bluuebunny/crossref_metadata_2025 huggingface dataset:
Fish Oil Monotherapy for Intestinal Failure-Associated Liver Disease on SMOFlipid in the Neonatal Intensive Care Unit
Authors: Lee Sanghoon , Sung Se In , Park Hyo Jung , Chang Yun Sil , Park Won Soon , Seo Jeong-Meen
Published: October 2020

Intestinal failure-associated liver disease (IFALD) is a life-threatening complication of parenteral nutrition (PN) and is most prevalent in the preterm neonatal population receiving long-term PN. In this study, we report the outcome of our experience with fish oil monotherapy for IFALD in a fish oil-based combination lipid emulsion administered to preterm low birth weight infants. Fasting neonates were administered as PN according to our center’s nutrition protocol. A diagnosis of IFALD was made when the serum direct bilirubin levels were >2.0 mg/dL in two consecutive measurements that were more than one week apart, without evidence of intrinsic causes of liver dysfunction. The management of IFALD was conducted by switching the lipid emulsion from combination lipid emulsion to fish oil monotherapy at 1.0 g/kg/day, infused over 24 h. Fifteen infants met the criteria for IFALD and received fish oil monotherapy. The median gestational age was 27.5 weeks and the median birth weight was 862.5 g. IFALD was successfully reversed in 11 infants (11/15, 73.3%). The median duration of fish oil monotherapy was 39 days. Direct bilirubin values were initially elevated and then steadily declined from the third week of treatment onward. The enteral tolerance increased in varying degrees during the treatment period. The mean weight gain was 26.0 g/day during fish oil monotherapy. Omegaven® (Fresenius Kabi Austria Gmbh, Graz, Austria) at a dose of 1.0 g/kg/day was well tolerated, and no adverse events related to Omegaven use were seen. The reversal of IFALD in preterm infants on combination lipid emulsion containing fish oil was achieved by switching to fish oil monotherapy.
The Maximum Stress Failure Criterion and the Maximum Strain Failure Criterion: Their Unification and Rationalization
Authors: Li Shuguang
Published: October 2020

The maximum strain failure criterion is unified with the maximum stress failure criterion, after exploring the implications of two considerations responsible for this: (1) the failure strains for the direct strain components employed in the maximum strain criterion are all defined under uniaxial stress states, not uniaxial strain states, and (2) the contributions to the strain in a direction as a result of the Poisson effect do not contribute to the failure of the material in that direction. Incorporating these considerations into the maximum strain criterion, the maximum stress criterion is reproduced. For 3D stress/strain state applications primarily, the unified maximum stress/strain criterion is then subjected to further rationalization in the context of transversely isotropic materials by eliminating the treatments that undermine the objectivity of the failure criterion. The criterion is then applied based on the maximum and minimum direct stresses, the maximum transverse shear stress and the maximum longitudinal shear stress as the invariants of the stress state, instead of the conventional stress components directly.
Simple Scheme for the Implementation of Low Voltage Fully Differential Amplifiers without Output Common-Mode Feedback Network
Authors: Renteria-Pinon Mario , Ramirez-Angulo Jaime , Diaz-Sanchez Alejandro
Published: October 2020

A simple scheme to implement class AB low-voltage fully differential amplifiers that do not require an output common-mode feedback network (CMFN) is introduced. It has a rail to rail output signal swing and high rejection of common-mode input signals. It operates in strong inversion with ±300 mV supplies in a 180 nm CMOS process. It uses an auxiliary amplifier that minimizes supply requirements by setting the op-amp input terminals very close to one of the rails and also serves as a common-mode feedback network to generate complementary output signals. The scheme is verified with simulation results of an amplifier that consumes 25 µW, has a gain-bandwidth product (GBW) of 16.1 MHz, slew rate (SR) of 8.4 V/µs, the small signal figure of merit (FOMSS) of 6.49 MHz*pF/µW, the large signal figure of merit (FOMLS) of 3.39 V/µs*pF/µW, and current efficiency (CE) of 2.03 in strong inversion, with a 10 pF load capacitance.
Application of Three-Dimensional Interpolation in Estimating Diapycnal Diffusivity in the South China Sea
Authors: Guo Junting , Nie Yafei , Li Shuang , Lv Xianqing
Published: October 2020

Diapycnal diffusivity is an important parameter to characterize oceanic turbulent mixing and vertical transport. However, due to the challenging accessibility of field observations, the observation of diapycnal diffusivity in the South China Sea (SCS) is rare. In this study, a three-dimensional field of diapycnal diffusivity in the SCS with high spatial resolution is performed by interpolating the rare field observations, which aims to provide a reference for the value of diapycnal diffusivity in ocean models. Given the anisotropy of diapycnal diffusivity and its rapid change in the magnitude in the vertical direction, several typical interpolation methods are compared in this study. Results of two cross-validation methods demonstrate that the three-dimensional (3D) thin-plate spline interpolation method yields the most reasonable and accurate results among a total of five typical methods used in this study.
Transient Breakage of the Nucleocytoplasmic Barrier Controls Spore Maturation via Mobilizing the Proteasome Subunit Rpn11 in the Fission Yeast Schizosaccharomyces pombe
Authors: Yang Hui-Ju , Asakawa Haruhiko , Ohtsuki Chizuru , Haraguchi Tokuko , Hiraoka Yasushi
Published: October 2020

