bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating Academic and Community Practices in the Management of Colorectal Cancer: The City of Hope Model
Authors: Karimi Misagh , Wang Chongkai , Bahadini Bahareh , Hajjar George , Fakih Marwan
Published: June 2020

Colorectal cancer (CRC) management continues to evolve. In metastatic CRC, several clinical and molecular biomarkers are now recommended to guide treatment decisions. Primary tumor location (right versus left) has been shown to predict benefit from anti-epidermal growth factor receptors (EGFRs) in rat sarcoma viral oncogene homologue (RAS) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) wild-type patients. Anti-EGFR therapy has not resulted in any benefit in RAS-mutated tumors, irrespective of the primary tumor location. BRAF-V600E mutations have been associated with poor prognosis and treatment resistance but may benefit from a combination of anti-EGFR therapy and BRAF inhibitors. Human epidermal growth factor receptor 2 (HER-2) amplification was recently shown to predict relative resistance to anti-EGFR therapy but a response to dual HER-2 targeting within the RAS wild-type population. Finally, the mismatch repair (MMR)-deficient subgroup benefits significantly from immunotherapeutic strategies. In addition to the increasingly complex biomarker landscape in CRC, metastatic CRC remains one of the few malignancies that benefits from metastasectomies, ablative therapies, and regional hepatic treatments. This treatment complexity requires a multi-disciplinary approach to treatment and close collaborations between various stakeholders in large cancer center networks. Here, we describe the City of Hope experience and strategy to enhance colorectal cancer care across its network.
Sol-Gel Derived Tertiary Bioactive Glass–Ceramic Nanorods Prepared via Hydrothermal Process and Their Composites with Poly(Vinylpyrrolidone-Co-Vinylsilane)
Authors: Mondal Dibakar , Zaharia Andrei , Mequanint Kibret , Rizkalla Amin S.
Published: June 2020

Bioactive glass (BG) nanoparticles have wide applications in bone repair due to their bone-bonding and biodegradable nature. In this work, nanometric rod-shaped ternary SiO2-CaO-P2O5 bioactive glass particles were prepared through sol-gel chemistry followed by a base-induced hydrothermal process at 130 °C and 170 °C for various times up to 36 h. This facile, low-temperature and surfactant-free hydrothermal process has shown to be capable of producing uniform nanorods and nanowires. One-dimensional growth of nanorods and the characteristics of siloxane bridging networks were dependent on the hydrothermal temperature and time. Hardened bioactive composites were prepared from BG nanorods and cryo-milled poly(vinylpyrrolidone-co-triethoxyvinylsilane) in the presence of ammonium phosphate as potential bone graft biomaterials. Covalent crosslinking has been observed between the organic and inorganic components within these composites. The ultimate compressive strength and modulus values increased with increasing co-polymer content, reaching 27 MPa and 500 MPa respectively with 30% co-polymer incorporation. The materials degraded in a controlled non-linear manner when incubated in phosphate-buffered saline from 6 h to 14 days. Fibroblast cell attachment and spreading on the composite were not as good as the positive control surfaces and suggested that they may require protein coating in order to promote favorable cell interactions.
Déjà vu All Over Again: A Unitary Biological Mechanism for Intelligence Is (Probably) Untenable
Authors: Matzel Louis D. , Crawford Dylan W. , Sauce Bruno
Published: June 2020

Nearly a century ago, Spearman proposed that “specific factors can be regarded as the ‘nuts and bolts’ of cognitive performance…, while the general factor is the mental energy available to power the specific engines”. Geary (2018; 2019) takes Spearman’s analogy of “mental energy” quite literally and doubles-down on the notion by proposing that a unitary energy source, the mitochondria, explains variations in both cognitive function and health-related outcomes. This idea is reminiscent of many earlier attempts to describe a low-level biological determinant of general intelligence. While Geary does an admirable job developing an innovative theory with specific and testable predictions, this new theory suffers many of the shortcomings of previous attempts at similar goals. We argue that Geary’s theory is generally implausible, and does not map well onto known psychological and genetic properties of intelligence or its relationship to health and fitness. While Geary’s theory serves as an elegant model of “what could be”, it is less successful as a description of “what is”.
The Effects of Glyphosate and Its Commercial Formulations to Marine Invertebrates: A Review
Authors: Matozzo Valerio , Fabrello Jacopo , Marin Maria Gabriella
Published: June 2020

Glyphosate is the active ingredient of numerous commercial formulations of herbicides applied in different sectors, from agriculture to aquaculture. Due to its widespread use around the world, relatively high concentrations of glyphosate have been detected in soil and aquatic environments. The presence of glyphosate in aquatic ecosystems has aroused the attention of researchers because of its potential negative effects on living organisms, both animals and plants. In this context, this review intends to summarize results of studies aimed at evaluating the effects of glyphosate (both as active ingredient and component of commercial formulations) on marine invertebrates. Generally, data obtained in acute toxicity tests indicate that glyphosate and its commercial formulations are lethal at high concentrations (not environmentally realistic), whereas results of long-lasting experiments indicate that glyphosate can markedly affect biological responses of marine invertebrates. Consequently, more efforts should be addressed at evaluating chronic or sub-chronic effects of such substances to marine invertebrate species.
Editorial for the Special Issue on Commercial Banking
Authors: Gan Christopher
Published: June 2020

