bluuebunny/crossref_metadata_2025 huggingface dataset:
The Laboratory-Based HySpex Features of Chlorite as the Exploration Tool for High-Grade Iron Ore in Anshan-Benxi Area, Liaoning Province, Northeast China
Authors: Hao Dahai , Yao Yuzeng , Fu Jianfei , Michalski Joseph R. , Song Kun
Published: October 2020

Anshan-Benxi area in Liaoning province is an important banded iron formations (BIFs) ore-mining district in China. Chlorite is widely distributed in this area, which is related to BIFs and high-grade iron ore, respectively. A fast and convenient method to identify the type and spatial distribution of different chlorites is crucial to the evaluation of high-grade iron ore in this area. Qidashan iron mine is a typical BIFs deposit, and its BIFs-related high-grade iron ore reserves are the second largest in the area. In this paper, the laboratory-based HySpex-320m hyperspectral imaging was used to study the wall rock in Qidashan iron mine. A hyperspectral imaging processing model was established for mineral identification, mineralogy mapping, and chlorite spectral features extraction. The results show that the wavelength positions of OH, Fe-OH, and Mg-OH absorptions of chlorite in the altered wall rock of high-grade iron ore are between 1400 and 1410, 2260 and 2265, and 2360 and 2370 nm, respectively, which are longer than those around BIFs. The relationship between cations in the octahedral layer of chlorite and the wavelengths of OH, Fe-OH, and Mg-OH indicates that Mg and Mg/(Mg + Fe) are inversely related to these wavelengths, whereas Fe is positively related. The wavelengths appear to be weakly influenced by AlVI. Since the bandpass of hyperspectral imaging systems is usually less than 10 nm, these chlorite wavelength differences can be used as a favorable tool for the high-grade iron ore exploration and the iron resources evaluation in the Anshan-Benxi area.
Modeling of a Village-Scale Multi-Energy System for the Integrated Supply of Electric and Thermal Energy
Authors: Stevanato Nicolo , Rinaldi Lorenzo , Pistolese Stefano , Balderrama Subieta Sergio Luis , Quoilin Sylvain , Colombo Emanuela
Published: October 2020

Energy system models for off-grid systems usually tend to focus solely on the provision of electricity for powering simple appliances, thus neglecting more energy-intensive and critical needs, such as water heating. The adoption of a Multi-Energy System (MES) perspective would allow us not only to provide comprehensive solutions addressing all types of energy demand, but also to exploit synergies between the electric and thermal sectors. To this end, we expand an existing open-source micro-grid optimization model with a complementary thermal model. Results show how the latter achieves optimal solutions that are otherwise restricted, allowing for a reduction in the Levelized Cost of Energy (LCOE) of 59% compared to a conventional microgrid, and an increase of reliance on renewable sources of 70%.
Sustainable Dewatering of Industrial Sludges in Sludge Treatment Reed Beds: Experiences from Pilot and Full-Scale Studies under Different Climates
Authors: Nielsen Steen , Stefanakis Alexandros I.
Published: October 2020

Sludge treatment reed beds (STRBs) are an established sludge treatment technology with multiple environmental and economic advantages in dewatering sludge generated during domestic wastewater treatment. However, little is reported regarding their appropriateness and efficiency for the treatment of sludge produced during industrial wastewater treatment and from water works. These sludge types may have significantly different quality characteristics than typical domestic sludge and may contain constituents that could affect their dewaterability. Therefore, the dewatering of these industrial sludge types is usually tested in small-scale pilot STRBs before the construction of full-scale systems. This paper presents and summarizes the state-of-the-art experience from existing pilot and full-scale STRB systems from various countries and climates treating sludge from various industrial sources, evaluates the suitability and the advantages of this sustainable treatment technology, and proposes the required dimensioning for efficient full-scale STRB operation and performance.
A Transitional Connection Method for the Design of Functionally Graded Cellular Materials
Authors: Liang Shihao , Gao Liang , Zheng Yongfeng , Li Hao
Published: October 2020

In recent years, the functionally graded materials (FGM) with cellular structure have become a hot spot in the field of materials research. For the continuously varying cellular structure in the layer-wise FGM, the connection of gradient cellular structures has become the main problem. Unfortunately, the effect of gradient connection method on the overall structural performance lacks attention, and the boundary mismatch has enormous implications. Using the homogenization theory and the level set method, this article presents an efficient topology optimization method to solve the connection issue. Firstly, a simple but efficient hybrid level set scheme is developed to generate a new level set surface that has the partial features of two candidate level sets. Then, when the new level set surface is formed by considering the level set functions of two gradient base cells, a special transitional cell can be constructed by finding the zero level set of this generated level set surface. Since the transitional cell has the geometric features of two gradient base cells, the shape of the transitional cell fits perfectly with its connected gradient cells on both sides. Thus, the design of FGM can have a smooth connectivity with C1 continuity without any complex numerical treatments during the optimization. A number of examples on both 2D and 3D are provided to demonstrate the characteristics of the proposed method. Finite element simulation has also been employed to calculate the mechanical properties of the designs. The simulation results show that the FGM devised by the proposed method exhibits better mechanical performances than conventional FGM with only C0 continuity.
A Study on Failure Analysis and High Performance of Hydraulic Servo Actuator
Authors: Lee Yong-bum , Park Jong-won , Lee Gi-chun
Published: October 2020

