bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Study Design Using Continuous Intravenous and Intraduodenal Infusions of Midazolam and Voriconazole for Mechanistic Quantitative Assessment of Hepatic and Intestinal CYP3A Inhibition
Authors: Li Xia , Junge Lisa , Taubert Max , von Georg Anabelle , Dahlinger Dominik , Starke Chris , Frechen Sebastian , Stelzer Christoph , Kinzig Martina , Sörgel Fritz , Jaehde Ulrich , Töx Ulrich , Goeser Tobias , Fuhr Uwe 
Published: May 2020

AbstractThe extent of a drug‐drug interaction (DDI) mediated by cytochrome P450 (CYP) 3A inhibitors is highly variable during a dosing interval, as it depends on the temporal course of victim and perpetrator drug concentrations at intestinal and hepatic CYP3A expression sites. Capturing the time course of inhibition is therefore difficult using standard DDI studies assessing changes in area under the curve; thus, a novel design was developed. In a 4‐period changeover pilot study, 6 healthy men received intraduodenal or intravenous infusions of the CYP3A substrate midazolam (MDZ) at a rate of 0.26 mg/h for 24 hours. This was combined with intraduodenal or intravenous infusion of the CYP3A inhibitor voriconazole (VRZ), administered at rates of 7.5 mg/h from 8 to 16 hours and of 15 mg/h from 16 to 24 hours, after starting midazolam administration. Plasma and urine concentrations of VRZ, MDZ, and its major metabolites were quantified by liquid chromatography‐tandem mass spectrometry and analyzed by semiphysiological population pharmacokinetic nonlinear mixed‐effects modeling. A model including mechanism‐based inactivation of the metabolizing enzymes (maximum inactivation rate constant kinact, 2.83 h−1; dissociation rate constant , 9.33 μM) described the pharmacokinetics of VRZ well. By introducing competitive inhibition by VRZ on primary and secondary MDZ metabolism, concentration‐time profiles, MDZ and its metabolites were captured appropriately. The model provides estimates of local concentrations of substrate and inhibitor at the major CYP3A expression sites and thus of the respective dynamic extent of inhibition. A combination of intravenous and intraduodenal infusions of inhibitors and substrates has the potential to provide a more accurate assessment of DDIs occurring in both gut wall and liver.
Prediction Model for Intermediate‐Stage Hepatocellular Carcinoma Response to Transarterial Chemoembolization
Authors: Jia Fei , Wu Baolin , Yan Ruifang , Li Lei , Wang Kaiyu , Han Dongming 
Published: May 2020

BackgroundThe outcome of intermediate‐stage hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) is greatly heterogeneous. Current means for predicting HCC response to TACE are lacking.PurposeTo investigate whether the combination of parameters derived from amide proton transfer (APT) and intravoxel incoherent motion (IVIM) imaging, and morphological characteristics of tumor can establish a better prediction model than the univariant model for HCC response to TACE.Study TypeProspective.Subjects56 patients with intermediate‐stage HCC (50 males and six females).Field Strength/Sequences3.0T; T2‐weighted‐fast spin echo, 3D liver acquisition with volume flex, single‐shot fast spin echo‐planar imaging (EPI), spin echo‐EPI.AssessmentPretreatment APT signal intensities (SIs), apparent diffusion coefficient (ADC), true molecular diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) for tumor, peritumoral, and normal tissues were measured. Follow‐up MRI scanning was performed, and the patients were classified as responders or nonresponders based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria.Statistical TestsThe imaging parameters were compared among the three tissues and between the two groups using analysis of variance (ANOVA) or two‐sample t‐test. The prediction model's variables were derived from univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was used to explore the predictive performance.ResultsBased on the logistic regression analysis results, we established a prediction model that integrated the APT SI and D values in the tumor tissue and the tumor size. ROC analyses revealed that the model was better able to predict tumor response to TACE (area under the ROC curve = 0.851) than the individual parameters on their own.Data ConclusionA prediction model incorporating pretreatment APT SI, D in the tumor tissue and tumor size may be useful for predicting the response of intermediate‐stage HCC to TACE.Level of Evidence1Technical EfficacyStage 1 J. MAGN. RESON. IMAGING 2020;52:1657–1667.
Precise analysis of the effect of basal core promoter/precore mutations on the main phenotype of chronic hepatitis B in mouse models
Authors: Liu Yang , Zhao Zhong Hua , Lv Xiao Qin , Tang Yu Wei , Cao Min , Xiang Qin , Wu Yue , Zhang Hua Tang , Lai Guo Qi 
Published: May 2020