Forespore membrane (FSM) closure is a process of specialized cytokinesis in yeast meiosis. FSM closure begins with the contraction of the FSM opening and finishes with the disassembly of the leading-edge proteins (LEPs) from the FSM opening. Here, we show that the FSM opening starts to contract when the event of virtual nuclear envelope breakdown (vNEBD) occurs in anaphase II of the fission yeast Schizosaccharomyces pombe. The occurrence of vNEBD controls the redistribution of the proteasomal subunit Rpn11 from the nucleus to the cytosol. To investigate the importance of Rpn11 re-localization during vNEBD, Rpn11 was sequestered at the inner nuclear membrane by fusion with the transmembrane region of Bqt4 (Rpn11-GFP-INM). Remarkably, in the absence of endogenous rpn11+, the cells carrying Rpn11-GFP-INM had abnormal or no spore formation. Live-cell imaging analysis further reveals that the FSM opening failed to contract when vNEBD occurred, and the LEP Meu14 was persistently present at the FSM in the rpn11-gfp-INM cells. The results suggest that the dynamic localization of Rpn11 during vNEBD is essential for spore development.
Let’s Get Physical: Bacterial-Fungal Interactions and Their Consequences in Agriculture and Health
Authors: Steffan Breanne N. , Venkatesh Nandhitha , Keller Nancy P.
Published: October 2020

Fungi serve as a biological scaffold for bacterial attachment. In some specialized interactions, the bacteria will invade the fungal host, which in turn provides protection and nutrients for the bacteria. Mechanisms of the physical interactions between fungi and bacteria have been studied in both clinical and agricultural settings, as discussed in this review. Fungi and bacteria that are a part of these dynamic interactions can have altered growth and development as well as changes in microbial fitness as it pertains to antibiotic resistance, nutrient acquisition, and microbial dispersal. Consequences of these interactions are not just limited to the respective microorganisms, but also have major impacts in the health of humans and plants alike. Examining the mechanisms behind the physical interactions of fungi and bacteria will provide us with an understanding of multi-kingdom community processes and allow for the development of therapeutic approaches for disease in both ecological settings.
Urine Sediment Findings and the Immune Response to Pathologies in Fungal Urinary Tract Infections Caused by Candida spp.
Authors: Poloni José Antonio Tesser , Rotta Liane Nanci
Published: October 2020

Fungi are pathogenic agents that can also cause disseminated infections involving the kidneys. Besides Candida, other agents like Cryptococcus spp. can cause urinary tract infection (UTI), as well as other non-yeast fungi, especially among immunocompromised patients. The detection and identification of fungi in urine samples (by microscopy and culture) plays an essential role in the diagnosis of fungal UTI. However, variable cutoff definitions and unreliable culture techniques may skew analysis of the incidence and outcome of candiduria. The sediment analysis plays a key role in the identification of fungal UTI because both yeasts and pseudohyphae are easily identified and can be used as a clinical sign of fungal UTI but should not be overinterpreted. Indeed, urine markers of the immune response (leukocytes), urine barriers of tissue protection (epithelial cells), and urine markers of kidney disease (urinary casts) can be found in urine samples. This work explores the manifestations associated with the fungal UTI from the urinalysis perspective, namely the urinary findings and clinical picture of patients with fungal UTI caused by Candida spp., aspects associated with the immune response, and the future perspectives of urinalysis in the diagnosis of this clinical condition.
Latent Segmentation of Stock Trading Strategies Using Multi-Modal Imitation Learning
Authors: Maeda Iwao , deGraw David , Kitano Michiharu , Matsushima Hiroyasu , Izumi Kiyoshi , Sakaji Hiroki , Kato Atsuo
Published: October 2020

While exchanges and regulators are able to observe and analyze the individual behavior of financial market participants through access to labeled data, this information is not accessible by other market participants nor by the general public. A key question, then, is whether it is possible to model individual market participants’ behaviors through observation of publicly available unlabeled market data alone. Several methods have been suggested in the literature using classification methods based on summary trading statistics, as well as using inverse reinforcement learning methods to infer the reward function underlying trader behavior. Our primary contribution is to propose an alternative neural network based multi-modal imitation learning model which performs latent segmentation of stock trading strategies. As a result that the segmentation in the latent space is optimized according to individual reward functions underlying the order submission behaviors across each segment, our results provide interpretable classifications and accurate predictions that outperform other methods in major classification indicators as verified on historical orderbook data from January 2018 to August 2019 obtained from the Tokyo Stock Exchange. By further analyzing the behavior of various trader segments, we confirmed that our proposed segments behaves in line with real-market investor sentiments.
Application of Genetic Algorithm to Optimal Income Taxation
Authors: Małecka-Ziembińska Edyta , Ziembiński Radosław
Published: October 2020

This paper, intended for researchers, introduces a stochastic method for calculating the optimal tax schedule based on taxpayer utility, population skill distribution, and wages. It implements and extends the classic approach to optimal income tax calculation introduced by J.A. Mirrlees. A genetic algorithm is applied instead of the numerical or analytical method of solving the problem. In the experimental part of the article, we took basic statistics for Germany in 2017 to infer about the distribution skills and wages of the working population. Their aim was to verify whether our approach would give similar results to those known from the literature on the subject. Thus, we have calculated the impact of the taxpayer attitude to work and budget external flows on the income tax schedule. Then, we measured the convergence of the search process across multiple runs of the algorithm. Analysis of obtained results brought us to the conclusion that they are similar to one known from the literature.
Does Teaching Your Native Language Abroad Increase L1 Attrition of Speech? The Case of Spaniards in the United Kingdom
Authors: Mayr Robert , Sánchez David , Mennen Ineke
Published: October 2020