The existence of financial intermediaries is arguably an artifact of information asymmetry. Beyond simple financial transactions, financial intermediation provides a mechanism for information transmission, which can reduce the degree of information asymmetry and consequently increase market efficiency. During the process of information transmission, the bank is able to provide unique services in the production and exchange of information. Therefore, banks have comparative advantages in information production, transmission, and utilisation. In credit provision, it is possible for lenders to make Type I and Type II errors. These types of errors are associated with whether banks decide to lend money to borrowers with low repayment capacity or risk missing out on potentially profitable lending. However, the recent US subprime loan crisis and previous financial crises (such as the Mexican, Argentinian, Chilean and Asian financial crises) show it is possible that banks can make both good and bad lending decisions. Does this mean that banks have lost their comparative advantages in leveraging information asymmetry? This Special Issue includes contribution in empirical methods in banking such risk and bank performance, capital regulation, bank competition and foreign bank entry, bank regulation on bank performance, and capital adequacy and deposit insurance.
Implications of Customary Land Rights Inequalities for Food Security: A Study of Smallholder Farmers in Northwest Ghana
Authors: Nara Baslyd B. , Lengoiboni Monica , Zevenbergen Jaap
Published: June 2020

Inequalities in land rights exist globally, both in formal and customary settings. This is because land rights are either strong or weak, and held by various categories of people. The weaker variants of the inequalities tend to stifle tenure security, reduce land use, and threaten the food security of those dependent on the land for survival. This paper investigated the implications of customary land rights inequalities and varying tenure insecurity for food security among smallholder farmers in northwest Ghana. It identified the nature of rights inequalities, the number of rights and in whose possession. The research also assessed the kinds and nature of land rights as well as how such rights affect people’s farm sizes and subsequently farming output for ultimate food security. The data collection techniques were focus group discussions and interviews of key informants and key players in key organisations. Results revealed the existence of food insecurity among smallholder farmers (settlers/migrants) who have both fewer and weaker land rights as compared to landowners who possess numerous and stronger rights in the study area. Results also showed that weak and unequally skewed land rights lead to uncertain tenure durations and reduced farm sizes, which affects farmed area, farm output, food availability, accessibility and food security. Furthermore, farmers expressed the need to apply coping strategies to overcome the impact of unequal land rights. This research recommends further studies to design intervention strategies to better understand land rights inequalities and their implications. The outcome is expected to contribute to informing interventions to narrow these inequalities and reduce the implications that can later enhance food security.
Villari Effect at Low Strain in Magnetoactive Materials
Authors: Riesgo Graciela , Elbaile Laura , Carrizo Javier , Crespo Rosario Díaz , García María Ángeles , Torres Yadir , García José Ángel
Published: June 2020

Magnetic composites of soft magnetic FeGa particles embedded in a silicone matrix have been synthesized. The Villari effect has been studied depending on the size and concentration of the particles and on the magnetic state of the composite. The results indicate a decrease in the Villari effect when the concentration of the magnetic particles increases. These results suggest a relationship between the Villari effect and the mechanical properties of the composites. The Young’s modulus of the composites has been obtained by microindentation and their values related to the intensity and slope of the Villari signals. The results are explained on the basis that the reduction in the cross section of the composite when submitted to stress is the main origin of the variation of the magnetic flux in the Villari effect in this kind of composite. It has also been obtained that the magnetic state of the composite plays an important role in the Villari signal. When the magnetization of the composite is greater, the magnetic flux across the composite is greater too and, so, the same reduction in the cross section originates a greater Villari signal.
Upscale Design, Process Development, and Economic Analysis of Industrial Plants for Nanomagnetic Particle Production for Environmental and Biomedical Use
Authors: Augusto Paulo A. , Castelo-Grande Teresa , Vargas Diana , Pascual Alvaro , Hernández Lorenzo , Estevez Angel M. , Barbosa Domingos
Published: June 2020

Very few economical and process engineering studies have been made concerning the scale-up and implementation of nanomagnetic particle manufacturing into a full-scale plant, and determination of its viability. In this work we describe such a study for two types of industrial plants, one for manufacturing magnetic particles for applications in the environmental area, and the other for manufacturing nanomagnetic particles for applications in the biotechnology area; the two different applications are compared. The following methodology was followed: establish the manufacturing process for each application; determine the market demand of the product (magnetic nanoparticles) for both applications; determine the production capacity of each plant; engineer all the manufacturing process, determining all the process units and performing all the mass and energy balances for both plants; scale-up the main equipment; and determine the global economic impact and profitability. At the end both plants are found to be technologically and economically viable, the characteristics of the final products being, however, quite different, as well as the process engineering, economic analysis, and scale-up.
Dual Electrochemical Treatments to Improve Properties of Ti6Al4V Alloy
Authors: Rossi Stefano , Volgare Luciana , Perrin-Pellegrino Carine , Chassigneux Carine , Dousset Erick , Eyraud Marielle
Published: June 2020

