bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Clinical MRSA Isolates from Northern Spain and Assessment of Their Susceptibility to Phage-Derived Antimicrobials
Authors: Salas Marina , Wernecki Maciej , Fernández Lucía , Iglesias Beatriz , Gutiérrez Diana , Álvarez Andrea , García Laura , Prieto Elisabeth , García Pilar , Rodríguez Ana
Published: July 2020

Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent nosocomial pathogen, causing a wide range of diseases. The increased frequency of MRSA isolates in hospitals and the emergence of vancomycin resistance have sparked the search for new control strategies. This study aimed to characterize sixty-seven MRSA isolates collected from both infected patients and asymptomatic carriers in a Spanish hospital. RAPD-PCR allowed the identification of six genetic patterns. We also investigated the presence of genes involved in producing adhesins, toxins and the capsule; the biofilm; and antimicrobial resistance. A notable percentage of the isolates carried virulence genes and showed medium-high ability to form biofilms. Next, we assessed the strains’ susceptibility to two phages (phiIPLA-C1C and phiIPLA-RODI) and one endolysin (LysRODI). All strains were resistant to phiIPLA-C1C, and most (70.2%) were susceptible to phiIPLA-RODI. Regarding LysRODI, all strains displayed susceptibility, although to varying degrees. There was a correlation between endolysin susceptibility and the random amplification of polymorphic DNA (RAPD) profile or the presence of some virulence genes (fnbA, eta, etb, PVL and czr), but that was not observed with biofilm-forming ability, strain origin or phage sensitivity. Taken together, these findings can help to explain the factors influencing endolysin effectiveness, which will contribute to the development of efficient therapies targeting MRSA infections.
Characterization of Five Novel Anti-MRSA Compounds Identified Using a Whole-Animal Caenorhabditis elegans/Galleria mellonella Sequential-Screening Approach
Authors: Khader Rajamohammed , Tharmalingam Nagendran , Mishra Biswajit , Felix LewisOscar , Ausubel Frederick M. , Kelso Michael J. , Mylonakis Eleftherios
Published: July 2020

There is a significant need to combat the growing challenge of antibacterial drug resistance. We have previously developed a whole-animal dual-screening platform that first used the nematode Caenorhabditis elegans, to identify low-toxicity antibacterial hits in a high-throughput format. The hits were then evaluated in the wax moth caterpillar Galleria mellonella infection model to confirm efficacy and low toxicity at a whole animal level. This multi-host approach is a powerful tool for revealing compounds that show antibacterial effects and relatively low toxicity at the whole organism level. This paper reports the use of the multi-host approach to identify and validate five new anti-staphylococcal compounds: (1) 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol(PPT), (2) (1S,2S)-2-[2-[[3-(1H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl cyclopropanecarboxylate dihydrochloride(NNC), (3) 4,5,6,7-tetrabromobenzotriazole (TBB), (4) 3-[2-[2-chloro-4-[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl] benzoic acid(GW4064), and (5) N-(cyclopropylmethoxy)-3,4,5-trifluoro-2-[(4-iodo-2-methylphenyl)amino] benzamide(PD198306). The compounds reduced the severity of methicillin-resistant Staphylococcus aureus (MRSA, strain MW2) infections in both C. elegans and G. mellonella and showed minimal inhibitory concentrations (MICs) in the range of 2–8 µg/mL. Compounds NNC, PPT, and TBB permeabilized MRSA-MW2 cells to SYTOX green, suggesting that they target bacterial membranes. Compound TBB showed synergistic activity with doxycycline and oxacillin against MRSA-MW2, and compounds PPT, NNC, GW4064, and PD198306 synergized with doxycycline, polymyxin-B, gentamicin, and erythromycin, respectively. The study demonstrates the utility of the multi-host approach with follow-up hit characterization for prioritizing anti-MRSA compounds for further evaluation.
Efficacy and Mechanisms of Flavonoids against the Emerging Opportunistic Nontuberculous Mycobacteria
Authors: Mickymaray Suresh , Alfaiz Faiz Abdulaziz , Paramasivam Anand
Published: July 2020

Nontuberculous mycobacteria (NTM) are the causative agent of severe chronic pulmonary diseases and is accountable for post-traumatic wound infections, lymphadenitis, endometritis, cutaneous, eye infections and disseminated diseases. These infections are extremely challenging to treat due to multidrug resistance, which encompasses the classical and existing antituberculosis agents. Hence, current studies are aimed to appraise the antimycobacterial activity of flavonoids against NTM, their capacity to synergize with pharmacological agents and their ability to block virulence. Flavonoids have potential antimycobacterial effects at minor quantities by themselves or in synergistic combinations. A cocktail of flavonoids used with existing antimycobacterial agents is a strategy to lessen side effects. The present review focuses on recent studies on naturally occurring flavonoids and their antimycobacterial effects, underlying mechanisms and synergistic effects in a cocktail with traditional agents.
Antioxidant Capacity of Anthocyanins and other Vegetal Pigments
Authors: Tena Noelia , Asuero Agustin G.
Published: July 2020

Anthocyanins are the largest group of phenolic pigments, being effective hydrogen donors [...]
Differential Distribution Analysis and Region and Grade Regulation on Auto-Parts Weathering External Factors with Non-Uniform Thermal Environment
Authors: Deng Zhiyong , Lan Fengchong , Chen Jiqing
Published: July 2020