Hydraulic servo actuator is used as the core actuator in tensile compression fatigue life test equipment as it operates the micro displacement very precisely at a high frequency and can be used continuously for a long period of time. Recently, the life expectancy of automobiles has been extended, the load conditions of accelerated life testing on auto parts have been increased, and the life test time and number of tests have increased significantly in order to secure the reliability of the guaranteed life of produced vehicles. Therefore, hydraulic servo actuators mounted on accelerated life testing equipment for automotive parts are essential for much higher performance and a longer life than those tested. However, small- and medium-sized companies that supply test equipment for the fatigue life of auto often fail to develop technology due to a lack of research personnel and the development budget compared to the capabilities of large automobile manufacturers, resulting in frequent breakdowns due to the technical overload of test equipment. In this study, servo actuators were used to test automotive parts, with a maximum output of 2 ton, a maximum frequency of 3.3 Hz and a maximum displacement of 50 mm. The hydraulic servo actuator, which was installed in the tensile compression fatigue life test equipment, failed to operate normally at the site, and by analyzing it, we realized this resulted from the heat generation of insulation compression due to the accumulation of air and gas into the hydraulic oil and the increase in friction due to the deterioration of flow. A static pressure bearing was adopted as a design change to improve the root cause for this failure mode, and a very high level of geometric concentricity was secured by inserting concentric tubes outside the labyrinth seal type piston. The newly designed and manufactured actuator is the result of research that has achieved a semi-permanent long life and improved performance up to 100 Hz by non-contact operation.
Highly Efficient Mid-Infrared Generation from Low-Power Single-Frequency Fiber Laser Using Phase-Matched Intracavity Difference Frequency Mixing
Authors: Feng Jiacheng , Cheng Xi , Li Xiao , Wang Peng , Hua Weihong , Han Kai
Published: October 2020

In this paper, we demonstrated efficient mid-infrared generation using a low-power 1064 nm single-frequency (SF) fiber laser based on phase-matched intracavity difference frequency generation (DFG) in a continuous-wave (CW) periodically poled lithium niobate (PPLN)-based optical parametric oscillator (OPO). This is the first time that the frequency down conversion of a low-power SF light source has been achieved using intracavity difference frequency mixing. A high power 1018 nm fiber laser was firstly used for building the parametric oscillation and providing the high power resonant signal wave. To realize an efficient DFG process between the SF pump wave and the intracavity signal wave, the temperature of periodically poled lithium niobate (PPLN) crystal was properly adjusted to satisfy the phase-matching conditions. Finally, the low-power 1064 nm SF pump wave was successfully converted to a 3.7 μm mid-infrared wave with a conversion efficiency of 21.6%. The conversion efficiency, to the best of our knowledge, is the highest for SF lasers in DFG processes. Meanwhile, taking advantage of SF laser pumping, a narrow linewidth of 271 pm (5.9 GHz) in the mid-infrared region was achieved without adding any etalons or devices in the cavity.
Noise Level and Similarity Analysis for Computed Tomographic Thoracic Image with Fast Non-Local Means Denoising Algorithm
Authors: Kim Bae-Guen , Kang Seong-Hyeon , Park Chan Rok , Jeong Hyun-Woo , Lee Youngjin
Published: October 2020

Although conventional denoising filters have been developed for noise reduction from digital images, these filters simultaneously cause blurring in the images. To address this problem, we proposed the fast non-local means (FNLM) denoising algorithm which would preserve the edge information of objects better than conventional denoising filters. In this study, we obtained thoracic computed tomography (CT) images from a male adult mesh (MASH) phantom modeled by computer and a five-year-old phantom to perform both the simulation study and the practical study. Subsequently, the FNLM denoising algorithm and conventional denoising filters, such as the Gaussian, median, and Wiener filters, were applied to the MASH phantom image adding Gaussian noise with a standard deviation of 0.002 and practical CT images. Finally, the results were compared quantitatively in terms of the coefficient of variation (COV), contrast-to-noise ratio (CNR), peak signal-to-noise ratio (PSNR), and correlation coefficient (CC). The results showed that the FNLM denoising algorithm was more efficient than the conventional denoising filters. In conclusion, through the simulation study and the practical study, this study demonstrated the feasibility of the FNLM denoising algorithm for noise reduction from thoracic CT images.
Estimating Surface Downward Longwave Radiation Using Machine Learning Methods
Authors: Feng Chunjie , Zhang Xiaotong , Wei Yu , Zhang Weiyu , Hou Ning , Xu Jiawen , Jia Kun , Yao Yunjun , Xie Xianhong , Jiang Bo , Cheng Jie , Zhao Xiang
Published: October 2020

The downward longwave radiation (Ld, 4–100 μm) is a major component of research for the surface radiation energy budget and balance. In this study, we applied five machine learning methods, namely artificial neural network (ANN), support vector regression (SVR), gradient boosting regression tree (GBRT), random forest (RF), and multivariate adaptive regression spline (MARS), to estimate Ld using ground measurements collected from 27 Baseline Surface Radiation Network (BSRN) stations. Ld measurements in situ were used to validate the accuracy of Ld estimation models on daily and monthly time scales. A comparison of the results demonstrated that the estimates on the basis of the GBRT method had the highest accuracy, with an overall root-mean-square error (RMSE) of 17.50 W m−2 and an R value of 0.96 for the test dataset on a daily time scale. These values were 11.19 W m−2 and 0.98, respectively, on a monthly time scale. The effects of land cover and elevation were further studied to comprehensively evaluate the performance of each machine learning method. All machine learning methods achieved better results over the grass land cover type but relatively worse results over the tundra. GBRT, RF, and MARS methods were found to show good performance at both the high- and low-altitude sites.
Numerical Simulation of Meteorological Conditions and Air Quality above Tomsk, West Siberia
Authors: Starchenko Alexander , Shelmina Elena , Kizhner Lubov
Published: October 2020

