bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulse Oximetry and Congenital Heart Disease Screening: Results of the First Pilot Study in Morocco
Authors: El Idrissi Slitine Nadia , Bennaoui Fatiha , Sable Craig A. , Martin Gerard R. , Hom Lisa A. , Fadel Amal , Moussaoui Soufiane , Inajjarne Nadir , Boumzebra Drissi , Mouaffak Youssef , Younous Said , Boukhanni Lahcen , Maoulainine Fadl Mrabih Rabou
Published: June 2020

Congenital heart disease (CHD) is the most common congenital malformation. Diagnosis of critical congenital heart disease (CCHD), the most severe type of congenital heart disease, in a newborn may be difficult. The addition of CCHD screening, using pulse oximetry, to clinical assessment significantly improves the rate of detection. We conducted a pilot study in Morocco on screening neonates for critical congenital heart disease. This study was conducted in the maternity ward of Mohammed VI University Hospital of Marrakesh, Morocco, and included asymptomatic newborns delivered between March 2019 and January 2020. The screening of CCHD was performed by pulse oximetry measuring the pre- and post-ductal saturation. Screening was performed on 8013/10,451 (76.7%) asymptomatic newborns. According to the algorithm, 7998 cases passed the screening test (99.82%), including one inconclusive test that was repeated an hour later and was normal. Fifteen newborns failed the screening test (0.18%): five CCHD, five false positives, and five CHD but non-critical. One false negative case was diagnosed at 2 months of age. Our results encourage us to strengthen screening for CCHD by adding pulse oximetry to the routine newborn screening panel.
Long-Term Evaluation of Breeding Scheme Alternatives for Endangered Honeybee Subspecies
Authors: Plate Manuel , Bernstein Richard , Hoppe Andreas , Bienefeld Kaspar
Published: June 2020

Modern breeding structures are emerging for European honeybee populations. However, while genetic evaluations of honeybees are becoming increasingly well understood, little is known about how selection decisions shape the populations’ genetic structures. We performed simulations evaluating 100 different selection schemes, defined by selection rates for dams and sires, in populations of 200, 500, or 1000 colonies per year and considering four different quantitative traits, reflecting different genetic parameters and numbers of influential loci. Focusing on sustainability, we evaluated genetic progress over 100 years and related it to inbreeding developments. While all populations allowed for sustainable breeding with generational inbreeding rates below 1% per generation, optimal selection rates differed and sustainable selection was harder to achieve in smaller populations and for stronger negative correlations of maternal and direct effects in the selection trait. In small populations, a third or a fourth of all candidate queens should be selected as dams, whereas this number declined to a sixth for larger population sizes. Furthermore, our simulations indicated that, particularly in small populations, as many sires as possible should be provided. We conclude that carefully applied breeding provides good prospects for currently endangered honeybee subspecies, since sustainable genetic progress improves their attractiveness to beekeepers.
Global Analysis of Small Non-Coding RNA Populations across Tissues in the Malaria Vector, Anopheles gambiae
Authors: Bryant William Bart , Ray Savanna , Mills Mary Katherine
Published: June 2020

Malaria is a major global health problem, where the anautogenous female mosquito Anopheles gambiae serves as a major vector. In order to combat this devastating disease, understanding mosquito physiology is paramount. Numerous studies in the vector field demonstrate that small non-coding RNAs (ncRNAs) play essential roles in numerous aspects of mosquito physiology. While our previous miRNA annotation work demonstrated expression dynamics across differing tissues, miRNAs represented less than 20% of all small ncRNAs in our small RNA-Seq libraries. To this end, we systematically classified multiple small ncRNA groups across mosquito tissues. Here we (i) determined a new enriched-midgut miRNA, (ii) updated the piRNA annotation in ovaries with a genomic map of unique-mapping piRNAs, (iii) identified pan-tissue and tissue-enriched mRNA-derived small ncRNAs, and (iv) assessed AGO1- and AGO2- loading of candidate small ncRNAs. Continued research will broaden our view of small ncRNAs and greatly aide in our understanding on how these molecules contribute to mosquito physiology.
Wide-Speed Range Sensorless Control of an IPM Motor for Multi-Purpose Applications
Authors: Bacci Maria Laura , Mapelli Ferdinando Luigi , Mossina Stefano , Tarsitano Davide , Vignati Michele
Published: June 2020

In a growing number of battery-driven applications the need of removing any position and speed transducer is taking over due to space, cost and mechanical reliability constraints, further than making the installation easier as requiring less wiring. This paper presents the development of a sensorless algorithm capable of running an Interior Permanent Magnet Synchronous Machine (IPMSM), assuring constant torque production in the whole speed range, form standstill to high speeds. This is achieved with an hybrid method: at standstill and very low speeds the saliency of the IPM is exploited through an High Frequency Signal Injection (HFSI), which assures a robust estimation of the rotor position. At medium to high speeds an advanced V-I estimator is adopted in order to enhance the motor performances. The developed algorithm comes out of being highly scalable as it requires very little tuning, resulting in a multi-purpose application which can be employed with any motor size.
Evaluation of Structured and Unstructured Models for Application in Operational Ocean Forecasting in Nearshore Waters
Authors: Nudds Shannon , Lu Youyu , Higginson Simon , Haigh Susan P. , Paquin Jean-Philippe , O’Flaherty-Sproul Mitchell , Taylor Stephanne , Blanken Hauke , Marcotte Guillaume , Smith Gregory C. , Bernier Natacha B. , MacAulay Phillip , Wu Yongsheng , Zhai Li , Hu Xianmin , Chanut Jérôme , Dunphy Michael , Dupont Frédéric , Greenberg David , Davidson Fraser J. M. , Page Fred
Published: June 2020