It is difficult to comprehensively master and precisely regulate the external factors distribution of automobile weathering in non-uniform thermal environment as well as the consequent disequilibrium weathering problem, while exploring weather-resistant materials in uniform thermal environment. Thus, a numerical calculation method for the weathering external factors is proposed, on the basis of annual experimental study on the outdoor weathering inconsistencies of auto-parts. The time–space distribution characteristics and day–night variation rules of the external factors are studied, and the disequilibrium weathering mechanism among parts is revealed from the perspective of non-uniform distribution of external factors. The laws of automotive physical parameters, orientations and locations, as well as their influences on external factors distribution are analyzed in detail, and hereby the targeted schemes to effectively reduce the local external factor intensity and the thermal gradient between parts are investigated. The method can be used to rapidly predict weathering external factors distribution of vehicle exposed to outdoor in any direction during day and night, so as to provide auto-parts with differentiated test schemes in accelerated tests and IP/DP box tests, and it also contributes to present some pertinence guidance for the accurate regulation of automobile disequilibrium weathering on regions at different levels.
The Effects of Stress on Second Harmonics in Plate-Like Structures
Authors: Niu Xiaochuan , Zhu Liqiang , Yu Zujun
Published: July 2020

Cumulative second harmonic of ultrasonic guided waves is considered to have great application potential in evaluating internal stress of structures. One difficulty with the application is the diversity and complexity of modal response to the stress change in waveguide. At present, there is a lack of relevant theoretical studies and experimental results to guide the applications. In this article, a method is proposed to characterize the amplitude change of cumulative second harmonic mode in a plate under stress through calculating the amplitude coefficient, which can be acquired based on mode shape analysis. The steel plate is taken as an example to demonstrate the analysis method. Experimental studies are presented with results consistent with the theoretical predictions. The results of this study indicate that the amplitudes of different cumulative second harmonic modes may increase or decrease monotonically with the change of stress. Therefore, when the phenomenon of modes mixing occurs in the waveguide, it is necessary to analyze and predict the amplitude of selected cumulative second harmonic mode with the change of stress in advance; otherwise, wrong results may be obtained. The method and conclusions proposed in this paper can also be applicable to waveguide of arbitrary cross-section and have universality.
Comparative Study of Glass Fiber Content Measurement Methods for Inspecting Fabrication Quality of Composite Ship Structures
Authors: Han Zhiqiang , Jeong Sookhyun , Noh Jackyou , Oh Daekyun
Published: July 2020

A comparative study of glass fiber content (Gc) measurement methods was conducted using actual glass fiber reinforced plastic laminates from the hull plate of a 26-ton yacht. Two prototype side hull plates with the design Gc (40 wt.%) and higher Gc (64 wt.%) were prepared. Four methods were used to study the samples: the calculation method suggested by classification societies’ rules; two direct measurement methods using either calipers and scales or a hydrometer; and the burn-off method, wherein the resin matrix is combusted from the laminates. The results were compared and analyzed to identify the accuracy and benefits of each method. The rule calculation method was found to be effective if the quality of the manufacturing process is known. However, fabrication errors in the laminate structures cannot be detected. Additionally, while direct methods are used to measure the density of glass fibers using measurements of the densities of raw materials and laminates, the volume of inner defects occurring during the fabrication of laminates could not be considered. Finally, it was found that the burn-off method measures Gc and considers the defect volume (voids) inside laminates as well as the non-uniformity of the external shape.
Seismic AVOA Inversion for Weak Anisotropy Parameters and Fracture Density in a Monoclinic Medium
Authors: Ge Zijian , Pan Shulin , Li Jingye
Published: July 2020

In shale gas development, fracture density is an important lithologic parameter to properly characterize reservoir reconstruction, establish a fracturing scheme, and calculate porosity and permeability. The traditional methods usually assume that the fracture reservoir is one set of aligned vertical fractures, embedded in an isotropic background, and estimate some alternative parameters associated with fracture density. Thus, the low accuracy caused by this simplified model, and the intrinsic errors caused by the indirect substitution, affect the estimation of fracture density. In this paper, the fractured rock of monoclinic symmetry assumes two non-orthogonal vertical fracture sets, embedded in a transversely isotropic background. Firstly, assuming that the fracture radius, width, and orientation are known, a new form of P-wave reflection coefficient, in terms of weak anisotropy (WA) parameters and fracture density, was obtained by substituting the stiffness coefficients of vertical transverse isotropic (VTI) background, normal, and tangential fracture compliances. Then, a linear amplitude versus offset and azimuth (AVOA) inversion method, of WA parameters and fracture density, was constructed by using Bayesian theory. Tests on synthetic data showed that WA parameters, and fracture density, are stably estimated in the case of seismic data containing a moderate noise, which can provide a reliable tool in fracture prediction.
Special Feature Vibration-Based Structural Health Monitoring
Authors: Park Junhong
Published: July 2020

Structural health monitoring by vibration requires the understanding of multidisciplinary fields of engineering sciences [...]
Axial Plasma Spraying of Mixed Suspensions: A Case Study on Processing, Characteristics, and Tribological Behavior of Al2O3-YSZ Coatings
Authors: Goel Sneha , Björklund Stefan , Curry Nicholas , Govindarajan Sivakumar , Wiklund Urban , Gaudiuso Caterina , Joshi Shrikant
Published: July 2020