The present study examines the perceived L1 accent of two groups of native Spaniards in the United Kingdom, Spanish teachers, and non-teachers, alongside monolingual controls in Spain. While the bilingual groups were carefully matched on a range of background variables, the teachers used Spanish significantly more at work where they constantly need to co-activate it alongside English. This allowed us to test the relative effect of reduced L1 use and dual language activation in first language attrition directly. To obtain global accentedness ratings, monolingual native Spanish listeners living in Spain participated in an online perception experiment in which they rated short speech samples extracted from a picture-based narrative produced by each speaker in terms of their perceived nativeness, and indicated which features they associated with non-nativeness. The results revealed significantly greater foreign-accent ratings for teachers than non-teachers and monolinguals, but no difference between the latter two. Non-native speech was associated with a range of segmental and suprasegmental features. These results suggest that language teachers who teach their L1 in an L2-speaking environment may be particularly prone to L1 attrition since they need to co-activate both their languages in professional settings and are regularly exposed to non-native speech from L2 learners.
Techniques for Thin-Walled Element Milling with Respect to Minimising Post-Machining Deformations
Authors: Zawada-Michałowska Magdalena , Kuczmaszewski Józef , Legutko Stanisław , Pieśko Paweł
Published: October 2020

The paper examines the impact of selected machining techniques and the semi-finished product technological history on deformations of thin-walled elements made of EN AW-2024 T351 aluminium alloy after milling. The following techniques have been implemented: High Performance Cutting, High Speed Cutting, conventional finishing (CF) and combinations of these techniques. As for the semi-finished product technological history, the rolling direction has been analysed. It has been assumed that it can be relevant in relation to the cutting tool feed direction and, in consequence, exert considerable impact on the stress, as well as deformation following machining. The interest in this issue proceeds from significant challenges faced by the industry, particularly in the aerospace sector. The analysis of results obtained has shown that milling in the direction perpendicular to the rolling direction results in larger deformations than milling in the parallel direction. Additionally, it has been revealed that applying a correctly selected machining technique makes it possible to minimise post-machining deformations of thin-walled elements.
Analysis and Prediction of Corrosion of Refractory Materials by Sodium Salts during Waste Liquid Incineration—Thermodynamic Study
Authors: Cheng Guishi , Zhao Ying , Long Fei , Zhang Jiahe , Zhao Tengfei , Liu Lu , Wang Xiaoqiang , Dong Changqing
Published: October 2020

Incineration of high-content sodium salt organic waste liquid will corrode the refractory material in the incinerator, causing the refractory material to peel off and be damaged. A thermodynamics method was used to study the thermodynamic properties of three common sodium salts (NaCl, Na2CO3 and Na2SO4) on the corrosion of refractory materials (MgO·Cr2O3, MgO·Al2O3, Al2O3, MgO and Cr2O3). The results determined that MgO has the best corrosion resistance and is not corroded by the three sodium salts. On this basis, the thermodynamic corrosion experiments of NaCl corrosion of magnesium oxide at three temperatures of 600, 1000 and 1200 °C were carried out. Analysis of the corrosion product by X-ray diffraction (XRD) showed no corrosion product formation. Studies have shown that thermodynamic calculation can accurately predict the thermodynamic mechanism of alkali metal corrosion to refractory materials, and MgO is a good anti-alkali metal corrosion refractory material.
Preparation of a New Iron-Carbon-Loaded Constructed Wetland Substrate and Enhanced Phosphorus Removal Performance
Authors: Zhao Jie , Gao Jingqing , Liu Junzhao
Published: October 2020

Iron-carbon substrates have attracted extensive attention in water treatment due to their excellent processing ability. The traditional iron-carbon substrate suffers from poor removal effects, separation of the cathode and anode, hardening, secondary pollution, etc. In this study, a new type of iron-carbon-loaded substrate (NICLS) was developed to solve the problems of traditional micro-electrolytic substrates. Through experimental research, a preparation method for the NICLS with Fe and C as the core, zeolite as the skeleton, and water-based polyurethane as the binder was proposed. The performance of the NICLS in phosphorus-containing wastewater was analyzed. The results are as follows: The optimal synthesis conditions of the NICLS are 1 g hydroxycellulose, wood activated carbon as the cathode, an activated carbon particle size of 200-60 mesh, and an Fe/C ratio of 1:1. Acidic conditions can promote the degradation of phosphorus by the NICLS. Through the characterization of the NICLS (scanning electron microscope (SEM), X-ray diffractometer (XRD), and energy-dispersive spectrometer (EDS), etc.), it is concluded that the mechanism of the NICLS phosphorus removal is a chemical reaction produced by micro-electrolysis. Using the NICLS to treat phosphorus-containing wastewater has the advantages of high efficiency and durability. Therefore, it can be considered that the NICLS is a promising material to remove phosphorus.
The Impact of 3D Printing Parameters on the Post-Buckling Behavior of Thin-Walled Structures
Authors: Kopecki Tomasz , Mazurek Przemysław , Święch Łukasz
Published: October 2020