The oceanography sub-initiative of Canada’s Oceans Protection Plan was tasked to develop high-resolution nearshore ocean models for enhanced marine safety and emergency response, fitting into the multi-scale, multi-level nested operational ocean forecasting systems. For decision making on eventual 24/7 operational support, two ocean models (a structured grid model, NEMO (Nucleus for European Modelling of the Ocean); and an unstructured grid model, FVCOM (Finite Volume Coastal Ocean Model), were evaluated. The evaluation process includes the selection of the study area, the requirements for model setup, and the evaluation metrics. The chosen study area, Saint John Harbour in the Bay of Fundy, features strong tides, significant river runoff and a narrow tidal-river channel. Both models were configured with the same sources of bathymetry and forcing data. FVCOM achieved 50-100 m horizontal resolution in the inner harbour and included wetting/drying. NEMO achieved 100 m resolution in the harbour with a three-level one-way nesting configuration. Statistical metrics showed that one-year simulations with both models achieved comparable accuracies against the observed tidal and non-tidal water levels and currents, temperature and salinity, and the trajectories of surface drifters, but the computational cost of FVCOM was significantly less than that of NEMO.
On the Use of the Hybrid Causal Logic Methodology in Ship Collision Risk Assessment
Authors: Wang Tengfei , Wu Qing , A. Diaconeasa Mihai , Yan Xinping , Mosleh Ali
Published: June 2020

A ship collision accident is one of the most dangerous and common types of maritime accidents. Traditional probabilistic risk assessment (PRA) of ship collision accidents is a methodology that can be adopted to ensure maritime safety. Nevertheless, a need for better approaches to model human behavior, such as risk identification, communication, and decision-making, has been identified. Such advanced PRA methods require a more explicit way of taking human factors into consideration than the traditional risk assessment methods. Hybrid causal logic (HCL) is an advanced PRA method due to its unique three-level framework that includes event sequence diagrams, fault trees, and Bayesian networks, which makes it suitable for modeling human behavior that is important to ship collision accidents. This paper discusses the applicability of the HCL methodology for the ship collision accident. Firstly, the event sequences of typical ship collision accidents are summarized based on the study of 50 accident investigation reports. Then, fault trees for mechanical failure events and the Bayesian networks for human error events are constructed to analyze the events in a structured way at a more detailed level. Finally, the three main end-state types of ship collision avoidance scenario have been quantified. The result of the probability of a ship collision accident is verified by estimating the annual frequency of collision accidents in the Singapore Strait. Comparing with the historical data, the estimation results are quite near to the real case. By taking advantage of the HCL methodology, the modeling of ship collision scenarios can be carried out at a deep logical level. At the same time, it is possible to combine a detailed analysis of various primary events with a comprehensive analysis at the system level.
Self-Similar Models: Relationship between the Diffusion Entropy Analysis, Detrended Fluctuation Analysis and Lévy Models
Authors: Mariani Maria C. , Kubin William , Asante Peter K. , Tweneboah Osei K. , Beccar-Varela Maria P. , Jaroszewicz Sebastian , Gonzalez-Huizar Hector
Published: June 2020

Financial and geophysical data, like many other low and high frequency time series, are known to exhibit some memory effects. These memory effects may be long or short, permanent or temporal depending on the event that is being modeled. The purpose of this study is to investigate the memory effects characterized by the financial market closing values and volcanic eruption time series as well as to investigate the relation between the self-similar models used and the Lévy process. This paper uses highly effective scaling methods including Lévy processes, Detrended Fluctuation Analysis (DFA) and Diffusion Entropy Analysis (DEA) to examine long-range persistence behavior in time series by estimating their respective parameters. We use the parameter of the Lévy process (α) characterizing the data and the scaling parameters of DFA (H) and DEA (δ) characterizing the self-similar property to generate a relationship between the three (3) aforementioned scaling methods. Findings from the numerical simulations confirm the existence of long-range persistence (long-memory behavior) in both the financial and geophysical time series. Furthermore, the numerical results from this study indicates an approximate inverse relationship between the parameter of the Lévy process and the scaling parameters of the DFA and DEA (i.e., H , δ ≈ 1 α ), which we prove analytically.
Fuzzy Stability Results of Finite Variable Additive Functional Equation: Direct and Fixed Point Methods
Authors: Alanazi Abdulaziz M. , Muhiuddin G. , Tamilvanan K. , Alenze Ebtehaj N. , Ebaid Abdelhalim , Loganathan K.
Published: June 2020

In this current work, we introduce the finite variable additive functional equation and we derive its solution. In fact, we investigate the Hyers–Ulam stability results for the finite variable additive functional equation in fuzzy normed space by two different approaches of direct and fixed point methods.
Multiple Roles of Diatom-Derived Oxylipins within Marine Environments and Their Potential Biotechnological Applications
Authors: Ruocco Nadia , Albarano Luisa , Esposito Roberta , Zupo Valerio , Costantini Maria , Ianora Adrianna
Published: June 2020