Thermal spraying deploying liquid feedstock offers an exciting opportunity to obtain coatings with characteristics vastly different from those produced using conventional spray-grade powders. The most extensively investigated variant of this technique is Suspension Plasma Spraying (SPS), which utilizes a suspension of fine powders in an appropriate medium. The relatively recent advent of axial feed capable plasma spray systems can enable higher throughputs during SPS, provides the possibility for spraying with longer stand-off distances, and also permit the use of suspensions with higher solid loading. The present work investigates axial plasma sprayed coatings produced using a mixed suspension of fine (submicron or nano-sized) powders of Al2O3 and YSZ as a case study. Deposition of the mixed suspension using axial injection plasma spraying, comprehensive evaluation of characteristics of the resulting coatings, and assessment of their tribological behavior were of particular interest. Evaluation of surface morphology, microstructure, and hardness of the coatings reveals that axial SPS of mixed suspensions provides an exciting pathway to realize finely structured multi-constituent coatings using suspensions with as high as 40 wt.% solid loading. The study of scratch, dry sliding wear, and erosion behavior also specifically shows that the addition of YSZ in the Al2O3 matrix can improve the tribological properties of the coating.
Modeling and NVH Analysis of a Full Engine Dynamic Model with Valve Train System
Authors: Zheng Xu , Luo Xuan , Qiu Yi , Hao Zhiyong
Published: July 2020

The valve train system is an important source of vibration and noise in an engine. An in-depth study on the dynamic model of the valve train is helpful in understanding the dynamic characteristics of the valve train and improving the prediction accuracy of vibration and noise. In the traditional approaches of the dynamic analyses, the simulations of the valve train system and the engine are carried out separately. The disadvantages of these uncoupled approaches are that the impact of the cylinder head deformation to the valve train and the support and constraints of the valve train on the cylinder head are not taken into consideration. In this study, a full engine dynamic model coupled with a valve train system is established and a dynamic simulation and noise vibration harshness (NVH) analysis are carried out. In the coupled approach, the valve train system is simulated simultaneously with the engine, and the complexity of the model has been greatly increased. Compared with the uncoupled approach, more detailed dynamic results of the valve train can be presented, and the subsequent predictions of vibration and noise can also be more accurate. The acoustic results show that the difference from the experimental sound power level is reduced from 1.8 dB(A) to 0.9 dB(A) after applying the coupled approach.
Three-Phase Three-Level Neutral Point Clamped Rectifier with Predictive Control Method without Employing Weighting Factor
Authors: Jun Eun-Su , Nguyen Minh Hoang , Kwak Sangshin
Published: July 2020

A predictive control method using injected offset voltage to achieve neutral point (NP) voltage balance of three-phase three-level neutral point clamped (NP) rectifiers, without employing a weighting factor, is proposed in this study. One of the biggest problems with the three-level NP rectifiers is the dc link capacitor voltage imbalance. Therefore, it is necessary to maintain the balance of the NP voltage in addition to synthesize the three-phase sinusoidal input current by control methods. Conventional predictive control methods for the NP rectifiers have used a weighting factor in a cost function that determines the control ratio of the input currents and the capacitor voltage balance. As a result, it is burdensome to empirically redesign the weighting factor when the rectifiers’ parameter values and control conditions change. Unlike the conventional methods, the proposed approach without the weighting factor can significantly eliminate differences between two DC capacitor voltages by utilizing an offset voltage, which is generated by using the difference between the upper and lower capacitor voltages. Consequently, the proposed approach using the offset voltage injection can control the input currents and retain the balance of NP voltage. Simulation and experiments are presented to verify the correctness of the NP voltage balancing of the proposed control method.
Classification of Small- and Medium-Sized Enterprises Based on the Level of Industry 4.0 Implementation
Authors: Pech Martin , Vrchota Jaroslav
Published: July 2020

Due to Industry 4.0 technologies, small- and medium-sized enterprises have a great opportunity to increase their competitiveness. However, the question remains as to whether they are truly able to implement such modern technologies faster and carry out digital transformation. The main aim of the paper is to classify small- and medium-sized enterprises into various groups, according to the level of implementation of Industry 4.0, using the Index of Industry 4.0. Based on the results of the cluster analysis, the small and medium enterprises are categorized into four different groups, according to the level of implementation of Industry 4.0. There are top Industry 4.0 technological enterprises, I4 start enterprises, noobs enterprises, and I4 advances enterprises. So far, the largest group consists of the small- and medium-sized enterprises that are just starting out with the introduction of Industry 4.0 technologies, such as IT infrastructure, digitalization (data, cloud, data analysis, and information systems), and sensors. On the other hand, the top I4 technological enterprises group is the least numerous. The analysis carried out comparing the small- and medium-sized enterprises with the large enterprises shows that the SMEs still have a lower level of Industry 4.0 implementation. This confirms the assumption that the large enterprises have greater opportunities to use new technologies and transform them into smart factories. However, this situation may change in the future if new technologies become more accessible, and SMEs are worth investing in Industry 4.0 in terms of the return on investment.
Review of Functionally Graded Thermal Sprayed Coatings
Authors: Łatka Leszek , Pawłowski Lech , Winnicki Marcin , Sokołowski Pawel , Małachowska Aleksandra , Kozerski Stefan
Published: July 2020

