bluuebunny/crossref_metadata_2025 huggingface dataset:
CFD Simulations of Radioembolization: A Proof-of-Concept Study on the Impact of the Hepatic Artery Tree Truncation
Authors: Lertxundi Unai , Aramburu Jorge , Ortega Julio , Rodríguez-Fraile Macarena , Sangro Bruno , Bilbao José Ignacio , Antón Raúl
Published: April 2021

Radioembolization (RE) is a treatment for patients with liver cancer, one of the leading cause of cancer-related deaths worldwide. RE consists of the transcatheter intraarterial infusion of radioactive microspheres, which are injected at the hepatic artery level and are transported in the bloodstream, aiming to target tumors and spare healthy liver parenchyma. In paving the way towards a computer platform that allows for a treatment planning based on computational fluid dynamics (CFD) simulations, the current simulation (model preprocess, model solving, model postprocess) times (of the order of days) make the CFD-based assessment non-viable. One of the approaches to reduce the simulation time includes the reduction in size of the simulated truncated hepatic artery. In this study, we analyze for three patient-specific hepatic arteries the impact of reducing the geometry of the hepatic artery on the simulation time. Results show that geometries can be efficiently shortened without impacting greatly on the microsphere distribution.
Large Time Decay of Solutions to a Linear Nonautonomous System in Exterior Domains
Authors: Hishida Toshiaki
Published: April 2021

In this expository paper, we study Lq-Lr decay estimates of the evolution operator generated by a perturbed Stokes system in n-dimensional exterior domains when the coefficients are time-dependent and can be unbounded at spatial infinity. By following the approach developed by the present author for the physically relevant case where the rigid motion of the obstacle is time-dependent, we clarify that some decay properties of solutions to the same system in whole space Rn together with the energy relation imply the desired estimates in exterior domains provided n≥3.
Antimicrobials from Seaweeds for Food Applications
Authors: Cabral Eduarda M. , Oliveira Márcia , Mondala Julie R. M. , Curtin James , Tiwari Brijesh K. , Garcia-Vaquero Marco
Published: April 2021

The exponential growth of emerging multidrug-resistant microorganisms, including foodborne pathogens affecting the shelf-life and quality of foods, has recently increased the needs of the food industry to search for novel, natural and eco-friendly antimicrobial agents. Macroalgae are a bio-diverse group distributed worldwide, known to produce multiple compounds of diverse chemical nature, different to those produced by terrestrial plants. These novel compounds have shown promising health benefits when incorporated into foods, including antimicrobial properties. This review aims to provide an overview of the general methods and novel compounds with antimicrobial properties recently isolated and characterized from macroalgae, emphasizing the molecular pathways of their antimicrobial mechanisms of action. The current scientific evidence on the use of macroalgae or macroalgal extracts to increase the shelf-life of foods and prevent the development of foodborne pathogens in real food products and their influence on the sensory attributes of multiple foods (i.e., meat, dairy, beverages, fish and bakery products) will also be discussed, together with the main challenges and future trends of the use of marine natural products as antimicrobials.
Efficacy of Modified Amnion-Assisted Conjunctival Epithelial Redirection (ACER) for Partial Limbal Stem Cell Deficiency
Authors: Han Sang Beom , Ibrahim Farah Nur Ilyana Mohd , Liu Yu-Chi , Mehta Jodhbir S.
Published: April 2021

Background and objectives: the aim of this study was to analyze the efficacy of a modified “amnion-assisted conjunctival epithelial redirection (ACER)” technique for the treatment of partial limbal stem cell deficiency (LSCD). Materials and methods: the medical records of three patients with partial LSCD who underwent corneal surface reconstruction with modified ACER following superficial keratectomy were retrospectively studied. Briefly, in this technique, an inner amniotic membrane (AM) layer was applied on the corneal surface to promote corneal re-epithelialization. The outer AM layer was applied as a barrier to prevent the invasion of conjunctival epithelial cells into the cornea before the corneal surface was completely covered by corneal epithelial cells derived from the remaining intact limbal stem cells. Results: in all three cases, the outer AM layer successfully kept the conjunctival epithelium away from the corneal surface and prevented an admixture of conjunctival epithelial cells with corneal epithelial cells. In all three patients, the cornea was completely re-epithelized with epithelial cells derived from the remaining healthy limbal stem cells, and a clear visual axis was maintained without recurrence for a mean follow-up period of 37.3 ± 8.6 months. Conclusions: the preliminary results suggest that modified ACER appears to be a viable option for patients with partial LSCD.
Long Non-Coding RNA Expression in Laser Micro-Dissected Luminal A and Triple Negative Breast Cancer Tissue Samples—A Pilot Study
Authors: Marcu Anca , Nitusca Diana , Vaduva Adrian , Baderca Flavia , Cireap Natalia , Coricovac Dorina , Dehelean Cristina Adriana , Seclaman Edward , Ilina Razvan , Marian Catalin
Published: April 2021