The chemical ecology of marine diatoms has been the subject of several studies in the last decades, due to the discovery of oxylipins with multiple simultaneous functions including roles in chemical defence (antipredator, allelopathic and antibacterial compounds) and/or cell-to-cell signalling. Diatoms represent a fundamental compartment of marine ecosystems because they contribute to about 45% of global primary production even if they represent only 1% of the Earth’s photosynthetic biomass. The discovery that they produce several toxic metabolites deriving from the oxidation of polyunsaturated fatty acids, known as oxylipins, has changed our perspectives about secondary metabolites shaping plant–plant and plant–animal interactions in the oceans. More recently, their possible biotechnological potential has been evaluated, with promising results on their potential as anticancer compounds. Here, we focus on some recent findings in this field obtained in the last decade, investigating the role of diatom oxylipins in cell-to-cell communication and their negative impact on marine biota. Moreover, we also explore and discuss the possible biotechnological applications of diatom oxylipins.
Dupuytren’s Contracture: Incidence of Injury-Induced Cases and Specific Clinical Expression
Authors: Samulėnas Gediminas , Rimdeika Rytis , Braziulis Kęstutis , Fomkinas Mantas , Paškevičius Rokas
Published: June 2020

Background and objectives: Dupuytren’s contracture is a chronic fibroproliferative hand disorder with a varying pattern of genetic predisposition across different regions and populations. Traumatic events have been found to have influence on the development of this illness and are likely to trigger different clinical forms of this disease. The aim of this study was to evaluate the phenomenon of development of Dupuytren’s contracture (DC) following an acute injury to the hand, and to observe the incidence and clinical diversity of such cases in daily clinical practice. Materials and Methods: We collected data of patients presenting with primary Dupuytren’s contracture in the Lithuanian population and evaluated the occurrence and clinical manifestation of this specific type of DC, arising following acute hand trauma. The diagnosis of DC was based on clinical signs and physical examination. Digit contractures were measured by goniometry, and the staging was done according to Tubiana classification. Injury-induced (injury-related) cases were identified using the “Criteria for recognition of Dupuytren’s contracture after acute injury” (established by Elliot and Ragoowansi). Results: 29 (22%) of a total of 132 cases were injury-induced DCs. Twenty-six of 29 patients in this group presented with stage I–II contractures. Duration of symptoms was 6 (SD 2.2) and 3.8 (SD 2.2) years in the injury-related and injury-unrelated DC groups, respectively. Mean age on the onset of symptoms in the injury-induced and non-injury-induced groups was 52 (SD 10.7) and 56 (SD 10.9), respectively. Patients from both groups expressed strong predisposition towards development of DC. Conclusions: Around one-fifth of patients seeking treatment for primary Dupuytren’s contracture seemed to suffer from injury-induced Dupuytren’s contracture. We noted that injury to the wrist and hand seems to trigger the development of less progressive Dupuytren’s contracture in younger age. Prospective randomized studies are required to confirm our findings.
Rolling Nanoelectrode Lithography
Authors: Hasan Rashed Md. Murad , Luo Xichun , Sun Jining
Published: June 2020

Non-uniformity and low throughput issues severely limit the application of nanoelectrode lithography for large area nanopatterning. This paper proposes, for the first time, a new rolling nanoelectrode lithography approach to overcome these challenges. A test-bed was developed to realize uniform pressure distribution over the whole contact area between the roller and the silicon specimen, so that the local oxidation process occurred uniformly over a large area of the specimen. In this work, a brass roller wrapped with a fabricated polycarbonate strip was used as a stamp to generate nanopatterns on a silicon surface. The experimental results show that a uniform pattern transfer for a large area can be achieved with this new rolling nanoelectrode lithography approach. The rolling speed and the applied bias voltage were identified as the primary control parameters for oxide growth. Furthermore, the pattern direction showed no significant influence on the oxide process. We therefore demonstrated that nanoelectrode lithography can be scaled up for large-area nanofabrication by incorporating a roller stamp.
Optimization of a Portable Adenosine Triphosphate Bioluminescence Assay Coupled with a Receiver Operating Characteristic Model to Assess Bioaerosol Concentrations on Site
Authors: Tseng Chun-Chieh , Lu Yi-Chian , Chang Kai-Chih , Hung Chien-Che
Published: June 2020