This study presents the results of experimental research and numerical calculations regarding models of a typical torsion box fragment, which is a common thin-walled load-bearing structure used in aviation technology. A fragment of this structure corresponding to the spar wall was made using 3D printing. The examined system was subjected to twisting and underwent post-critical deformation. The research was aimed at determining the influence of the printing direction of the structure’s individual layers on the system stiffness. The experimental phase was supplemented by nonlinear numerical analyses of the models of the studied systems, taking into account the details of the structure mapping using the laminate concept. The purpose of the calculations was to determine the usefulness of the adopted method for modeling the examined structures by assessing the compliance of numerical solutions with the results of the experiment.
Influence of Oxide Glass Modifiers on the Structural and Spectroscopic Properties of Phosphate Glasses for Visible and Near-Infrared Photonic Applications
Authors: Kuwik Marta , Pisarska Joanna , Pisarski Wojciech A.
Published: October 2020

The effect of oxide modifiers on multiple properties (structural and spectroscopic) of phosphate glasses with molar composition 60P2O5-(10−x)Ga2O3-30MO-xEu2O3 and 60P2O5-(10−y)Ga2O3-30MO-yEr2O3 (where M = Ca, Sr, Ba; x = 0, 0.5; y = 0, 1) were systematically examined and discussed. The local structure of systems was evidenced by the infrared (IR-ATR) and Raman spectroscopic techniques. The spectroscopic behaviors of the studied glass systems were determined based on analysis of recorded spectra (excitation and emission) as well as luminescence decay curves. Intense red and near-infrared emissions (1.5 μm) were observed for samples doped with Eu3+ and Er3+ ions, respectively. It was found that the value of fluorescence intensity ratio R/O related to 5D0→7F2 (red) and 5D0→7F1 (orange) transition of Eu3+ ions depends on the oxide modifiers MO in the glass host. However, no clear influence of glass modifiers on the luminescence linewidth (FWHM) was observed for phosphate systems doped with Er3+ ions. Moreover, the 5D0 and 4I13/2 luminescence lifetimes of Eu3+ and Er3+ ions increase with the increasing ionic radius of M2+ (M = Ca, Sr, Ba) in the host matrix. The obtained results suggest the applicability of the phosphate glasses with oxide modifiers as potential red and near-infrared photoluminescent materials in photonic devices.
Real-Time Hybrid Simulation with Deep Learning Computational Substructures: System Validation Using Linear Specimens
Authors: Bas Elif Ecem , Moustafa Mohamed A.
Published: October 2020

Hybrid simulation (HS) is an advanced simulation method that couples experimental testing and analytical modeling to better understand structural systems and individual components’ behavior under extreme events such as earthquakes. Conducting HS and real-time HS (RTHS) can be challenging with complex analytical substructures due to the nature of direct integration algorithms when the finite element method is employed. Thus, alternative methods such as machine learning (ML) models could help tackle these difficulties. This study aims to investigate the quality of the RTHS tests when a deep learning algorithm is used as a metamodel to represent the dynamic behavior of a nonlinear analytical substructure. The compact HS laboratory at the University of Nevada, Reno was utilized to conduct exclusive RTHS tests. Simulating a braced frame structure, the RTHS tests combined, for the first time, linear brace model specimens (physical substructure) along with nonlinear ML models for the frame (analytical substructure). Deep long short-term memory (Deep-LSTM) networks were employed and trained to develop the metamodels of the analytical substructure using the Python environment. The training dataset was obtained from pure analytical finite element simulations for the complete structure under earthquake excitation. The RTHS evaluations were first conducted for virtual RTHS tests, where substructuring was sought between the LSTM metamodel and virtual experimental substructure. To validate the proposed RTHS testing methodology and full system, several actual RTHS tests were conducted. The results from ML-based RTHS were evaluated for different ML models and compared against results from conventional RTHS with finite element models. The paper demonstrates the potential of conducting successful experimental RTHS using Deep-LSTM models, which could open the door for unparalleled new opportunities in structural systems design and assessment.
An Integrated Decision Approach with Probabilistic Linguistic Information for Test Case Prioritization
Authors: Shrivathsan A. D. , Krishankumar R. , Mishra Arunodaya Raj , S. Ravichandran K. , Kar Samarjit , Badrinath V.
Published: October 2020

This paper focuses on an exciting and essential problem in software companies. The software life cycle includes testing software, which is often time-consuming, and is a critical phase in the software development process. To reduce time spent on testing and to maintain software quality, the idea of a systematic selection of test cases is needed. Attracted by the claim, researchers presented test case prioritization (TCP) by applying the concepts of multi-criteria decision-making (MCDM). However, the literature on TCP suffers from the following issues: (i) difficulty in properly handling uncertainty; (ii) systematic evaluation of criteria by understanding the hesitation of experts; and (iii) rational prioritization of test cases by considering the nature of criteria. Motivated by these issues, an integrated approach is put forward that could circumvent the problem in this paper. The main aim of this research is to develop a decision model with integrated methods for TCP. The core importance of the proposed model is to (i) provide a systematic/methodical decision on TCP with a reduction in testing time and cost; (ii) help software personnel choose an apt test case from the suite for testing software; (iii) reduce human bias by mitigating intervention of personnel in the decision process. To this end, probabilistic linguistic information (PLI) is adopted as the preference structure that could flexibly handle uncertainty by associating occurrence probability to each linguistic term. Furthermore, an attitude-based entropy measure is presented for criteria weight calculation, and finally, the EDAS ranking method is extended to PLI for TCP. An empirical study of TCP in a software company is presented to certify the integrated approach’s effectiveness. The strengths and weaknesses of the introduced approach are conferred by comparing it with the relevant methods.
On the Relationship of Cryptocurrency Price with US Stock and Gold Price Using Copula Models
Authors: Kim Jong-Min , Kim Seong-Tae , Kim Sangjin
Published: October 2020

