bluuebunny/crossref_metadata_2025_split huggingface dataset:
O6‐Alkylguanine DNA Alkyltransferase Mediated Disassembly of a DNA Tetrahedron
Authors: Copp William , Wilds Christopher J. 
Published: June 2020

AbstractTetrahedron DNA structures were formed by the assembly of three‐way junction (TWJ) oligonucleotides containing O6‐2′‐deoxyguanosine‐alkylene‐O6‐2′‐deoxyguanosine (butylene and heptylene linked) intrastrand cross‐links (IaCLs) lacking a phosphodiester group between the 2′‐deoxyribose residues. The DNA tetrahedra containing TWJs were shown to undergo an unhooking reaction by the human DNA repair protein O6‐alkylguanine DNA alkyltransferase (hAGT) resulting in structure disassembly. The unhooking reaction of hAGT towards the DNA tetrahedra was observed to be moderate to virtually complete depending on the protein equivalents. DNA tetrahedron structures have been explored as drug delivery platforms that release their payload in response to triggers, such as light, chemical agents or hybridization of release strands. The dismantling of DNA tetrahedron structures by a DNA repair protein contributes to the armamentarium of approaches for drug release employing DNA nanostructures.
Flow Cytometric Quantification of Granulocytic Alkaline Phosphatase Activity in Unlysed Whole Blood
Authors: Bardina Jorge , Rico Laura G. , Ward Michael D. , Bradford Jolene A. , Juncà Jordi , Petriz Jordi 
Published: June 2020

AbstractTranslational research has improved the diagnosis and follow‐up of hematological diseases and malignancies. However, some classical diagnostics used for research and clinical practice that have remain practically unchanged for decades may be better addressed through advances in flow cytometry technology, whereby more precise measurements may be implemented in a straightforward manner. The current method for semiquantitative analysis of granulocytic alkaline phosphatase (GAP) activity is still based on observer‐dependent color‐intensity classification. Here, we describe a novel strategy for flow cytometric quantification of GAP activity in which staining and analytical flow cytometry facilitate the detection and quantification of subpopulations of leukocytes with different GAP activities. Our experiments demonstrate the potential of flow cytometry as a simple and highly sensitive approach for measuring GAP activity in unlysed whole blood. Notably, a comparison of flow cytometry and enzyme cytochemistry techniques showed that enzyme activity scores were not similar, indicating that results needs to be interpreted with caution, given that the enzyme‐substrate binding affinities may differ, as well as the subjective evaluation of the intensity of the precipitated dye. © 2020 Wiley Periodicals LLC.Basic Protocol: Protocol preparation, sample acquisition, and gating strategy for flow cytometric identification of alkaline phosphatase activity in granulocytes from whole blood samplesSupport Protocol 1: Sample preparation for granulocyte alkaline phosphatase determination by flow cytometry using no‐lyse no‐wash methodsSupport Protocol 2: Data analysis and formula to calculate the GAP score
A Randomized, Single‐Blind, Placebo‐Controlled, 3‐Way Crossover Study to Evaluate the Effect of Therapeutic and Supratherapeutic Doses of Edaravone on QT/QTc Interval in Healthy Subjects
Authors: Shimizu Hidetoshi , Inoue Shinsuke , Endo Mai , Nakamaru Yoshinobu , Yoshida Kaori , Natori Tomoko , Kakubari Masae , Akimoto Makoto , Kondo Kazuoki 
Published: June 2020

AbstractThis randomized, single‐blind, 3‐way crossover study assessed the effect of edaravone on QT interval, including an exposure‐response analysis. Twenty‐seven healthy Japanese male volunteers, aged 20 to 49 years, were randomly assigned to receive a single intravenous dose of each treatment in 1 of 3 sequences (n = 9 each): ACB, BAC, and CBA, where A was edaravone 60 mg (therapeutic dose), B was edaravone 300 mg (supratherapeutic dose), and C was normal saline (placebo). Electrocardiographs were collected to assess treatment effects. In an exposure‐response analysis, a linear model was determined to be valid and indicated no statistically significant positive slope for the relationship between change from baseline in QTcF (ΔQTcF) and edaravone concentration (0.000155 ms/(ng/mL); P = .1478); upper bounds of 2‐sided 90% confidence intervals after placebo adjustment (ΔΔQTcF) were <10 milliseconds at the geometric mean maximum concentration for each edaravone dose. Overall estimated values by time point of ΔΔQTcF ≤0.9 milliseconds, no outlier values, and no morphologic changes suggestive of repolarization abnormalities were observed. Analysis of heart rate, PR interval, and QRS duration also revealed no adverse findings. These data indicate that edaravone, even at supratherapeutic doses, does not produce clinically meaningful QT prolongation and has no clinically relevant cardiac effects.
Flufenamic acid alleviates sepsis‐induced lung injury by up‐regulating CBR1
Authors: Jiang Qiannan , Chen Zhenzhen , Jiang Hong 
Published: June 2020