The paper briefly describes major thermal spray techniques used to spray functionally graded coatings such as atmospheric plasma spraying, high velocity oxy-fuel spraying, suspension and solution precursor plasma spraying, and finally low and high pressure cold gas spray method. The examples of combined spray processes as well as some examples of post spray treatment including laser and high temperature treatments or mechanical one, are described. Then, the solid and liquid feedstocks used to spray and their properties are shortly discussed. The reviewed properties of functional coatings include: (i) mechanical (adhesion, toughness, hardness); (ii) physical (porosity, thermal conductivity and diffusivity, thermal expansion, photo-catalytic activity), and; (iii) bioactivity and simulated body fluid (SBF) corrosion. These properties are useful in present applications of functionally graded coatings as thermal barriers, the bioactive coatings in prostheses, photo-catalytic coatings in water treatment, coatings used in printing industry (anilox and corona rolls). Finally, some of the future possible fields of functional thermal sprayed coatings applications are discussed, e.g., to coat polymer substrates or to use the cheap technology of low pressure cold gas spray method instead of expensive technology of vacuum plasma spraying to obtain bond coatings.
Distributed Cell Clustering Based on Multi-Layer Message Passing for Downlink Joint Processing Coordinated Multipoint Transmission
Authors: Dewa Gilang Raka Rayuda , Park Cheolsoo , Sohn Illsoo
Published: July 2020

Joint processing coordinated multipoint transmission (JP-CoMP) has gained high attention as part of the effort to cope with the increasing levels of demand in the next-generation wireless communications systems. By clustering neighboring cells and with cooperative transmission within each cluster, JP-CoMP efficiently mitigates inter-cell interference and improves the overall system throughput. However, choosing the optimal clustering is formulated as a nonlinear mathematical problem, making it very challenging to find a practical solution. In this paper, we propose a distributed cell clustering algorithm that maximizes the overall throughput of the JP-CoMP scheme. The proposed algorithm renders the nonlinear mathematical problem of JP-CoMP clustering into an approximated linear formulation and introduces a multi-layer message-passing framework in order to find an efficient solution with a very low computational load. The main advantages of the proposed algorithm are that i) it enables distributed control among neighboring cells without the need for any central coordinators of the network; (ii) the computational load imposed on each cell is kept to a minimum; and, (iii) required message exchanges via backhaul result in only small levels of overhead on the network. The simulation results verify that the proposed algorithm finds an efficient JP-CoMP clustering that outperforms previous algorithms in terms of both the sum throughput and edge user throughput. Moreover, the convergence properties and the computational complexity of the proposed algorithm are compared with those of previous algorithms, confirming its usefulness in practical implementations.
Utilizing an Adaptive Neuro-Fuzzy Inference System (ANFIS) for Overcrowding Level Risk Assessment in Railway Stations
Authors: Alawad Hamad , An Min , Kaewunruen Sakdirat
Published: July 2020

The railway network plays a significant role (both economically and socially) in assisting the reduction of urban traffic congestion. It also accelerates the decarbonization in cities, societies and built environments. To ensure the safe and secure operation of stations and capture the real-time risk status, it is imperative to consider a dynamic and smart method for managing risk factors in stations. In this research, a framework to develop an intelligent system for managing risk is suggested. The adaptive neuro-fuzzy inference system (ANFIS) is proposed as a powerful, intelligently selected model to improve risk management and manage uncertainties in risk variables. The objective of this study is twofold. First, we review current methods applied to predict the risk level in the flow. Second, we develop smart risk assessment and management measures (or indicators) to improve our understanding of the safety of railway stations in real-time. Two parameters are selected as input for the risk level relating to overcrowding: the transfer efficiency and retention rate of the platform. This study is the world’s first to establish the hybrid artificial intelligence (AI) model, which has the potency to manage risk uncertainties and learns through artificial neural networks (ANNs) by integrated training processes. The prediction result shows very high accuracy in predicting the risk level performance, and proves the AI model capabilities to learn, to make predictions, and to capture risk level values in real time. Such risk information is extremely critical for decision making processes in managing safety and risks, especially when uncertain disruptions incur (e.g., COVID-19, disasters, etc.). The novel insights stemmed from this study will lead to more effective and efficient risk management for single and clustered railway station facilities towards safer, smarter, and more resilient transportation systems.
Optimal Spectral Combination of a Hyperspectral Camera for Intraoperative Hemodynamic and Metabolic Brain Mapping
Authors: Caredda Charly , Mahieu-Williame Laurent , Sablong Raphaël , Sdika Michaël , Guyotat Jacques , Montcel Bruno
Published: July 2020