This paper examines the relationship of the leading financial assets, Bitcoin, Gold, and S&P 500 with GARCH-Dynamic Conditional Correlation (DCC), Nonlinear Asymmetric GARCH DCC (NA-DCC), Gaussian copula-based GARCH-DCC (GC-DCC), and Gaussian copula-based Nonlinear Asymmetric-DCC (GCNA-DCC). Under the high volatility financial situation such as the COVID-19 pandemic occurrence, there exist a computation difficulty to use the traditional DCC method to the selected cryptocurrencies. To solve this limitation, GC-DCC and GCNA-DCC are applied to investigate the time-varying relationship among Bitcoin, Gold, and S&P 500. In terms of log-likelihood, we show that GC-DCC and GCNA-DCC are better models than DCC and NA-DCC to show relationship of Bitcoin with Gold and S&P 500. We also consider the relationships among time-varying conditional correlation with Bitcoin volatility, and S&P 500 volatility by a Gaussian Copula Marginal Regression (GCMR) model. The empirical findings show that S&P 500 and Gold price are statistically significant to Bitcoin in terms of log-return and volatility.
Bioavailability of Orally Administered Active Lipid Compounds from four Different Greenshell™ Mussel Formats
Authors: Miller Matthew R. , Kruger Marlena C. , Wynne Chris , Waaka Devonie , Li Weili , Frampton Chris , Wolber Fran M. , Eason Charles
Published: October 2020

Greenshell™ mussel (GSM, Perna canaliculus) is New Zealand’s most important aquaculture species. They are a good source of long chain-polyunsaturated fatty acids (n-3 LC PUFA). Beyond a traditional food product, GSMs are also sold as mussel powders and oil extract formats in the nutraceutical markets. In this study, a four-sequence, single dose, randomized crossover human trial with eight evaluable healthy male participants was undertaken to determine the bioavailability of the n-3 LC PUFA in four different GSM formats (oil, powder, food ingredient and half-shell unprocessed whole mussel) by measuring area under the curve (AUC) and maximal concentration (CMax). Blood samples were collected at baseline and up to 48 h after initiation of product consumption in each administration period. There were minor differences between the bioavailability of FA (fatty acid) between the different GSM formats. Eicosapentaenoic acid (EPA) peak concentrations and plasma exposures were significantly lower with GSM oil compared to GSM half-shell and GSM powder formats, which resulted in AUC0–48 for the intake of GSM half-shell mussel and GSM powder being significantly higher than that for GSM oil (p = 0.013, f= 4.84). This equated to a 20.6% and 24.3% increase in the amount of EPA present in the plasma after consumption of half-shell mussels and mussel powder respectively compared to GSM oil. GSM oil produced the shortest median time to maximal plasma n-3 LC PUFA concentration of all evaluated products demonstrated by a shorter maximum measured plasma concentration (TMax = 5 h). Docosahexaenoic acid (DHA) and n-3 LC PUFA plasma exposure parameters were statistically comparable across the four GSM products evaluated.
The Impact of Obesity on Left Ventricular Assist Device Outcomes
Authors: Zhigalov Konstantin , Sá Michel Pompeu Barros Oliveira , Arjomandi Rad Arian , Vardanyan Robert , Goerdt Lukas , Chrosch Thomas , Zubarevich Alina , Wendt Daniel , Pizanis Nikolaus , Koch Achim , Kamler Markus , Berger Rafal , Schmack Bastian , Ruhparwar Arjang , Popov Aron-Frederik , Weymann Alexander
Published: October 2020

Background and Objectives: The understanding of high body mass index (BMI) and outcomes after Left Ventricular Assist Device (LVAD) implantation continues to evolve and the relationship has not been established yet. In this study, we investigated the effects of obesity (BMI > 30 kg/m2) on post–LVAD implantation outcomes. HeartWare LVAD and Heart Mate III LVAD were implanted. The primary outcome that was measured was mortality (in-hospital and on follow-up). The secondary outcomes that were measured were major adverse events. Materials and Methods: At our institution, the West German Heart and Vascular Center (Essen, Germany), from August 2010 to January 2020, a total of 210 patients received a long-term LVAD. Patients were stratified according to BMI ≥ 30 kg/m2 representing the obesity threshold. The first group (n = 162) had an average BMI of 24.2 kg/m2 (±2.9), and the second group (n = 48) had an average BMI of 33.9 kg/m2 (±3.2). Baseline demographics were analysed alongside comorbidities per group. Results: Overall mortality was not significantly different between the obese group (51.1% n = 24) and the nonobese group (55.2%, n = 85) (p = 0.619). The difference between the mean duration of survival of patients who expired after hospital discharge was insignificant (2.1 years ± 1.6, group 1; 2.6 years ± 1.5, group 2; p = 0.29). In-hospital mortality was unvaried between the two groups: group 1: n = 34 (44% out of overall group 1 deaths); group 2: n = 11 (45.8% out of overall group 2 deaths) (p > 0.05). Postoperative complications were unvaried between the obese and the non-obese group (all with p > 0.05). However, a significant difference was found with regards to follow-up neurological complications (18.5% vs. 37.8%, p = 0.01) and LVAD thrombosis (14.7% vs. 33.3%, p = 0.01), as both were higher in the obese population. Conclusion: Obesity does not form a barrier for LVAD implantation in terms of mortality (in-hospital and on follow up). However, a significantly higher incidence of follow-up LVAD thrombosis and neurological complications has been found in the obese group of patients.
Novel Biomarkers to Distinguish between Type 3c and Type 2 Diabetes Mellitus by Untargeted Metabolomics
Authors: Jimenez-Luna Cristina , Martin-Blazquez Ariadna , Dieguez-Castillo Carmelo , Diaz Caridad , Martin-Ruiz Jose Luis , Genilloud Olga , Vicente Francisca , del Palacio Jose Perez , Prados Jose , Caba Octavio
Published: October 2020