This paper presents the simulation results of meteorological and air quality parameters for the Siberian city of Tomsk predicted by mesoscale meteorological and chemical transport models. Changes in the numerically predicted wind velocity fields, temperature, and concentration of major air pollutants were modelled in detail for the selected dates, when anticyclonic weather with cloud free and calm wind conditions was observed in Tomsk. The simulation results have shown that stable or neutral atmospheric stratification with light wind and low ambient air temperature (−30, −20 °C) are the most unfavorable meteorological conditions leading to the near surface pollutants accumulation. The numerical calculation results were compared with observation data from the Joint Use Center (JUC) “Atmosphere” of V.E. Zuev Institute of Atmospheric Optics (IAO) and showed good agreement.
Rapid Clinical Management of Leishmaniasis in Emergency Department: A Case Report with Clinical Review of Recent Literature
Authors: Piccioni Andrea , Valletta Federico , Zanza Christian , Longhitano Yaroslava , Torelli Enrico , de Cunzo Tommaso , Esperide Alessandra , Brigida Mattia , Ojetti Veronica , Covino Marcello , Taurone Samanta , Ralli Massimo , Artico Marco , Franceschi Francesco
Published: October 2020

Systemic or localized lympho-adenomegaly is a common cause of access to the emergency department (ED), and differential diagnosis is often complicated. The combination of anamnesis, physical examination, laboratory tests, and instrumental diagnosis are extremely important to orientate toward a rapid and correct therapy, even if a prompt discrimination of the etiology of this lymphadenomegaly is not often possible. Our aim with this review is to improve the management of a differential diagnosis between hematological and infective diseases as leishmaniasis in ED and suggest quick diagnostic techniques that might be useful for early identification. Together in the review, we describe a case report of a young man affected from visceral leishmaniasis who presented to our ED and was incorrectly addressed to the wrong ward for the study of his condition. Subsequently, we focus on the clinical presentation of visceral leishmaniasis and compare it to the most common differential diagnoses that are usually taken into account in the management of such patients.
Identification of Putative Non-Substrate-Based XT-I Inhibitors by Natural Product Library Screening
Authors: Ly Thanh-Diep , Kleine Anika , Fischer Bastian , Schmidt Vanessa , Hendig Doris , Kuhn Joachim , Knabbe Cornelius , Faust Isabel
Published: October 2020

Fibroproliferative diseases are characterized by excessive accumulation of extracellular matrix (ECM) components leading to organ dysfunction. This process is characterized by an increase in myofibroblast content and enzyme activity of xylosyltransferase-I (XT-I), the initial enzyme in proteoglycan (PG) biosynthesis. Therefore, the inhibition of XT-I could be a promising treatment for fibrosis. We used a natural product-inspired compound library to identify non-substrate-based inhibitors of human XT-I by UPLC-MS/MS. We combined this cell-free approach with virtual and molecular biological analyses to confirm and prioritize the inhibitory potential of the compounds identified. The characterization for compound potency in TGF-β1-driven XYLT1 transcription regulation in primary dermal human fibroblasts (key cells in ECM remodeling) was addressed by gene expression analysis. Consequently, we identified amphotericin B and celastrol as new non-substrate-based XT-I protein inhibitors. Their XT-I inhibitory effects were mediated by an uncompetitive or a competitive inhibition mode, respectively. Both compounds reduced the cellular XYLT1 expression level and XT-I activity. We showed that these cellular inhibitor-mediated changes involve the TGF-β and microRNA-21 signaling pathway. The results of our study provide a strong rationale for the further optimization and future usage of the XT-I inhibitors identified as promising therapeutic agents of fibroproliferative diseases.
Curcumin’s Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions
Authors: Zhai Kevin , Brockmüller Aranka , Kubatka Peter , Shakibaei Mehdi , Büsselberg Dietrich
Published: October 2020

Curcumin, a natural polyphenolic compound derived from the South Asian turmeric plant (Curcuma longa), has well-characterized antioxidant, anti-inflammatory, anti-protein-aggregate, and anticancer properties. Neuroblastoma (NB) is a cancer of the nervous system that arises primarily in pediatric patients. In order to reduce the multiple disadvantages and side effects of conventional oncologic modalities and to potentially overcome cancer drug resistance, natural substances such as curcumin are examined as complementary and supportive therapies against NB. In NB cell lines, curcumin by itself promotes apoptosis and cell cycle arrest through the suppression of serine–threonine kinase Akt and nuclear factor kappa of activated B-cells (NF-κB) signaling, induction of mitochondrial dysfunction, and upregulation of p53 and caspase signaling. While curcumin demonstrates anti-NB efficacy in vitro, cross-validation between NB cell types is currently lacking for many of its specific mechanistic activities. Furthermore, curcumin’s low bioavailability by oral administration, poor absorption, and relative insolubility in water pose challenges to its clinical introduction. Numerous curcumin formulations, including nanoparticles, nanocarriers, and microemulsions, have been developed, with these having some success in the treatment of NB. In the future, standardization and further basic and preclinical trials will be required to ensure the safety of curcumin formulations. While the administration of curcumin is clinically safe even at high doses, clinical trials are necessary to substantiate the practical efficacy of curcumin in the prevention and treatment of NB.
Biophysical and Lipidomic Biomarkers of Cardiac Remodeling Post-Myocardial Infarction in Humans
Authors: Samouillan Valerie , Martinez de Lejarza Samper Ignacio Miguel , Benitez Amaro Aleyda , Vilades David , Dandurand Jany , Casas Josefina , Jorge Esther , de Gonzalo Calvo David , Gallardo Alberto , Lerma Enrique , Guerra Jose Maria , Carreras Francesc , Leta Ruben , Llorente Cortes Vicenta
Published: October 2020