Rapid monitoring of the microbial content in indoor air is an important issue. In this study, we develop a method for applying a Coriolis sampler coupled with a portable ATP luminometer for characterization of the collection efficiency of bioaerosol samplers and then test this approach in field applications. The biological collection efficiencies of the Coriolis sampler and a BioSampler for collecting four different types of bioaerosols, including Escherichia coli, Staphylococcus aureus, Candida famata and endospores of Bacillus subtilis, were compared in a chamber study. The results showed that the ATP assay may indicate the four microbes’ viability, and that their defined viabilities were positively correlated with their culturability. In addition, the optimal sampling conditions of the Coriolis sampler were a 200 L/min flow rate and a sampling time of 30 min. Under these conditions, there was no significant difference in sampling performance between the BioSampler and Coriolis sampler. In field applications, the best ATP benchmark that corresponded to culturable levels of < 500 CFU/m3 was 287 RLUs (sensitivity: 100%; specificity: 80%) for bacteria and 370 RLUs (sensitivity: 79%; specificity: 82%) for fungi according to receiver operating characteristic curve analysis. Consequently, an ATP criterion is recommended for indicating whether the corresponding airborne culturable concentrations of microbes meet those of published guidelines.
Calcineurin Inhibitor-Based Immunosuppression and COVID-19: Results from a Multidisciplinary Cohort of Patients in Northern Italy
Authors: Cavagna Lorenzo , Seminari Elena , Zanframundo Giovanni , Gregorini Marilena , Di Matteo Angela , Rampino Teresa , Montecucco Carlomaurizio , Pelenghi Stefano , Cattadori Barbara , Pattonieri Eleonora Francesca , Vitulo Patrizio , Bertani Alessandro , Sambataro Gianluca , Vancheri Carlo , Biglia Alessandro , Bozzalla-Cassione Emanuele , Bonetto Valentina , Monti Maria Cristina , Ticozzelli Elena , Turco Annalisa , Oggionni Tiberio , Corsico Angelo , Bertuccio Francesco , Zuccaro Valentina , Codullo Veronica , Morosini Monica , Marena Carlo , Gnecchi Massimiliano , Pellegrini Carlo , Meloni Federica
Published: June 2020

The role of immunosuppression in SARS-CoV-2-related disease (COVID-19) is a matter of debate. We here describe the course and the outcome of COVID-19 in a cohort of patients undergoing treatment with calcineurin inhibitors. In this monocentric cohort study, data were collected from the COVID-19 outbreak in Italy up to 28 April 2020. Patients were followed at our hospital for solid organ transplantation or systemic rheumatic disorders (RMDs) and were on calcineurin inhibitor (CNI)-based therapy. Selected patients were referred from the North of Italy. The aim of our study was to evaluate the clinical course of COVID-19 in this setting. We evaluated 385 consecutive patients (220 males, 57%; median age 61 years, IQR 48–69); 331 (86%) received solid organ transplantation and 54 (14%) had a RMD. CNIs were the only immunosuppressant administered in 47 patients (12%). We identified 14 (4%) COVID-19 patients, all transplanted, mainly presenting with fever (86%) and diarrhea (71%). Twelve patients were hospitalized and two of them died, both with severe comorbidities. No patients developed acute respiratory distress syndrome or infectious complications. The surviving 10 patients are now fully recovered. The clinical course of COVID-19 patients on CNIs is generally mild, and the risk of superinfection seems low.
Isolation and Characterization of Extracellular Vesicles Secreted In Vitro by Porcine Microbiota
Authors: Lagos Leidy , Leanti La Rosa Sabina , Ø. Arntzen Magnus , Ånestad Ragnhild , Terrapon Nicolas , Gaby John , Westereng Bjørge
Published: June 2020

The secretion of extracellular vesicles, EVs, is a common process in both prokaryotic and eukaryotic cells for intercellular communication, survival, and pathogenesis. Previous studies have illustrated the presence of EVs in supernatants from pure cultures of bacteria, including Gram-positive and Gram-negative glycan-degrading gut commensals. However, the isolation and characterization of EVs secreted by a complex microbial community have not been clearly reported. In a recent paper, we showed that wood-derived, complex β-mannan, which shares a structural similarity with conventional dietary fibers, can be used to modulate the porcine gut microbiota composition and activity. In this paper, we investigated the production, size, composition, and proteome of EVs secreted by pig fecal microbiota after 24 h enrichment on complex β-mannan. Using transmission electron microscopy and nanoparticle tracking analysis, we identified EVs with an average size of 165 nm. We utilized mass spectrometry-based metaproteomic profiling of EV proteins against a database of 355 metagenome-assembled genomes (MAGs) from the porcine colon and thereby identified 303 proteins. For EVs isolated from the culture grown on β-mannan, most proteins mapped to two MAGs, MAG53 and MAG272, belonging to the orders Clostridiales and Bacilli, respectively. Furthermore, the MAG with the third-most-detected protein was MAG 343, belonging to the order Enterobacteriales. The most abundant proteins detected in the β-mannan EVs proteome were involved in translation, energy production, amino acid, and carbohydrate transport, as well as metabolism. Overall, this proof-of-concept study demonstrates the successful isolation of EVs released from a complex microbial community; furthermore, the protein content of the EVs reflects the response of specific microbes to the available carbohydrate source.
Case Report of an Injectional Anthrax in France, 2012
Authors: Thouret Jean-Marc , Rogeaux Olivier , Beaudouin Emmanuel , Levast Marion , Ramisse Vincent , Biot Fabrice V. , Valade Eric , Thibault François , Gorgé Olivier , Tournier Jean-Nicolas
Published: June 2020

(1) Background: Bacillus anthracis is a spore-forming, Gram-positive bacterium causing anthrax, a zoonosis affecting mainly livestock. When occasionally infecting humans, B. anthracis provokes three different clinical forms: cutaneous, digestive and inhalational anthrax. More recently, an injectional anthrax form has been described in intravenous drug users. (2) Case presentation: We report here the clinical and microbiological features, as well as the strain phylogenetic analysis, of the only injectional anthrax case observed in France so far. A 27-year-old patient presented a massive dermohypodermatitis with an extensive edema of the right arm, and the development of drug-resistant shocks. After three weeks in an intensive care unit, the patient recovered, but the microbiological identification of B. anthracis was achieved after a long delay. (3) Conclusions: Anthrax diagnostic may be difficult clinically and microbiologically. The phylogenetic analysis of the Bacillus anthracis strain PF1 confirmed its relatedness to the injectional anthrax European outbreak group-II.
Analysis of Tick Surface Decontamination Methods
Authors: Hoffmann Angeline , Fingerle Volker , Noll Matthias
Published: June 2020

