , Payne Daniel , McKinley Claire , Clarke Deborah , Newton Darren J , Hill Anita , Ariëns Robert A. S. 
Published: April 2020

AbstractParoxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder, characterized by complement‐mediated intravascular hemolysis and thrombosis. The increased incidence of PNH‐driven thrombosis is still poorly understood, but unlike other thrombotic disorders, is thought to largely occur through complement‐mediated mechanisms. Treatment with a C5 inhibitor, eculizumab, has been shown to significantly reduce the number of thromboembolic events in these patients. Based on previously described links between changes in fibrin clot structure and thrombosis in other disorders, our aim was to investigate clot structure as a possible mechanism of thrombosis in patients with PNH and the anti‐thrombotic effects of eculizumab treatment on clot structure. Clot structure, fibrinogen levels and thrombin generation were examined in plasma samples from 82 patients from the National PNH Service in Leeds, UK. Untreated PNH patients were found to have increased levels of fibrinogen and thrombin generation, with subsequent prothrombotic changes in clot structure. No link was found between increasing disease severity and fibrinogen levels, thrombin generation, clot formation or structure. However, eculizumab treated patients showed decreased fibrinogen levels, thrombin generation and clot density, with increasing time spent on treatment augmenting these antithrombotic effects. These data suggest that PNH patients have a prothrombotic clot phenotype due to increased fibrinogen levels and thrombin generation, and that the antithrombotic effects of eculizumab are, in‐part, due to reductions in fibrinogen and thrombin generation with downstream effects on clot structure.
The effects of data collection and observation methods on uncertainty of social networks in wild primates
Authors: Canteloup Charlotte , Puga‐Gonzalez Ivan , Sueur Cédric , van de Waal Erica 
Published: April 2020

AbstractIn social species, network centralities of group members shape social transmission and other social phenomena. Different factors have been found to influence the measurement of social networks, such as data collection and observation methods. In this study, we collected data on adults and juveniles and examined the effect of data collection method (ad libitum sampling vs. focal animal sampling) and observation method (interaction—grooming; play—vs. association—arm‐length; 2 m; 5 m proximities—) on social networks in wild vervet monkeys. First, we showed using a bootstrapping method, that uncertainty of ad libitum grooming and play matrices were lesser than uncertainty of focal matrices. Nevertheless, grooming and play networks constructed from ad libitum and focal animal sampling were very similar and highly correlated. We improved the certainty of both grooming and play networks by pooling focal and ad libitum matrices. Second, we reported a high correlation between the proximity arm‐length network and the focal grooming one making an arm‐length proximity network a reasonable proxy for a grooming one in vervet monkeys. However, we did not find such a correlation between proximity networks and the play one. Studying the effects of methodological issues as data collection and observation methods can help improve understanding of what shapes social networks and which data collection method to choose to study sociality.
Isolation and Characterization of the Free Phenylphosphinidene Chalcogenides C6H5P=O and C6H5P=S, the Phosphorous Analogues of Nitrosobenzene and Thionitrosobenzene
Authors: Mardyukov Artur , Keul Felix , Schreiner Peter R. 
Published: April 2020

AbstractThe structures and reactivities of organic phosphinidene chalcogenides have been mainly inferred from trapping or complexation experiments. Phosphinidene chalcogenide derivatives appear to be an elusive family of molecules that have been suggested as reactive intermediates in multiple organophosphorus reactions. The quest to isolate “free” phosphinidene chalcogenides remains a challenge in the field. Here, we present the synthesis, IR, and UV/Vis spectroscopic identification of hitherto elusive phenylphosphinidene oxide and phenylphosphinidene sulfide from the corresponding phosphonic diazide precursors. We isolated these higher congeners of nitroso‐ and thionitrosobenzene in argon matrices at 10 K. The spectral assignments are supported by B3LYP/6–311++G(3df,3pd) and MP2/cc‐pVTZ computations.
Synthesis, cytotoxicity, and molecular docking of substituted 3‐(2‐methylbenzofuran‐3‐yl)‐5‐(phenoxymethyl)‐1,2,4‐oxadiazoles
Authors: Mokenapelli Sudhakar , Thalari Gangadhar , Vadiyaala Naveen , Yerrabelli Jayaprakash R. , Irlapati Vamshi K. , Gorityala Neelima , Sagurthi Someswar R. , Chitneni Prasad R. 
Published: April 2020

