bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Checkpoint Inhibitors as Monotherapy or Within a Combinatorial Strategy in Advanced Hepatocellular Carcinoma
Authors: Guardascione Michela , Toffoli Giuseppe
Published: August 2020

In advanced-stage hepatocellular carcinoma (HCC), systemic treatment represents the standard therapy. Target therapy has marked a new era based on a greater knowledge of molecular disease signaling. Nonetheless, survival outcomes and long-term response remain unsatisfactory, mostly because of the onset of primary or acquired resistance. More recently, results from clinical trials with immune targeting agents, such as the immune checkpoint inhibitors (ICIs), have shown a promising role for these drugs in the treatment of advanced HCC. In the context of an intrinsic tolerogenic liver environment, since HCC-induced immune tolerance, it is supported by multiple immunosuppressive mechanisms and several clinical trials are now underway to evaluate ICI-based combinations, including their associations with antiangiogenic agents or multikinase kinase inhibitors and multiple ICIs combinations. In this review, we will first discuss the basic principles of hepatic immunogenic tolerance and the evasive mechanism of antitumor immunity in HCC; furthermore we will elucidate the consistent biological rationale for immunotherapy in HCC even in the presence of an intrinsic tolerogenic environment. Subsequently, we will critically report and discuss current literature on ICIs in the treatment of advanced HCC, including a focus on the currently explored combinatorial strategies and their rationales. Finally, we will consider both challenges and future directions in this field.
Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases
Authors: Arrazola Sastre Alazne , Luque Montoro Miriam , Gálvez-Martín Patricia , Lacerda Hadriano M , Lucia Alejandro , Llavero Francisco , Zugaza José Luis
Published: August 2020

Small guanosine triphosphatases (GTPases) of the Ras superfamily are key regulators of many key cellular events such as proliferation, differentiation, cell cycle regulation, migration, or apoptosis. To control these biological responses, GTPases activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and in some small GTPases also guanine nucleotide dissociation inhibitors (GDIs). Moreover, small GTPases transduce signals by their downstream effector molecules. Many studies demonstrate that small GTPases of the Ras family are involved in neurodegeneration processes. Here, in this review, we focus on the signaling pathways controlled by these small protein superfamilies that culminate in neurodegenerative pathologies, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Specifically, we concentrate on the two most studied families of the Ras superfamily: the Ras and Rho families. We summarize the latest findings of small GTPases of the Ras and Rho families in neurodegeneration in order to highlight these small proteins as potential therapeutic targets capable of slowing down different neurodegenerative diseases.
Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting
Authors: Fiani Maria Luisa , Barreca Valeria , Sargiacomo Massimo , Ferrantelli Flavia , Manfredi Francesco , Federico Maurizio
Published: August 2020

Immunosuppression at tumor microenvironment (TME) is one of the major obstacles to be overcome for an effective therapeutic intervention against solid tumors. Tumor-associated macrophages (TAMs) comprise a sub-population that plays multiple pro-tumoral roles in tumor development including general immunosuppression, which can be identified in terms of high expression of mannose receptor (MR or CD206). Immunosuppressive TAMs, like other macrophage sub-populations, display functional plasticity that allows them to be re-programmed to inflammatory macrophages. In order to mitigate immunosuppression at the TME, several efforts are ongoing to effectively re-educate pro-tumoral TAMs. Extracellular vesicles (EVs), released by both normal and tumor cells types, are emerging as key mediators of the cell to cell communication and have been shown to have a role in the modulation of immune responses in the TME. Recent studies demonstrated the enrichment of high mannose glycans on the surface of small EVs (sEVs), a subtype of EVs of endosomal origin of 30–150 nm in diameter. This characteristic renders sEVs an ideal tool for the delivery of therapeutic molecules into MR/CD206-expressing TAMs. In this review, we report the most recent literature data highlighting the critical role of TAMs in tumor development, as well as the experimental evidences that has emerged from the biochemical characterization of sEV membranes. In addition, we propose an original way to target immunosuppressive TAMs at the TME by endogenously engineered sEVs for a new therapeutic approach against solid tumors.
The Development of Hyaluronan/Fucoidan-Based Nanoparticles as Macrophages Targeting an Epigallocatechin-3-Gallate Delivery System
Authors: Ho Chang-Hsun , Chu Pei-Yi , Peng Shin-Lei , Huang Shun-Chih , Lin Yu-Hsin
Published: August 2020

The aim of this study was to develop a macrophage-targeted nanoparticle composed of hyaluronan/fucoidan complexes with polyethylene glycol-gelatin to encapsulate and deliver epigallocatechin-3-gallate (EGCG), a compound that can regulate macrophage activation and pro-inflammatory mediator production. We show that our nanoparticles can successfully bond to macrophages and deliver more EGCG than an EGCG solution treatment, confirming the anti-inflammatory effects of these nanoparticles in lipopolysaccharide-stimulated macrophages. The prepared nanoparticles were established with a small mean particle size (217.00 ± 14.00 nm), an acceptable polydispersity index (0.28 ± 0.07), an acceptable zeta potential value (−33.60 ± 1.30 mV), and a high EGCG loading efficiency (52.08% ± 5.37%). The targeting abilities of CD44 binding were increased as the hyaluronan concentration increased and decreased by adding a competitor CD44 antibody. Moreover, we found that fucoidan treatment significantly reduced macrophage migration after lipopolysaccharide treatment in a dose-responsive manner. In summary, we successfully created macrophage-targeted nanoparticles for effective targeted delivery of EGCG, which should aid in the development of future anti-inflammatory drugs against macrophage-related diseases.
Targeted Therapies in Early Stage NSCLC: Hype or Hope?
Authors: Friedlaender Alex , Addeo Alfredo , Russo Alessandro , Gregorc Vanesa , Cortinovis Diego , Rolfo Christian
Published: August 2020