Surface treatments are considered as a good alternative to increase biocompatibility and the lifetime of Ti-based alloys used for implants in the human body. The present research reports the comparison of bare and modified Ti6Al4V substrates on hydrophilicity and corrosion resistance properties in body fluid environment at 37 °C. Several surface treatments were conducted separately to obtain either a porous oxide layer using nanostructuration (N) in ethylene glycol containing fluoride solution, or bulk oxide thin films through heat treatment at 450 °C for 3 h (HT), or electrochemical oxidation at 1 V for 3 h (EO), as well as combined treatments (N-HT and N-EO). In-situ X-ray diffraction and ex-situ transmission electron microscopy have shown that heat treatment gave first rise to the formation of a 30 nm thick amorphous layer which crystallized in rutile around 620 °C. Electrochemical oxidations gave rise to a 10 nm thick amorphous film on the top of the surface (EO) or below the amorphous nanotube layer (N-EO). Dual treated samples presented similar results with a more stable behavior for N-EO. Finally, for both corrosion and hydrophilicity points of view, the new combined treatment to get a total amorphous N-EO sample seems to be the best and even better than the partially crystallized N-HT sample.
Evaluation of Cracking Patterns in Cement Composites—From Basics to Advances: A Review
Authors: Szeląg Maciej
Published: June 2020

The structure and the development degree of a cracking pattern has a key impact on the durability of cement composites. This literature review focuses on the four most important aspects related to the evaluation of the surface cracking patterns, i.e., the process of formation, propagation and evolution of cracks into a branched system of cracks from the point of view of the fracture mechanics; the detection techniques of the cracking patterns on the surface of cement composites, where the tools of computer image analysis are the most used; parameters which can quantify the development degree and morphology of the cracks system; and also the influence of a cracking pattern on the functional features of cement composites. The studies described so far indicate the necessity of continuous development of this research area, because the knowledge of key relationships between the cracking patterns and functional properties of a cement composite is necessary to estimate the degree of material degradation. Researchers agree that the works carried out in the field of evaluation of the cracking patterns, to a large extent, contributes to the development of non-destructive testing methods in the field of cement composites technology.
Reduction of Energy Input in Wire Arc Additive Manufacturing (WAAM) with Gas Metal Arc Welding (GMAW)
Authors: Henckell Philipp , Gierth Maximilian , Ali Yarop , Reimann Jan , Bergmann Jean Pierre
Published: June 2020

Wire arc additive manufacturing (WAAM) by gas metal arc welding (GMAW) is a suitable option for the production of large volume metal parts. The main challenge is the high and periodic heat input of the arc on the generated layers, which directly affects geometrical features of the layers such as height and width as well as metallurgical properties such as grain size, solidification or material hardness. Therefore, processing with reduced energy input is necessary. This can be implemented with short arc welding regimes and respectively energy reduced welding processes. A highly efficient strategy for further energy reduction is the adjustment of contact tube to work piece distance (CTWD) during the welding process. Based on the current controlled GMAW process an increase of CTWD leads to a reduction of the welding current due to increased resistivity in the extended electrode and constant voltage of the power source. This study shows the results of systematically adjusted CTWD during WAAM of low-alloyed steel. Thereby, an energy reduction of up to 40% could be implemented leading to an adaptation of geometrical and microstructural features of additively manufactured work pieces.
Deformation Behavior and Precipitation Features in a Stretched Al–Cu Alloy at Intermediate Temperatures
Authors: Lin Y.C. , Dong Wen-Yong , Zhu Xu-Hao , Wu Qiao , He Ying-Jie
Published: June 2020

Deformation behavior and precipitation features of an Al–Cu alloy are investigated using uniaxial tensile tests at intermediate temperatures. It is found that the true stress drops with the decreased strain rate or the increased deformation temperature. The number of substructures and the degree of grain elongation decrease with the raised temperature or the decreased strain rate. At high temperatures or low strain rates, some dynamic recrystallized grains can be found. The type of precipitates is influenced by the heating process before hot tensile deformation. The content and size of precipitates increase during tensile deformation at intermediate temperatures. As the temperature increases over 200 °C, the precipitation process (Guinier Preston zone (G.P. zones)→θ′′ phase→θ′ phase) is enhanced, resulting in increased contents of θ′′ and θ′ phases. However, θ′′ and θ′ phases prefer to precipitate along the {020}Al direction, resulting in an uneven distribution of phases. Considering the flow softening degree and the excessive heterogeneous precipitation of θ′′ and θ′ phases during hot deformation, the reasonable strain rate and temperature are about 0.0003 s−1 and 150 °C, respectively.
Mechanical Anisotropy and Surface Roughness in Additively Manufactured Parts Fabricated by Stereolithography (SLA) Using Statistical Analysis
Authors: Aravind Shanmugasundaram Sunil , Razmi Jafar , Mian Md Jamal , Ladani Leila
Published: June 2020