Background and Objectives: Breast cancer (BC) remains one of the major causes of cancer death in women worldwide. The difficulties in assessing the deep molecular mechanisms involved in this pathology arise from its high complexity and diverse tissue subtypes. Long non-coding RNAs (lncRNAs) were shown to have great tissue specificity, being differentially expressed within the BC tissue subtypes. Materials and Methods: Herein, we performed lncRNA profiling by PCR array in triple negative breast cancer (TNBC) and luminal A tissue samples from 18 BC patients (nine TNBC and nine luminal A), followed by individual validation in BC tissue and cell lines. Tissue samples were previously archived in formalin-fixed paraffin-embedded (FFPE) samples, and the areas of interest were dissected using laser capture microdissection (LCM) technology. Results: Two lncRNAs (OTX2-AS1 and SOX2OT) were differentially expressed in the profiling analysis (fold change of 205.22 and 0.02, respectively, p < 0.05 in both cases); however, they did not reach statistical significance in the individual validation measurement (p > 0.05) when analyzed with specific individual assays. In addition, GAS5 and NEAT1 lncRNAs were individually assessed as they were previously described in the literature as being associated with BC. GAS5 was significantly downregulated in both TNBC tissues and cell lines compared to luminal A samples, while NEAT1 was significantly downregulated only in TNBC cells vs. luminal A. Conclusions: Therefore, we identified GAS5 lncRNA as having a differential expression in TNBC tissues and cells compared to luminal A, with possible implications in the molecular mechanisms of the TNBC subtype. This proof of principle study also suggests that LCM could be a useful technique for limiting the sample heterogeneity for lncRNA gene expression analysis in BC FFPE tissues. Future studies of larger cohort sizes are needed in order to assess the biomarker potential of lncRNA GAS5 in BC.
Lingual Lymph Node Metastases as a Prognostic Factor in Oral Squamous Cell Carcinoma—A Retrospective Multicenter Study
Authors: Kikuchi Masahiro , Harada Hiroyuki , Asato Ryo , Hamaguchi Kiyomi , Tamaki Hisanobu , Mizuta Masanobu , Hori Ryusuke , Kojima Tsuyoshi , Honda Keigo , Tsujimura Takashi , Kumabe Yohei , Ichimaru Kazuyuki , Kitani Yoshiharu , Ushiro Koji , Kitamura Morimasa , Shinohara Shogo , Omori Koichi
Published: April 2021

Backgrounds and Objectives: The epidemiology and prognostic role of lingual lymph node (LLN) metastasis in patients with oral squamous cell carcinoma (OSCC) remain unclear. Here, we aimed to analyze the clinicopathological features, risk factors, and prognostic role of LLN metastasis in patients with OSCC. Materials and Methods: In total, 945 patients with OSCC were retrospectively analyzed. Clinicopathological features were compared between patients with and without LLN metastasis. The risk factors of LLN metastasis and its effects on survival outcomes were evaluated using multi-variate analysis. Results: LLN metastasis was noted in 67 patients (7.1%). Habitual alcohol consumption and clinical neck node metastasis were independent risk factors for LLN metastasis. LLN metastasis was an independent prognostic factor for disease-free and overall survival, although LLN dissection did not improve survival outcomes. Conclusion: LLN metastasis is an independent adverse prognostic factor. Further prospective studies are needed to fully assess the extent of LLN dissection required in OSCC patients.
Impact of the Addition of Pyrolysed Forestry Waste to the Coking Process on the Resulting Green Biocoke
Authors: Solar Jon , Caballero Blanca María , Barriocanal Carmen , Lopez-Urionabarrenechea Alexander , Acha Esther
Published: April 2021

The suitability of the charcoal obtained from woody biomass pyrolysis in a continuous screw reactor at 573, 773, 973, 1173 K temperature profile as fuel and reducing agent in metallurgical applications has been evaluated, in order to reduce the CO2 emissions in these processes. On the one hand, a comparative study between charcoal and commercial reducers has been carried out. On the other hand, different proportions of this charcoal have been added to an industrial coking coal blend and carbonized together in a semi-pilot movable wall oven, to study the influence in the plastic and mechanical properties of the produced biocoke. The charcoal obtained fulfills the requirements to be used as fuel and reducer in non-ferrous processes where no mechanical strength is required, like rotary kilns, in substitution of fossil reducers. Its higher heating value (>32 MJ kg−1) is in the range or over those of fossil coals, with the advantage of not containing polluting elements (S, N) and having less ash. The addition of up to 0.9 wt.% almost does not affect the quality of the biocoke; but the addition of ≥2 wt.% degrades the biocoke mechanical and plastic properties below the demanded requirements. Moreover, biocoke reactivity seems independent of the amount of charcoal added.
Effect of Pre-Stretching on Residual Stresses and Microstructures of Inconel 718 Superalloy
Authors: Zhu Jiajia , Yuan Wuhua
Published: April 2021