AbstractInvestigate the effect of flufenamic acid (FFA) on lung injury of sepsis rats. Rat sepsis model was established using cecal ligation and puncture (CLP). The pathomorphology of lung tissue was detected by Hematoxylin–eosin (H&E) staining. The expression levels of tumor necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6), and high mobility group box‐1 (HMGB‐1) in serum and TNF‐α, IL‐6, malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) in lung tissues. The viability of RLE‐6TN cells was detected by CCK‐8 assay. The expression of carbonyl reductase 1 (CBR1) in RLE‐6TN cells was analyzed by Western blot analysis and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) analysis. The inflammatory response was obviously enhanced in CLP‐constructed sepsis rats and alleviated by FFA treatment. Sepsis induced the increase of W/D ratio, promoted the levels of TNF‐α, IL‐6, HMGBR1, and MDA and inhibited the levels of SOD and GSH. FFA could effectively alleviate the sepsis‐induced lung injury. The viability of RLE‐6TN cells induced by LPS was improved with the treatment of FFA. CBR1 expression in LPS‐induced RLE‐6TN cells was decreased and FFA could up‐regulate the CBR1 expression. In addition, LPS‐induced lung injury promoted the inflammatory response in lung tissues, increased the W/D ratio and levels of TNF‐α, IL‐6, HMGBR1, and MDA while inhibited the levels of SOD and GSH. FFA could effectively improve the LPS‐induced lung injury while the effect of FFA on LPS‐induced lung injury was alleviated by CBR1 interference. FFA may alleviate sepsis‐induced lung injury by up‐regulating CBR1.
Diabetes mellitus induced by immune checkpoint inhibitors
Authors: Zheng Zhenjiang , Liu Ya , Yang Jie , Tan Chunlu , Zhou Li , Wang Xing , Xiao Li , Zhang Shu , Chen Yonghua , Liu Xubao 
Published: June 2020

AbstractImmune checkpoint inhibitors (ICIs) are widely used in oncology for their favourable antitumor efficacy. ICI therapy is associated with a unique toxicity profile known as immune‐related adverse events (irAEs). One such irAE is ICI‐related diabetes mellitus (DM), which is relatively uncommon but can become extremely severe, leading to irreversible impairment of β‐cells, and even lead to death if not promptly recognised and properly managed. The precise mechanisms of ICI‐related DM are not well understood. In this review, we summarise the clinical characteristics, pathophysiology, and management of this adverse effect caused by ICI therapy. Deeper investigation of ICI‐related DM may contribute to elucidate the molecular mechanisms of classical type 1 DM.
Machine‐learning‐based detection of adaptive divergence of the stream mayfly Ephemera strigata populations
Authors: Li Bin , Yaegashi Sakiko , Carvajal Thaddeus M. , Gamboa Maribet , Chiu Ming‐Chih , Ren Zongming , Watanabe Kozo 
Published: June 2020

AbstractAdaptive divergence is a key mechanism shaping the genetic variation of natural populations. A central question linking ecology with evolutionary biology is how spatial environmental heterogeneity can lead to adaptive divergence among local populations within a species. In this study, using a genome scan approach to detect candidate loci under selection, we examined adaptive divergence of the stream mayfly Ephemera strigata in the Natori River Basin in northeastern Japan. We applied a new machine‐learning method (i.e., random forest) besides traditional distance‐based redundancy analysis (dbRDA) to examine relationships between environmental factors and adaptive divergence at non‐neutral loci. Spatial autocorrelation analysis based on neutral loci was employed to examine the dispersal ability of this species. We conclude the following: (a) E. strigata show altitudinal adaptive divergence among the populations in the Natori River Basin; (b) random forest showed higher resolution for detecting adaptive divergence than traditional statistical analysis; and (c) separating all markers into neutral and non‐neutral loci could provide full insight into parameters such as genetic diversity, local adaptation, and dispersal ability.
Epileptic spasms in individuals with Down syndrome: A review of the current literature
Authors: Kats Daniel J. , Roche Katherine J. , Skotko Brian G. 
Published: June 2020