In this study, the degree of mechanical anisotropy was investigated through tensile testing of specimens built in different orientations and designed according to the ASTM D638 standard. The mechanical properties that were evaluated include Young’s modulus, ultimate tensile strength (UTS), and percentage elongation. Additionally, physical properties, such as mean surface roughness (Ra), density and dimension of the cross-sectional area, were also measured. These properties were then compared with the available standard data to see how SLA performs comparing to the traditional manufacturing methods. The obtained modulus of elasticity and UTS values of the printed samples were 2481 ± 50 MPa and 51.9 ± 1.3 MPa respectively, which were very similar to the standard data (2550 and 52 MPa, respectively) as provided by the material suppliers. The percentage elongation values (4.8% ± 0.4%) were a bit lower than the expected value of 6%. However, the surfaces of all the printed samples were quite smooth, with a surface roughness range of 2.28 ± 0.59 µm. A design of experiments was created to study the influence of the independent variables such as build orientation and angular orientation on the mechanical properties. Extensive statistical analysis, using the Taguchi method and analysis of variance (ANOVA), was performed to examine the effect of these independent variables on the mechanical properties. The SLA printed parts can be classified as isotropic since the build orientation and the angular orientation did not have a statistically significant impact on the mechanical properties. The effect of aging on the mechanical properties was also evaluated and it shows that the specimens that had been aged for a longer time resulted in superior mechanical properties. For example, the UTS increased from 24 to 54 MPa when the sample aligned parallel to the XY plane was aged from 1 week to 6 months, respectively. This significant increase implies that aging has a substantial effect on the mechanical properties of the parts fabricated by stereolithography. The resin used for this study, Visijet Sl Clear, produced very consistent mechanical properties in different directions.
Coumarin Derivatives as New Toxic Compounds to Selected K12, R1–R4 E. coli Strains
Authors: Kowalczyk Paweł , Madej Arleta , Paprocki Daniel , Szymczak Mateusz , Ostaszewski Ryszard
Published: June 2020

Coumarins are natural compounds that were detected in 80 species of plants. They have numerous applications including the medical, food, tobacco, perfumery, and spirit industries. They show anti-swelling and diastolic effects. However, excess consumption of coumarins may adversely affect our health, because they are easily absorbed from the intestines into the lymph and blood, causing cirrhosis of the liver. Peptidomimetics are molecules whose structure and function are similar to those of peptides. They are an important group of compounds with biological, microbiological, anti-inflammatory, and anti-cancer properties. Therefore, studies on new peptidomimetics, which load the effect of native peptides, whose half-life in the body is much longer due to structural modifications, are extremely important. A preliminary study of coumarin analogues and its derivatives as new potential antimicrobial drugs containing carboxylic acid or ester was performed to determine their basic structure related to their biological features against various types of Gram-stained bacteria by lipopolysaccharide (LPS). We hypothesized that the toxicity (antibacterial activity) of coumarin derivatives is dependent on the of LPS in bacteria and nature and position of the substituent which may be carboxylic acid, hydroxyl groups, or esters. In order to verify this hypothesis, we used K12 (smooth) and R1–R4 (rough) Escherichia coli strains which are characterized by differences in the type of LPS, especially in the O-antigen region, the outermost LPS layer. In our work, we synthesized 17 peptidomimetics containing a coumarin scaffold and checked their influence on K12 and R1–R4 E. coli strains possessing smooth and rough LPS. We also measured the damage of plasmid DNA caused by target compounds. The results of our studies clearly support the conclusion that coumarin peptidomimetics are antagonistic compounds to many of the currently used antibiotics. The high biological activity of the selected coumarin peptidomimetic was associated with identification of the so-called magic methyl groups, which substantially change the biochemical properties of target compounds. Investigating the effects of these compounds is particularly important in the era of increasingly common resistance in bacteria.
Influence of Fly Ash on Mechanical Properties and Hydration of Calcium Sulfoaluminate-Activated Supersulfated Cement
Authors: Sun Zhengning , Zhou Jian , Qi Qiulin , Li Hui , Zhang Na , Mu Ru
Published: June 2020

This paper aimed to report the effects of fly ash (FA) on the mechanical properties and hydration of calcium sulfoaluminate-activated supersulfated cement (CSA-SSC). The CSA-SSC comprises of 80% granulated blast furnace slag (GBFS), 15% anhydrite, and 5% high-belite calcium sulfoaluminate cement (HB-CSA) clinker. The hydration products of CSA-SSC with or without FA were investigated by X-ray diffraction and thermogravimetric analysis. The experimental results indicated that the addition of FA by 10% to 30% resulted in a decrease in the rate of heat evolution and total heat evolution of CSA-SSC. As the content of FA was increased in the CSA-SSC system, the compressive and flexural strengths of the CSA-SSC with FA after 1 day of hydration were decreased. After 7 days of hydration, the compressive and flexural strength of CSA-SSC mixed with 10 wt.% and 20 wt.% of FA rapidly increased and exceeded that of ordinary Portland cement (OPC), especially the flexural strength. Moreover, the compressive strength of CSA-SSC mixed with 30 wt.% of FA after 90 days of hydration was close to that of OPC, and flexural strength of CSA-SSC mixed with 30 wt.% of FA after 7 days of hydration was close to that of OPC. The hydration products of the CSA-SSC and CSA-SSC mixed with FA were mainly ettringite and calcium silicate hydrate (C-S-H).
Energy Transfer Study on Tb3+/Eu3+ Co-Activated Sol-Gel Glass-Ceramic Materials Containing MF3 (M = Y, La) Nanocrystals for NUV Optoelectronic Devices
Authors: Pawlik Natalia , Szpikowska-Sroka Barbara , Pisarski Wojciech A.
Published: June 2020