The residual stress generated in a superalloy during heat treatment affects the subsequent processing of the workpiece and may even adversely affect its performance. This paper investigates the effects of pre-stretching (in the range from 0% to 9%) before aging treatment on residual stress generated during quenching process and microstructure of Inconel 718 superalloy. After pre-stretching treatment, the residual stress deriving from quenching process can be well reduced. When the pre-stretch level was 3%, the quenching residual stress reached a maximum reduction of 72%, and the strength increased by 7.1%, while the product of strength and elongation hardly changed. Simultaneously, the microstructures of the pre-stretched specimens are observed by electron back scatter diffraction (EBSD) and transmission electron microscopy (TEM). It was found that the fraction of high-angle grain boundaries in the alloy decreased while that of low-angle grain boundaries increased with increasing pre-stretch level. As the pre-stretch level was further increased to 9%, the proliferating entanglement of internal dislocations in the specimen was intensified, resulting in rod-shaped γ″ precipitates coarsening and volume fraction reduction of precipitates, which further led to a reduction in the product of strength and elongation of material.
Synergism Red Mud-Acid Mine Drainage as a Sustainable Solution for Neutralizing and Immobilizing Hazardous Elements
Authors: Lucas Hugo , Stopic Srecko , Xakalashe Buhle , Ndlovu Sehliselo , Friedrich Bernd
Published: April 2021

Acid mine drainage (AMD) and red mud (RM) are frequently available in the metallurgical and mining industry. Treating AMD solutions require the generation of enough alkalinity to neutralize the acidity excess. RM, recognized as a waste generating high alkalinity solution when it is in contact with water, was chosen to treat AMD from South Africa at room temperature. A German and a Greek RM have been evaluated as a potential low-cost material to neutralize and immobilize harmful chemical ions from AMD. Results showed that heavy metals and other hazardous elements such as As, Se, Cd, and Zn had been immobilized in the mineral phase. According to European environmental standards, S and Cr, mainly present in RM, were the only two elements not immobilized below the concentration established for inert waste.
The Atmosphere’s Effect on Stainless Steel Slabs’ Oxide Formation in a CH4-Fuelled Reheating Furnace
Authors: Laukka Aleksi , Heikkinen Eetu-Pekka , Fabritius Timo
Published: April 2021

Utilising the oxyfuel practice for CH4-fuelled combustion has positive effects on the emissions, efficiency and cost of high temperature furnace practices. However, especially in older installations, oxyfuel usage requires retrofitting and alters the atmosphere in which the oxidation of the steel occurs, when compared to using air as the oxidiser. Stainless steel slab oxide growth during reheating was studied in different atmospheres. The simulated post-burn atmospheres from oxyfuel, lean oxyfuel and air-fuel practices were used to compare oxide-scale layer growth and morphology during simulated typical AISI 304 stainless steel slab reheating prior to hot rolling. Thermogravimetric measurements, glow discharge optical emission spectrometer (GDOES) and field-emission scanning electron microscope energy dispersive X-ray (FESEM-EDS) methodology were applied to discern differences between oxide growth and inner oxide layer morphology between the three practices. Switching from air to oxyfuel practice at a single temperature had the same increasing effect on the scale formation amount as a 25 °C temperature increase in air atmosphere. Inner oxide layer depth profiling revealed C, Si and Ni to be the main elements that differed between temperatures and atmospheres. A morphology study showed Si and Ni behaviour to be linked to breakaway oxidation.
Clinical Insights into Mitochondrial Neurodevelopmental and Neurodegenerative Disorders: Their Biosignatures from Mass Spectrometry-Based Metabolomics
Authors: Li Haorong , Uittenbogaard Martine , Hao Ling , Chiaramello Anne
Published: April 2021

Mitochondria are dynamic multitask organelles that function as hubs for many metabolic pathways. They produce most ATP via the oxidative phosphorylation pathway, a critical pathway that the brain relies on its energy need associated with its numerous functions, such as synaptic homeostasis and plasticity. Therefore, mitochondrial dysfunction is a prevalent pathological hallmark of many neurodevelopmental and neurodegenerative disorders resulting in altered neurometabolic coupling. With the advent of mass spectrometry (MS) technology, MS-based metabolomics provides an emerging mechanistic understanding of their global and dynamic metabolic signatures. In this review, we discuss the pathogenetic causes of mitochondrial metabolic disorders and the recent MS-based metabolomic advances on their metabolomic remodeling. We conclude by exploring the MS-based metabolomic functional insights into their biosignatures to improve diagnostic platforms, stratify patients, and design novel targeted therapeutic strategies.
Targeted Metabolic Profiles of the Leaves and Xylem Sap of Two Sugarcane Genotypes Infected with the Vascular Bacterial Pathogen Leifsonia xyli subsp. xyli
Authors: Castro-Moretti Fernanda R. , Cocuron Jean-Christophe , Cia Mariana C. , Cataldi Thais R. , Labate Carlos A. , Alonso Ana Paula , Camargo Luis E. A.
Published: April 2021

Ratoon stunt (RS) is a worldwide disease that reduces biomass up to 80% and is caused by the xylem-dwelling bacterium Leifsonia xyli subsp. xyli. This study identified discriminant metabolites between a resistant (R) and a susceptible (S) sugarcane variety at the early stages of pathogen colonization (30 and 120 days after inoculation—DAI) by untargeted and targeted metabolomics of leaves and xylem sap using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), respectively. Bacterial titers were quantified in sugarcane extracts at 180 DAI through real-time polymerase chain reaction. Bacterial titers were at least four times higher on the S variety than in the R one. Global profiling detected 514 features in the leaves and 68 in the sap, while 119 metabolites were quantified in the leaves and 28 in the sap by targeted metabolomics. Comparisons between mock-inoculated treatments indicated a greater abundance of amino acids in the leaves of the S variety and of phenolics, flavonoids, and salicylic acid in the R one. In the xylem sap, fewer differences were detected among phenolics and flavonoids, but also included higher abundances of the signaling molecule sorbitol and glycerol in R. Metabolic changes in the leaves following pathogen inoculation were detected earlier in R than in S and were mostly related to amino acids in R and to phosphorylated compounds in S. Differentially represented metabolites in the xylem sap included abscisic acid. The data represent a valuable resource of potential biomarkers for metabolite-assisted selection of resistant varieties to RS.
Modeling Between-Subject Variability in Subcutaneous Absorption of a Fast-Acting Insulin Analogue by a Nonlinear Mixed Effects Approach
Authors: Faggionato Edoardo , Schiavon Michele , Dalla Man Chiara
Published: April 2021