Intraoperative optical imaging is a localization technique for the functional areas of the human brain cortex during neurosurgical procedures. These areas are assessed by monitoring the oxygenated (HbO2) and deoxygenated hemoglobin (Hb) concentration changes occurring in the brain. Sometimes, the functional status of the brain is assessed using metabolic biomarkers: the oxidative state of cytochrome-c-oxidase (oxCCO). A setup composed of a white light source and a hyperspectral or a standard RGB camera could be used to identify the functional areas. The choice of the best spectral configuration is still based on an empirical approach. We propose in this study a method to define the optimal spectral combinations of a commercial hyperspectral camera for the computation of hemodynamic and metabolic brain maps. The method is based on a Monte Carlo framework that simulates the acquisition of the intrinsic optical signal following a neuronal activation. The results indicate that the optimal spectral combination of a hyperspectral camera aims to accurately quantify the HbO2 (0.5% error), Hb (4.4% error), and oxCCO (15% error) responses in the brain following neuronal activation. We also show that RGB imaging is a low cost and accurate solution to compute Hb maps (4% error), but not accurate to compute HbO2 (48% error) or oxCCO (1036% error) maps.
Current Research Related to Wine Sensory Perception Since 2010
Authors: Yang Jiyun , Lee Jeehyun
Published: July 2020

Due to socioeconomic changes, the demand for and interest in alcoholic beverages have recently been increasing. Among various alcoholic drinks, consumer preference for wine could be varied. It might be related with its complexity, as wine is known to have characteristics that are difficult to understand. Several factors, such as intrinsic or extrinsic factors interact to influence wine complexity and consumer perception. Many studies have been conducted to understand the complexity of wine, allowing deeper insight into its perception by consumers. Studies over the last decade on wine sensory perception using descriptive analysis and consumer tests were reviewed. Additionally, chemical analysis studies were included because flavor constituents information would contribute to a better understanding of sensory perception. Descriptive sensory analysis of wine was reviewed considering panels and flavor characterization for better understanding wine-related research. Several consumer studies regarding liking/preference, emotion, context, and extrinsic factors to understand consumer preference or perception were reviewed. Research on chemical constituents may affect consumer perception and is thus presented in this review. However, most of the research was focused on a narrow range of wine, thus is missing overall wine category evaluations. Furthermore, evaluations were mainly in wine-producing countries, resulting in limited understanding of an emergent market. This review will help guide wine researchers and industry by providing information on factors influencing consumer wine perception.
Processing High-Solid and High-Ammonia Rich Manures in a Two-Stage (Liquid-Solid) Low-Temperature Anaerobic Digestion Process: Start-Up and Operating Strategies
Authors: Mahato Prativa , Goyette Bernard , Rahaman Md. Saifur , Rajagopal Rajinikanth
Published: July 2020

Globally, livestock and poultry production leads to total emissions of 7.1 Gigatonnes of CO2-equiv per year, representing 14.5% of all anthropogenic greenhouse gas emissions. Anaerobic digestion (AD) is one of the sustainable approaches to generate methane (CH4) from manure, but the risk of ammonia inhibition in high-solids AD can limit the process. Our objective was to develop a two-stage (liquid–solid) AD biotechnology, treating chicken (CM) + dairy cow (DM) manure mixtures at 20 °C using adapted liquid inoculum that could make livestock farming more sustainable. The effect of organic loading rates (OLR), cycle length, and the mode of operation (particularly liquid inoculum recirculation-percolation mode) was evaluated in a two-stage closed-loop system. After the inoculum adaptation phase, aforementioned two-stage batch-mode AD operation was conducted for the co-digestion of CM + DM (Total Solids (TS): 48–51% and Total Kjeldahl Nitrogen (TKN): 13.5 g/L) at an OLR of 3.7–4.7 gVS/L.d. Two cycles of different cycle lengths (112-d and 78-d for cycles 1 and 2, respectively) were operated with a CM:DM mix ratio of 1:1 (w/w) based on a fresh weight basis. Specific methane yield (SMY) of 0.35 ± 0.11 L CH4g/VSfed was obtained with a CH4 concentration of above 60% for both the cycles and Soluble Chemical Oxygen Demand (CODs) and volatile solid (VS) reductions up to 85% and 60%, respectively. For a comparison purpose, a similar batch-mode operation was conducted for mono-digestion of CM (TS: 65–73% and TKN: 21–23 g/L), which resulted in a SMY of 0.52 ± 0.13 L CH4g/VSfed. In terms of efficiency towards methane-rich biogas production and ammonia inhibitions, CM + DM co-digestion showed comparatively better quality methane and generated lower free ammonia than CM mono-digestion. Further study is underway to optimize the operating parameters for the co-digestion process and to overcome inhibitions and high energy demand, especially for cold countries.
Role of Antioxidants in Alleviating Bisphenol A Toxicity
Authors: Amjad Shehreen , Rahman Md Saidur , Pang Myung-Geol
Published: July 2020

Bisphenol A (BPA) is an oestrogenic endocrine disruptor widely used in the production of certain plastics, e.g., polycarbonate, hard and clear plastics, and epoxy resins that act as protective coating for food and beverage cans. Human exposure to this chemical is thought to be ubiquitous. BPA alters endocrine function, thereby causing many diseases in human and animals. In the last few decades, studies exploring the mechanism of BPA activity revealed a direct link between BPA-induced oxidative stress and disease pathogenesis. Antioxidants, reducing agents that prevent cellular oxidation reactions, can protect BPA toxicity. Although the important role of antioxidants in minimizing BPA stress has been demonstrated in many studies, a clear consensus on the associated mechanisms is needed, as well as the directives on their efficacy and safety. Herein, considering the distinct biochemical properties of BPA and antioxidants, we provide a framework for understanding how antioxidants alleviate BPA-associated stress. We summarize the current knowledge on the biological function of enzymatic and non-enzymatic antioxidants, and discuss their practical potential as BPA-detoxifying agents.
Does Periodontal Tactile Input Uniquely Increase Cerebral Blood Flow in the Prefrontal Cortex?
Authors: Goto Takaharu , Higaki Nobuaki , Kishimoto Takahiro , Tomotake Yoritoki , Ichikawa Tetsuo
Published: July 2020