Non-small-cell lung cancer (NSCLC) represents roughly 85% of lung cancers, with an incidence that increases yearly across the world. The introduction in clinical practice of several new and more effective molecules has led to a consistent improvement in survival and quality of life in locally advanced and metastatic NSCLC. In particular, oncogenic drivers have indeed transformed the therapeutic algorithm for NSCLC. Nearly 25% of patients are diagnosed in an early stage when NSCLC is still amenable to radical surgery. In spite of this, five-year survival rates for fully resected early stage remains rather disappointing. Adjuvant chemotherapy has shown a modest survival benefit depending on the stage, but more than half of patients relapse. Given this need for improvement, over the last years different targeted therapies have been evaluated in early-stage NSCLC with no survival benefit in unselected patients. However, the identification of reliable predictive biomarkers to these agents in the metastatic setting, the design of molecularly-oriented studies, and the availability of novel potent and less toxic agents opened the way for a novel era in early stage NSCLC treatment. In this review, we will discuss the current landscape of targeted therapeutic options in early NSCLC.
Risk Assessment Framework for Outbound Supply-Chain Management
Authors: Krystofik Mark , Valant Christopher J. , Archbold Jeremy , Bruessow Preston , Nenadic Nenad G.
Published: August 2020

We developed a framework for the risk assessment of delaying the delivery of shipments to customers in the presence of incomplete information pertaining to a significant, e.g., weather-related, event that could cause substantial disruption. The approach was anchored in existing manual practices, but equipped with a mechanism for collecting critical data and incorporating it into decision-making, paving the path to gradual automation. Two key variables that affect the risk were: the likelihood of an event and the importance of the specific shipment. User-specified event likelihood, with elliptical spatial component, allowed the model to attach different probabilistic interpretations; uniform and Gaussian probability distributions were discussed, including possible paths for extensions. The framework development included a practical implementation in the Python scientific ecosystem. Although the framework was demonstrated in a prototype environment, the results clearly showed that the framework was quickly able to show scheduled and in-process shipments that were at risk of delay, while also providing a prioritized ranking of these shipments in order for personnel within the manufacturing organization to quickly implement mitigation actions and proactive communications with customers to ensure critical shipments were delivered when needed. Since the framework pulled in data from various business information systems, the framework proved to assist personnel to quickly identify potentially impacted shipments much faster than existing methods, which resulted in improved efficiency and customer satisfaction.
Measurement of Text Similarity: A Survey
Authors: Wang Jiapeng , Dong Yihong
Published: August 2020

Text similarity measurement is the basis of natural language processing tasks, which play an important role in information retrieval, automatic question answering, machine translation, dialogue systems, and document matching. This paper systematically combs the research status of similarity measurement, analyzes the advantages and disadvantages of current methods, develops a more comprehensive classification description system of text similarity measurement algorithms, and summarizes the future development direction. With the aim of providing reference for related research and application, the text similarity measurement method is described by two aspects: text distance and text representation. The text distance can be divided into length distance, distribution distance, and semantic distance; text representation is divided into string-based, corpus-based, single-semantic text, multi-semantic text, and graph-structure-based representation. Finally, the development of text similarity is also summarized in the discussion section.
A Nonlinear Analysis Interpretation of Off-Axis Test Results in Metal Matrix Composites
Authors: Ahmad Jalees , Santhosh Unni , Chandu Swamy
Published: August 2020

A unit-cell based micromechanics approach is used to perform nonlinear finite element analyses of off-axis tensile tests on an SCS-6/Ti-6Al-4V composite. The results are used in predicting the global deformation response of the composite that includes the effect of fiber-matrix interface damage. The predictions are compared with laboratory test data of uniaxial off-axis specimens. Based on the comparison, it is found that the procedure effectively predicts global composite response with reasonable accuracy under a general multiaxial stress state.
Learning-Based Prediction of Pose-Dependent Dynamics
Authors: Finkeldey Felix , Wirtz Andreas , Merhofe Torben , Wiederkehr Petra
Published: August 2020