Despite the great progress made in insulin preparation and titration, many patients with diabetes are still experiencing dangerous fluctuations in their blood glucose levels. This is mainly due to the large between- and within-subject variability, which considerably hampers insulin therapy, leading to defective dosing and timing of the administration process. In this work, we present a nonlinear mixed effects model describing the between-subject variability observed in the subcutaneous absorption of fast-acting insulin. A set of 14 different models was identified on a large and frequently-sampled database of lispro pharmacokinetic data, collected from 116 subjects with type 1 diabetes. The tested models were compared, and the best one was selected on the basis of the ability to fit the data, the precision of the estimated parameters, and parsimony criteria. The selected model was able to accurately describe the typical trend of plasma insulin kinetics, as well as the between-subject variability present in the absorption process, which was found to be related to the subject’s body mass index. The model provided a deeper understanding of the insulin absorption process and can be incorporated into simulation platforms to test and develop new open- and closed-loop treatment strategies, allowing a step forward toward personalized insulin therapy.
Applicability of Artificial Vascularized Liver Tissue to Proteomic Analysis
Authors: Mori Nobuhito , Kida Yasuyuki S.
Published: April 2021

Artificial vascularized tubular liver tissue has perfusable blood vessels that allow fluid access to the tissue interior, enabling the injection of drugs and collection of metabolites, which are valuable for drug discovery. It is amenable to standard evaluation methods, such as paraffin-embedded sectioning, qPCR, and RNA sequencing, which makes it easy to implement into existing research processes. However, the application of tissues vascularized by the self-assembly of cells, (including tubular liver tissue, has not yet been tested in comprehensive proteomic analysis relevant for drug discovery. Here, we established a method to efficiently separate cells from the tubular liver tissue by adding a pipetting step during collagenase treatment. By using this method, we succeeded in obtaining a sufficient number of cells for the proteomic analysis. In addition, to validate this approach, we compared the cells separated from the tissue with those grown in 2D culture, focusing on the proteins related to drug metabolism. We found that the levels of proteins involved in metabolic phases II and III were slightly higher in the tubular liver tissue than those in the 2D cell culture. Taken together, our suggested method demonstrates the applicability of tubular liver tissue to the proteomic analysis in drug assays.
Design, Simulation, Fabrication, and Characterization of an Electrothermal Tip-Tilt-Piston Large Angle Micromirror for High Fill Factor Segmented Optical Arrays
Authors: Torres David , Starman LaVern , Hall Harris , Pastrana Juan , Dooley Sarah
Published: April 2021

Micro-electromechanical system (MEMS) micromirrors have been in development for many years, but the ability to steer beams to angles larger than 20° remains a challenging endeavor. This paper details a MEMS micromirror device capable of achieving large motion for both tip/tilt angles and piston motion. The device consists of an electrothermal actuation assembly fabricated from a carefully patterned multilayer thin-film stack (SiO2/Al/SiO2) that is epoxy bonded to a 1 mm2 Au coated micromirror fabricated from an SOI wafer. The actuation assembly consists of four identical actuators, each comprised of a series of beams that use the inherent residual stresses and coefficient of thermal expansion (CTE) mismatches of the selected thin films to enable the large, upward, out-of-plane deflections necessary for large-angle beamsteering. Finite element simulations were performed (COMSOL v5.5) to capture initial elevations and tip/tilt motion displacements and achieved <10% variance in comparison to the experiment. The measured performance metrics of the micromirror include tip/tilt angles of ±23°, piston motion of 127 µm at sub-resonance, and dynamics characterization with observed resonant frequencies at ~145 Hz and ~226 Hz, for tip/tilt and piston motion, respectively. This unique single element design can readily be scaled into a full segmented micromirror array exhibiting an optical fill-factor >85%, making it suitable for optical phased array beam control applications.
Genome-Wide Analysis of the Temporal Genetic Changes in Streptococcus pneumoniae Isolates of Genotype ST320 and Serotype 19A from South Korea
Authors: Baek Jin Yang , Kim Sun Ju , Shin Juyoun , Chung Yeun-Jun , Kang Cheol-In , Chung Doo Ryeon , Song Jae-Hoon , Ko Kwan Soo
Published: April 2021