In the present work, the Tb3+/Eu3+ co-activated sol-gel glass-ceramic materials (GCs) containing MF3 (M = Y, La) nanocrystals were fabricated during controlled heat-treatment of silicate xerogels at 350 °C. The studies of Tb3+ → Eu3+ energy transfer process (ET) were performed by excitation and emission spectra along with luminescence decay analysis. The co-activated xerogels and GCs exhibit multicolor emission originated from 4fn–4fn optical transitions of Tb3+ (5D4 → 7FJ, J = 6–3) as well as Eu3+ ions (5D0 → 7FJ, J = 0–4). Based on recorded decay curves, it was found that there is a significant prolongation in luminescence lifetimes of the 5D4 (Tb3+) and the 5D0 (Eu3+) levels after the controlled heat-treatment of xerogels. Moreover, for both types of prepared GCs, an increase in ET efficiency was also observed (from ηET ≈ 16% for xerogels up to ηET = 37.3% for SiO2-YF3 GCs and ηET = 60.8% for SiO2-LaF3 GCs). The changes in photoluminescence behavior of rare-earth (RE3+) dopants clearly evidenced their partial segregation inside low-phonon energy fluoride environment. The obtained results suggest that prepared SiO2-MF3:Tb3+, Eu3+ GC materials could be considered for use as optical elements in RGB-lighting optoelectronic devices operating under near-ultraviolet (NUV) excitation.
Te Nanoneedles Induced Entanglement and Thermoelectric Improvement of SnSe
Authors: Ju Hyun , Kim Myeongjin , Yang Jinglei , Kim Jooheon
Published: June 2020

Chalcogenide-based materials have attracted widespread interest in high-performance thermoelectric research fields. A strategy for the application of two types of chalcogenide for improved thermoelectric performance is described herein. Tin selenide (SnSe) is used as a base material, and Te nanoneedles are crystallized in the SnSe, resulting in the generation of a composite structure of SnSe with Te nanoneedles. The thermoelectric properties with various reaction times are investigated to reveal the optimum conditions for enhanced thermoelectric performance. A reaction time of 4 h at 450 K generated a composite Te nanoneedles/SnSe sample with the maximum ZT value, 3.2 times larger than that of the pristine SnSe. This result is attributed to both the reduced thermal conductivity from the effective phonon scattering of heterointerfaces and the improved electrical conductivity value due to the introduction of Te nanoparticles. This strategy suggests an approach to generating high-performance practical thermoelectric materials.
The Mean Minkowski Content of Homogeneous Random Fractals
Authors: Zähle Martina
Published: June 2020

Homogeneous random fractals form a probabilistic generalisation of self-similar sets with more dependencies than in random recursive constructions. Under the Uniform Strong Open Set Condition we show that the mean D-dimensional (average) Minkowski content is positive and finite, where the mean Minkowski dimension D is, in general, greater than its almost sure variant. Moreover, an integral representation extending that from the special deterministic case is derived.
Rational Limit Cycles on Abel Polynomial Equations
Authors: Valls Claudia
Published: June 2020

In this paper we deal with Abel equations of the form d y / d x = A 1 ( x ) y + A 2 ( x ) y 2 + A 3 ( x ) y 3 , where A 1 ( x ) , A 2 ( x ) and A 3 ( x ) are real polynomials and A 3 ≢ 0 . We prove that these Abel equations can have at most two rational (non-polynomial) limit cycles when A 1 ≢ 0 and three rational (non-polynomial) limit cycles when A 1 ≡ 0 . Moreover, we show that these upper bounds are sharp. We show that the general Abel equations can always be reduced to this one.
Strong Convergence Theorems for Generalized Split Feasibility Problems in Banach Spaces
Authors: Zi Xuejiao , Ma Zhaoli , Du Wei-Shih
Published: June 2020

In this paper, we establish new strong convergence theorems of proposed algorithms under suitable new conditions for the generalized split feasibility problem in Banach spaces. As applications, new strong convergence theorems for equilibrium problems, fixed point problems and split common fixed point problems are also studied. Our new results are distinct from recent results on the topic in the literature.
About Some Possible Implementations of the Fractional Calculus
Authors: Velasco María Pilar , Usero David , Jiménez Salvador , Vázquez Luis , Vázquez-Poletti José Luis , Mortazavi Mina
Published: June 2020

We present a partial panoramic view of possible contexts and applications of the fractional calculus. In this context, we show some different applications of fractional calculus to different models in ordinary differential equation (ODE) and partial differential equation (PDE) formulations ranging from the basic equations of mechanics to diffusion and Dirac equations.
Lipid Annotation by Combination of UHPLC-HRMS (MS), Molecular Networking, and Retention Time Prediction: Application to a Lipidomic Study of In Vitro Models of Dry Eye Disease
Authors: Magny Romain , Regazzetti Anne , Kessal Karima , Genta-Jouve Gregory , Baudouin Christophe , Mélik-Parsadaniantz Stéphane , Brignole-Baudouin Françoise , Laprévote Olivier , Auzeil Nicolas
Published: June 2020