AbstractHigh replication and mutation rates of hepatitis B virus (HBV) often lead to reduced or suppressed hepatitis B e antigen expression. The most common mutations are genomic variations in the basal core promoter (BCP) and pre‐core (PC) regions. However, the effect of BCP/PC mutations on HBV phenotype in vivo remains unclear. We compared and analyzed BCP/PC mutations and BCP/PC reverse mutations in mouse models. In addition to terminating the expression of HBeAg, BCP/PC mutations also resulted in a significant decrease in HBsAg, HBV DNA, and cccDNA in the early stage, and an obvious increase in serum alanine aminotransferase throughout the transfection period. In both groups, serum HBV DNA was positively correlated with intracellular HBV DNA and cccDNA. Further, we found that interleukin‐4 (IL‐4) and L‐10 levels were significantly lower in the BCP/PC(M) group than in the BCP/PC(R) group at 4 weeks post‐injection. However, IL‐1β was significantly lower in the BCP/PC(M) group than in the BCP/PC(R) group at 26 weeks post‐injection. In summary, we precisely analyzed the effect of BCP/PC mutations on the phenotype in vivo, which is important to evaluating disease progression and treatment responses of variable chronic hepatitis B patients.
Coagulation and heparin requirements during ablation in patients under oral anticoagulant drugs
Authors: Maury Philippe , Belaid Slimane , Ribes Agnès , Voglimacci‐Stephanopoli Quentin , Mondoly Pierre , Blaye Marie , Mandel Franck , Monteil Benjamin , Carrié Didier , Galinier Michel , Bongard Vanina , Rollin Anne , Voisin Sophie 
Published: May 2020

AbstractBackgroundAnticoagulation during catheter ablation should be closely monitored with activated clotting time (ACT). However vitamin K antagonists (VKA) or direct oral anticoagulant drugs (DOAC) may act differently on ACT and on heparin needs. The aim of this study was to compare ACT and heparin requirements during catheter ablation under various oral anticoagulant drugs and in controls.MethodsSixty consecutive patients referred for ablation were retrospectively included: group I (n = 15, VKA), group 2 (n = 15, uninterrupted rivaroxaban), group 3 (n = 15, uninterrupted apixaban), and group 4 (n = 15, controls). Heparin requirements and ACT were compared throughout the procedure.ResultsHeparin requirements during the procedure were significantly lower in patients under VKA compared to DOAC, but similar between DOAC patients and controls.Activated clotting time values were significantly higher in patients under VKA compared to DOAC and similar in DOAC patients versus controls. Furthermore, anticoagulation control as evaluated by the number/proportion of ACT> 300 as well as the time passed over 300 seconds was significantly better in patients under VKA versus DOAC, without significant differences between DOAC and controls. Finally, the number of patients/ACT with excessive ACT values was significantly higher in VKA versus DOAC patients versus controls.There was no significant difference between rivaroxaban and apixaban for ACT or heparin dosing throughout the procedure.ConclusionVitamin K antagonists allowed less heparin requirement despite reaching higher ACT values and more efficient anticoagulation control (with more excessive values) compared to patients under DOAC therapy and to controls. There was no difference in heparin requirements or ACT between DOAC patients and controls.
Efficacy of Argentinean propolis extracts on control of potato soft rot caused by Erwinia carotovora subsp.
Authors: Sampietro Diego Alejandro , Bertini Sampietro Maria Sofia , Vattuone Marta Amelia 
Published: May 2020