AbstractA series of new benzofuran/oxadiazole hybrids (8a–n) was synthesized from 2H‐chromene‐3‐carbonitriles (3a–c) through the multistep synthetic methodology, and these hybrids are known to exhibit anticancer activities. All the compounds were evaluated for their in vitro cytotoxicity against the HCT116 and MIA PaCa2 cell lines. Compounds 6a (IC50: 9.71 ± 1.9 μM), 6b (IC50: 7.48 ± 0.6 μM), and 6c (IC50: 3.27 ± 1.1 μM) displayed a significant cytotoxic activity, whereas compounds 8d and 8e exhibited good activity against both cell lines. The depletion of glycogen synthase kinase‐3β (GSK3β) induces apoptosis through the inhibition of basal NF‐κB activity in HCT116 colon cancer cells and MIA PaCa2 pancreatic cancer cells. Molecular docking of compounds 6a, 6b, 6c, 8d, and 8e with GSK3β demonstrated the best binding affinity, correlating with the biological activity assay. Furthermore, the structure–activity relationship of these novel compounds reveals promising features for their use in anticancer therapy.
Application of grey system theory to phosphorite sinter process: From modeling to control
Authors: Toktassynova Nigina , Fourati Hassen , Suleimenov Batyrbek 
Published: April 2020

AbstractThe sintering process of phosphorite ore occurs with a large amount of return caused by untimely process control. The control task of phosphorite ore sintering is to regulate the parameters of the process to obtain a high quality sinter. The parameter clearly responsible for sinter quality is the temperature in the wind box. Therefore, in order to solve the control task, it is necessary to predict the highest temperature of the charge (also known as the burn through point (BTP)). In this paper, the theory of grey systems is used as a predictive model, which makes it possible to obtain an adequate model that uses a small number of initial samples of real temperature data. Based on the grey model GMC(1,n) a new optimal model is presented, which is constructed by using optimization algorithm. Optimal model predicts the BTP, and to establish an optimal regulation, a control synthesis is carried out through an optimization of the prediction according to the “particle swarm” algorithm.
The potential for uncertainty in Numerical Weather Prediction model verification when using solid precipitation observations
Authors: Buisán Samuel T. , Smith Craig D. , Ross Amber , Kochendorfer John , Collado José Luís , Alastrué Javier , Wolff Mareile , Roulet Yves‐Alain , Earle Michael E. , Laine Timo , Rasmussen Roy , Nitu Rodica 
Published: April 2020

AbstractPrecipitation forecasts made by Numerical Weather Prediction (NWP) models are typically verified using precipitation gauge observations that are often prone to the wind‐induced undercatch of solid precipitation. Therefore, apparent model biases in solid precipitation forecasts may be due in part to the measurements and not the model. To reduce solid precipitation measurement biases, adjustments in the form of transfer functions were derived within the framework of the World Meteorological Organization Solid Precipitation Inter‐Comparison Experiment (WMO‐SPICE). These transfer functions were applied to single‐Alter shielded gauge measurements at selected SPICE sites during two winter seasons (2015–2016 and 2016–2017). Along with measurements from the WMO automated field reference configuration at each of these SPICE sites, the adjusted and unadjusted gauge observations were used to analyze the bias in a Global NWP model precipitation forecast. The verification of NWP winter precipitation using operational gauges may be subject to verification uncertainty, the magnitude and sign of which varies with the gauge‐shield configuration and the relation between model and site‐specific local climatologies. The application of a transfer function to alter‐shielded gauge measurements increases the amount of solid precipitation reported by the gauge and therefore reduces the NWP precipitation bias at sites where the model tends to overestimate precipitation, and increases the bias at sites where the model underestimates the precipitation. This complicates model verification when only operational (non‐reference) gauge observations are available. Modelers, forecasters, and climatologists must consider this when comparing modeled and observed precipitation.
Testing bias adjustment methods for regional climate change applications under observational uncertainty and resolution mismatch
Authors: Casanueva Ana , Herrera Sixto , Iturbide Maialen , Lange Stefan , Jury Martin , Dosio Alessandro , Maraun Douglas , Gutiérrez José M. 
Published: April 2020