Few studies have analyzed the potential of biophysical parameters as markers of cardiac remodeling post-myocardial infarction (MI), particularly in human hearts. Fourier transform infrared spectroscopy (FTIR) illustrates the overall changes in proteins, nucleic acids and lipids in a single signature. The aim of this work was to define the FTIR and lipidomic pattern for human left ventricular remodeling post-MI. A total of nine explanted hearts from ischemic cardiomyopathy patients were collected. Samples from the right ventricle (RV), left ventricle (LV) and infarcted left ventricle (LV INF) were subjected to biophysical (FTIR and differential scanning calorimetry, DSC) and lipidomic (liquid chromatography–high-resolution mass spectrometry, LC–HRMS) studies. FTIR evidenced deep alterations in the myofibers, extracellular matrix proteins, and the hydric response of the LV INF compared to the RV or LV from the same subject. The lipid and esterified lipid FTIR bands were enhanced in LV INF, and both lipid indicators were tightly and positively correlated with remodeling markers such as collagen, lactate, polysaccharides, and glycogen in these samples. Lipidomic analysis revealed an increase in several species of sphingomyelin (SM), hexosylceramide (HexCer), and cholesteryl esters combined with a decrease in glycerophospholipids in the infarcted tissue. Our results validate FTIR indicators and several species of lipids as useful markers of left ventricular remodeling post-MI in humans.
Archaeal DNA Repair Mechanisms
Authors: Marshall Craig J. , Santangelo Thomas J.
Published: October 2020

Archaea often thrive in environmental extremes, enduring levels of heat, pressure, salinity, pH, and radiation that prove intolerable to most life. Many environmental extremes raise the propensity for DNA damaging events and thus, impact DNA stability, placing greater reliance on molecular mechanisms that recognize DNA damage and initiate accurate repair. Archaea can presumably prosper in harsh and DNA-damaging environments in part due to robust DNA repair pathways but surprisingly, no DNA repair pathways unique to Archaea have been described. Here, we review the most recent advances in our understanding of archaeal DNA repair. We summarize DNA damage types and their consequences, their recognition by host enzymes, and how the collective activities of many DNA repair pathways maintain archaeal genomic integrity.
New Antibacterial Peptides from the Freshwater Mollusk Pomacea poeyana (Pilsbry, 1927)
Authors: González García Melaine , Rodríguez Armando , Alba Annia , Vázquez Antonio A. , Morales Vicente Fidel E. , Pérez-Erviti Julio , Spellerberg Barbara , Stenger Steffen , Grieshober Mark , Conzelmann Carina , Münch Jan , Raber Heinz , Kubiczek Dennis , Rosenau Frank , Wiese Sebastian , Ständker Ludger , Otero-González Anselmo
Published: October 2020

Antimicrobial peptides (AMPs) are biomolecules with antimicrobial activity against a broad group of pathogens. In the past few decades, AMPs have represented an important alternative for the treatment of infectious diseases. Their isolation from natural sources has been widely investigated. In this sense, mollusks are promising organisms for the identification of AMPs given that their immune system mainly relies on innate response. In this report, we characterized the peptide fraction of the Cuban freshwater snail Pomacea poeyana (Pilsbry, 1927) and identified 37 different peptides by nanoLC-ESI-MS-MS technology. From these peptide sequences, using bioinformatic prediction tools, we discovered two potential antimicrobial peptides named Pom-1 (KCAGSIAWAIGSGLFGGAKLIKIKKYIAELGGLQ) and Pom-2 (KEIERAGQRIRDAIISAAPAVETLAQAQKIIKGG). Database search revealed that Pom-1 is a fragment of Closticin 574 previously isolated from the bacteria Clostridium tyrobutyrium, and Pom-2 is a fragment of cecropin D-like peptide first isolated from Galleria mellonella hemolymph. These sequences were chemically synthesized and evaluated against different human pathogens. Interestingly, structural predictions of both peptides in the presence of micelles showed models that comprise two alpha helices joined by a short loop. The CD spectra analysis of Pom-1 and Pom-2 in water showed for both structures a high random coil content, a certain content of α-helix and a low β-sheet content. Like other described AMPs displaying a disordered structure in water, the peptides may adopt a helical conformation in presence of bacterial membranes. In antimicrobial assays, Pom-1 demonstrated high activity against the Gram-negative bacteria Pseudomonas aeruginosa and moderate activity against Klebsiella pneumoniae and Listeria monocytogenes. Neither of the two peptides showed antifungal action. Pom-1 moderately inhibits Zika Virus infection but slightly enhances HIV-1 infectivion in vitro. The evaluation of cell toxicity on primary human macrophages did not show toxicity on THP-1 cells, although slight overall toxicity was observed in high concentrations of Pom-1. We assume that both peptides may play a key role in innate defense of P. poeyana and represent promising antimicrobial candidates for humans.
Dual Effects of Beta-Hydroxy-Beta-Methylbutyrate (HMB) on Amino Acid, Energy, and Protein Metabolism in the Liver and Muscles of Rats with Streptozotocin-Induced Type 1 Diabetes
Authors: Holeček Milan , Vodeničarovová Melita , Fingrová Radana
Published: October 2020