Since the introduction of the pneumococcal conjugate vaccine, an increase in the incidence of Streptococcus pneumoniae serotype 19A and sequence type 320 (19A-ST320) isolates have been observed worldwide including in South Korea. We conducted a genome-wide analysis to investigate the temporal genetic changes in 26 penicillin-non-susceptible 19A-ST320 pneumococcal isolates from a hospital in South Korea over a period of 17 years (1999; 2004 to 2015). Although the strains were isolated from a single hospital and showed the same genotype and serotype, a whole-genome sequencing (WGS) analysis revealed that the S. pneumoniae isolates showed more extensive genetic variations compared with a reference isolate obtained in 1999. A phylogenetic analysis based on single nucleotide polymorphisms (SNPs) showed that the pneumococcal isolates from South Korea were not grouped together into limited clusters among the 19A-ST320 isolates from several continents. It was predicted that recombination events occurred in 11 isolates; larger numbers of SNPs were found within recombination blocks compared with point mutations identified in five isolates. WGS data indicated that S. pneumoniae 19A-ST320 isolates might have been introduced into South Korea from various other countries. In addition, it was revealed that recombination may play a great role in the evolution of pneumococci even in very limited places and periods.
Implementing SARS-CoV-2 Rapid Antigen Testing in the Emergency Ward of a Swiss University Hospital: The INCREASE Study
Authors: Caruana Giorgia , Croxatto Antony , Kampouri Eleftheria , Kritikos Antonios , Opota Onya , Foerster Maryline , Brouillet René , Senn Laurence , Lienhard Reto , Egli Adrian , Pantaleo Giuseppe , Carron Pierre-Nicolas , Greub Gilbert
Published: April 2021

Following the Swiss Federal Office of Public Health (FOPH) authorization of the rapid antigen test (RAT), we implemented the use of the RAT in the emergency ward of our university hospital for patients’ cohorting. RAT triaging in association with RT-PCR allowed us to promptly isolate positive patients and save resources. Among 532 patients, overall sensitivities were 48.3% for Exdia and 41.2% for Standard Q®, PanbioTM and BD Veritor™. All RATs exhibited specificity above 99%. Sensitivity increased to 74.6%, 66.2%, 66.2% and 64.8% for Exdia, Standard Q®, PanbioTM and BD Veritor™, respectively, for viral loads above 105 copies/mL, to 100%, 97.8%, 96.6% and 95.6% for viral loads above 106 copies/mL and 100% for viral loads above 107 copies/mL. Sensitivity was significantly higher for patients with symptoms onset within four days (74.3%, 69.2%, 69.2% and 64%, respectively) versus patients with the evolution of symptoms longer than four days (36.8%, 21.1%, 21.1% and 23.7%, respectively). Among COVID-19 asymptomatic patients, sensitivity was 33%. All Immunoglobulin-A-positive patients resulted negative for RAT. The RAT might represent a useful resource in selected clinical settings as a complementary tool in RT-PCR for rapid patient triaging, but the lower sensitivity, especially in late presenters and COVID-19 asymptomatic subjects, must be taken into account.
Early Post-Prandial Regulation of Protein Expression in the Midgut of Chagas Disease Vector Rhodnius prolixus Highlights New Potential Targets for Vector Control Strategy
Authors: Ouali Radouane , Vieira Larissa Rezende , Salmon Didier , Bousbata Sabrina
Published: April 2021

Chagas disease is a vector-borne parasitic disease caused by the flagellated protozoan Trypanosoma cruzi and transmitted to humans by a large group of bloodsucking triatomine bugs. Triatomine insects, such as Rhodnius prolixus, ingest a huge amount of blood in a single meal. Their midgut represents an important interface for triatomine–trypanosome interactions. Furthermore, the development of parasites and their vectorial transmission are closely linked to the blood feeding and digestion; thus, an understanding of their physiology is essential for the development of new strategies to control triatomines. In this study, we used label-free quantitative proteomics to identify and analyze the early effect of blood feeding on protein expression in the midgut of Rhodnius prolixus. We both identified and quantified 124 proteins in the anterior midgut (AM) and 40 in the posterior midgut (PM), which vary significantly 6 h after feeding. The detailed analysis of these proteins revealed their predominant involvement in the primary function of hematophagy, including proteases, proteases inhibitors, amino acids metabolism, primary metabolites processing, and protein folding. Interestingly, our proteomics data show a potential role of the AM in protein digestion. Moreover, proteins related to detoxification processes and innate immunity, which are largely accepted to be triggered by blood ingestion, were mildly modulated. Surprisingly, one third of blood-regulated proteins in the AM have unknown function. This work contributes to the improvement of knowledge on the digestive physiology of triatomines in the early hours post-feeding. It provides key information for selecting new putative targets for the development of triatomine control tools and their potential role in the vector competence, which could be applied to other vector species.
A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis
Authors: Pappa Vasiliki , Bouchla Anthi , Terpos Evangelos , Thomopoulos Thomas P. , Rosati Margherita , Stellas Dimitris , Antoniadou Anastasia , Mentis Andreas , Papageorgiou Sotirios G. , Politou Marianna , Kotanidou Anastasia , Kalomenidis Ioannis , Poulakou Garyfalia , Jahaj Edison , Korompoki Eleni , Grigoropoulou Sotiria , Hu Xintao , Bear Jenifer , Karaliota Sevasti , Burns Robert , Pagoni Maria , Trontzas Ioannis , Grouzi Elisavet , Labropoulou Stavroula , Stamoulis Kostantinos , Bamias Aristotelis , Tsiodras Sotirios , Felber Barbara K. , Pavlakis George N. , Dimopoulos Meletios- Athanasios
Published: April 2021

COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention (n = 59) to a control group (n = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004–0.36), p: 0.005], significantly better overall survival by Kaplan–Meir analysis (p < 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64–348.9), p: 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209).
The Fluid Mobilities of K and Zr in Subduction Zones: Thermodynamic Constraints
Authors: Zhong Richen , Zhang Min , Yu Chang , Cui Hao
Published: April 2021

A subduction zone plays a critical role in forging continental crust via formation of arc magmas, which are characteristically enriched in large ion lithophile elements (LILEs) and depleted in high field strength elements (HFSEs). This trace element pattern results from the different mobilities of LILEs and HFSEs during slab-to-wedge mass transfer, but the mechanisms of trace element transfer from subducting crusts are not fully understood. In this study, thermodynamic simulations are carried out to evaluate the mobilities of K and Zr, as representative cases of LILE and HFSE, respectively, in slab fluids. The fluids buffered by basaltic eclogite can dissolve > 0.1 molal of K at sub-arc depths (~3 to 5.5 GPa). However, only minor amounts of K can be liberated by direct devolatilization of altered oceanic basalt, because sub-arc dehydration mainly takes place at temperatures < 600 °C (talc-out), wherein the fluid solubility of K is very limited (<0.01 molal). Therefore, serpentinite-derived fluids are required to flush K from the eclogite. The solubility of K can be enhanced by the addition of NaCl to the fluid, because fluid Na+ can unlock phengite-bonded K via a complex ion exchange. Finally, it is further confirmed that Zr and other HFSEs are immobile in slab fluids.
Industrial Vertical Stirred Mills Screw Liner Wear Profile Compared to Discrete Element Method Simulations
Authors: Esteves Priscila M. , Mazzinghy Douglas B. , Galéry Roberto , Machado Luís C. R.
Published: April 2021

Vertical stirred mills have been widely applied in the minerals industry, due to its greater efficiency in comparison with conventional tumbling mills. In this context, the agitator liner wear plays an important role in maintenance planning and operational costs. In this paper, we use the discrete element method (DEM) wear simulation to evaluate the screw liner wear. Three different mill rotational velocities are evaluated in the simulation, according to different scale-up procedures. The wear profile, wear measurement, power consumption, and particle contact information are used for obtaining a better understanding of the wear behavior and its effects on grinding mechanisms. Data from a vertical stirred mill screw liner wear measurement obtained in a full-scale mill are used to correlate with simulation results. The results indicate a relative agreement with industrial measurement in most of the liner lifecycle, when using a proper mill velocity scale-up.
Origin of the Moroccan Touissit-Bou Beker and Jbel Bou Dahar Supergene Non-Sulfide Biomineralization and Its Relevance to Microbiological Activity, Late Miocene Uplift and Climate Changes
Authors: Bouabdellah Mohammed , Boukirou Wissale , Potra Adriana , Melchiorre Erik , Bouzahzah Hassan , Yans Johan , Zaid Khadra , Idbaroud Mohammed , Poot Julien , Dekoninck Augustin , Levresse Gilles
Published: April 2021

Through integration of Pb-Zn ± Cu non-sulfide mineralogy, texture, and stable isotope (C, O, S) geochemistry, the world-class Touissit- Bou Beker and Jbel Bou Dahar Mississippi Valley-type districts of the Moroccan Atlasic system have been investigated in order to gain insights into the origin and processes that contributed to the formation of the base metal non-sulfide mineralization. In both districts, direct replacement (“red calamine”) and wallrock replacement (“white calamine”) ores are observed. Based on the mineral assemblages, ore textures, and crosscutting relations, three distinct mineralizing stages are recognized. The earliest, pre-non-sulfide gossanous stage was a prerequisite for the following supergene stages and constituted the driving force that ultimately promoted the leaching of most base metals such as Zn and Cu and alkalis from their rock sources. The following two stages, referred to as the main supergene “red calamine” and late “white calamine” ore stages, generated the bulk of mineable “calamine” ores in the Touissit-Bou Beker and Jbel Bou Dahar districts. Stable isotope compositions (δ13CV-PDB, δ18OV-SMOW, δ34SCDT) support a three-stage model whereby metals were released by supergene acidic fluids and then precipitated by bacteria and archaea-mediated metal-rich meteoric fluids due to a decrease in temperature and/or increase of fO2. Oxygen isotope thermometry indicates decreasing precipitation temperatures with advancing paragenetic sequence from 33° to 18 °C, with wet to semi-arid to arid climatic conditions. The close spatial relationships between coexisting sulfide and non-sulfide mineralization along with stable isotope constraints suggest that the oxidation of sulfides occurred concurrently after the main stage of the Alpine orogeny between 15 Ma and the present. More importantly, the current data show for the first time the involvement of biologically controlled activity as the major driving process that triggered both oxidation and deposition of supergene mineralization at Jbel Bou Dahar and Touissit-Bou Beker districts. Conclusions drawn from this study therefore have implications for supergene Mississippi Valley-type (MVT) -derived non-sulfide deposits worldwide and account for the prominent role of biological processes in the genesis of this category of ore deposits.
Disseminated Gold–Sulfide Mineralization in Metasomatites of the Khangalas Deposit, Yana–Kolyma Metallogenic Belt (Northeast Russia): Analysis of the Texture, Geochemistry, and S Isotopic Composition of Pyrite and Arsenopyrite
Authors: Kudrin Maxim V. , Fridovsky Valery Yu. , Polufuntikova Lena I. , Kryuchkova Lyudmila Yu.
Published: April 2021