The constantly increasing demand for both, higher production output and more complex product geometries, which can only be achieved using five-axis milling processes, requires elaborated analysis approaches to optimize the regarded process. This is especially necessary when the used tool is susceptible to vibrations, which can deteriorate the quality of the machined workpiece surface. The prediction of tool vibrations based on the used NC path and process configuration can be achieved by, e.g., applying geometric physically-based process simulation systems prior to the machining process. However, recent research showed that the dynamic behavior of the system, consisting of the machine tool, the spindle, and the milling tool, can change significantly when using different inclination angles to realize certain machined workpiece shapes. Intermediate dynamic properties have to be interpolated based on measurements due to the impracticality of measuring the frequency response functions for each position and inclination angle that are used along the NC path. This paper presents a learning-based approach to predict the frequency response function for a given pose of the tool center point.
Progress in Operational Modeling in Support of Oil Spill Response
Authors: Barker Christopher H. , Kourafalou Vassiliki H. , Beegle-Krause CJ , Boufadel Michel , Bourassa Mark A. , Buschang Steve G. , Androulidakis Yannis , Chassignet Eric P. , Dagestad Knut-Frode , Danmeier Donald G. , Dissanayake Anusha L. , Galt Jerry A. , Jacobs Gregg , Marcotte Guillaume , Özgökmen Tamay , Pinardi Nadia , Schiller Rafael V. , Socolofsky Scott A. , Thrift-Viveros Dalina , Zelenke Brian , Zhang Aijun , Zheng Yangxing
Published: August 2020

Following the 2010 Deepwater Horizon accident of a massive blow-out in the Gulf of Mexico, scientists from government, industry, and academia collaborated to advance oil spill modeling and share best practices in model algorithms, parameterizations, and application protocols. This synergy was greatly enhanced by research funded under the Gulf of Mexico Research Initiative (GoMRI), a 10-year enterprise that allowed unprecedented collection of observations and data products, novel experiments, and international collaborations that focused on the Gulf of Mexico, but resulted in the generation of scientific findings and tools of broader value. Operational oil spill modeling greatly benefited from research during the GoMRI decade. This paper provides a comprehensive synthesis of the related scientific advances, remaining challenges, and future outlook. Two main modeling components are discussed: Ocean circulation and oil spill models, to provide details on all attributes that contribute to the success and limitations of the integrated oil spill forecasts. These forecasts are discussed in tandem with uncertainty factors and methods to mitigate them. The paper focuses on operational aspects of oil spill modeling and forecasting, including examples of international operational center practices, observational needs, communication protocols, and promising new methodologies.
The UK Government’s Covid-19 Response and Article 2 of the ECHR (Title I Dignity; Right to Life, Charter of Fundamental Rights of the EU)
Authors: Baros Miroslav
Published: August 2020

The purpose of this article is to assess the impact of the UK government’s response to the Covid-19 outbreak from a human rights perspective, particularly its apparent tension with Article 2 of the European Convention on Human Rights (ECHR) in relation to non-Covid-19 patients whose lives were put at risk by not being able to attend appointments and treatments for pre-existing conditions and illnesses. The UK has also rejected the application of the Charter of Fundamental Rights of the European Union with the European Union Withdrawal Act 2018, which will leave the population even more exposed to potential human rights violations. This seems to be a direct consequence of the narrative and slogan employed by the government: “Stay Home; Protect the NHS; Save Lives”. Other potentially threatened categories, the NHS staff and prisoners are also mentioned in the same context. The latter have already launched a judicial review application along the same lines: Article 2 of the ECHR and the due regard duty stemming from the Equality Act 2010. The NHS staff were directly at risk, and evidence was emerging almost on a daily basis that implied authorities’ responsibility for the shortage of personal protective equipment and testing kits. While there have been a number of discussions on other issues in relation to the lockdown and the strategy directly or indirectly impacting human rights, it appears that no discussion on the impact of the strategy for non-Covid-19 patients and other categories from a human rights perspective has taken place. This gap in analyses and literature merits the present analysis.
Nanostructure and Fracture Behavior of Carbon Nanofiber-Reinforced Cement Using Nanoscale Depth-Sensing Methods
Authors: Akono Ange-Therese
Published: August 2020

In recent years, carbon nanofibers have been investigated as a suitable reinforcement for cementitious composites to yield novel multifunctional materials with improved mechanical, electrical, magnetic, and self-sensing behavior. Despite several studies, the interactions between carbon nanofibers and Portland cement hydration products are not fully understood, with significant implications for the mechanical response and the durability at the macroscopic lengthscale. Thus, the research objective is to investigate the influence of carbon nanofibers on the nanostructure and on the distribution of hydration products within Portland cement paste. Portland cement w/c = 0.44 specimens reinforced with 0.0 wt%, 0.1 wt%, and 0.5 wt% CNF by mass fraction of cement are cast using a novel synthesis procedure. A uniform dispersion of carbon nanofibers (CNF) via a multi-step approach: after pre-dispersing carbon nanofibers using ultrasonic energy, the carbon nanofibers are further dispersed using un-hydrated cement particles in high shear mixing and mechanical stirring steps. High-resolution scanning electron microscopy analysis shows that carbon nanofibers fill nanopores and connect calcium–silicate hydrates (C–S–H) grains. Grid nano-indentation testing shows that Carbon nanofibers influence the probability distribution function of the local packing density by inducing a shift towards higher values, η = 0.76–0.93. Statistical deconvolution analysis shows that carbon nanofibers result in an increase in the fraction of high-density C–S–H by 6.7% from plain cement to cement + 0.1 wt% CNF and by 10.7% from plain cement to cement + 0.5 wt% CNF. Moreover, CNF lead to an increase in the C–S–H gel porosity and a decrease in both the capillary porosity and the total porosity. Based on scratch testing, adding 0.1 wt% CNF yields a 4.5% increase in fracture toughness and adding 0.5 wt% CNF yields a 7.6% increase in fracture toughness. Finally, micromechanical modelling predicts an increase of respectively 5.97% and 21.78% in the average Young’s modulus following CNF modification at 0.1 wt% CNF and 0.5 wt% CNF levels.
Metal Ions Supported Porous Coatings by Using AC Plasma Electrolytic Oxidation Processing
Authors: Rokosz Krzysztof , Hryniewicz Tadeusz , Raaen Steinar , Gaiaschi Sofia , Chapon Patrick , Matýsek Dalibor , Pietrzak Kornel , Szymańska Monika , Dudek Łukasz
Published: August 2020