Annotation of lipids in untargeted lipidomic analysis remains challenging and a systematic approach needs to be developed to organize important datasets with the help of bioinformatic tools. For this purpose, we combined tandem mass spectrometry-based molecular networking with retention time (tR) prediction to annotate phospholipid and sphingolipid species. Sixty-five standard compounds were used to establish the fragmentation rules of each lipid class studied and to define the parameters governing their chromatographic behavior. Molecular networks (MNs) were generated through the GNPS platform using a lipid standards mixture and applied to lipidomic study of an in vitro model of dry eye disease, i.e., human corneal epithelial (HCE) cells exposed to hyperosmolarity (HO). These MNs led to the annotation of more than 150 unique phospholipid and sphingolipid species in the HCE cells. This annotation was reinforced by comparing theoretical to experimental tR values. This lipidomic study highlighted changes in 54 lipids following HO exposure of corneal cells, some of them being involved in inflammatory responses. The MN approach coupled to tR prediction thus appears as a suitable and robust tool for the discovery of lipids involved in relevant biological processes.
Insights into the Natural Defenses of a Coral Reef Fish Against Gill Ectoparasites: Integrated Metabolome and Microbiome Approach
Authors: Reverter Miriam , Sasal Pierre , Suzuki Marcelino T. , Raviglione Delphine , Inguimbert Nicolas , Pare Alan , Banaigs Bernard , Voisin Sébastien N. , Bulet Philippe , Tapissier-Bontemps Nathalie
Published: June 2020

Understanding natural defense mechanisms against parasites can be a valuable tool for the development of innovative therapies. We have previously identified a butterflyfish species (Chaetodon lunulatus) that avoids gill monogenean parasites while living amongst closely related parasitized species. The metabolome and microbiome of several sympatric butterflyfish species from the island of Moorea (French Polynesia) were previously described. In this study, we used the previously generated datasets in an attempt to identify metabolites and bacteria potentially involved in parasite defense mechanisms. We investigated the interplay between the gill mucus metabolome and microbiome of the non-susceptible C. lunulatus versus sympatric butterflyfish species that were always found parasitized in the Central and Eastern Indo-Pacific. After observing significant differences between the metabolome and bacteria of susceptible versus non-susceptible fish, we obtained the discriminant metabolites and operational taxonomic units (OTUs) using a supervised analysis. Some of the most important discriminant metabolites were identified as peptides, and three new peptides derived from β-subunit hemoglobin from C. lunulatus (CLHbβ-1, CLHbβ-2, and CLHbβ-3) were purified, characterized and synthesized to confirm their structures. We also identified specific bacterial families and OTUs typical from low-oxygen habitats in C. lunulatus gill mucus. By using a correlation network between the two datasets, we found a Fusobacteriaceae strain exclusively present in C. lunulatus and highly correlated to the peptides. Finally, we discuss the possible involvement of these peptides and Fusobacteriaceae in monogenean avoidance by this fish species.
An Intertwined Network of Regulation Controls Membrane Permeability Including Drug Influx and Efflux in Enterobacteriaceae
Authors: Ferrand Aurélie , Vergalli Julia , Pagès Jean-Marie , Davin-Regli Anne
Published: June 2020

The transport of small molecules across membranes is a pivotal step for controlling the drug concentration into the bacterial cell and it efficiently contributes to the antibiotic susceptibility in Enterobacteriaceae. Two types of membrane transports, passive and active, usually represented by porins and efflux pumps, are involved in this process. Importantly, the expression of these transporters and channels are modulated by an armamentarium of tangled regulatory systems. Among them, Helix-turn-Helix (HTH) family regulators (including the AraC/XylS family) and the two-component systems (TCS) play a key role in bacterial adaptation to environmental stresses and can manage a decrease of porin expression associated with an increase of efflux transporters expression. In the present review, we highlight some recent genetic and functional studies that have substantially contributed to our better understanding of the sophisticated mechanisms controlling the transport of small solutes (antibiotics) across the membrane of Enterobacteriaceae. This information is discussed, taking into account the worrying context of clinical antibiotic resistance and fitness of bacterial pathogens. The localization and relevance of mutations identified in the respective regulation cascades in clinical resistant strains are discussed. The possible way to bypass the membrane/transport barriers is described in the perspective of developing new therapeutic targets to combat bacterial resistance.
Novel Rifampicin and Indocyanine Green Co-Loaded Perfluorocarbon Nanodroplets Provide Effective In Vivo Photo–Chemo–Probiotic Antimicrobility against Pathogen of Acne Vulgaris Cutibacterium acnes
Authors: Hsiao Kuang-Hung , Huang Chun-Ming , Lee Yu-Hsiang
Published: June 2020