At the orogenic gold deposits of the Yana–Kolyma metallogenic belt (northeast Russia) both Au–quartz-sulfide mineralization with native gold and disseminated sulfide mineralization with invisible Au developed. The textural and mineralogical-geochemical features, isotope-geochemical characteristics of gold-bearing sulfides from proximal metasomatites, and possible forms of Au occurrence in pyrite and arsenopyrite have been studied using electron microprobe, atomic absorption, LA-ICP-MS trace element, isotope analysis, and computed microtomography. Four generations of pyrite (Py1, diagenetic; Py2, metamorphic; Py3, metasomatic; Py4, veined) and two generations of arsenopyrite (Apy1, metasomatic; Apy2, veined) have been identified at the Khangalas deposit. In the proximal metasomatites, the most common are Py3 and Apy1. Studying their chemical composition makes it possible to identify the features of the distribution patterns of typochemical trace elements in pyrite and arsenopyrite, and to establish the nature of the relationship between Au and these elements. In Py3 and Apy1, structurally bound (solid solution) Au+ prevails, isomorphically entering the crystal lattice or its defects. Isotope characteristics of hydrothermal sulfides (δ34S = −2.0 to −0.6‰) indicate that mantle/magmatic sulfur was involved in the formation of the deposit, though the participation of sulfur from the host rocks of the Verkhoyansk clastic complex cannot be ruled out. The Khangalas deposit has much in common with other gold deposits of the Yana–Kolyma metallogenic belt, and from this point of view, the results obtained will help to better reveal their gold potential and understand their origin.
Novel Semi-Synthetic Cu (II)–Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway
Authors: Hossan Md Shahadat , Break Mohammed Khaled Bin , Bradshaw Tracey D. , Collins Hilary M. , Wiart Christophe , Khoo Teng-Jin , Alafnan Ahmed
Published: April 2021

Cardamonin is a polyphenolic natural product that has been shown to possess cytotoxic activity against a variety of cancer cell lines. We previously reported the semi-synthesis of a novel Cu (II)–cardamonin complex (19) that demonstrated potent antitumour activity. In this study, we further investigated the bioactivity of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective treatment for triple-negative breast cancer (TNBC) and pancreatic cancer, respectively. Results revealed that 19 abolished the formation of MDA-MB-468 and PANC-1 colonies, exerted growth-inhibitory activity, and inhibited cancer cell migration. Further mechanistic studies showed that 19 induced DNA damage resulting in gap 2 (G2)/mitosis (M) phase arrest and microtubule network disruption. Moreover, 19 generated reactive oxygen species (ROS) that may contribute to induction of apoptosis, corroborated by activation of caspase-3/7, PARP cleavage, and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1, which indicates that the compound exerts its activity, at least in part, via inhibition of Akt signalling. Furthermore, 19 decreased the expression of c-Myc in PANC-1 cells only, which suggests that it may exert its bioactivity via multiple mechanisms of action. These results demonstrate the potential of 19 as a therapeutic agent for TNBC and pancreatic cancer.
A Pilot Metabolomic Study on Myocardial Injury Caused by Chronic Alcohol Consumption—Alcoholic Cardiomyopathy
Authors: Cao Zhipeng , Wang Tianqi , Xia Wei , Zhu Baoli , Tian Meihui , Zhao Rui , Guan Dawei
Published: April 2021

Chronic alcohol consumption leads to myocardial injury, ventricle dilation, and cardiac dysfunction, which is defined as alcoholic cardiomyopathy (ACM). To explore the induced myocardial injury and underlying mechanism of ACM, the Liber-DeCarli liquid diet was used to establish an animal model of ACM and histopathology, echocardiography, molecular biology, and metabolomics were employed. Hematoxylin-eosin and Masson’s trichrome staining revealed disordered myocardial structure and local fibrosis in the ACM group. Echocardiography revealed thinning wall and dilation of the left ventricle and decreased cardiac function in the ACM group, with increased serum levels of brain natriuretic peptide (BNP) and expression of myocardial BNP mRNA measured through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (PCR), respectively. Through metabolomic analysis of myocardium specimens, 297 differentially expressed metabolites were identified which were involved in KEGG pathways related to the biosynthesis of unsaturated fatty acids, vitamin digestion and absorption, oxidative phosphorylation, pentose phosphate, and purine and pyrimidine metabolism. The present study demonstrated chronic alcohol consumption caused disordered cardiomyocyte structure, thinning and dilation of the left ventricle, and decreased cardiac function. Metabolomic analysis of myocardium specimens and KEGG enrichment analysis further demonstrated that several differentially expressed metabolites and pathways were involved in the ACM group, which suggests potential causes of myocardial injury due to chronic alcohol exposure and provides insight for further research elucidating the underlying mechanisms of ACM.
A Review on the Biological Activity of Camellia Species
Authors: Teixeira Ana Margarida , Sousa Clara
Published: April 2021