AbstractSystematic biases in climate models hamper their direct use in impact studies and, as a consequence, many statistical bias adjustment methods have been developed to calibrate model outputs against observations. The application of these methods in a climate change context is problematic since there is no clear understanding on how these methods may affect key magnitudes, for example, the climate change signal or trend, under different sources of uncertainty. Two relevant sources of uncertainty, often overlooked, are the sensitivity to the observational reference used to calibrate the method and the effect of the resolution mismatch between model and observations (downscaling effect). In the present work, we assess the impact of these factors on the climate change signal of temperature and precipitation considering marginal, temporal and extreme aspects. We use eight standard and state‐of‐the‐art bias adjustment methods (spanning a variety of methods regarding their nature—empirical or parametric—, fitted parameters and trend‐preservation) for a case study in the Iberian Peninsula. The quantile trend‐preserving methods (namely quantile delta mapping (QDM), scaled distribution mapping (SDM) and the method from the third phase of ISIMIP‐ISIMIP3) preserve better the raw signals for the different indices and variables considered (not all preserved by construction). However, they rely largely on the reference dataset used for calibration, thus presenting a larger sensitivity to the observations, especially for precipitation intensity, spells and extreme indices. Thus, high‐quality observational datasets are essential for comprehensive analyses in larger (continental) domains. Similar conclusions hold for experiments carried out at high (approximately 20 km) and low (approximately 120 km) spatial resolutions.
Sequencing Strategies for Fusion Gene Detection
Authors: Heyer Erin E. , Blackburn James 
Published: April 2020

AbstractFusion genes formed by chromosomal rearrangements are common drivers of cancer. Recent innovations in the field of next‐generation sequencing (NGS) have seen a dynamic shift from traditional fusion detection approaches, such as visual characterization by fluorescence, to more precise multiplexed methods. There are many different NGS‐based approaches to fusion gene detection and deciding on the most appropriate method can be difficult. Beyond the experimental approach, consideration needs to be given to factors such as the ease of implementation, processing time, associated costs, and the level of expertise required for data analysis. Here, the different NGS‐based methods for fusion gene detection, the basic principles underlying the techniques, and the benefits and limitations of each approach are reviewed. This article concludes with a discussion of how NGS will impact fusion gene detection in a clinical context and from where the next innovations are evolving.
Production of the bioactive plant‐derived triterpenoid morolic acid in engineered Saccharomyces cerevisiae
Authors: Srisawat Pisanee , Yasumoto Shuhei , Fukushima Ery O. , Robertlee Jekson , Seki Hikaru , Muranaka Toshiya 
Published: April 2020

AbstractMorolic acid is a plant‐derived triterpenoid that possesses pharmacological properties such as cytotoxicity, as well as anti‐HIV, anti‐HSV, anti‐inflammatory, and antidiabetic effects. The significant therapeutic properties of morolic acid are desirable in the context of pharmacological and drug development research, but the low accessibility of morolic acid from natural resources limits its applications. In the present study, we developed a microbial system for the production of morolic acid. Using a combinatorial biosynthesis approach, a novel production pathway was constructed in Saccharomycescerevisiae by coexpressing BfOSC2 (germanicol synthase) from Bauhinia forficata and CYP716A49 (triterpene C‐28 oxidase) from Beta vulgaris. Moreover, we reconstructed the cellular galactose regulatory network by introducing a chimeric transcriptional activator (fusion of Gal4dbd.ER.VP16) to overdrive the genes under the control of the galactose promoter. We also overexpressed truncated HMG1, encoding feedback‐inhibition‐resistant form of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase 1 and sterol‐regulating transcription factor upc2‐1, to increase the isoprenoid precursors in the mevalonate pathway. Using this yeast system, we achieved morolic acid production up to 20.7 ± 1.8 mg/L in batch culture. To our knowledge, this is the highest morolic acid titer reported from a heterologous host, indicating a promising approach for obtaining rare natural triterpenoids.
LC–MS/MS assay for the quantification of foretinib in rat plasma and its application to preclinical pharmacokinetic study
Authors: Guo Nan , Zhang Aiying , Zhuang Hui , Zhang Changzhen 
Published: April 2020