Pancreatogenic diabetes mellitus (T3cDM) is a highly frequent complication of pancreatic disease, especially chronic pancreatitis, and it is often misdiagnosed as type 2 diabetes mellitus (T2DM). A correct diagnosis allows the appropriate treatment of these patients, improving their quality of life, and various technologies have been employed over recent years to search for specific biomarkers of each disease. The main aim of this metabolomic project was to find differential metabolites between T3cDM and T2DM. Reverse-phase liquid chromatography coupled to high-resolution mass spectrometry was performed in serum samples from patients with T3cDM and T2DM. Multivariate Principal Component and Partial Least Squares-Discriminant analyses were employed to evaluate between-group variations. Univariate and multivariate analyses were used to identify potential candidates and the area under the receiver-operating characteristic (ROC) curve was calculated to evaluate their diagnostic value. A panel of five differential metabolites obtained an area under the ROC curve of 0.946. In this study, we demonstrate the usefulness of untargeted metabolomics for the differential diagnosis between T3cDM and T2DM and propose a panel of five metabolites that appear altered in the comparison between patients with these diseases.
Topological Regulation of the Bioactive Conformation of a Disulfide-Rich Peptide, Heat-Stable Enterotoxin
Authors: Shimamoto Shigeru , Fukutsuji Mayu , Osumi Toi , Goto Masaya , Toyoda Hiroshi , Hidaka Yuji
Published: October 2020

Heat-stable enterotoxin (STa) produced by enterotoxigenic E. coli causes acute diarrhea and also can be used as a specific probe for colorectal cancer cells. STa contains three intra-molecular disulfide bonds (C1–C4, C2–C5, and C3–C6 connectivity). The chemical synthesis of STa provided not only the native type of STa but also a topological isomer that had the native disulfide pairings. Interestingly, the activity of the topological isomer was approximately 1/10–1/2 that of the native STa. To further investigate the bioactive conformation of this molecule and the regulation of disulfide-coupled folding during its chemical syntheses, we examined the folding mechanism of STa that occurs during its chemical synthesis. The folding intermediate of STa with two disulfide bonds (C1–C4 and C3–C6) and two Cys(Acm) residues, the precursor peptide, was treated with iodine to produce a third disulfide bond under several conditions. The topological isomer was predominantly produced under all conditions tested, along with trace amounts of the native type of STa. In addition, NMR measurements indicated that the topological isomer has a left-handed spiral structure similar to that of the precursor peptide, while the native type of STa had a right-handed spiral structure. These results indicate that the order of the regioselective formation of disulfide bonds is important for the regulation of the final conformation of disulfide-rich peptides in chemical synthesis.
Tri-Herbal Medicine Divya Sarva-Kalp-Kwath (Livogrit) Regulates Fatty Acid-Induced Steatosis in Human HepG2 Cells through Inhibition of Intracellular Triglycerides and Extracellular Glycerol Levels
Authors: Balkrishna Acharya , Gohel Vivek , Singh Rani , Joshi Monali , Varshney Yash , Srivastava Jyotish , Bhattacharya Kunal , Varshney Anurag
Published: October 2020

Steatosis is characterized by excessive triglycerides accumulation in liver cells. Recently, application of herbal formulations has gained importance in treating complex diseases. Therefore, this study explores the efficacy of tri-herbal medicine Divya Sarva-Kalp-Kwath (SKK; brand name, Livogrit) in treating free fatty acid (FFA)-induced steatosis in human liver (HepG2) cells and rat primary hepatocytes. Previously, we demonstrated that cytosafe SKK ameliorated CCl4-induced hepatotoxicity. In this study, we evaluated the role of SKK in reducing FFA-induced cell-death, and steatosis in HepG2 through analysis of cell viability, intracellular lipid and triglyceride accumulation, extracellular free glycerol levels, and mRNA expression changes. Plant metabolic components fingerprinting in SKK was performed via High Performance Thin Layer Chromatography (HPTLC). Treatment with SKK significantly reduced the loss of cell viability induced by 2 mM-FFA in a dose-dependent manner. SKK also reduced intracellular lipid, triglyceride accumulation, secreted AST levels, and increased extracellular free glycerol presence in the FFA-exposed cells. SKK normalized the FFA-stimulated overexpression of SREBP1c, FAS, C/EBPα, and CPT1A genes associated with the induction of steatosis. In addition, treatment of rat primary hepatocytes with FFA and SKK concurrently, reduced intracellular lipid accumulation. Thus, SKK showed efficacy in reducing intracellular triglyceride accumulation and increasing extracellular glycerol release, along with downregulation of related key genetic factors for FFA-associated steatosis.
Semisynthetic Cardenolides Acting as Antiviral Inhibitors of Influenza A Virus Replication by Preventing Polymerase Complex Formation
Authors: Boff Laurita , Schreiber André , da Rocha Matos Aline , Del Sarto Juliana , Brunotte Linda , Munkert Jennifer , Melo Ottoni Flaviano , Silva Ramos Gabriela , Kreis Wolfgang , Castro Braga Fernão , José Alves Ricardo , Maia de Pádua Rodrigo , Maria Oliveira Simões Cláudia , Ludwig Stephan
Published: October 2020