Medicinal plants have been used since antiquity to cure illnesses and injuries. In the last few decades, natural compounds extracted from plants have garnered the attention of scientists and the Camellia species are no exception. Several species and cultivars are widespread in Asia, namely in China, Japan, Vietnam and India, being also identified in western countries like Portugal. Tea and oil are the most valuable and appreciated Camellia subproducts extracted from Camellia sinensis and Camellia oleifera, respectively. The economic impact of these species has boosted the search for additional information about the Camellia genus. Many studies can be found in the literature reporting the health benefits of several Camellia species, namely C. sinensis, C. oleifera and Camellia japonica. These species have been highlighted as possessing antimicrobial (antibacterial, antifungal, antiviral) and antitumoral activity and as being a huge source of polyphenols such as the catechins. Particularly, epicatechin (EC), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and specially epigallocatechin-3-gallate (EGCG), the major polyphenols of green tea. This paper presents a detailed review of Camellia species’ antioxidant properties and biological activity.
Temperature Dependent Excitonic Transition Energy and Enhanced Electron-Phonon Coupling in Layered Ternary SnS2-xSex Semiconductors with Fully Tunable Stoichiometry
Authors: Lin Der-Yuh , Hsu Hung-Pin , Tsai Chi-Feng , Wang Cheng-Wen , Shih Yu-Tai
Published: April 2021

In this study, a series of SnS2-xSex (0 ≤ x ≤ 2) layered semiconductors were grown by the chemical–vapor transport method. The crystal structural and material phase of SnS2-xSex layered van der Waals crystals was characterized by X-ray diffraction measurements and Raman spectroscopy. The temperature dependence of the spectral features in the vicinity of the direct band edge excitonic transitions of the layered SnS2-xSex compounds was measured in the temperature range of 20–300 K using the piezoreflectance (PzR) technique. The near band-edge excitonic transition energies of SnS2-xSex were determined from a detailed line-shape fit of the PzR spectra. The PzR characterization has shown that the excitonic transitions were continuously tunable with the ratio of S and Se. The parameters that describe the temperature variation of the energies of the excitonic transitions are evaluated and discussed.
Modern Approaches to the Synthesis and Transformations of Practically Valuable Benzothiazole Derivatives
Authors: Zhilitskaya Larisa V. , Shainyan Bagrat A. , Yarosh Nina O.
Published: April 2021

The review is devoted to modern trends in the chemistry of 2-amino and 2-mercapto substituted benzothiazoles covering the literature since 2015. The reviewed heterocycles belong to biologically active and industrially demanded compounds. Newly developed synthesis methods can be divided into conventional multistep processes and one-pot, atom economy procedures, realized using green chemistry principles and simple reagents. The easy functionalization of the 2-NH2 and 2-SH groups and the benzene ring of the benzothiazole moiety allows considering them as highly reactive building blocks for organic and organoelement synthesis, including the synthesis of pharmacologically active heterocycles. The review provides a summary of findings, which may be useful for developing new drugs and materials and new synthetic approaches and patterns of reactivity.
Beneficial Effects of Cyclic Ether 2-Butoxytetrahydrofuran from Sea Cucumber Holothuria scabra against Aβ Aggregate Toxicity in Transgenic Caenorhabditis elegans and Potential Chemical Interaction
Authors: Tangrodchanapong Taweesak , Sornkaew Nilubon , Yurasakpong Laphatrada , Niamnont Nakorn , Nantasenamat Chanin , Sobhon Prasert , Meemon Krai
Published: April 2021

The pathological finding of amyloid-β (Aβ) aggregates is thought to be a leading cause of untreated Alzheimer’s disease (AD). In this study, we isolated 2-butoxytetrahydrofuran (2-BTHF), a small cyclic ether, from Holothuria scabra and demonstrated its therapeutic potential against AD through the attenuation of Aβ aggregation in a transgenic Caenorhabditis elegans model. Our results revealed that amongst the five H. scabra isolated compounds, 2-BTHF was shown to be the most effective in suppressing worm paralysis caused by Aβ toxicity and in expressing strong neuroprotection in CL4176 and CL2355 strains, respectively. An immunoblot analysis showed that CL4176 and CL2006 treated with 2-BTHF showed no effect on the level of Aβ monomers but significantly reduced the toxic oligomeric form and the amount of 1,4-bis(3-carboxy-hydroxy-phenylethenyl)-benzene (X-34)-positive fibril deposits. This concurrently occurred with a reduction of reactive oxygen species (ROS) in the treated CL4176 worms. Mechanistically, heat shock factor 1 (HSF-1) (at residues histidine 63 (HIS63) and glutamine 72 (GLN72)) was shown to be 2-BTHF’s potential target that might contribute to an increased expression of autophagy-related genes required for the breakdown of the Aβ aggregate, thus attenuating its toxicity. In conclusion, 2-BTHF from H. scabra could protect C. elegans from Aβ toxicity by suppressing its aggregation via an HSF-1-regulated autophagic pathway and has been implicated as a potential drug for AD.