bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Utility and the Yield of Single Nucleotide Polymorphism Array in Prenatal Diagnosis of Fetal Central Nervous System Abnormalities
Authors: Cai Meiying , Huang Hailong , Xu Liangpu , Lin Na
Published: May 2021

Applying single nucleotide polymorphism (SNP) array to identify the etiology of fetal central nervous system (CNS) abnormality, and exploring its association with chromosomal abnormalities, copy number variations, and obstetrical outcome. 535 fetuses with CNS abnormalities were analyzed using karyotype analysis and SNP array. Among the 535 fetuses with CNS abnormalities, chromosomal abnormalities were detected in 36 (6.7%) of the fetuses, which were consistent with karyotype analysis. Further, additional 41 fetuses with abnormal copy number variations (CNVs) were detected using SNP array (the detection rate of additional abnormal CNVs was 7.7%). The rate of chromosomal abnormalities, but not that of pathogenic CNVs in CNS abnormalities with other ultrasound abnormalities was significantly higher than that in isolated CNS abnormalities. The rates of chromosomal abnormalities and pathogenic CNVs in fetuses with spine malformation (50%), encephalocele (50%), subependymal cyst (20%), and microcephaly (16.7%) were higher than those with other isolated CNS abnormalities. The pregnancies for 36 cases with chromosomal abnormalities, 18 cases with pathogenic CNVs, and three cases with VUS CNVs were terminated. SNP array should be used in the prenatal diagnosis of fetuses with CNS abnormalities, which can enable better prenatal assessment and genetic counseling, and affect obstetrical outcomes.
Chronic Sulfasalazine Treatment in Mice Induces System xc− - Independent Adverse Effects
Authors: Verbruggen Lise , Sprimont Lindsay , Bentea Eduard , Janssen Pauline , Gharib Azzedine , Deneyer Lauren , De Pauw Laura , Lara Olaya , Sato Hideyo , Nicaise Charles , Massie Ann
Published: May 2021

Despite ample evidence for the therapeutic potential of inhibition of the cystine/glutamate antiporter system xc− in neurological disorders and in cancer, none of the proposed inhibitors is selective. In this context, a lot of research has been performed using the EMA- and FDA-approved drug sulfasalazine (SAS). Even though this molecule is already on the market for decades as an anti-inflammatory drug, serious side effects due to its use have been reported. Whereas for the treatment of the main indications, SAS needs to be cleaved in the intestine into the anti-inflammatory compound mesalazine, it needs to reach the systemic circulation in its intact form to allow inhibition of system xc−. The higher plasma levels of intact SAS (or its metabolites) might induce adverse effects, independent of its action on system xc−. Some of these effects have however been attributed to system xc− inhibition, calling into question the safety of targeting system xc−. In this study we chronically treated system xc− - deficient mice and their wildtype littermates with two different doses of SAS (160 mg/kg twice daily or 320 mg/kg once daily, i.p.) and studied some of the adverse effects that were previously reported. SAS had a negative impact on the survival rate, the body weight, the thermoregulation and/or stress reaction of mice of both genotypes, and thus independent of its inhibitory action on system xc−. While SAS decreased the total distance travelled in the open-field test the first time the mice encountered the test, it did not influence this parameter on the long-term and it did not induce other behavioral changes such as anxiety- or depressive-like behavior. Finally, no major histological abnormalities were observed in the spinal cord. To conclude, we were unable to identify any undesirable system xc−-dependent effect of chronic administration of SAS.
Does Oral Apigenin Have Real Potential for a Therapeutic Effect in the Context of Human Gastrointestinal and Other Cancers?
Authors: DeRango-Adem Eva F. , Blay Jonathan
Published: May 2021

Apigenin (4′, 5, 7-trihydroxyflavone) is a plant flavone that has been found to have various actions against cancer cells. We evaluated available evidence to determine whether it is feasible for apigenin to have such effects in human patients.