AbstractEpilepsy can occur in individuals with Down syndrome (DS), with epileptic spasms representing the most frequent seizure type in this population. Epileptic spasms can have devastating consequences on the development of individuals with the condition. This review sought to explore the lifetime prevalence and underlying mechanism of epileptic spasms in this population. We also aimed to review the response rate to various treatments, the relapse rate, and the development of subsequent epilepsy or autism in this population. A comprehensive literature search was conducted for articles discussing the lifetime prevalence, diagnosis, treatment, outcomes, or underlying etiology of epileptic spasms in animal models or individuals with DS. According to available literature, the global clinic‐based lifetime prevalence of epilepsy in individuals with DS ranged from 1.6% to 23.1%, with epileptic spasms representing 6.7%‐66.7% of these cases. Response rate to treatment with adrenocorticotropic hormone/corticosteroids was highest (81%) and has the most literature supporting its use, with other regimens, including vigabatrin and other antiepileptic drugs, having lower response rates. Epileptic spasms occur more frequently in children with DS than in the general population, though more studies are needed to determine the true lifetime prevalence of epileptic spasms in this population. Generally, children with DS and epileptic spasms tend to be more responsive to treatment and have better outcomes than children with epileptic spasms of unknown etiology (ie, without DS), in terms of response and relapse rates as well as the development of intractable epilepsy (eg, Lennox‐Gastaut syndrome).
Energy efficiency enhancement of cell‐free massive multiple‐input multiple‐output network employing threshold‐based beamforming
Authors: Khodkar Zeynab , Abouei Jamshid 
Published: June 2020

AbstractThe downlink of cell‐free massive multiple‐input multiple‐output network is considered. It is assumed that both access points (APs) and users are equipped with multiple antennas. A heuristic threshold‐based‐beamforming (TBF) protocol is proposed, which performs an AP selection algorithm to significantly improve the total energy efficiency (EE) of the network. The beamforming method that fits the model is the maximum eigenmode beamforming (MEB). The threshold level is determined in such a way that the strongest channel eigenmodes contribute in the downlink transmissions. Indeed, power control coefficients are chosen in such a way that the number of users served by each AP is limited according to the TBF‐based AP selection scheme. The spectral efficiency of the proposed method is investigated considering both perfect and imperfect knowledge of the channel state information at transmitters. Simulation results show that the proposed TBF protocol greatly enhances the total EE of the network compared to the MEB, conjugate beamforming, and zero‐force precoding techniques. Furthermore, a modification algorithm is proposed to obtain the minimum per‐user quality of service requirement, which prevents the dramatic reduction in the EE caused by high inter‐user interference levels.
Sensitivity equation method for the Navier‐Stokes equations applied to uncertainty propagation
Authors: Fiorini Camilla , Després Bruno , Puscas Maria Adela 
Published: June 2020

SummaryThis works deals with sensitivity analysis (SA) for the Navier‐Stokes equations. The aim is to provide an estimate of the variance of the velocity field when some of the parameters are uncertain and then to use the variance to compute confidence intervals for the output of the model. First, we introduce the physical model and analyze its stability. The sensitivity equations are derived, and their stability analyzed as well. We propose a finite element‐volume numerical scheme for the state and the sensitivity, which is integrated into the open‐source industrial code TrioCFD. Finally, we present some numerical results: a steady and an unsteady test case for the channel flow problem are investigated. For the steady case, we compare the results to the Monte Carlo method and show how the SA technique succeeds in providing very accurate estimates of the variance. For the unsteady case, a new filtering procedure is proposed to deal with a sensitivity that grows in time. The filtered sensitivity is then used to compute the variance of the output and to provide confidence intervals.
Effects of corn distillers dried grains on dough properties and quality of Chinese steamed bread
Authors: Li Xiaona , Wang Chunyang , Krishnan Padmanaban G. 
Published: June 2020