Various microbial pathogens have been found in ticks such as Ixodes ricinus. However, most studies assessed tick microbiomes without prior decontamination of the tick surface, which may alter the results and mislead conclusions regarding the composition of the tick-borne microbiome. The aim of this study was to test four different decontamination methods, namely (i.) 70% ethanol, (ii.) DNA Away, (iii.) 5% sodium hypochlorite and (iv.) Reactive Skin Decontamination Lotion (RSDL), which have been previously reported for tick surface and animal or human skin decontamination. To test the efficiency of decontamination, we contaminated each tick with a defined mixture of Escherichia coli, Micrococcus luteus, Pseudomonas fluorescens, dog saliva and human sweat. No contamination was used as a negative control, and for a positive control, a no decontamination strategy was carried out. After nucleic acid extraction, the recovery rate of contaminants was determined for RNA and DNA samples by qPCR and tick-borne microbiome analyses by bacterial 16S rRNA and 16S rRNA gene amplicon sequencing. Ticks treated with 5% sodium hypochlorite revealed the lowest number of contaminants followed by DNA Away, RSDL and 70% ethanol. Moreover, tick microbiomes after 5% sodium hypochlorite decontamination clustered with negative controls. Therefore, the efficiency of decontamination was optimal with 5% sodium hypochlorite and is recommended for upcoming studies to address the unbiased detection of tick-borne pathogens.
Data and Text Mining Help Identify Key Proteins Involved in the Molecular Mechanisms Shared by SARS-CoV-2 and HIV-1
Authors: Tarasova Olga , Ivanov Sergey , Filimonov Dmitry A. , Poroikov Vladimir
Published: June 2020

Viruses can be spread from one person to another; therefore, they may cause disorders in many people, sometimes leading to epidemics and even pandemics. New, previously unstudied viruses and some specific mutant or recombinant variants of known viruses constantly appear. An example is a variant of coronaviruses (CoV) causing severe acute respiratory syndrome (SARS), named SARS-CoV-2. Some antiviral drugs, such as remdesivir as well as antiretroviral drugs including darunavir, lopinavir, and ritonavir are suggested to be effective in treating disorders caused by SARS-CoV-2. There are data on the utilization of antiretroviral drugs against SARS-CoV-2. Since there are many studies aimed at the identification of the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) infection and the development of novel therapeutic approaches against HIV-1, we used HIV-1 for our case study to identify possible molecular pathways shared by SARS-CoV-2 and HIV-1. We applied a text and data mining workflow and identified a list of 46 targets, which can be essential for the development of infections caused by SARS-CoV-2 and HIV-1. We show that SARS-CoV-2 and HIV-1 share some molecular pathways involved in inflammation, immune response, cell cycle regulation.
Near-Infrared Spectroscopy in Bio-Applications
Authors: Beć Krzysztof B. , Grabska Justyna , Huck Christian W.
Published: June 2020

Near-infrared (NIR) spectroscopy occupies a specific spot across the field of bioscience and related disciplines. Its characteristics and application potential differs from infrared (IR) or Raman spectroscopy. This vibrational spectroscopy technique elucidates molecular information from the examined sample by measuring absorption bands resulting from overtones and combination excitations. Recent decades brought significant progress in the instrumentation (e.g., miniaturized spectrometers) and spectral analysis methods (e.g., spectral image processing and analysis, quantum chemical calculation of NIR spectra), which made notable impact on its applicability. This review aims to present NIR spectroscopy as a matured technique, yet with great potential for further advances in several directions throughout broadly understood bio-applications. Its practical value is critically assessed and compared with competing techniques. Attention is given to link the bio-application potential of NIR spectroscopy with its fundamental characteristics and principal features of NIR spectra.
Properties of Dicationic Disiloxane Ionic Liquids
Authors: Krasovskiy Vladimir G. , Kapustin Gennady I. , Gorbatsevich Olga B. , Glukhov Lev M. , Chernikova Elena A. , Koroteev Anatoly A. , Kustov Leonid M.
Published: June 2020

A number of dicationic ionic liquids with a disiloxane linker between imidazolium cations and bis(trifluoromethylsulfonyl)imide anion were synthesized and characterized. Melting points, viscosity, and volatility in a vacuum were measured; the thermal and hydrolytic stability of ionic liquids were also studied. The dependence of the properties on the structure of substituents in the cation of the ionic liquid was demonstrated.
The Lipoxin Receptor/FPR2 Agonist BML-111 Protects Mouse Skin Against Ultraviolet B Radiation
Authors: Martinez Renata M. , Fattori Victor , Saito Priscila , Pinto Ingrid C. , Rodrigues Camilla C. A. , Melo Cristina P. B. , Bussmann Allan J. C. , Staurengo-Ferrari Larissa , Bezerra Julia Rojo , Vignoli Josiane A. , Baracat Marcela M. , Georgetti Sandra R. , Verri Jr. Waldiceu A , Casagrande Rubia
Published: June 2020