Coatings enriched with zinc and copper as well as calcium or magnesium, fabricated on titanium substrate by Plasma Electrolytic Oxidation (PEO) under AC conditions (two cathodic voltages, i.e., −35 or −135 V, and anodic voltage of +400 V), were investigated. In all experiments, the electrolytes were based on concentrated orthophosphoric acid (85 wt%) and zinc, copper, calcium and/or magnesium nitrates. It was found that the introduced calcium and magnesium were in the ranges 5.0–5.4 at% and 5.6–6.5 at%, respectively, while the zinc and copper amounts were in the range of 0.3–0.6 at%. Additionally, it was noted that the metals of the block S (Ca and Mg) could be incorporated into the structure about 13 times more than metals of the transition group (Zn and Cu). The incorporated metals (from the electrolyte) into the top-layer of PEO phosphate coatings were on their first (Cu+) or second (Cu2+, Ca2+ and Mg2+) oxidation states. The crystalline phases (TiO and Ti3O) were detected only in coatings fabricated at cathodic voltage of −135 V. It has also been pointed that fabricated porous calcium–phosphate coatings enriched with biocompatible magnesium as well as with antibacterial zinc and copper are dedicated mainly to medical applications. However, their use for other applications (e.g., catalysis and photocatalysis) after additional functionalizations is not excluded.
Stimuli-Responsive Rifampicin-Based Macromolecules
Authors: Zaborniak Izabela , Macior Angelika , Chmielarz Paweł
Published: August 2020

This paper presents the modification of the antibiotic rifampicin by an anionic polyelectrolyte using a simplified electrochemically mediated atom transfer radical polymerization (seATRP) technique to receive stimuli-responsive polymer materials. Initially, a supramolecular ATRP initiator was prepared by an esterification reaction of rifampicin hydroxyl groups with α-bromoisobutyryl bromide (BriBBr). The structure of the initiator was successfully proved by nuclear magnetic resonance (1H and 13C NMR), Fourier-transform infrared (FT-IR) and ultraviolet–visible (UV-vis) spectroscopy. The prepared rifampicin-based macroinitiator was electrochemically investigated among various ATRP catalytic complexes, by a series of cyclic voltammetry (CV) measurements, determining the rate constants of electrochemical catalytic (EC’) process. Macromolecules with rifampicin core and hydrophobic poly (n-butyl acrylate) (PnBA) and poly(tert-butyl acrylate) (PtBA) side chains were synthesized in a controlled manner, receiving polymers with narrow molecular weight distribution (Mw/Mn = 1.29 and 1.58, respectively). “Smart” polymer materials sensitive to pH changes were provided by transformation of tBA into acrylic acid (AA) moieties in a facile route by acidic hydrolysis. The pH-dependent behavior of prepared macromolecules was investigated by dynamic light scattering (DLS) determining a hydrodynamic radius of polymers upon pH changes, followed by a control release of quercetin as a model active substance upon pH changes.
Optimizing Secondary Electrospray Ionization High-Resolution Mass Spectrometry (SESI-HRMS) for the Analysis of Volatile Fatty Acids from Gut Microbiome
Authors: Lee Jisun H. J. , Zhu Jiangjiang
Published: August 2020

Gut microbiota plays essential roles in maintaining gut homeostasis. The composition of gut microbes and their metabolites are altered in response to diet and remedial agents such as antibiotics. However, little is known about the effect of antibiotics on the gut microbiota and their volatile metabolites. In this study, we evaluated the impact of a moderate level of ampicillin treatment on volatile fatty acids (VFAs) of gut microbial cultures using an optimized real-time secondary electrospray ionization coupled with high-resolution mass spectrometry (SESI-HRMS). To evaluate the ionization efficiency, different types of electrospray solvents and concentrations of formic acid as an additive (0.01, 0.05, and 0.1%, v/v) were tested using VFAs standard mixture (C2–C7). As a result, the maximum SESI-HRMS signals of all studied m/z values were observed from water with 0.01% formic acid than those from the aqueous methanolic solutions. Optimal temperatures of sample inlet and ion chamber were set at 130 °C and 85 °C, respectively. SESI spray pressure at 0.5 bar generated the maximum intensity than other tested values. The optimized SESI-HRMS was then used for the analysis of VFAs in gut microbial cultures. We detected that the significantly elevated C4 and C7 VFAs in the headspace of gut microbial cultures six hours after ampicillin treatment (1 mg/L). In conclusion, our results suggested that the optimized SESI-HRMS method can be suitable for the analysis of VFAs from gut microbes in a rapid, sensitive, and non-invasive manner.
Comparative Lipidomics of Different Yeast Species Associated to Drosophila suzukii
Authors: Bianchi Flavia , Spitaler Urban , Robatscher Peter , Vogel Rudi F. , Schmidt Silvia , Eisenstecken Daniela
Published: August 2020