AbstractChinese steamed bread (CSB) accounts for 30% of the wheat end‐use in China. CSB was studied as a platform for fiber and protein enrichment, employing corn distillers dried grains. Food grade distiller's grain (FDDG) processed from co‐products from the corn ethanol industry was used as the enrichment ingredient. Since CSB uses a lean formula with little or no added sugar or fat, it relies entirely on fermentation and steaming for flavor and texture development. FDDG was used to replace 0%–25% all‐purpose flour (APF) in CSB formulations. Effects of FDDG on dough properties and quality of CSB were evaluated by instrumental (Farinograph, Mixolab, and Texture Analyzer), nutritional, and sensory methods. Protein and dietary fiber contents showed significant increases to 18.8% and 15.3%, respectively, for 100 g of steamed bread (25% FDDG db). Fiber in 100 g of fresh FDDG CSB ranged from 2.8 to 7.7 g. FDDG fortified doughs demonstrated higher water absorption, while dough development time, dough stability, and dough extensibility decreased significantly with partial APF replacement. FDDG contributed to increased hardness and adhesiveness in the CSB. Crumb analysis revealed reduced number of gas cells at higher FDDG substitution. FDDG enrichment reduced brightness (L*) of flour blends and CSB. Rheological and sensory analysis showed an upper level of FDDG substitution of 15% was acceptable without detriment to dough functionality, texture, and taste.
Decoding attention control and selection in visual spatial attention
Authors: Hong Xiangfei , Bo Ke , Meyyappan Sreenivasan , Tong Shanbao , Ding Mingzhou 
Published: June 2020

AbstractEvent‐related potentials (ERPs) are used extensively to investigate the neural mechanisms of attention control and selection. The univariate ERP approach, however, has left important questions inadequately answered. We addressed two questions by applying multivariate pattern classification to multichannel ERPs in two cued visual spatial attention experiments (N = 56): (a) impact of cueing strategies (instructional vs. probabilistic) on attention control and selection and (b) neural and behavioral effects of individual differences. Following cue onset, the decoding accuracy (cue left vs. cue right) began to rise above chance level earlier and remained higher in instructional cueing (~80 ms) than in probabilistic cueing (~160 ms), suggesting that unilateral attention focus leads to earlier and more distinct formation of the attention control set. A similar temporal sequence was also found for target‐related processing (cued target vs. uncued target), suggesting earlier and stronger attention selection under instructional cueing. Across the two experiments: (a) individuals with higher cue‐related decoding accuracy showed higher magnitude of attentional modulation of target‐evoked N1 amplitude, suggesting that better formation of anticipatory attentional state leads to stronger modulation of target processing, and (b) individuals with higher target‐related decoding accuracy showed faster reaction times (or larger cueing effects), suggesting that stronger selection of task‐relevant information leads to better behavioral performance. Taken together, multichannel ERPs combined with machine learning decoding yields new insights into attention control and selection that complement the univariate ERP approach, and along with the univariate ERP approach, provides a more comprehensive methodology to the study of visual spatial attention.
The impact of drug quality ratings from health technology assessments on the adoption of new drugs by physicians in Germany
Authors: Blankart Katharina Elisabeth , Stargardt Tom 
Published: June 2020

AbstractPayers are increasingly calling for the value of new drugs to be measured explicitly. We analyze how the availability of drug quality ratings by health technology assessment (HTA) agencies affects the adoption of new drugs by physicians in Germany. We combine data from drug quality ratings, promotional spending, and a physician panel. In a latent utility model, time to adoption is specified as a function of quality rating, promotional spending by manufacturers, and physician‐specific variables. As expected, drugs with a positive rating were adopted faster (p < 0.001) than those without. However, our results suggest that it was the publication of the quality rating itself that affected adoption. Indeed, before a quality rating was published, drugs that went on to receive a positive quality rating were not adopted significantly faster than drugs that went on to receive a negative quality rating. In contrast, after the publication of the HTA quality rating, drugs with a positive rating were adopted significantly faster than those without (p < 0.05). The per physician value of a positive quality rating was EUR 393.50. Our results suggest that there are returns from HTAs beyond their use in price negotiations.
miR‐448‐3p alleviates diabetic vascular dysfunction by inhibiting endothelial–mesenchymal transition through DPP‐4 dysregulation
Authors: Guan Guo‐Ying , Wei Nan , Song Tao , Zhao Chao , Sun Yang , Pan Ru‐Xin , Zhang Lu‐lu , Xu Ying‐Ying , Dai Ya‐mei , Han Hui 
Published: June 2020