Excessive exposure to UV, especially UVB, is the most important risk factor for skin cancer and premature skin aging. The identification of the specialized pro-resolving lipid mediators (SPMs) challenged the preexisting paradigm of how inflammation ends. Rather than a passive process, the resolution of inflammation relies on the active production of SPMs, such as Lipoxins (Lx), Maresins, protectins, and Resolvins. LXA4 is an SPM that exerts its action through ALX/FPR2 receptor. Stable ALX/FPR2 agonists are required because SPMs can be quickly metabolized within tissues near the site of formation. BML-111 is a commercially available synthetic ALX/FPR2 receptor agonist with analgesic, antioxidant, and anti-inflammatory properties. Based on that, we aimed to determine the effect of BML-111 in a model of UVB-induced skin inflammation in hairless mice. We demonstrated that BML-111 ameliorates the signs of UVB-induced skin inflammation by reducing neutrophil recruitment and mast cell activation. Reduction of these cells by BML-111 led to lower number of sunburn cells formation, decrease in epidermal thickness, collagen degradation, cytokine production (TNF-α, IL-1β, IL-6, TGF, and IL-10), and oxidative stress (observed by an increase in total antioxidant capacity and Nrf2 signaling pathway), indicating that BML-111 might be a promising drug to treat skin disorders.
Metabolism of the Flavonol Kaempferol in Kidney Cells Liberates the B-ring to Enter Coenzyme Q Biosynthesis
Authors: Fernández-del-Río Lucía , Soubeyrand Eric , Basset Gilles J. , Clarke Catherine F.
Published: June 2020

Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and an important antioxidant present in all cellular membranes. CoQ deficiencies are frequent in aging and in age-related diseases, and current treatments are limited to CoQ supplementation. Strategies that rely on CoQ supplementation suffer from poor uptake and trafficking of this very hydrophobic molecule. In a previous study, the dietary flavonol kaempferol was reported to serve as a CoQ ring precursor and to increase the CoQ content in kidney cells, but neither the part of the molecule entering CoQ biosynthesis nor the mechanism were described. In this study, kaempferol labeled specifically in the B-ring was isolated from Arabidopsis plants. Kidney cells treated with this compound incorporated the B-ring of kaempferol into newly synthesized CoQ, suggesting that the B-ring is metabolized via a mechanism described in plant cells. Kaempferol is a natural flavonoid present in fruits and vegetables and possesses antioxidant, anticancer, and anti-inflammatory therapeutic properties. A better understanding of the role of kaempferol as a CoQ ring precursor makes this bioactive compound a potential candidate for the design of interventions aiming to increase endogenous CoQ biosynthesis and may improve CoQ deficient phenotypes in aging and disease.
Ceria-Containing Hybrid Multilayered Microcapsules for Enhanced Cellular Internalisation with High Radioprotection Efficiency
Authors: Popova N. R. , Popov A. L. , Ermakov A. M. , Reukov V. V. , Ivanov V. K.
Published: June 2020

Cerium oxide nanoparticles (nanoceria) are believed to be the most versatile nanozyme, showing great promise for biomedical applications. At the same time, the controlled intracellular delivery of nanoceria remains an unresolved problem. Here, we have demonstrated the radioprotective effect of polyelectrolyte microcapsules modified with cerium oxide nanoparticles, which provide controlled loading and intracellular release. The optimal (both safe and uptake efficient) concentrations of ceria-containing microcapsules for human mesenchymal stem cells range from 1:10 to 1:20 cell-to-capsules ratio. We have revealed the molecular mechanisms of nanoceria radioprotective action on mesenchymal stem cells by assessing the level of intracellular reactive oxygen species (ROS), as well as by a detailed 96-genes expression analysis, featuring genes responsible for oxidative stress, mitochondrial metabolism, apoptosis, inflammation etc. Hybrid ceria-containing microcapsules have been shown to provide an indirect genoprotective effect, reducing the number of cytogenetic damages in irradiated cells. These findings give new insight into cerium oxide nanoparticles’ protective action for living beings against ionising radiation.
Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes
Authors: Mirza Zeynep , Soto Ernesto R. , Hu Yan , Nguyen Thanh-Thanh , Koch David , Aroian Raffi V. , Ostroff Gary R.
Published: June 2020

Soil-transmitted nematodes (STN) infect 1–2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many instances of reduced activity. Terpenes are a class of compounds with anthelmintic activity. Thymol, a natural monoterpene phenol, was used to help eradicate hookworms in the U.S. South circa 1910. However, the use of terpenes as anthelmintics was discontinued because of adverse side effects associated with high doses and premature stomach absorption. Furthermore, the dose–response activity of specific terpenes against STNs has been understudied. Here we used hollow, porous yeast particles (YPs) to efficiently encapsulate (>95%) high levels of terpenes (52% w/w) and evaluated their anthelmintic activity on hookworms (Ancylostoma ceylanicum), a rodent parasite (Nippostrongylus brasiliensis), and whipworm (Trichuris muris). We identified YP–terpenes that were effective against all three parasites. Further, YP–terpenes overcame albendazole-resistant Caenorhabditis elegans. These results demonstrate that terpenes are broad-acting anthelmintics. Terpenes are predicted to be extremely difficult for parasites to resist, and YP encapsulation provides water-suspendable terpene materials without surfactants and sustained terpene release that could lead to the development of formulations for oral delivery that overcome fast absorption in the stomach, thus reducing dosage and toxic side effects.
Carbon Nanotube Reinforced High Density Polyethylene Materials for Offshore Sheathing Applications
Authors: Okolo Chinyere , Rafique Rafaila , Iqbal Sadia Sagar , Saharudin Mohd Shahneel , Inam Fawad
Published: June 2020