Beta-hydroxy-beta-methyl butyrate (HMB) is a unique product of leucine catabolism with positive effects on protein balance. We have examined the effects of HMB (200 mg/kg/day via osmotic pump for 7 days) on rats with diabetes induced by streptozotocin (STZ, 100 mg/kg intraperitoneally). STZ induced severe diabetes associated with muscle wasting, decreased ATP in the liver, and increased α-ketoglutarate in muscles. In plasma, liver, and muscles increased branched-chain amino acids (BCAAs; valine, isoleucine, and leucine) and decreased serine. The decreases in mass and protein content of muscles and increases in BCAA concentration were more pronounced in extensor digitorum longus (fast-twitch muscle) than in soleus muscle (slow-twitch muscle). HMB infusion to STZ-treated animals increased glycemia and serine in the liver, decreased BCAAs in plasma and muscles, and decreased ATP in the liver and muscles. The effects of HMB on the weight and protein content of tissues were nonsignificant. We concluded that fast-twitch muscles are more sensitive to STZ than slow-twitch muscles and that HMB administration to STZ-treated rats has dual effects. Adjustments of BCAA concentrations in plasma and muscles and serine in the liver can be considered beneficial, whereas the increased glycemia and decreased ATP concentrations in the liver and muscles are detrimental.
Plasma Membrane Protein Nce102 Modulates Morphology and Function of the Yeast Vacuole
Authors: Vaskovicova Katarina , Vesela Petra , Zahumensky Jakub , Folkova Dagmar , Balazova Maria , Malinsky Jan
Published: October 2020

Membrane proteins are targeted not only to specific membranes in the cell architecture, but also to distinct lateral microdomains within individual membranes to properly execute their biological functions. Yeast tetraspan protein Nce102 has been shown to migrate between such microdomains within the plasma membrane in response to an acute drop in sphingolipid levels. Combining microscopy and biochemistry methods, we show that upon gradual ageing of a yeast culture, when sphingolipid demand increases, Nce102 migrates from the plasma membrane to the vacuole. Instead of being targeted for degradation it localizes to V-ATPase-poor, i.e., ergosterol-enriched, domains of the vacuolar membrane, analogous to its plasma membrane localization. We discovered that, together with its homologue Fhn1, Nce102 modulates vacuolar morphology, dynamics, and physiology. Specifically, the fusing of vacuoles, accompanying a switch of fermenting yeast culture to respiration, is retarded in the strain missing both proteins. Furthermore, the absence of either causes an enlargement of ergosterol-rich vacuolar membrane domains, while the vacuoles themselves become smaller. Our results clearly show decreased stability of the V-ATPase in the absence of either Nce102 or Fhn1, a possible result of the disruption of normal microdomain morphology of the vacuolar membrane. Therefore, the functionality of the vacuole as a whole might be compromised in these cells.
Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches
Authors: Fania Luca , Didona Dario , Morese Roberto , Campana Irene , Coco Valeria , Di Pietro Francesca Romana , Ricci Francesca , Pallotta Sabatino , Candi Eleonora , Abeni Damiano , Dellambra Elena
Published: October 2020

Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhibitors, such as vismodegib and sonidegib, are successfully used as targeted treatment for advanced or metastatic BCC. Furthermore, the implementation of prevention measures has demonstrated to be useful in the patient management.
Development of a Rapid, Antimicrobial Susceptibility Test for E. coli Based on Low-Cost, Screen-Printed Electrodes
Authors: Hannah Stuart , Dobrea Alexandra , Lasserre Perrine , Blair Ewen O. , Alcorn David , Hoskisson Paul A. , Corrigan Damion K.
Published: October 2020

Antibiotic resistance has been cited by the World Health Organisation (WHO) as one of the greatest threats to public health. Mitigating the spread of antibiotic resistance requires a multipronged approach with possible interventions including faster diagnostic testing and enhanced antibiotic stewardship. This study employs a low-cost diagnostic sensor test to rapidly pinpoint the correct antibiotic for treatment of infection. The sensor comprises a screen-printed gold electrode, modified with an antibiotic-seeded hydrogel to monitor bacterial growth. Electrochemical growth profiles of the common microorganism, Escherichia coli (E. coli) (ATCC 25922) were measured in the presence and absence of the antibiotic streptomycin. Results show a clear distinction between the E. coli growth profiles depending on whether streptomycin is present, in a timeframe of ≈2.5 h (p < 0.05), significantly quicker than the current gold standard of culture-based antimicrobial susceptibility testing. These results demonstrate a clear pathway to a low cost, phenotypic and reproducible antibiotic susceptibility testing technology for the rapid detection of E. coli within clinically relevant concentration ranges for conditions such as urinary tract infections.
The Aetiology of Olfactory Dysfunction and Its Relationship to Diet Quality
Authors: Stevenson Richard J. , Mahmut Mehmet K. , Horstmann Annette , Hummel Thomas
Published: October 2020