Yeasts constitute a dietary source for the spotted wing drosophila (SWD) and produce compounds that attract these flies. The study of the chemical composition of the yeast communities associated with SWD should therefore help to understand the relationship between the biology of the insect and the yeast’s metabolism. In the present study, the lipidome of five yeast species isolated from grapes infested by SWD (three Hanseniaspora uvarum strains, Candida sp., Issatchenkia terricola, Metschnikowia pulcherrima and Saccharomycopsis vini) and a laboratory strain of Saccharomyces cerevisiae was explored using an untargeted approach. Additionally, the lipid profile of two species, S. cerevisiae and H. uvarum, which were reported to elicit different responses on SWD flies based on feeding and behavioral trials, was compared with a chemical enrichment approach. Overall, 171 lipids were annotated. The yeast species could be distinguished from each other based on their lipid profile, except for the three strains of H. uvarum, which were very similar to each other. The chemical enrichment analysis emphasized diversities between S. cerevisiae and H. uvarum, that could not be detected based on their global lipid profile. The information concerning differences between species in their lipidome may be of interest to future entomological studies concerning the yeast-insect interaction and could help to explain the responses of SWD to diverse yeast species.
A Novel Ultra-Broadband Polarization Filter Based on a Microstructured Optical Fiber with a Gold-Coated Air Hole
Authors: Wang Chao , Zhang Yajing , Wu Zheng , Wang Qian , Zhang Guoxu , Zhang Yiyang , Jiang Linghong
Published: August 2020

In this paper, a pentagonal microstructured optical fiber polarization filter by utilizing a surface plasmon resonance effect is proposed. The characteristics of the mode-coupling and filtering of the filter are studied by making use of the full-vector finite element method. The performance of the filter is greatly affected by the structure parameters. The losses of Y and X polarization of the fiber core are 665.97 and 0.17 dB/cm at 1.55 μm, respectively, and the loss ratio is 3917.47. This shows that the filter has a greater loss ratio. Moreover, both the extinction ratio and tolerance are also researched, which shows that the proposed filter has a wider filtering bandwidth and better fabrication tolerance. The designed filter has an important role in wavelength-division multiplexing (WDM) and coherent optical fiber communication systems.
Dissecting Transcription Factor-Target Interaction in Bovine Coronavirus Infection
Authors: Morenikeji Olanrewaju B. , Strutton Ellis , Wallace Madeleine , Bernard Kahleel , Yip Elaine , Thomas Bolaji N.
Published: August 2020

Coronaviruses are RNA viruses that cause significant disease within many species, including cattle. Bovine coronavirus (BCoV) infects cattle and wild ruminants, both as a respiratory and enteric pathogen, and possesses a significant economic threat to the cattle industry. Transcription factors are proteins that activate or inhibit transcription through DNA binding and have become new targets for disease therapies. This study utilized in silico tools to identify potential transcription factors that can serve as biomarkers for regulation of BCoV pathogenesis in cattle, both for testing and treatment. A total of 11 genes were identified as significantly expressed during BCoV infection through literature searches and functional analyses. Eleven transcription factors were predicted to target those genes (AREB6, YY1, LMO2, C-Rel, NKX2-5, E47, RORAlpha1, HLF, E4BP4, ARNT, CREB). Function, network, and phylogenetic analyses established the significance of many transcription factors within the immune response. This study establishes new information on the transcription factors and genes related to host-pathogen interactome in BCoV infection, particularly transcription factors YY1, AREB6, LMO2, and NKX2, which appear to have strong potential as diagnostic markers, and YY1 as a potential target for drug therapies.
Trichoderma harzianum Inoculation Reduces the Incidence of Clubroot Disease in Chinese Cabbage by Regulating the Rhizosphere Microbial Community
Authors: Li Junhui , Philp Joshua , Li Jishun , Wei Yanli , Li Hongmei , Yang Kai , Ryder Maarten , Toh Ruey , Zhou Yi , Denton Matthew D. , Hu Jindong , Wang Yan
Published: August 2020