Multiwall carbon nanotube (CNT)-filled high density polyethylene (HDPE) nanocomposites were prepared by extrusion and considered for their suitability in the offshore sheathing applications. Transmission electron microscopy was conducted to analyse dispersion after bulk extrusion. Monolithic and nanocomposite samples were subjected to accelerated weathering and photodegradation (carbonyl and vinyl indices) characterisations, which consisted of heat, moisture (seawater) and UV light, intended to imitate the offshore conditions. The effects of accelerated weathering on mechanical properties (tensile strength and elastic modulus) of the nanocomposites were analysed. CNT addition in HDPE produced environmentally resilient nanocomposites with improved mechanical properties. The energy utilised to extrude nanocomposites was also less than the energy used to extrude monolithic HDPE samples. The results support the mass substitution of CNT-filled HDPE nanocomposites in high-end offshore applications.
High Preventive Effect of G2-S16 Anionic Carbosilane Dendrimer against Sexually Transmitted HSV-2 Infection
Authors: Rodriguez-Izquierdo Ignacio , Gasco Samanta , Muñoz-Fernández Maria Angeles
Published: June 2020

Anionic carbosilane dendrimers such as G2-S16 are very effective in preventing HSV-2 infection both in vitro and in vivo. We present the main achievements obtained for the G2-S16 dendrimer in vivo, especially related to its efficacy against HSV-2 infection. Moreover, we discuss the mechanisms by which the G2-S16 dendrimer applied vaginally as a topical microbicide has been demonstrated to be safe and harmless for the vaginal microbiome balance, as both conditions present an essential step that has to be overcome during microbicide development. This review points to the marked protective effect of the G2-S16 dendrimer against sexually transmitted HSV-2 infection, supporting its role as a possible microbicide against HSV-2 infection.
Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–7
Authors: Gütschow Michael , Vanden Eynde Jean Jacques , Jampilek Josef , Kang CongBao , Mangoni Arduino A. , Fossa Paola , Karaman Rafik , Trabocchi Andrea , Scott Peter J. H. , Reynisson Jóhannes , Rapposelli Simona , Galdiero Stefania , Winum Jean-Yves , Brullo Chiara , Prokai-Tatrai Katalin , Sharma Arun K. , Schapira Matthieu , Azuma Yasu-Taka , Cerchia Laura , Spetea Mariana , Torri Giangiacomo , Collina Simona , Geronikaki Athina , García-Sosa Alfonso T. , Vasconcelos M. Helena , Sousa Maria Emília , Kosalec Ivan , Tuccinardi Tiziano , Duarte Iola F. , Salvador Jorge A. R. , Bertinaria Massimo , Pellecchia Maurizio , Amato Jussara , Rastelli Giulio , Gomes Paula A. C. , Guedes Rita C. , Sabatier Jean-Marc , Estévez-Braun Ana , Pagano Bruno , Mangani Stefano , Ragno Rino , Kokotos George , Brindisi Margherita , González Florenci V. , Borges Fernanda , Miloso Mariarosaria , Rautio Jarkko , Muñoz-Torrero Diego
Published: June 2020

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of editorials which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...]
A Practical Perspective on the Roles of Solution NMR Spectroscopy in Drug Discovery
Authors: Li Qingxin , Kang CongBao
Published: June 2020

Solution nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to study structures and dynamics of biomolecules under physiological conditions. As there are numerous NMR-derived methods applicable to probe protein–ligand interactions, NMR has been widely utilized in drug discovery, especially in such steps as hit identification and lead optimization. NMR is frequently used to locate ligand-binding sites on a target protein and to determine ligand binding modes. NMR spectroscopy is also a unique tool in fragment-based drug design (FBDD), as it is able to investigate target-ligand interactions with diverse binding affinities. NMR spectroscopy is able to identify fragments that bind weakly to a target, making it valuable for identifying hits targeting undruggable sites. In this review, we summarize the roles of solution NMR spectroscopy in drug discovery. We describe some methods that are used in identifying fragments, understanding the mechanism of action for a ligand, and monitoring the conformational changes of a target induced by ligand binding. A number of studies have proven that 19F-NMR is very powerful in screening fragments and detecting protein conformational changes. In-cell NMR will also play important roles in drug discovery by elucidating protein-ligand interactions in living cells.
A Novel Approach to Improve Acid Diversion in Carbonate Rocks Using Thermochemical Fluids: Experimental and Numerical Study
Authors: Ba Alawi Mustafa , Hassan Amjed , Aljawad Murtada Saleh , Kamal Muhammad Shahzad , Mahmoud Mohamed , Al-Nakhli Ayman
Published: June 2020