People with olfactory loss may choose foods rich in sugar, salt and fat to compensate their loss—foods that constitute a Western-style diet (WSD). However, olfactory dysfunction has not been consistently linked to any particular type of dietary change. Here we considered whether the aetiology of olfactory dysfunction may affect consumption of a WSD. Two-hundred and twenty-two people with olfactory dysfunction of varying cause, were tested for chemosensory performance and their frequency of consumption of a WSD. There was no evidence of a link between a WSD and olfactory dysfunction at the aggregate level, but an aetiology-based approach revealed various patterns, showing both positive and negative associations between olfactory performance and consumption of a WSD. We suggest a number of reasons why, in certain cases, greater olfactory dysfunction may be linked to lower intakes of a WSD, and the role that different aetiologies may have in affecting choices for foods that may appeal following olfactory impairment.
The COVID-19 Pandemic Can Impact Perinatal Mental Health and the Health of the Offspring
Authors: Caparros-Gonzalez Rafael A. , Ganho-Ávila Ana , Torre-Luque Alejandro de la
Published: October 2020

The COVID-19 ongoing pandemic constitutes a major challenge for countries throughout the world due to the rapid spread of SARS-CoV-2 and devastating consequences in health. No one is free from COVID-19 impact. In this regard, pregnant women are not the exception. The COVID-19 outbreak represents a massive source of stressful agents for women and their babies during the perinatal period. The COVID-19 pandemic has been suggested to potentially have short- and long-term detrimental effects on pregnant women and the baby. These adverse consequences range from mental to medical diseases. During the last centuries, several dreadful and fatal incidents have put pregnant women and their babies at higher risk of mortality and health deterioration. For example, it has been informed that women exposed to the 1918 flu pandemic (commonly known as the Spanish flu) while pregnant showed higher rates of premature delivery in the short term. Long-term consequences have also been reported and individuals (both males and females) who were exposed to the 1918 flu pandemic while in utero had a higher risk of developing schizophrenia, diabetes, coronary heart disease or cancer throughout their lifespan.
Characterization of Molecular Spacer-Functionalized Nanostructured Carbons for Electrical Energy Storage Supercapacitor Materials
Authors: Zuczek Justin , Bonfield Matthew , Elathram Nesreen , R. Hixson William , Kongruengkit Terawit , B. Mitchell James , Zelenka Nickolas , D. Popov Leonid , Morozov Andrey , N. Shcherbakov Igor , C. Poler Jordan
Published: October 2020

The use of molecular spacers between Carbon Nanotubes (CNTs) has been shown to increase the ion-accessible surface area for use in supercapacitor materials. Maintaining porosity and electrical conductivity is important for maximizing capacitance, energy storage, and power. Two reported novel coordination complexes have shown exceptional Faradaic charge transfer and binding capabilities to prevent CNT aggregation. Dispersion stability measurements show less aggregation of HiPco Single Walled CNTs (SWCNTs) compared to other chirality and multilayered nanotubes. Cu2FcOH binds weakly to CNTs compared +2Zn2 and +2Ru2 due to Columbic electrostatic interactions, which is favorable because it does not collapse the electrical double layer as strongly as +2Zn2 or +2Ru2. Adsorption isotherms and a full characterization (1H NMR, ATR FT-IR, UV-Vis, CV) of these novel complexes are presented. Electrical characterization using CV, charge discharge, and electrochemical impedance spectroscopy and the supercapacitor performance of functionalized thin film electrodes are presented as a function of spacer properties and nanostructured carbon tube diameter. This study uses rigid, earth-abundant coordination complexes that bind to and intercalate between SWCNTs. These functionalized nanostructured carbons are then used to make electrodes for electrical double layer supercapacitors. A complete description of the synthesis, characterization, and processing of these materials is described.
Prognostic Significance of Oxidation Pathway Mutations in Recurrent Laryngeal Squamous Cell Carcinoma
Authors: Heft Neal Molly E. , Bhangale Apurva D. , Birkeland Andrew C. , McHugh Jonathan B. , Shuman Andrew G. , Rosko Andrew J. , Swiecicki Paul L. , Spector Matthew E. , Brenner J. Chad
Published: October 2020