Clubroot is a disease of cruciferous crops that causes significant economic losses to vegetable production worldwide. We applied high-throughput amplicon sequencing technology to quantify the effect of Trichodermaharzianum LTR-2 inoculation on the rhizosphere community of Chinese cabbage (Brassica rapa subsp. pekinensis cv. Jiaozhou) in a commercial production area. T. harzianum inoculation of cabbage reduced the incidence of clubroot disease by 45.4% (p < 0.05). The disease control efficacy (PDIDS) was 63%. This reduction in disease incidence and severity coincided with a drastic reduction in both the relative abundance of Plasmodiaphora brassicae, the causative pathogen of cabbage clubroot disease, and its copy number in rhizosphere soil. Pathogenic fungi Alternaria and Fusarium were also negatively associated with Trichoderma inoculation according to co-occurrence network analysis. Inoculation drastically reduced the relative abundance of the dominant bacterial genera Delftia and Pseudomonas, whilst increasing others including Bacillus. Our results demonstrate that T. harzianum LTR-2 is an effective biological control agent for cabbage clubroot, which acts through modulation of the soil and rhizosphere microbial community.
Synergistic Effects of Ginkgolide B and Protocatechuic Acid on the Treatment of Parkinson’s Disease
Authors: Wu Tingting , Fang Xianying , Xu Jiahui , Jiang Yan , Cao Fuliang , Zhao Linguo
Published: August 2020

Ginkgo biloba extract (EGB) has many pharmacological activities. In the quality standard of EGB, the main quality control indexes are total flavone (content ≥ 24%) and total lactone (content ≥ 6%). There are no specific limits for nearly 70% of “other components”. In recent years, in order to pursue the production of a high-ketone ester, some enterprises removed the unwanted components, including some organic acids. Protocatechuic acid (PCA), as an important organic acid, has been reported to have a variety of biological activities. It is necessary to explore whether it can promote the biological activities of the main functional components of EGB. In this study, PCA was selected to be combined with Ginkgolide B (GB) for the treatment of Parkinson’s disease. In vitro, rotenone (rot) was used to induce PC12 cells. The survival rate was tested by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dimethyltetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) and antioxidase were detected to analyze the effects of drugs on oxidative stress. The apoptosis was tested via Western blot. The results show that the cell viability was increased, morphology was improved, the oxidative stress level decreased, and the apoptosis was inhibited after the combination treatment of GB and PCA, and the effect was better than GB or PCA alone. In vivo, MPTP (30 mg/kg) was used to induce Parkinson’s disease (PD) in male C57BL/6 mice. The motor ability of the mice was measured by pole-climbing and the suspension. The injury of nerve cells was indicated by HE staining. Oxidative stress levels were tested via antioxidant enzyme activity. The number of dopaminergic neurons was reflected by TH staining. Results show that the combination treatment of GB and PCA could significantly restore the motor ability of PD mice, reduce the injury of nerve cells, improve the activity of the antioxidant enzyme in the brain tissue, and increase the expression of TH in the substantia nigra of midbrain. Our study shows that PCA increases the efficacy of GB (the main functional ingredient of EGB) in the treatment of Parkinson’s disease, which provides a new idea for the treatment of nervous system diseases and a new concept for the efficient utilization of active components in Ginkgo biloba leaves.
Characterization of Competitive ELISA and Formulated Alhydrogel Competitive ELISA (FAcE) for Direct Quantification of Active Ingredients in GMMA-Based Vaccines
Authors: Rossi Omar , Aruta Maria Grazia , Acquaviva Alessandra , Mancini Francesca , Micoli Francesca , Necchi Francesca
Published: August 2020

Generalized modules for membrane antigens (GMMA) represent a technology particularly attractive for designing affordable vaccines against Gram-negative bacteria. We explored such technology for the development of O-antigen-based vaccines against Shigella and nontyphoidal Salmonella. Adsorption of GMMA on Alhydrogel was required for abrogation of pyrogenicity in rabbits, and Shigella sonnei GMMA on Alhydrogel was well tolerated and immunogenic in humans. Quantification of key antigens in formulated vaccines was fundamental for release and to check stability overtime. Traditionally, the direct quantification of antigens adsorbed on aluminum salts has been challenging, and the quantification of each active ingredient in multicomponent formulated vaccines has been even more complicated. To directly quantify each active ingredient and unbound drug substances in formulated vaccines, we developed the Formulated Alhydrogel competitive ELISA (FAcE) and the competitive ELISA method, respectively. The methods were both fully characterized, assessing specificity, repeatability, intermediate precision, and accuracy, for S. sonnei OAg quantification, both in a single component or multicomponent GMMA formulation also containing S. flexneri GMMA. The developed immunological methods allowed us to fully characterize Shigella GMMA drug products, supporting their preclinical and clinical development. The same methods, already extended to GMMA from nontyphoidal Salmonella and Neisseria meningitidis, could be potentially extended to any antigen formulated on Alhydrogel.
Mid-Air Gesture Control of Multiple Home Devices in Spatial Augmented Reality Prototype
Authors: Vogiatzidakis Panagiotis , Koutsabasis Panayiotis
Published: August 2020