Acne vulgaris is one of the most prevalent dermatological diseases among adolescents and is often associated with overgrowth of Cutibacterium acnes (C. acnes) in the pilosebaceous units. In this study, we aimed to develop novel rifampicin (RIF) and indocyanine green (ICG) co-loaded perfluorocarbon nanodroplets named RIPNDs which can simultaneously provide photo-, chemo-, and probiotic-antimicrobility, and explore their efficacy in treatment of C. acnes in vitro and in vivo. The RIPNDs were first characterized as being spherical in shape, with a size of 238.6 ± 7.51 nm and surface charge of −22.3 ± 3.5 mV. Then, the optimal dosages of Staphylococcus epidermidis–produced fermentation product medium (FPM) and RIPND were determined as 25% (v/v) and [RIF]/[ICG] = 3.8/20 μM, respectively, based on the analyses of inhibition zone and cytotoxicity in vitro. Through the in vivo study using C. acnes–inoculated mice, our data showed that the group treated with FPM followed by RIPNDs + near infrared (NIR) irradiation obtained the least granulocytes/macrophage-inflammatory protein 2 expression level in the epidermis, and showed a significantly lower microbial colony population compared to the groups treated with equal amount of RIF, FPM, RIPNDs, and/or combination of the above ± NIR. These results indicated that the RIPND-mediated photo–chemo–probiotic therapeutics was indeed able to rapidly suppress inflammatory response of the skin and provide a robust antibacterial effect against C. acnes with limited use of antibiotics. Taken altogether, we anticipate that the RIPND is highly potential for use in the clinical treatment of acne vulgaris.
Laser Induced Anchoring of Nickel Oxide Nanoparticles on Polymeric Graphitic Carbon Nitride Sheets Using Pulsed Laser Ablation for Efficient Water Splitting under Visible Light
Authors: Baig Umair , Khan Abuzar , Gondal Mohammad A. , Dastageer Mohamed A. , Falath Wail S.
Published: June 2020

A visible-light-active nickel oxide–graphitic carbon nitride (NiO@g-CN) hetero-structured nanocomposite was synthesized for the first time by pulsed laser ablation in liquid and used as a photoanode material in photoelectrochemical water-splitting reaction with a solar simulator. It was found that the photoelectrochemical performance of PLAL synthesized NiO@g-CN nanocomposite as photoanode, compared to g-CN as photoanode showed fourfold enhancements in photocurrent density under visible light. FT-IR, XRD, FE-SEM, and EDX consistently showed the proper anchoring of nano-sized NiO on g-CN. UV-DRS and the band gap estimation showed the narrowing down of the band gap energy and consequent enhancement in the visible-light absorption, whereas photoluminescence spectroscopy confirmed the reduction of the recombination of photo-excited electron hole pairs as a result of the anchoring of NiO on g-CN. The photoelectrochemical performance of g-CN and the NiO@g-CN nanocomposite photoanodes was compared by linear sweep voltammetry (LSV), Chronoamperometry (I-t), and Electrochemical Impedance Spectroscopy (EIS). All of these results of the characterization studies account for the observed fourfold enhancement of photocurrent density of NiO@g-CN nanocomposite as photoanode in the photoelectrochemical reaction.
The Characterization of Ground Raspberry Seeds and the Physiological Response to Supplementation in Hypertensive and Normotensive Rats
Authors: Majewski Michał , Kucharczyk Ewa , Kaliszan Roman , Markuszewski Michał , Fotschki Bartosz , Juśkiewicz Jerzy , Borkowska-Sztachańska Małgorzata , Ognik Katarzyna
Published: June 2020

This study aimed to evaluate the protective role of ground raspberry seeds (RBS) as a source of polyphenols and essential fatty acids on blood plasma enzymatic antioxidant status, lipid profile, and endothelium-intact vasodilation during physiological and pathological conditions. Young normotensive Wistar–Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) at ten weeks of age were fed with either a control diet or were supplemented with added 7% RBS for six weeks (n = 6). The main component of RBS was dietary fiber (64%) and the main polyphenols were ellagitannins (1.2%) and flavan-3-ols (0.45%). Irrespective of the rat model, ground RBS decreased liver enzyme aspartate aminotransferase (0.9-fold) and hydrogen peroxide scavenging capacity (Catalase, 0.9-fold). In supplemented SHRs, preincubation with inducible nitric oxide synthase (iNOS) inhibitor 1400W, nonselective cyclooxygenase (COX) inhibitor indomethacin, selective COX-2 inhibitor NS-398, prostacyclin (PGI2) synthesis inhibitor tranylcypromine (TCP), thromboxane receptor (TP) antagonist SQ-29548, thromboxane synthesis inhibitor furegrelate, and 20-HETE synthesis inhibitor HET0016 induced the same relaxant response to acetylcholine as in the nonsupplemented control group. In supplemented WKYs, atherogenic index was decreased (0.8-fold), while iNOS and COX-2-derived PGI2 increased acetylcholine-induced vasodilation. These effects of ground RBS may constitute a potential mechanism for preventing cardiovascular diseases.
Nutritional Status and Bone Microarchitecture in a Cohort of Systemic Sclerosis Patients
Authors: Paolino Sabrina , Pacini Greta , Schenone Carlotta , Patanè Massimo , Sulli Alberto , Sukkar Samir Giuseppe , Lercara Adriano , Pizzorni Carmen , Gotelli Emanuele , Cattelan Francesco , Goegan Federica , Smith Vanessa , Cutolo Maurizio
Published: June 2020