We previously studied the effect of peripheral sensory information from sensory periodontal ligament receptors on prefrontal cortex (PFC) activity. In the dental field, an alternative dental implant without periodontal sensation can be applied for missing teeth. In this study, we examine whether periodontal tactile input could increase cerebral blood flow (CBF) in the PFC against elderly patients with dental implants lacking periodontal tactile (implant group), elderly individuals with natural teeth (elderly group), and young individuals with natural teeth (young group). The experimental task of maintaining occlusal force as closed-loop stimulation was performed. Compared with the young group, the elderly group showed significantly lower CBF. Contrastingly, compared with the young group, the implant group showed significantly lower CBF. There were no significant differences between the elderly and implant groups. Regarding the mean occlusal force value, compared with the young group and the elderly group, the implant group had a numerically, but not significantly, larger occlusal force exceeding the directed range. In conclusion, the periodontal tactile input does not uniquely increase PFC activity. However, increased CBF in the PFC due to the periodontal tactile input in the posterior region requires existing attention behavior function in the PFC.
Effects of Direct-Acting Antiviral Agents on the Mental Health of Patients with Chronic Hepatitis C: A Prospective Observational Study
Authors: Fabrazzo Michele , Zampino Rosa , Vitrone Martina , Sampogna Gaia , Del Gaudio Lucia , Nunziata Daniela , Agnese Salvatore , Santagata Anna , Durante-Mangoni Emanuele , Fiorillo Andrea
Published: July 2020

In chronic hepatitis C (CHC) patients, interferon-based treatments showed toxicity, limited efficacy, and psychiatric manifestations. Direct-acting antiviral (DAA) agents appeared safer, though it remains unclear if they may exacerbate or foster mood symptoms in drug-naïve CHC patients. We evaluated 62 CHC patients’ mental status, before and 12 weeks after DAA therapy, by assessment scales and psychometric instruments. We subdivided patients into two groups, CHC patients with (Group A) or without (Group B) a current and/or past psychiatric history. After DAA treatment, Group A patients showed low anxiety and improved depression, no variation in self-report distress, but worse general health perceptions. No significant difference emerged from coping strategies. Depression and anxiety improved in Group B, and no change emerged from total self-reported distress, except for somatization. Moreover, Group B increased problem-focused strategies for suppression of competing activities, and decreased strategies of instrumental social support. Contrarily, Group B reduced significantly emotion-focused strategies, such as acceptance and mental disengagement, and improved vitality, physical and social role functioning. DAA therapy is safe and free of hepatological and psychiatric side effects in CHC patients, regardless of current and/or past psychiatric history. In particular, patients without a psychiatric history also remarkably improved their quality of life.
Interplay between Cellular Metabolism and the DNA Damage Response in Cancer
Authors: Moretton Amandine , Loizou Joanna I.
Published: July 2020

Metabolism is a fundamental cellular process that can become harmful for cells by leading to DNA damage, for instance by an increase in oxidative stress or through the generation of toxic byproducts. To deal with such insults, cells have evolved sophisticated DNA damage response (DDR) pathways that allow for the maintenance of genome integrity. Recent years have seen remarkable progress in our understanding of the diverse DDR mechanisms, and, through such work, it has emerged that cellular metabolic regulation not only generates DNA damage but also impacts on DNA repair. Cancer cells show an alteration of the DDR coupled with modifications in cellular metabolism, further emphasizing links between these two fundamental processes. Taken together, these compelling findings indicate that metabolic enzymes and metabolites represent a key group of factors within the DDR. Here, we will compile the current knowledge on the dynamic interplay between metabolic factors and the DDR, with a specific focus on cancer. We will also discuss how recently developed high-throughput technologies allow for the identification of novel crosstalk between the DDR and metabolism, which is of crucial importance to better design efficient cancer treatments.
PARP Inhibitor Resistance Mechanisms and Implications for Post-Progression Combination Therapies
Authors: Lee Elizabeth K. , Matulonis Ursula A.
Published: July 2020

The use of PARP inhibitors (PARPi) is growing widely as FDA approvals have shifted its use from the recurrence setting to the frontline setting. In parallel, the population developing PARPi resistance is increasing. Here we review the role of PARP, DNA damage repair, and synthetic lethality. We discuss mechanisms of resistance to PARP inhibition and how this informs on novel combinations to re-sensitize cancer cells to PARPi.
The Impact of BRAF Mutation on the Recurrence of Papillary Thyroid Carcinoma: A Meta-Analysis
Authors: Li Xin , Kwon Hyungju
Published: July 2020