AbstractA simple and sensitive ultra‐high‐performance liquid chromatography tandem mass spectrometric method was developed and validated for the determination of foretinib in rat plasma. The analyte and internal standard were extracted from the bio‐samples with acetonitrile and then separated on an Acquity UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm) using 0.1% formic acid aqueous and acetonitrile as mobile phase, at a flow rate of 0.4 ml/min. The mass detection was performed in positive selected reaction monitoring mode with precursor‐to‐product transitions at m/z 317.1 > 128.1 for foretinib and m/z 502.2 > 323.1 for internal standard. The assay was demonstrated to be linear in the concentration range of 0.5–1000 ng/ml, with correlation coefficient >0.999. The mean extraction recovery of foretinib from rat plasma was within the range of 84.55–88.09%, while the matrix effect was in the range of 88.56–99.21%. The intra‐ and inter‐day precisions were <12.95% and the accuracy ranged from −7.55 to 8.57%. Foretinib was stable in rat plasma under the tested storage conditions. The validated assay was successfully applied to the pharmacokinetic study of foretinib in the rats. The results revealed that foretinib showed moderate elimination half‐life, low clearance and dose‐independent pharmacokinetic profiles inrats.
Mechanism of microRNA‐22 in regulating neuroinflammation in Alzheimer’s disease
Authors: Han Chenyang , Guo Li , Yang Yi , Guan Qiaobing , Shen Heping , Sheng Yongjia , Jiao Qingcai 
Published: April 2020

AbstractBackgroundStudy on the expression of miRNA‐22 in serum of Alzheimer's disease (AD) patients and the mechanism of neuroinflammation regulation.MethodsELISA assay was used to detect the serum level of inflammatory factors, including interleukin‐1β (IL‐1β), interleukin‐18 (IL‐18), and tumor necrosis factor‐α in AD patients. TargetScan database and luciferase reporter gene assay indicated that gasdermin D (GSDMD) was the target gene of miRNA‐22. miRNA‐22 mimic was transfected into microglia, followed by administration of LPS and Nigericin to induce pyroptosis.ResultsIn this study, we found that the expression level of miRNA‐22 in peripheral blood was lower in AD patients than that in healthy population. The expression of inflammatory factors was higher in AD patients than that in healthy people, which was negatively correlated with miRNA‐22. miRNA‐22 mimic could significantly inhibit pyroptosis, the expression of GSDMD and p30‐GSDMD was down‐regulated, the release of inflammatory factor was decreased, and the expression of NLRP3 inflammasome was down‐regulated as feedback. In the APP/PS1 double transgenic mouse model, the injection of miRNA‐22 mimic significantly improved the memory ability and behavior of mice. In addition, the expression of the vital protein of pyroptosis in mouse brain tissue, including GSDMD and p30‐GSDMD, was down‐regulated, and the expression of inflammatory factors was also decreased.ConclusionmiRNA‐22 was negatively correlated with the expression of inflammatory factors in AD patients, and miRNA‐22 could inhibit the release of inflammatory cytokines by regulating the inflammatory pyroptosis of glial cells via targeting GSDMD, thereby improving cognitive ability in AD mice. miRNA‐22 and pyroptosis are potential novel therapeutic targets in the treatment of AD.
Comatose within 6 weeks, but still alive after 3 years, Creutzfeldt‐Jakob disease with unusual progression
Authors: Christopher Julia Kathleen , Khong Brian , Abolfazli Amin , Liu Antonio 
Published: April 2020

AbstractCreutzfeldt‐Jakob disease (CJD) should still be considered in a patient presenting with rapidly progressive dementia and negative CSF 14‐3‐3 protein and RT‐QulC. Treatable causes of encephalopathy must be ruled out. Neurodegenerative diseases must also be considered.
Detection of the early stage of spontaneous hemopneumothorax by CT attenuation values
Authors: Koike Yukiko , Namkoong Ho , Otake Sotaro , Asamura Hisao 
Published: April 2020

AbstractSpontaneous hemopneumothorax is potentially fatal and can mimic spontaneous pneumothorax when changes in vital signs and bloody discharge from the chest tube are absent. Attenuation values at computed tomography may help detect this condition.
Stabilisation of [WF5]+ and WF5 by Pyridine: Facile Access to [WF5(NC5H5)3]+ and WF5(NC5H5)2
Authors: Turnbull Douglas , Hazendonk Paul , Wetmore Stacey D. , Gerken Michael 
Published: April 2020