AbstractBACKGROUNDErwinia carotovora subsp. cause the potato soft rot, which is a major disease in agriculture. Antibacterial agents currently applied on potato soft rot often offer a restricted control and have several disadvantages. Propolis has shown a wide range of antimicrobial activity, although its effect has not been investigated on E. carotovora subsp. In this work, we tested extracts from propolis samples of Northwest Argentina against E. carotovora subsp.RESULTSEthanolic propolis extracts (EPEs) from samples of Santiago del Estero province, particularly from sample 4 (EPE4), showed the highest antibacterial activity, which was associated with the highest content of flavonoids. 2′,4′‐Dihydroxychalcone, 2′,4′‐dihydroxy‐3′‐methoxychalcone, galangin, and pinocembrin were identified as antibacterial constituents of EPE4. 2′,4′‐Dihydroxychalcone showed an antibacterial activity (minimum inhibitory concentration, MIC = 0.3–1.2 μg gallic acid equivalents (GAE) mL−1; minimum bactericidal concentration, MBC = 0.6–4.8 μg GAE mL−1) lower than that of bacterimycin (MIC = 2.4–9.6 μg mL−1; MBC = 19.2–38.4 μg GAE mL−1) and streptocycline (MIC = 19.2–38.4 μg mL−1; MBC = 38.4–76.8 μg mL−1). Preventive assays on unwounded and wounded potatoes showed that their immersion in EPE4 containing 87.5 μg GAE mL−1 or streptocycline containing 40 μg mL−1 was equally effective in controlling potato soft rot, reducing the disease incidence by 64.6–67.0% (unwounded tubers) and 88.0–86.0% (wounded tubers) and the disease severity by 49.8–49.8% (unwounded tubers) and 54.5–68.5% (wounded tubers).CONCLUSIONSFlavonoid‐rich propolis extracts from Northwest Argentina efficiently reduced in vivo the incidence and severity of potato soft rot caused by E. carotovora subsp.
Metabolomics study of polysaccharide extracts from Polygonatum sibiricum in mice based on 1H NMR technology
Authors: Li Tingting , Xu Sheng , Bi Jianli , Huang Shengtang , Fan Baolei , Qian Chunqi 
Published: May 2020

AbstractBACKGROUNDPolygonatum sibiricum Liliaceae perennial herb, as a commonly used medicine and food homologous plant, has been widely used in clinical practice of Chinese medicine since ancient times, with a history of 2000 years. As the main active ingredient, P. sibiricum polysaccharides have important pharmacological effects in blood sugar reduction and antitumor, antioxidant and liver protection.RESULTSMouse models of P. sibiricum polysaccharides were used in combination with 1H NMR to investigate the metabolic regulation mechanism in mouse tissue and blood. The metabolite maps of the control group and the drug group in the liver had significant changes. The main differential metabolites were glucose 6‐phosphate, inositol, lactose, glutamylglycine, galactose, rhamnose, cis‐aconitic acid and histidine, indicating that there was definite correlation between the metabolic detection based on 1H NMR and the metabolic characteristics of P. sibiricum. The common differential metabolites obtained by overall metabolism analysis were 3‐hydroxybutyric acid, d‐ribose, adenosine phosphate, inositol, fructose 6‐phosphate, histidine, aspartic acid and cis‐aconitic acid.CONCLUSIONSThis work forms the basis for identification of metabolic states combined with metabolic pathways, which could be used as diagnostic and prognostic indicators, providing therapeutic targets for new diseases. © 2020 Society of Chemical Industry
An environmentally friendly sodium dodecyl sulfate‐synergistic microwave‐assisted extraction followed by ultra‐high‐performance liquid chromatography with photodiode array method for the simultaneous extraction and determination of iridoids, phenylpropanoids, and lignans from Eucommiae Cortex
Authors: Guo Jiading , Li Jin , Yang Xuejing , Wang Hui , He Jun , Liu Erwei , Gao Xiu‐mei , Chang Yan‐xu 
Published: May 2020