Previous meta-analyses indicated that the BRAF V600E mutation was associated with an increased recurrence rate of papillary thyroid carcinoma (PTC). However, with recent publications of large cohort studies, the need for an updated meta-analysis increases. Therefore, we conducted a comprehensive meta-analysis to assess the impact of the BRAF V600E mutation on PTC recurrences. We performed a literature search using PubMed, SCOPUS, the Cochrane Database of Systematic Reviews, and the Web of Science Core Collection, from their inception to May 31, 2020. The relevant studies compared recurrence rates using the hazard ratio (HR) of BRAF mutations; 11 studies comprising 4674 patients were identified and included. Recurrence rates in patients with the BRAF V600E mutation were comparable with BRAF wild-type patients (HR 1.16, 95% CI 0.78–1.71), after adjustment for possible confounders. In subgroup analysis, both geographical region (HRs for America, Asia, and Europe were 2.16, 1.31 and 0.66, respectively) and tumor stage (HRs for stage I and II were 1.51 and 4.45, respectively) can affect the HRs of the BRAF mutation for recurrence. In conclusion, the BRAF mutation does not increase the risk of recurrences in patients with PTC. Differences in the geographical region or tumor stage should be considered when interpreting the impact of a BRAF mutation on recurrence.
The Role of Pro-Resolving Lipid Mediators in Colorectal Cancer-Associated Inflammation: Implications for Therapeutic Strategies
Authors: Ungaro Federica , D’Alessio Silvia , Danese Silvio
Published: July 2020

Inflammation is a recognized hallmark of cancer that contributes to the development and progression of colorectal cancer (CRC). Anti-inflammatory drugs currently used for the treatment of CRC show many adverse side effects that prompted researchers to propose the polyunsaturated fatty acids-derived specialized pro-resolving mediators (SPMs) as promoters of resolution of cancer-associated inflammation. SPMs were found to inhibit the CRC-associated pro-inflammatory milieu via specific G-coupled protein receptors, although clinical data are still lacking. This review aims to summarize the state-of-the-art in this field, ultimately providing insights for the development of innovative anti-CRC therapies that promote the endogenous lipid-mediated resolution of CRC-associated inflammation.
Carcinoma-Associated Mesenchymal Stem Cells Promote Chemoresistance in Ovarian Cancer Stem Cells via PDGF Signaling
Authors: Raghavan Shreya , Snyder Catherine S. , Wang Anni , McLean Karen , Zamarin Dmitriy , Buckanovich Ronald J. , Mehta Geeta
Published: July 2020

Within the ovarian cancer tumor microenvironment, cancer stem-like cells (CSC) interact with carcinoma associated mesenchymal stem/stromal cells (CA-MSC) through multiple secreted cytokines and growth factors. These paracrine interactions have been revealed to cause enrichment of CSC and their chemoprotection; however, it is still not known if platelet-derived growth factor (PDGF) signaling is involved in facilitating these responses. In order to probe this undiscovered bidirectional communication, we created a model of ovarian malignant ascites in the three-dimensional (3D) hanging drop heterospheroid array, with CSC and CA-MSC. We hypothesized that PDGF secretion by CA-MSC increases self-renewal, migration, epithelial to mesenchymal transition (EMT) and chemoresistance in ovarian CSC. Our results indicate that PDGF signaling in the CSC-MSC heterospheroids significantly increased stemness, metastatic potential and chemoresistance of CSC. Knockdown of PDGFB in MSC resulted in abrogation of these phenotypes in the heterospheroids. Our studies also reveal a cross-talk between PDGF and Hedgehog signaling in ovarian cancer. Overall, our data suggest that when the stromal signaling via PDGF to ovarian CSC is blocked in addition to chemotherapy pressure, the tumor cells are significantly more sensitive to chemotherapy. Our results emphasize the importance of disrupting the signals from the microenvironment to the tumor cells, in order to improve response rates. These findings may lead to the development of combination therapies targeting stromal signaling (such as PDGF and Hedgehog) that can abrogate the tumorigenic, metastatic and platinum resistant phenotypes of ovarian CSC through additional investigations.
Bitter Melon (Momordica Charantia), a Nutraceutical Approach for Cancer Prevention and Therapy
Authors: Sur Subhayan , Ray Ratna B.
Published: July 2020

Cancer is the second leading cause of death worldwide. Many dietary plant products show promising anticancer effects. Bitter melon or bitter gourd (Momordica charantia) is a nutrient-rich medicinal plant cultivated in tropical and subtropical regions of many countries. Traditionally, bitter melon is used as a folk medicine and contains many bioactive components including triterpenoids, triterpene glycoside, phenolic acids, flavonoids, lectins, sterols and proteins that show potential anticancer activity without significant side effects. The preventive and therapeutic effects of crude extract or isolated components are studied in cell line-based models and animal models of multiple types of cancer. In the present review, we summarize recent progress in testing the cancer preventive and therapeutic activity of bitter melon with a focus on underlying molecular mechanisms. The crude extract and its components prevent many types of cancers by enhancing reactive oxygen species generation; inhibiting cancer cell cycle, cell signaling, cancer stem cells, glucose and lipid metabolism, invasion, metastasis, hypoxia, and angiogenesis; inducing apoptosis and autophagy cell death, and enhancing the immune defense. Thus, bitter melon may serve as a promising cancer preventive and therapeutic agent.
Distinct Molecular Landscape of Epstein–Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing
Authors: Chau Shuk-Ling , Tong Joanna Hung-Man , Chow Chit , Kwan Johnny Sheung-Him , Lung Raymond Wai-Ming , Chung Lau-Ying , Tin Edith Ka-Yee , Wong Shela Shu-Yan , Cheung Alvin Ho-Kwan , Lau Rainbow Wing-Hung , Ng Calvin Sze-Hang , Mok Tony Shu-Kam , Lo Kwok-Wai , To Ka-Fai
Published: July 2020