Touchless, mid-air gesture-based interactions with remote devices have been investigated as alternative or complementary to interactions based on remote controls and smartphones. Related studies focus on user elicitation of a gesture vocabulary for one or a few home devices and explore recommendations of respective gesture vocabularies without validating them by empirical testing with interactive prototypes. We have developed an interactive prototype based on spatial Augmented Reality (AR) of seven home devices. Each device responds to touchless gestures (identified from a previous elicitation study) via the MS Kinect sensor. Nineteen users participated in a two-phase test (with and without help provided by a virtual assistant) according to a scenario that required from each user to apply 41 gestural commands (19 unique). We report on main usability indicators: task success, task time, errors (false negative/positives), memorability, perceived usability, and user experience. The main conclusion is that mid-air interaction with multiple home devices is feasible, fairly easy to learn and apply, and enjoyable. The contributions of this paper are (a) validation of a previously elicited gesture set; (b) development of a spatial AR prototype for testing of mid-air gestures, and (c) extensive assessment of gestures and evidence in favor of mid-air interaction in smart environments.
Association of Weight Loss from Early to Middle Adulthood and Incident Hypertension Risk Later in Life
Authors: Zhou Yunping , Wang Tao , Yin Xin , Sun Yun , Seow Wei Jie
Published: August 2020

Background: The effect of obesity in early adulthood and weight loss on incident hypertension in older age has not been well characterized. This study aimed to examine the association of weight loss from young adulthood to midlife with risk of incident hypertension later in life. Methods: We performed a retrospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES). Five weight change groups were categorized: stable normal, weight loss, weight gain, maximum overweight and stable obese. The hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between weight change and risk of hypertension in later life were estimated using Cox regression models. Results: Compared with participants who maintained normal weight, the stable obese, weight gain, maximum overweight and weight loss groups exhibited significantly higher risks of incident hypertension, with HR of 3.28 (95% CI = 2.71 to 3.96), 2.93 (95% CI = 2.62 to 3.28), 1.76 (95% CI = 1.55 to 2.00) and 1.97 (95% CI = 1.17 to 3.31), respectively. We also observed a lower risk among those in the weight loss group (HR = 0.60, 95% CI = 0.35 to 1.02) compared with those who were stable obese. Conclusions: Weight loss from early to middle adulthood was associated with lower risk of incident hypertension as compared to those who stayed obese and higher risk of incident hypertension as compared to those who maintained normal weight. Thus, maintaining normal weight throughout adulthood may be important for the primary prevention of hypertension.
A Nursery-Based Cooking Skills Programme with Parents and Children Reduced Food Fussiness and Increased Willingness to Try Vegetables: A Quasi-Experimental Study
Authors: Garcia Ada L. , Brown Emma , Goodale Tom , McLachlan Mairi , Parrett Alison
Published: August 2020

Children’s fussy eating is associated with a reduced vegetable intake. This quasi-experimental study evaluated “Big Chef Little Chef” (BCLC), a nursery-based cooking skills programme aimed at reducing food fussiness and increasing willingness to try green vegetables by incorporating repeated exposure and sensory learning. Parent and child (3–5 years) dyads attended BCLC for four/1.5 h weekly sessions. A comparison group was recruited after BCLC completion and attended a single education session at week 1. A questionnaire measured food fussiness at week 1 and week 4. At week 4, all children were offered six green vegetables (raw and cooked) and an average score (1 = did not try; 2 = tried it/ate some; 3 = ate it all) was calculated for willingness to try vegetables. In total, 121 dyads (intervention: n = 64; comparison: n = 57) participated. The food fussiness score (1 min–5 max) in the intervention group decreased significantly from 3.0 to 2.6 (p < 0.01) between time points, while there was no change in the comparison group (3.1 (week 1) and 3.0 (week 4)). The intervention group was more willing to try green vegetables with significantly higher (p < 0.001) median scores for raw and cooked vegetables (2.5 for both) compared with the comparison group (2.0 and 1.7, respectively). The BCLC reduced food fussiness and increased willingness to try green vegetables.
Oxidative Stress in Chronic Liver Disease and Portal Hypertension: Potential of DHA as Nutraceutical
Authors: Boyer-Diaz Zoe , Morata Paloma , Aristu-Zabalza Peio , Gibert-Ramos Albert , Bosch Jaime , Gracia-Sancho Jordi
Published: August 2020

Chronic liver disease constitutes a growing public health issue worldwide, with no safe and effective enough treatment clinical scenarios. The present review provides an overview of the current knowledge regarding advanced chronic liver disease (ACLD), focusing on the major contributors of its pathophysiology: inflammation, oxidative stress, fibrosis and portal hypertension. We present the benefits of supplementation with docosahexaenoic acid triglycerides (TG-DHA) in other health areas as demonstrated experimentally, and explore its potential as a novel nutraceutical approach for the treatment of ACLD and portal hypertension based on published pre-clinical data.
Nettle Tea Inhibits Growth of Acute Myeloid Leukemia Cells In Vitro by Promoting Apoptosis
Authors: Hodroj Mohammad Hassan , Al Bast Nour al Hoda , Taleb Robin I. , Borjac Jamilah , Rizk Sandra
Published: August 2020