Organ preservation protocols are commonly used as first line therapy for advanced laryngeal cancer. Recurrence thereafter is associated with poor survival. The aim of this study is to identify genetic alterations associated with survival among patients with recurrent laryngeal cancer undergoing salvage laryngectomy. Sixty-two patients were sequenced using a targeted panel, of which twenty-two also underwent transcriptome sequencing. Alterations were grouped based on biologic pathways and survival outcomes were assessed using Kaplan-Meier analysis and multivariate cox regression. Select pathways were evaluated against The Cancer Genome Atlas (TCGA) data. Patients with mutations in the Oxidation pathway had significantly worse five-year disease specific survival (1% vs. 76%, p = 0.02), while mutations in the HN-Immunity pathway were associated with improved five-year disease specific survival (100% vs. 62%, p = 0.02). Multivariate analysis showed mutations in the Oxidation pathway remained an independent predictor of disease specific survival (HR 3.2, 95% CI 1.1–9.2, p = 0.03). Transcriptome analysis of recurrent tumors demonstrated that alterations in the Oxidation pathway were associated a positive Ragnum hypoxia signature score, consistent with enhanced pathway activity. Further, TCGA analyses demonstrated the prognostic value of oxidation pathway alterations in previously untreated disease. Alterations in the Oxidation pathway are associated with survival among patients with recurrent laryngeal cancer. These prognostic genetic biomarkers may inform precision medicine protocols and identify putatively targetable pathways to improve survival in this cohort.
Is There a Causal Relationship between Childhood Obesity and Acute Lymphoblastic Leukemia? A Review
Authors: Dushnicky Molly J. , Nazarali Samina , Mir Adhora , Portwine Carol , Samaan Muder Constantine
Published: October 2020

Childhood obesity is a growing epidemic with numerous global health implications. Over the past few years, novel insights have emerged about the contribution of adult obesity to cancer risk, but the evidence base is far more limited in children. While pediatric patients with acute lymphoblastic leukemia (ALL) are at risk of obesity, it is unclear if there are potential causal mechanisms by which obesity leads to ALL development. This review explores the endocrine, metabolic and immune dysregulation triggered by obesity and its potential role in pediatric ALL’s genesis. We describe possible mechanisms, including adipose tissue attraction and protection of lymphoblasts, and their impact on ALL chemotherapies’ pharmacokinetics. We also explore the potential contribution of cytokines, growth factors, natural killer cells and adipose stem cells to ALL initiation and propagation. While there are no current definite causal links between obesity and ALL, critical questions persist as to whether the adipose tissue microenvironment and endocrine actions can play a causal role in childhood ALL, and there is a need for more research to address these questions.
Regulation of Epithelial–Mesenchymal Plasticity by the E3 Ubiquitin-Ligases in Cancer
Authors: Rodríguez-Alonso Andrea , Casas-Pais Alba , Roca-Lema Daniel , Graña Begoña , Romay Gabriela , Figueroa Angélica
Published: October 2020

The epithelial–mesenchymal plasticity (EMP) is a process by which epithelial cells acquire the ability to dynamically switch between epithelial and mesenchymal phenotypic cellular states. Epithelial cell plasticity in the context of an epithelial-to-mesenchymal transition (EMT) confers increased cell motility, invasiveness and the ability to disseminate to distant sites and form metastasis. The modulation of molecularly defined targets involved in this process has become an attractive therapeutic strategy against cancer. Protein degradation carried out by ubiquitination has gained attention as it can selectively degrade proteins of interest. In the ubiquitination reaction, the E3 ubiquitin-ligases are responsible for the specific binding of ubiquitin to a small subset of target proteins, and are considered promising anticancer drug targets. In this review, we summarize the role of the E3 ubiquitin-ligases that control targeted protein degradation in cancer-EMT, and we highlight the potential use of the E3 ubiquitin-ligases as drug targets for the development of small-molecule drugs against cancer.
An Escape from Noble Metals for Generating Urethanes via Reductive Carbonylation of Nitroarenes over FeSe2/γ-Al2O3 †
Authors: Tran Anh Vy , Huynh Nguyen Thuy Tram , Nguyen Thanh Tung , Lee Hye Jin , Baek Jayeon , Kim Yong Jin
Published: October 2020

The reaction of FeCl3, SeO2, and Pyridine (Py) in the presence of methanol (MeOH) under CO pressure generates a black precipitate, which has been confirmed as ferric di-selenide, FeSe2 through different structure characterization methods. Furthermore, impregnation of 5 wt% of FeSe2 onto γ-Al2O3 exhibits better catalytic performance than FeSe2 due to the highly dispersed and smaller particle sizes ca. 200–300 nm. The reductive carbonylation of nitrobenzene (NB) was investigated over FeSe2/γ-Al2O3 as a heterogeneous catalyst, delivering an excellent yield and high selectivity of methyl-N-phenyl carbamate (MPC). Moreover, a set of reactions was performed with variation in the reaction time, temperature, and pressure to investigate the effects of these factors. In particular, FeSe2/γ-Al2O3 is highly stable and can be recycled for up to five cycles without significant loss in catalytic performance. A mechanistic study was also conducted on this low-cost catalyst system, especially proposing a crucial role of FeSe2 (μ-CO) active species.
Impact of Polyallylamine Hydrochloride on Gene Expression and Karyotypic Stability of Multidrug Resistant Transformed Cells
Authors: Alekseenko Larisa , Shilina Mariia , Kozhukharova Irina , Lyublinskaya Olga , Fridlyanskaya Irina , Nikolsky Nikolay , Grinchuk Tatiana
Published: October 2020