Pulmonary lymphoepithelioma-like carcinoma (LELC) is a subtype of non-small cell lung cancer (NSCLC) characterized by marked lymphocytic infiltration and association with Epstein–Barr virus (EBV). The molecular basis underlying the disease remains unclear. We sought to study the molecular landscape by multiple approaches including whole genomic sequencing, capture-based targeted sequencing, fluorescent in situ hybridization and immunohistochemistry. Tumor cells from 57 EBV-positive pulmonary LELCs were isolated by careful microdissection prior to genomic sequencing. Integrated analysis revealed a distinct genomic landscape of low TP53 mutation rate (11%), low incidence of known drivers in the RTK/RAS/RAF (11%) and PI3K/AKT/mTOR pathways (7%), but enriched for loss-of-function mutations in multiple negative regulators of the NF-κB pathway. High level programmed cell death ligand-1 (PD-L1) expression was shown with 47% and 79% of the cases showing positive PD-L1 immunoreactivity at ≥50% and ≥1% tumor proportion score, respectively. Subsets of the patients with actionable fibroblast growth factor receptor 3 (FGFR3) aberrations (4%) and mismatch repair deficiency (4%) were potentially eligible for precision medicine. Pulmonary LELC showed a distinct genomic landscape, different from major NSCLC subtypes but resembled that of EBV-associated nasopharyngeal carcinoma. Our work facilitated the understanding of molecular basis underlying pulmonary LELC to explore potential therapeutic options.
Erratum: Majewska, E. et al. Transfection with GLS2 Glutaminase (GAB) Sensitizes Human Glioblastoma Cell Lines to Oxidative Stress by a Common Mechanism Involving Suppression of the PI3K/AKT Pathway. Cancers 2019, 11, 115
Authors: Majewska Ewelina , Márquez Javier , Albrecht Jan , Szeliga Monika
Published: July 2020

The authors wish to make the following corrections to this paper [...]
The Interplay of Tumor Stroma and Translational Factors in Endometrial Cancer
Authors: Sobočan Monika , Smolle Maria Anna , Schatz Christoph , Haybaeck Johannes
Published: July 2020

Endometrial cancer (EC) is a common gynecologic malignancy which continues to have a poor prognosis in advanced stages due to current therapeutic limitations. A significant mechanism of chemoresistance in EC has been shown to also be the enhancement of epithelial to mesenchymal transition (EMT) and the subsequent obtainment of stem cell-like characteristics of EC. Current evidence on EMT in EC however fails to explain the relationship leading to an EMT signaling enhancement. Our review therefore focuses on understanding eukaryotic translation initiation factors (eIFs) as key regulators of the translational process in enhancing EMT and subsequently impacting higher chemoresistance of EC. We identified pathways connected to the development of a microenvironment for EMT, inducers of the process specifically related to estrogen receptors as well as their interplay with eIFs. In the future, investigation elucidating the translational biology of EC in EMT may therefore focus on the signaling between protein kinase RNA-like ER kinase (PERK) and eIF2alpha as well as eIF3B.
Gas6 Induces Myelination through Anti-Inflammatory IL-10 and TGF-β Upregulation in White Matter and Glia
Authors: Goudarzi Salman , Gilchrist Shannon E. , Hafizi Sassan
Published: July 2020

The Gas6–TAM (Tyro3, Axl, Mer) ligand–receptor system is believed to promote central nervous system (CNS) (re)myelination and glial cell development. An additional important function of Gas6–TAM signalling appears to be the regulation of immunity and inflammation, which remains to be fully elucidated in the CNS. Here, we characterised the expression of TAM receptors and ligands in individual CNS glial cell types, observing high expression of Gas6 and the TAM receptors, Mer and Axl, in microglia, and high expression of Tyro3 in astrocytes. We also investigated the effect of Gas6 on the inflammatory cytokine response in the optic nerve and in mixed glial cell cultures from wildtype and single TAM receptor knockout mice. In wildtype and Mer-deficient cultures, Gas6 significantly stimulated the expression of the anti-inflammatory/pro-repair cytokines interleukin 10 (IL-10) and transforming growth factor β (TGF-β), whereas this effect was absent in either Tyro3 or Axl knockout cultures. Furthermore, Gas6 caused upregulation of myelin basic protein (MBP) expression in optic nerves, which was blocked by a neutralising antibody against IL-10. In conclusion, our data show that microglia are both a major source of Gas6 as well as an effector of Gas6 action in the CNS through the upregulation of anti-inflammatory and pro-repair mediators. Furthermore, the presence of both Axl and Tyro3 receptors appears to be necessary for these effects of Gas6. In addition, IL-10, alongside suppressing inflammation and immunity, mediates the pro-myelinating mechanism of Gas6 action in the optic nerve. Therefore, Gas6 may present an attractive target for novel therapeutic interventions for demyelinating as well as neuroinflammatory disorders of the CNS.