Influenza virus infections represent a major public health issue by causing annual epidemics and occasional pandemics that affect thousands of people worldwide. Vaccination is the main prophylaxis to prevent these epidemics/pandemics, although the effectiveness of licensed vaccines is rather limited due to the constant mutations of influenza virus antigenic characteristics. The available anti-influenza drugs are still restricted and there is an increasing viral resistance to these compounds, thus highlighting the need for research and development of new antiviral drugs. In this work, two semisynthetic derivatives of digitoxigenin, namely C10 (3β-((N-(2-hydroxyethyl)aminoacetyl)amino-3-deoxydigitoxigenin) and C11 (3β-(hydroxyacetyl)amino-3-deoxydigitoxigenin), showed anti-influenza A virus activity by affecting the expression of viral proteins at the early and late stages of replication cycle, and altering the transcription and synthesis of new viral proteins, thereby inhibiting the formation of new virions. Such antiviral action occurred due to the interference in the assembly of viral polymerase, resulting in an impaired polymerase activity and, therefore, reducing viral replication. Confirming the in vitro results, a clinically relevant ex vivo model of influenza virus infection of human tumor-free lung tissues corroborated the potential of these compounds, especially C10, to completely abrogate influenza A virus replication at the highest concentration tested (2.0 µM). Taken together, these promising results demonstrated that C10 and C11 can be considered as potential new anti-influenza drug candidates.
Chemical Composition and Bioactivity of Essential Oil of Ten Labiatae Species
Authors: Liu Mengting , Luo Feiya , Qing Zhixing , Yang Huichao , Liu Xiubin , Yang Zihui , Zeng Jianguo
Published: October 2020

Using antibiotics as feed additives have been successively banned worldwide from 1986; therefore, it is an urgent task to finding safe and effective alternatives. As natural products of plant origin, essential oils (EOs) are an outstanding option due to their reported bioactivity. In this research, ten EOs of Labiatae species were extracted by steam distillation and its chemical constituents were identified by gas chromatography-mass spectrometry (GC-MS). A total of 123 chemical compounds, including alkenes, phenols, aldehydes and ketones, were identified. The results of antioxidant activity carried out through DPPH free radical scavenging (DPPH) and ferric reducing antioxidant power (FRAP), showing that EOs of Ocimum basilicum Linn. (ObEO), Thymus mongolicus Ronn. (TmEO), Origanum vulgare Linn. (OvEO) and Mosla chinensis Maxim. (McEO) have strong antioxidant activities. Their 50%-inhibitory concentration (IC50) value was <1.00, 1.42, 1.47 and 1.92 μg/mL, respectively; and their FRAP value was 1536.67 ± 24.22, 271.84 ± 4.93, 633.71 ± 13.14 and 480.66 ± 29.90, respectively. The results of filter paper diffusion showing that McEO, OvEO and TmEO inhibition zone diameter (IZD) are all over 30 mm. The results of two-fold dilution method showed that McEO, OvEO and TmEO have strong antibacterial activities against Staphylococcus aureus (S. aureus) and their minimal inhibitory concentrations (MIC) value was 1 μL/mL, 2 μL/mL, and 2 μL/mL, respectively. In conclusion, the results in this work demonstrate the possibility for development and application of EOs as potential feed additives.
Past, Present and Future Perspectives on Halloysite Clay Minerals
Authors: Massaro Marina , Noto Renato , Riela Serena
Published: October 2020

Halloysite nanotubes (HNTs), clay minerals belonging to the kaolin groups, are emerging nanomaterials which have attracted the attention of the scientific community due to their interesting features, such as low-cost, availability and biocompatibility. In addition, their large surface area and tubular structure have led to HNTs’ application in different industrial purposes. This review reports a comprehensive overview of the historical background of HNT utilization in the last 20 years. In particular it will focus on the functionalization of the surfaces, both supramolecular and covalent, following applications in several fields, including biomedicine, environmental science and catalysis.
Use of Biodegradable, Chitosan-Based Nanoparticles in the Treatment of Alzheimer’s Disease
Authors: Manek Eniko , Darvas Ferenc , Petroianu Georg A.
Published: October 2020

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects more than 24 million people worldwide and represents an immense medical, social and economic burden. While a vast array of active pharmaceutical ingredients (API) is available for the prevention and possibly treatment of AD, applicability is limited by the selective nature of the blood-brain barrier (BBB) as well as by their severe peripheral side effects. A promising solution to these problems is the incorporation of anti-Alzheimer drugs in polymeric nanoparticles (NPs). However, while several polymeric NPs are nontoxic and biocompatible, many of them are not biodegradable and thus not appropriate for CNS-targeting. Among polymeric nanocarriers, chitosan-based NPs emerge as biodegradable yet stable vehicles for the delivery of CNS medications. Furthermore, due to their mucoadhesive character and intrinsic bioactivity, chitosan NPs can not only promote brain penetration of drugs via the olfactory route, but also act as anti-Alzheimer therapeutics themselves. Here we review how chitosan-based NPs could be used to address current challenges in the treatment of AD; with a specific focus on the enhancement of blood-brain barrier penetration of anti-Alzheimer drugs and on the reduction of their peripheral side effects.
Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop
Authors: Lenarčič Živković Martina , Rozman Jan , Plavec Janez
Published: October 2020