The synthetic polymer, polyallylamine hydrochloride (PAA), is found in a variety of applications in biotechnology and medicine. It is used in gene and siRNA transfer, to form microcapsules for targeted drug delivery to damaged and tumor cells. Conventional chemotherapy often does not kill all cancer cells and leads to multidrug resistance (MDR). Until recently, studies of the effects of PAA on cells have mainly focused on their morphological and genetic characteristics immediately or several hours after exposure to the polymer. The properties of the cell progeny which survived the sublethal effects of PAA and resumed their proliferation, were not monitored. The present study demonstrated that treatment of immortalized Chinese hamster cells CHLV-79 RJK sensitive (RJK) and resistant (RJKEB) to ethidium bromide (EB) with cytotoxic doses of PAA, selected cells with increased karyotypic instability, were accompanied by changes in the expression of p53 genes c-fos, topo2-α, hsp90, hsc70. These changes did not contribute to the progression of MDR, accompanied by the increased sensitivity of these cells to the toxic effects of doxorubicin (DOX). Our results showed that PAA does not increase the oncogenic potential of immortalized cells and confirmed that it can be used for intracellular drug delivery for anticancer therapy.
Tafazzin Mutation Affecting Cardiolipin Leads to Increased Mitochondrial Superoxide Anions and Mitophagy Inhibition in Barth Syndrome
Authors: Petit Patrice , Ardilla-Osorio Hector , Penalvia Lucile , Rainey Nathan E.
Published: October 2020

Tafazzin is a phospholipid transacylase that catalyzes the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation. Mutations of the tafazzin gene cause Barth syndrome, which is characterized by mitochondrial dysfunction and dilated cardiomyopathy, leading to premature death. However, the molecular mechanisms underlying the cause of mitochondrial dysfunction in Barth syndrome remain poorly understood. We again highlight the fact that the tafazzin deficiency is also linked to defective oxidative phosphorylation associated with oxidative stress. All the mitochondrial events are positioned in a context where mitophagy is a key element in mitochondrial quality control. Here, we investigated the role of tafazzin in mitochondrial homeostasis dysregulation and mitophagy alteration. Using a HeLa cell model of tafazzin deficiency, we show that dysregulation of tafazzin in HeLa cells induces alteration of mitophagy. Our findings provide some additional insights into mitochondrial dysfunction associated with Barth syndrome, but also show that mitophagy inhibition is concomitant with apoptosis dysfunction through the inability of abnormal mitochondrial cardiolipin to assume its role in cytoplasmic signal transduction. Our work raises hope that pharmacological manipulation of the mitophagic pathway together with mitochondrially targeted antioxidants may provide new insights leading to promising treatment for these highly lethal conditions.
The Ionophores CCCP and Gramicidin but Not Nigericin Inhibit Trypanosoma brucei Aquaglyceroporins at Neutral pH
Authors: Petersen Lea Madlen , Beitz Eric
Published: October 2020

Human African trypanosomiasis (HAT) is caused by Trypanosoma brucei parasites. The T. brucei aquaglyceroporin isoform 2, TbAQP2, has been linked to the uptake of pentamidine. Negative membrane potentials and transmembrane pH gradients were suggested to promote transport of the dicationic antitrypanosomal drug. Application of ionophores to trypanosomes further hinted at direct inhibition of TbAQP2 by carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Here, we tested for direct effects of three classical ionophores (CCCP, nigericin, gramicidin) on the functionality of TbAQP2 and the related TbAQP3 at conditions that are independent from the membrane potential or a proton gradient. We expressed TbAQP2 and TbAQP3 in yeast, and determined permeability of uncharged glycerol at neutral pH using stopped-flow light scattering. The mobile proton carrier CCCP directly inhibited TbAQP2 glycerol permeability at an IC50 of 2 µM, and TbAQP3 to a much lesser extent (IC50 around 1 mM) likely due to different selectivity filter layouts. Nigericin, another mobile carrier, left both isoforms unaffected. The membrane-integral pore-forming gramicidin evenly inhibited TbAQP2 and TbAQP2 in the double-digit micromolar range. Our data exemplify the need for suitable controls to detect unwanted ionophore side effects even when used at concentrations that are typically recommended to disturb the transmembrane ion distribution.
Discovery of Targetable Genetic Alterations in NSCLC Patients with Different Metastatic Patterns Using a MassARRAY-Based Circulating Tumor DNA Assay
Authors: Belloum Yassine , Janning Melanie , Mohme Malte , Simon Ronald , Kropidlowski Jolanthe , Sartori Alexander , Irwin Darryl , Westphal Manfred , Lamszus Katrin , Loges Sonja , Riethdorf Sabine , Pantel Klaus , Wikman Harriet
Published: October 2020

Circulating tumor DNA (ctDNA) has shown great promise as a minimally invasive liquid biopsy for personalized cancer diagnostics especially among metastatic patients. Here, we used a novel sensitive assay to detect clinically relevant mutations in ctDNA in blood plasma from metastatic non-small cell lung cancer (NSCLC) patients, including patients with a limited oligo–brain metastatic disease. We analyzed 66 plasma samples from 56 metastatic NSCLC patients for 74 hotspot mutations in five genes commonly mutated in NSCLC using a novel MassARRAY-based lung cancer panel with a turnaround time of only 3 days. Mutations in plasma DNA could be detected in 28 out of 56 patients (50.0%), with a variant allele frequency (VAF) ranging between 0.1% and 5.0%. Mutations were detected in 50.0% of patients with oligo–brain metastatic disease, although the median VAF was lower (0.4%) compared to multi-brain metastatic patients (0.9%) and patients with extra-cranial metastatic progression (1.2%). We observed an overall concordance of 86.4% (n = 38/44) for EGFR status between plasma and tissue. The MassARRAY technology can detect clinically relevant mutations in plasma DNA from metastatic NSCLC patients including patients with limited, oligo–brain metastatic disease.