AbstractDiabetes mellitus (DM) often causes vascular endothelial damage and alters vascular microRNA (miR) expression. miR‐448‐3p has been reported to be involved in the development of DM, but whether miR‐448‐3p regulates diabetic vascular endothelial dysfunction remains unclear. To investigate the molecular mechanism of diabetic vascular endothelial dysfunction and the role of miR‐448‐3p therein, Sprague‐Dawley rats were injected with streptozotocin (STZ) to establish diabetic animal model and the rat aortic endothelial cells were treated with high glucose to establish diabetic cell model. For the treatment group, after the induction of diabetes, the miR‐448‐3p levels in vivo and in vitro were upregulated by adeno‐associated virus serotype 2 (AAV2)‐miR‐448‐3p injection and miR‐448‐3p mimic transfection, respectively. Our results showed that AAV2‐miR‐448‐3p injection alleviated the body weight loss and blood glucose level elevation induced by STZ injection. The miR‐448‐3p level was significantly decreased and the dipeptidyl peptidase‐4 (DPP‐4) messenger RNA level was increased in diabetic animal and cell models, which was reversed by miR‐448‐3p treatment. Moreover, the diabetic rats exhibited endothelial damage and endothelial–mesenchymal transition (EndMT), while AAV2‐miR‐448‐3p injection relieved those situations. In vitro experiments demonstrated that miR‐448‐3p overexpression in endothelial cells alleviated endothelial damage by inhibiting EndMT through blocking the transforming growth factor‐β/Smad pathway. We further proved that miR‐448‐3p negatively regulated DPP‐4 by binding to its 3′‐untranslated region, and DPP‐4 overexpression reversed the effect of miR‐448‐3p overexpression on EndMT. Overall, we conclude that miR‐448‐3p overexpression inhibits EndMT via targeting DPP‐4 and further ameliorates diabetic vascular endothelial dysfunction, indicating that miR‐448‐3p may serve as a promising therapeutic target for diabetic endothelial dysfunction.
LncRNA 0003250 accelerates heart autophagy and binds to miR‐17‐5p as a competitive endogenous RNA in chicken induced by selenium deficiency
Authors: Yang Jie , Shi Guangliang , Gong Yafan , Cai Jingzeng , Zheng Yingying , Zhang Ziwei 
Published: June 2020

AbstractLong noncoding RNAs (LncRNAs) have been demonstrated to be associated with a variety of myocardial diseases, but how LncRNAs regulate autophagy in selenium (Se)‐deficient myocardial injury is infrequently reported. Here, we screened out a novel long noncoding RNA, microRNA, and ATG7 through transcriptomic results. We employed a Se‐deficient chicken model in vivo, and primary cultured cardiomyocytes treated by correlation in vitro. The results showed that Se deficiency upregulated the expression of ATG7, and miR‐17‐5p inhibited cardiomyocyte autophagy by targeting ATG7. Furthermore, we found that LncRNA 0003250 regulated miR‐17‐5p, and thus affected the expression of ATG7 and autophagic cell death. Our present study proposed a novel model for the regulation of cardiomyocytes autophagy, which includes LncRNA 0003250, miR‐17‐5p and ATG7 in the chicken heart. Our conclusions may provide a feasible diagnostic tool for Se‐deficient cardiomyocyte injury.
Fibroblast growth factor inducible 14 signaling facilitates anti‐dsDNA IgG penetration into mesangial cells
Authors: Li Ruilian , Jia Fangyan , Ren Kaixuan , Luo Mai , Min Xiaoyun , Xiao Shengxiang , Xia Yumin 
Published: June 2020

AbstractAnti‐double‐stranded DNA (dsDNA) antibodies induce renal damage in patients with systemic lupus erythematosus by triggering fibrotic processes in kidney cells. However, the precise mechanism underlying penetration of anti‐dsDNA immunoglubolin G (IgG) into cells remains unclear. This study was designed to investigate the effect of tumor necrosis factor‐like weak inducer of apoptosis (TWEAK)/fibroblast growth factor inducible 14 (Fn14) signaling on anti‐dsDNA IgG penetration into cells. Mesangial cells were cultured in vitro, and stimulated with TWEAK and anti‐dsDNA IgG. The results revealed that TWEAK dose‐dependently enhanced cellular internalization of anti‐dsDNA IgG and the expression of high‐mobility group box 1 (HMGB1). In addition, TWEAK and anti‐dsDNA IgG synthetically downregulate suppressor of cytokine signaling 1, and induce the expression of various fibrotic factors. Furthermore, inhibition of HMGB1 attenuates the enhancement effect of TWEAK on anti‐dsDNA IgG internalization. The TWEAK upregulation of HMGB1 involves the nuclear factor‐κB and phosphatidylinositide 3‐kinase/protein kinase B pathways. Therefore, TWEAK/Fn14 signaling contributes to the penetration of anti‐dsDNA IgG and relevant fibrotic processes in mesangial cells.