AbstractThe enhanced reactivity of [WF5]+ over WF6 has been exploited to access a neutral derivative of elusive WF5. The reaction of WF6(NC5H5)2 with [(CH3)3Si(NC5H5)][O3SCF3] in CH2Cl2 results in quantitative formation of trigonal‐dodecahedral [WF5(NC5H5)3]+, which has been characterised as its [O3SCF3]− salt by Raman spectroscopy in the solid state and variable‐temperature NMR spectroscopy in solution. The salt is susceptible to slow decomposition in solution at ambient temperature via dissociation of a pyridyl ligand, and the resultant [WF5(NC5H5)2]+ is reduced to WF5(NC5H5)2 in the presence of excess C5H5N, as determined by 19F NMR spectroscopy. Pentagonal‐bipyramidal WF5(NC5H5)2 was isolated and characterised by X‐ray crystallography and Raman spectroscopy in the solid state, representing the first unambiguously characterised WF5 adduct, as well as the first heptacoordinate adduct of a transition‐metal pentafluoride. DFT‐B3LYP methods have been used to investigate the reduction of [WF5(NC5H5)2]+ to WF5(NC5H5)2, supporting a two‐electron reduction of WVI to WIV by nucleophilic attack and diprotonation of a pyridyl ligand in the presence of free C5H5N, followed by comproportionation to WV.
Recent Advances and Optoelectronic Applications of Lead‐Free Halide Double Perovskites
Authors: Lu Lei , Pan Xiong , Luo Junhua , Sun Zhihua 
Published: April 2020

AbstractOrganic–inorganic metal halide perovskites (most notably CH3NH3PbI3) have demonstrated remarkable physical attributes for photovoltaic and diverse optoelectronic applications, whereas concerns about toxicity owing to the use of lead in the chemical composition still motivate further exploration of new, nontoxic candidates. Lead‐free halide double perovskites (HDPs), designed by the rational chemical substitution of Pb2+ with other nontoxic candidate elements, have recently attracted interest as a fascinating alternative to their Pb‐based counterparts. Herein, recent advances in crystal structures, physical properties, and versatile optoelectronic applications of lead‐free HDPs, such as solar cells, photodetectors, X‐ray detectors, and light‐emitting diodes, are reviewed. Perspectives to improve the physical and photoelectric properties of existing HDP materials are also discussed and will favor future development of new, lead‐free HDP candidates.
Central afferents to the nucleus of the solitary tract in rats and mice
Authors: Gasparini Silvia , Howland Jacob M. , Thatcher Andrew J. , Geerling Joel C. 
Published: April 2020

AbstractThe nucleus of the solitary tract (NTS) regulates life‐sustaining functions ranging from appetite and digestion to heart rate and breathing. It is also the brain's primary sensory nucleus for visceral sensations relevant to symptoms in medical and psychiatric disorders. To better understand which neurons may exert top‐down control over the NTS, here we provide a brain‐wide map of all neurons that project axons directly to the caudal, viscerosensory NTS, focusing on a medial subregion with aldosterone‐sensitive HSD2 neurons. Injecting an axonal tracer (cholera toxin b) into the NTS produces a similar pattern of retrograde labeling in rats and mice. The paraventricular hypothalamic nucleus (PVH), lateral hypothalamic area, and central nucleus of the amygdala (CeA) contain the densest concentrations of NTS‐projecting neurons. PVH afferents are glutamatergic (express Slc17a6/Vglut2) and are distinct from neuroendocrine PVH neurons. CeA afferents are GABAergic (express Slc32a1/Vgat) and are distributed largely in the medial CeA subdivision. Other retrogradely labeled neurons are located in a variety of brain regions, including the cerebral cortex (insular and infralimbic areas), bed nucleus of the stria terminalis, periaqueductal gray, Barrington's nucleus, Kölliker‐Fuse nucleus, hindbrain reticular formation, and rostral NTS. Similar patterns of retrograde labeling result from tracer injections into different NTS subdivisions, with dual retrograde tracing revealing that many afferent neurons project axon collaterals to both the lateral and medial NTS subdivisions. This information provides a roadmap for studying descending axonal projections that may influence visceromotor systems and visceral “mind–body” symptoms.