AbstractA simple and green sodium dodecyl sulfate‐synergistic microwave‐assisted extraction method was developed to extract and determine the iridoids, phenylpropanoids, and lignans in Eucommiae Cortex followed by ultra‐high‐performance liquid chromatography with photodiode array detection. The biodegradable solution (sodium dodecyl sulfate) was used as a promising alternative to organic solvents. The response surface methodology provided the optimum extraction conditions (2 mg/mL sodium dodecyl sulfate, 1100 W microwave power, and 6 min extraction time). The recoveries of three types of components ranged from 95.0 to 105% (RSDs < 5%). The intra‐ and inter‐day precision and accuracy were less than 3.40% and within the range of 97.1‐105%, respectively. Compared with other extraction methods, this newly established method was more efficient and environmental friendly. The results demonstrated that sodium dodecyl sulfate‐synergistic microwave‐assisted extraction followed by ultra‐high‐performance liquid chromatography with photodiode array method was applicable for the simultaneous extraction and determination of these three types of compounds for quality evaluation of Eucommiae Cortex.
Development of a Novel High‐Performance Thin Layer Chromatography–Based Method for the Simultaneous Quantification of Clinically Relevant Lipids from Cells and Tissue Extracts
Authors: Pinault Michelle , Guimaraes Cyrille , Ben Hassen Céline , Gutierrez‐Pajares Jorge L. , Chevalier Stéphan , Goupille Caroline , Bernard‐Savary Pierre , Frank Philippe G. 
Published: May 2020

AbstractLipids such as cholesterol, triacylglycerols, and fatty acids play important roles in the regulation of cellular metabolism and cellular signaling pathways and, as a consequence, in the development of various diseases. It is therefore important to understand how their metabolism is regulated to better define the components involved in the development of various human diseases. In the present work, we describe the development and validation of a high‐performance thin layer chromatography (HPTLC) method allowing the separation and quantification of free cholesterol, cholesteryl esters, nonesterified fatty acids, and triacylglycerols. This method will be of interest as the quantification of these lipids in one single assay is difficult to perform.
Generalized boundary triples, I. Some classes of isometric and unitary boundary pairs and realization problems for subclasses of Nevanlinna functions
Authors: Derkach Volodymyr , Hassi Seppo , Malamud Mark 
Published: May 2020

AbstractWith a closed symmetric operator A in a Hilbert space a triple of a Hilbert space and two abstract trace operators Γ0 and Γ1 from to is called a generalized boundary triple for if an abstract analogue of the second Green's formula holds. Various classes of generalized boundary triples are introduced and corresponding Weyl functions are investigated. The most important ones for applications are specific classes of boundary triples for which Green's second identity admits a certain maximality property which guarantees that the corresponding Weyl functions are Nevanlinna functions on , i.e. , or at least they belong to the class of Nevanlinna families on . The boundary condition determines a reference operator . The case where A0 is selfadjoint implies a relatively simple analysis, as the joint domain of the trace mappings Γ0 and Γ1 admits a von Neumann type decomposition via A0 and the defect subspaces of A. The case where A0 is only essentially selfadjoint is more involved, but appears to be of great importance, for instance, in applications to boundary value problems e.g. in PDE setting or when modeling differential operators with point interactions. Various classes of generalized boundary triples will be characterized in purely analytic terms via the Weyl function and close interconnections between different classes of boundary triples and the corresponding transformed/renormalized Weyl functions are investigated. These characterizations involve solving direct and inverse problems for specific classes of operator functions . Most involved ones concern operator functions for which
defines a closable nonnegative form on . It turns out that closability of does not depend on and, moreover, that the closure then is a form domain invariant holomorphic function on while itself need not be domain invariant. In this study we also derive several additional new results, for instance, Kreĭn‐type resolvent formulas are extended to the most general setting of unitary and isometric boundary triples appearing in the present work.In part II of the present work all the main results are shown to have applications in the study of ordinary and partial differential operators.
A sensitive on‐chip probe–based portable nuclear magnetic resonance for detecting low parasitaemia plasmodium falciparum in human blood
Authors: Gupta Manish , Singh Kundan , Lobiyal Daya Krishan , Safvan Cholakka Parambath , Sahu Bhuban Kumar , Yadav Preeti , Singh Shailja 
Published: May 2020