The distribution of acid over all layers of interest is a critical measure of matrix acidizing efficiency. Chemical and mechanical techniques have been widely adapted for enhancing acid diversion. However, it was demonstrated that these often impact the formation with damage after the acid job is completed. This study introduces, for the first time, a novel solution to improve acid diversion using thermochemical fluids. This method involves generating nitrogen gas at the downhole condition, where the generated gas will contribute in diverting the injected acids into low-permeability formations. In this work, both lab-scale numerical and field-scale analytical models were developed to evaluate the performance of the proposed technique. In addition, experimental measurements were carried out in order to demonstrate the application of thermochemical in improving the acid diversion. The results showed that a thermochemical approach has an effective performance in diverting the injected acids into low-permeability rocks. After treatment, continuous wormholes were generated in the high-permeability rocks as well as in low-permeability rocks. The lab-scale model was able to replicate the wormholing impact observed in the lab. In addition, alternating injection of thermochemical and acid fluids reduced the acid volume 3.6 times compared to the single stage of thermochemical injection. Finally, sensitivity analysis indicates that the formation porosity and permeability have major impacts on the acidizing treatment, while the formations pressures have minor effect on the diversion performance.
DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis—Challenges and Critical Points in Implementation into Clinical Routine
Authors: Meisenheimer Michael , Kürpig Stefan , Essler Markus , Eppard Elisabeth
Published: June 2020

The novel compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-ZOL (DOTA-conjugated zoledronic acid) is a promising candidate for the diagnosis and therapy of bone metastasis. The combination of the published methodology for this bisphosphonate with pharmaceutical and regulatory requirements turned out to be unexpectedly challenging. The scope of this work is the presentation and discussion of problems encountered during this process. Briefly, the radiolabelling process and purification, as well as the quality control published, did not meet the expectations. The constant effort setting up an automated radiolabelling procedure resulted in (a) an enhanced manual method using coated glass reactors, (b) a combination of three different reliable radio thin-layer chromatography (TLC) methods instead of the published and (c) a preliminary radio high-pressure liquid chromatography (HPLC) method for identification of the compound. Additionally, an automated radiolabelling process was developed, but it requires further improvement, e.g., in terms of a reactor vessel or purification of the crude product. The published purification method was found to be unsuitable for clinical routine, and an intense screening did not lead to a satisfactory result; here, more research is necessary. To sum up, implementation of DOTA-ZOL was possible but revealed a lot of critical points, of which not all could be resolved completely yet.
Magnetically Recoverable TiO2/SiO2/γ-Fe2O3/rGO Composite with Significantly Enhanced UV-Visible Light Photocatalytic Activity
Authors: Kaveh Reyhaneh , Mokhtarifar Maryam , Bagherzadeh Mojtaba , Lucotti Andrea , Diamanti Maria Vittoria , Pedeferri MariaPia
Published: June 2020

In this paper, we report the preparation of a new composite (TiO2/SiO2/γ-Fe2O3/rGO) with a high photocatalytic efficiency. The properties of the composite were examined by different analyses, including X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM), photoluminescence (PL), UV-Visible light diffuse reflectance spectroscopy, Fourier transform infrared spectroscopy (FTIR), Raman, vibrating-sample magnetometer (VSM), and nitrogen gas physisorption (BET) studies. The photocatalytic efficiency of the proposed composite was evaluated by the degradation of methylene blue under UV and visible light, and the results were compared with titanium dioxide (TiO2), where degradation increased from 30% to 84% and 4% to 66% under UV and visible light, respectively. The significant increase in photocatalytic activity may be explained by the higher adsorption of dye on the surface of the composite and the higher separation and transfer of charge carriers, which in turn promote active sites and photocatalytic efficiency.
In Vitro Anthelmintic Evaluation of Gliricidia sepium, Leucaena leucocephala, and Pithecellobium dulce: Fingerprint Analysis of Extracts by UHPLC-Orbitrap Mass Spectrometry
Authors: Romero Néstor , Areche Carlos , Cubides-Cárdenas Jaime , Escobar Natalia , García-Beltrán Olimpo , Simirgiotis Mario J. , Céspedes Ángel
Published: June 2020

In the present work, the anthelmintic activity (AA) of ethanolic extracts obtained from Gliricidia sepium, Leucaena leucocephala, and Pithecellobium dulce was evaluated using the third-stage-larval (L3) exsheathment inhibition test (LEIT) and egg hatch test (EHT) on Haemonchus contortus. Extracts were tested at concentrations of 0.3, 0.6, 1.2, 2.5, 5.0, 10, 20, and 40 mg/mL. The larval exsheathment inhibition (LEI) results showed that G. sepium achieved the highest average inhibition of 91.2%, compared with 44.6% for P. dulce and 41.0% for L. leucocephala at a concentration of 40 mg/mL; the corresponding IC50 values were 22.4, 41.7, and 43.3 mg/mL, respectively. The rates of egg hatching inhibition (EHI) at a concentration of 5 mg/mL were 99.5% for G. sepium, 64.2% for P. dulce, and 54% for L. leucocephala; the corresponding IC50 values were 1.9 mg/mL for G. sepium, 3.9 mg/mL for P. dulce, and 4.3 mg/mL for L. leucocephala. The species extracts studied here were also analyzed by ultra-high performance liquid chromatography and Orbitrap high resolution mass spectrometry (UHPLC-Q/Orbitrap/MS/MS), resulting in the compounds’ identification associated with AA. Glycosylated flavonoids and methoxyphenols were observed in all three species: fatty acids in G. sepium and P. dulce; phenylpropanoids, anthraquinone glycosides, amino acids and glycosylated phenolic acids in G. sepium; and flavonoids in L. leucocephala. Comparatively, G. sepium presented a greater diversity of compounds potentially active against the control of gastrointestinal nematodes, which was associated with the results obtained in the applied tests.