Bone remodeling is a fine-tuned process principally regulated by a cascade triggered by interaction of receptor activator of NF-κB (RANK) and RANK ligand (RANKL). Excessive activity of the RANKL gene leads to increased bone resorption and can influence the incidence of osteoporosis. Although much has been learned about the intracellular signals activated by RANKL/RANK complex, significantly less is known about the molecular mechanisms of regulation of RANKL expression. Here, we report on the structure of an unprecedented DNA G-quadruplex, well-known secondary structure-mediated gene expression regulator, formed by a G-rich sequence found in the regulatory region of a RANKL gene. Solution-state NMR structural study reveals the formation of a three-layered parallel-type G-quadruplex characterized by an unique features, including a G-A bulge. Although a guanine within a G-tract occupies syn glycosidic conformation, bulge-forming residues arrange in a pseudo-loop conformation to facilitate partial 5/6-ring stacking, typical of G-quadruplex structures with parallel G-tracts orientation. Such distinctive structural features protruding from the core of the structure can represent a novel platform for design of highly specific ligands with anti-osteoporotic function. Additionally, our study suggests that the expression of RANKL gene may be regulated by putative folding of its G-rich region into non-B-DNA structure(s).
Enhancement of Phthalocyanine Mediated Photodynamic Therapy by Catechin on Lung Cancer Cells
Authors: Senapathy Giftson J. , George Blassan P. , Abrahamse Heidi
Published: October 2020

Worldwide, lung cancer remains one of the leading cancers with increasing mortality rates. Though chemotherapy for lung cancer is effective, it is always accompanied by unavoidable and grave side effects. Photodynamic therapy (PDT), using novel photosensitizers, is an advanced treatment method with relatively few side effects. Plant products are emerging as potent photosensitizers (PSs). The dose-dependent effect of Catechin (CA) (20–100 µM) on cellular morphological changes, cell viability, cytotoxicity, proliferation, DNA damage and apoptosis were studied on A549 adenocarcinoma alveolar basal epithelial cells. The effect of CA, along with Zinc phthalocyanine PS at 680 nm and 5 J/cm2 fluency was also studied. As the doses of CA increased, the results showed a pattern of increased cytotoxicity, accompanied by decreased cell viability and proliferation in A549 cells. Also, at 52 µM (IC50), CA in combination with PS significantly increased the cytotoxicity, DNA damage, and apoptosis, as compared to control and PS alone, treated cells in PDT experiments. These findings leave a possible thread that CA can be used in the application of phyto-photodynamic therapy of cancer in future.
Trifluoromethanesulfonamide vs. Non-Fluorinated Sulfonamides in Oxidative Sulfamidation of the C=C Bond: An In Silico Study
Authors: Kuzmin Anton V. , Moskalik Mikhail Yu. , Shainyan Bagrat A.
Published: October 2020

A theoretical analysis of the reaction of oxidative sulfamidation of several alkenes was performed in order to explain the various experimental observations and different reactivity of triflamide and non-fluorinated sulfonamides. Transformations occurring in the system alkene–sulfonamide in the presence of oxidative system (ButOCl + NaI) were analyzed at the MP2/DGDZVP//B3LYP/DGDZVP level of theory using the IEF-PCM method for taking into account the solvent acetonitrile (MeCN) effect. As the model substrates, styrene, trimethyl(vinyl)silane, dimethyl(divinyl)silane and diphenyl(divinyl)silane were chosen and mesylamide, triflamide, tosylamide and p-nosylamide were taken as the reagents. ButOI generated from ButOCl and NaI reacts with sulfonamides to give N-iodinated sulfonamides RSO2NHI and RSO2NI2 as active intermediates, the iodinating activity of the latter being notably higher. The analysis allowed to answer such challenging questions as different reactivity of nonfluorinated sulfonamides leading to aziridination and of triflamide resulting in the formation the main products of bis-triflamidation, or different regioselectivity of halogenation of styrene and trimethyl(vinyl)silane caused by a linear intermediate iodonium cation in the former case and a cyclic one in the latter.
Identification of a Novel Pyrrole Alkaloid from the Edible Mushroom Basidiomycetes-X (Echigoshirayukidake)
Authors: Sakamoto Toshio , Nishida Ayaka , Wada Naoki , Nakamura Yutaka , Sato Shinji , Konishi Tetsuya , Matsugo Seiichi
Published: October 2020

Three pyrrole alkaloid derivatives were isolated from the edible mushroom Basidiomycetes-X (Echigoshirayukidake) by water extraction followed by ethyl acetate fractionation. The chemical structures determined by MS and NMR were 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanoic acid (compound I), 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanamide (compound II), and 5-(hydroxymethyl)-1H-pyrrole-2-carboxaldehyde (compound III). Compound I was found to be the major component, followed by compound II, and compound III was the minor component. The dry powder of Basidiomycetes-X contained approximately 825 μg g−1 compound I and 484 μg g−1 compound II. Compound II was found to be a novel pyrrole aldehyde homologue not previously reported and thus is a specific component of this mushroom.