AbstractMalaria elimination programmes are dependent on a rapid, cost‐effective and portable diagnostic tool to detect and quantify malaria parasites in human blood. Herein, we report a cost‐effective and portable nuclear magnetic resonance (pNMR) for malaria diagnosis. In this present study, we have developed and characterized a sensitive and low‐cost novel on‐chip NMR probe. This NMR probe has improved mismatching problem between radiofrequency (RF) coil and transmission line that results in enhancement in NMR sensitivity. Developed pNMR represents a rapid, cost‐effective and highly sensitive method to detect very low parasitaemia plasmodium falciparum (0.0001%) in infected human blood in comparison with other available malaria diagnosis techniques. The experimental results show that very low parasitic load can be detected rapidly by the change in the transverse relaxation rate (T2) of NMR, suggesting a good sensitivity. A good linear relationship with a correlation coefficient of 0.94 between the change in transverse relaxation rate (ΔT2) and the different parasitaemia (%) has been observed, indicating that pNMR is a potential tool for real‐time, reusable and high‐sensitivity analysis of malaria parasite in human blood.
Nonlinear sensors for biomaterials—Principles and applications
Authors: Brantley William A. 
Published: May 2020

AbstractCertain laboratory testing methods for the characterization of biomaterials, which can be regarded as essentially nonlinear sensors, have become widely adopted in recent decades. These techniques, namely dynamic mechanical analysis (DMA), electrochemical impedance spectroscopy (EIS) and temperature‐modulated differential scanning calorimetry (TMDSC), employ similar fundamental approaches in their different analyses, wherein materials are subjected to alternating (sinusoidal) stress, electrical potential and temperature change, respectively, and both the linear (in‐phase) and nonlinear (out‐of‐phase) responses are analysed to yield novel information unavailable with the corresponding traditional linear analytical techniques. This review article discusses the general experimental procedures and underlying principles for these three nonlinear analytical techniques and the type of information obtained with each approach, compared with that from the corresponding linear tests, and presents examples from the literature about their wide‐ranging application. While the focus is on dental biomaterials, additional examples for medical biomaterials are provided to illustrate further examples of the novel information that can be obtained from the use of these three nonlinear tests. The underlying philosophical similarity (analyses of nonlinear responses to different types of sinusoidal physical inputs) of these three sensor techniques is emphasized.
A novel low‐radar cross section microstrip antenna based on slotted frequency selective surface
Authors: Huang Xujing , Wan Guobin , Wang Nan , Ma Xin 
Published: May 2020

AbstractA novel low‐radar cross section (RCS) microstrip antenna with radiation performance and antenna volume maintained is proposed in this paper. Different from other antenna RCS reduction methods, the proposed antenna applies shaping method on frequency selective surface (FSS) ground plate to achieve further RCS reduction. In order to obtain the effect of subtracting square slots, an antenna with normal FSS ground is designed as reference antenna. The modified antenna with slotted FSS ground shows more significant RCS reduction compared with reference antenna in the frequency range 4 to 7.5 GHz, the maximum RCS reduction is 14.62 dBsm at 4.22 GHz. And the gain of the modified antenna is increased about 0.2 dB in contrast with the reference antenna. Besides, the modified and reference antenna are fabricated and measured. It is shown that the simulation and measured results are in good agreement.
Design and simulation of a W‐band gyrotron oscillator based on self‐consistent nonlinear theory
Authors: Geng Zhihui , Zhang Rui , Yang Xiudong , Liao Yunfeng , Xu Shouxi 
Published: May 2020

AbstractBased on the self‐consistent nonlinear theory, a W‐band continuous wave 30 kW fundamental harmonic gyrotron oscillator is designed and simulated. With a 30.0 kV, 3.0 A electron beam, the output power of more than 35 kW is obtained and the maximum electronic efficiency is equal to 40.3%. The effects of electron beam voltage, beam current, magnetic field intensity, guiding center radius, and velocity spread on electron efficiency and output power are analyzed in detail. In addition, the images of correlative electron clustering states in the process of beam‐wave interaction are presented intuitively.