Systemic sclerosis (SSc) is a connective tissue disease characterized by initial microvascular damage, immune system activation and progressive fibrosis with insufficiency of internal organs. Gastrointestinal (GI) involvement is characterized by atrophy of the smooth muscle and small bowel hypomotility, mainly resulting from an autonomic nerve dysfunction. These modifications significantly affect gut transit and nutrient absorption, thus leading to malnutrition deficit induced by malabsorption. Nutritional deficit induced by malabsorption might also lead to bone alterations. This study aims to evaluate the relationship between malnutrition and bone status. Thirty-six postmenopausal female patients fulfilling the ACR 2013 criteria for SSc underwent dual-energy X-ray absorptiometry scan (DXA) to detect quantitative lumbar spine bone mineral density (BMD) and trabecular bone score (TBS) analysis to detect bone quality. Data from DXA also allow to assess body composition and provide several quantitative parameters, including free fat mass index (FFMI) that identifies the patient with malnutrition (values <15 kg/m2 in women and 17 kg/m2 in men), according to the ESPEN criteria. Body mass index (BMI) was calculated for all SSc patients and every patient completed a diary reporting GI symptoms. Two groups of SSc patients with or without diagnosed malnutrition according to FFMI parameter were identified. Malnourished SSc patients showed significantly lower weight (p = 0.01) and BMI (p = 0.001), as well as lower serum levels of hemoglobin (p = 0.009), albumin (p = 0.002), PTH (p = 0.02) and 25OH-vitamin D (p = 0.008). DXA analysis showed significantly lower lumbar L1-L4 T-score (p = 0.009) and BMD values (p = 0.029) in malnourished SSc patients. Consistently, TBS values were significantly lower in malnourished patients (p = 0.008) and correlated with BMD (at any site) and serum albumin levels (p = 0.02). In addition, FFMI positively correlated with bone parameters as well as with symptoms of intestinal impairment in malnourished SSc patients. Finally, GI symptoms significantly correlated with BMD but not with TBS. This pilot study shows that in malnourished SSc patients (2015 ESPEN criteria: FFMI<15 kg/m2), an altered bone status significantly correlates with GI involvement, in terms of symptoms being mainly due to intestinal involvement together with the presence of selected serum biomarkers of malnutrition.
Energy Balance of Canadian Armed Forces Personnel during an Arctic-Like Field Training Exercise
Authors: Ahmed Mavra , Mandic Iva , Desilets Elliot , Smith Ingrid , Sullivan-Kwantes Wendy , Jones Peter J. , Goodman Len , Jacobs Ira , L’Abbé Mary
Published: June 2020

Operating in temperature extremes frequently leads to a discrepancy in energy balance. Investigating the effects of operating in extreme cold temperatures on metabolic requirements has not been well described in Canadian Armed Forces (CAF) personnel. The objective was to accurately assess energy deficits using the “gold standard” methodology for measuring energy intake (EI) and energy expenditure (EE). Nutritional intake of a convenience sample of 10 CAF Class A Reservists, completing a basic military qualification (land) course under winter weather conditions, was assessed using the daily measured food intake/food waste collections. EE was measured by the doubly-labelled water method. Average EI was 2377 ± 1144 kcal/day, which was below the EE (4917 ± 693 kcal/day), despite having ~5685 kcal available in the field rations. A significant body weight loss of 2.7% was associated with the average daily energy deficit of 2539 ± 1396 kcal. As a result, participants demonstrated voluntary anorexia. Such results may have important implications for the impairment of performance and health under longer duration operations.
Development and Evaluation of Matrices Composed of β-cyclodextrin and Biodegradable Polyesters in the Controlled Delivery of Pindolol
Authors: Lis-Cieplak Agnieszka , Charuk Filip , Sobczak Marcin , Zgadzaj Anna , Drobniewska Agata , Szeleszczuk Łukasz , Oledzka Ewa
Published: June 2020

Polymer-drug conjugates are currently being more widely investigated for the treatment of hypertension. In view of the above, in the first stage of our work, we used nontoxic β-cyclodextrin (β-CD) as effective, simple, inexpensive, and safe for the human body initiator for the synthesis of biocompatible and biodegradable functionalized polymers suitable for the medical and pharmaceutical applications. The obtained polymeric products were synthesized through a ring-opening polymerization (ROP) of ε-caprolactone (CL), d,l-, and l,l-lactide (LA and LLA). The chemical structures of synthesized materials were elucidated based on 1H NMR and solid-state carbon-13 cross-polarization/magic angle spinning nuclear magnetic resonance (13C CP/MAS NMR) analysis, while the incorporation of β-CD molecule into the polymer chain was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Furthermore, molecular modeling has been applied to investigate the intrachain rigidities and chain architectures for several representative structures. The obtained and thoroughly characterized branched matrices were then used to generate the first β-cyclodextrin/biodegradable polymer/β-blocker conjugate through the successful conjugation of pindolol. The conjugates were fabricated by carbodiimide-mediated coupling reaction. The branched biodegradable materials released the drug in vitro in a sustained manner and without “burst release” and thus have the ability to treat different heart diseases.
Mucoadhesive Electrospun Fibre-Based Technologies for Oral Medicine
Authors: Edmans Jake , Clitherow Katharina , Murdoch Craig , Hatton Paul , Spain Sebastian , Colley Helen
Published: June 2020

Oral disease greatly affects quality of life, as the mouth is required for a wide range of activities including speech, food and liquid consumption. Treatment of oral disease is greatly limited by the dose forms that are currently available, which suffer from short contact times, poor site specificity, and sensitivity to mechanical stimulation. Mucoadhesive devices prepared using electrospinning offer the potential to address these challenges by allowing unidirectional site-specific drug delivery through intimate contact with the mucosa and with high surface areas to facilitate drug release. This review will discuss the range of electrospun mucoadhesive devices that have recently been reported to address oral inflammatory diseases, pain relief, and infections, as well as new treatments that are likely to be enabled by this technology in the future.