Urtica dioica (UD), commonly known as “stinging nettle”, is a herbaceous flowering plant that is a widely used agent in traditional medicine worldwide. Several formulations of UD leaf extract have been reported to exhibit anti-inflammatory and antioxidant properties, with anticancer potential. The current study investigated the possible anticancer properties of nettle tea, prepared from Urtica dioica leaves, on acute myeloid leukemia (AML) cell lines, and deciphered the underlying molecular mechanisms. Treatment of AML cell lines (U-937 and KG-1) with UD aqueous leaf extract resulted in a dose- and time-dependent inhibition of proliferation, an increase in apoptotic hallmarks such as phosphatidylserine flipping to the outer membrane leaflet, and DNA fragmentation as revealed by cell-death ELISA and cell-cycle analysis assays. Apoptosis induction in U937 cells involves alterations in the expression of Bax and Bcl-2 upon exposure to nettle tea. Furthermore, the chemical composition of UD aqueous extract indicated the presence of multiple chemical agents, such as flavonoids and phenolics, mainly patuletin, m/p-hydroxybenzoic acid, and caffeic acid, among others, to which the pro-apoptotic and anti-tumor effects may be attributed.
Nicardipine Loaded Solid Phospholipid Extrudates for the Prevention of Cerebral Vasospasms: In Vitro Characterization
Authors: Zlomke Christin , Albrecht Johannes , Mäder Karsten
Published: August 2020

The aim of the study was to develop nicardipine loaded phospholipid extrudates as an alternative for PLA/PLGA-based implants for the prevention of cerebral vasospasms. Extrudates of different mixtures of saturated and unsaturated phosphatidylcholine (PC) were produced and characterized by DSC, microscopy and texture analysis. Single phospholipid components were identified by ELSD-HPLC. Extrudates of 2 mm diameter were obtained by twin screw extrusion temperatures below 50 °C. The ratio of unsaturated and saturated phosphatidylcholine components determines the physicochemical properties of the extrudates as well as the rate of erosion. Nicardipine loaded phospholipids extrudates released the drug over several weeks in vitro. The phospholipid composition of the remaining extrudate changed during the release, the content of unsaturated phospholipids decreased faster compared to the saturated ones. In conclusion, solid phospholipid extrudates are promising materials for the development of new parenteral controlled release systems.
Long-Lasting, Patient-Controlled, Procedure-Free Contraception: A Review of Annovera with a Pharmacist Perspective
Authors: Virro Jennifer J. , Besinque Kathleen , Carney Christiane E. , Gross Danielle , Bernick Brian , Mirkin Sebastian
Published: August 2020

Annovera (segesterone acetate and ethinyl estradiol vaginal system) is a US Food and Drug Administration FDA-approved long-lasting, reversible contraceptive that is fully administered by the user and does not require a procedure for insertion or removal. The vaginal system is in the shape of a ring and contains low doses of a novel progestin, egesterone acetate, and ethinyl estradiol. It is made of silicone and is fully pliable and flexible. The vaginal system is reusable for 13 cycles, using a 21 days in/7 days out regimen, providing women with the ability to control their fertility. Particularly now during the COVID-19 pandemic when access to contraception has been further reduced, patients may benefit from a method that is both long-lasting and patient-controlled.
Advancing the Adoption of Continuing Professional Development (CPD) in the United States
Authors: Owen James A. , Skelton Jann B. , Maine Lucinda L.
Published: August 2020

Over the last four decades, the expanded patient care roles of pharmacists in the United States (U.S.) have increased focus on ensuring the implementation of processes to enhance continuing professional development within the profession. The transition from a model of continuing pharmacy education (CPE) to a model of continuing professional development (CPD) is still evolving. As pharmacists assume more complex roles in patient care delivery, particularly in community-based settings, the need to demonstrate and maintain professional competence becomes more critical. In addition, long-held processes for post-graduate education and licensure must also continue to adapt to meet these changing needs. Members of the pharmacy profession in the U.S. must adopt the concept of CPD and implement processes to support the thoughtful completion of professional development plans. Comprehensive, state-of-the-art technology solutions are available to assist pharmacists with understanding, implementing and applying CPD to their professional lives.
Topography-Mediated Myotube and Endothelial Alignment, Differentiation, and Extracellular Matrix Organization for Skeletal Muscle Engineering
Authors: Almonacid Suarez Ana Maria , Brinker Marja G. L. , Brouwer Linda A. , van der Ham Iris , Harmsen Martin C. , van Rijn Patrick
Published: August 2020

Understanding the response of endothelial cells to aligned myotubes is important to create an appropriate environment for tissue-engineered vascularized skeletal muscle. Part of the native tissue environment is the extracellular matrix (ECM). The ECM is a supportive scaffold for cells and allows cellular processes such as proliferation, differentiation, and migration. Interstitial matrix and basal membrane both comprise proteinaceous and polysaccharide components for strength, architecture, and volume retention. Virtually all cells are anchored to their basal lamina. One of the physical factors that affects cell behavior is topography, which plays an important role on cell alignment. We tested the hypothesis that topography-driven aligned human myotubes promote and support vascular network formation as a prelude to in vitro engineered vascularized skeletal muscle. Therefore, we used a PDMS-based topography substrate to investigate the influence of pre-aligned myotubes on the network formation of microvascular endothelial cells. The aligned myotubes produced a network of collagen fibers and laminin. This network supported early stages of endothelial network formation.