Apigenin taken orally is systemically absorbed and recirculated by enterohepatic and local intestinal pathways. Its bioavailability is in the region of 30%. Once absorbed from the oral route it reaches maximal circulating concentration (Cmax) after a time (Tmax) of 0.5–2.5h, with an elimination half-life (T1/2) averaging 2.52 ± 0.56h.

Using a circulating concentration for efficacy of 1–5μmol/L as the target, we evaluated data from both human and rodent pharmacokinetic studies to determine if a therapeutic concentration would be feasible. We find that oral intake of dietary materials would require heroic ingestion amounts and is not feasible. However, use of supplements of semi-purified apigenin in capsule form could reach target blood levels using amounts that are within the range currently acceptable for other supplements and medications. Modified formulations or parenteral injection are suitable but may not be necessary.

Further work with direct studies of pharmacokinetics and clinical outcomes are necessary to fully evaluate whether apigenin will contribute to a useful clinical strategy, but given emerging evidence that it may interact beneficially with chemotherapeutic drugs, this is worthy of emphasis. In addition, more effective access to intestinal tissues from the oral route raises the possibility that apigenin may be of particular relevance to gastrointestinal disorders including colorectal cancer.
Eimeria acervulina Microneme Protein 3 Inhibits Apoptosis of the Chicken Duodenal Epithelial Cell by Targeting the Casitas B-Lineage Lymphoma Protein
Authors: Wang Pu , Jia Yukun , Han Yue , Wang Weirong , Zhu Yiran , Xu Jiali , Guan Chiyu , Ying Jinpeng , Deng Simin , Wang Jing , Zhang Xian , Chen Mianmian , Cheng Changyong , Song Houhui
Published: May 2021

Eimeria acervulina (E. acervulina) causes coccidiosis in poultry which persists as economic pain worldwide. Most damage to the intestinal mucosa results from apoptosis of the infected intestinal epithelial cells. The Microneme protein 3 (MIC3) protein is a key virulence factor in some parasites involved in host cell apoptosis inhibition. Here, we studied whether and how MIC3 affects the apoptosis in E. acervulina infected chicken duodenal epithelial cells. Through flow cytometry (FCM), we found that the presence of merozoites and the overexpression of MIC3 significantly decreased apoptosis and the activity of caspase-3 in chicken duodenal epithelial cells at 4, 6, and 8 h post merozoite infection (P < 0.01). Silencing the Casitas B-lineage lymphoma (CBL) protein, a host receptor for MIC3 with shRNA was shown to promote apoptosis in the chicken duodenal epithelial cells. The early apoptotic rate of host cells in the lentiviral-MIC3 group was significantly lower than that in the lentiviral-MIC3 + shRNA CBL group at 4 h after MIC3 expression (P < 0.01), and it was moderately decreased in the lentiviral-MIC3 + shRNA CBL group compared with that in the shRNA CBL group. Our data indicated that MIC3 inhibited early apoptosis of E. acervulina infected chicken duodenal epithelial cells by targeting host receptor-CBL protein. These findings unveiled one of the mechanisms of how intracellular parasites affect the apoptosis of infected host cells, which provided a deeper understanding of their pathogenesis.
Multispacer Sequence Typing for Mycobacterium bovis Genotyping
Authors: Sales Érica Bravo , Fonseca Antônio Augusto , Gonçalves Cristina Magalhães , Lage Andrey Pereira , Andrade Giovanna Ivo , Suffys Philip Noel , Gomes Harrison Magdinier , Dias Natanael Lamas , Ferreira Neto José Soares , Guimarães Ana Marcia de Sá , Heinemann Marcos Bryan
Published: May 2021

The molecular typing of Mycobacterium bovis, which causes bovine tuberculosis, can be accomplished by combining different polymorphic markers, contributing to its epidemiological investigation. Multispacer sequence typing (MST) is a sequencing-based method that employs intergenic regions susceptible to higher mutation rates given the low selection pressure. It has been applied to M. tuberculosis, but not to M. bovis. The aim of this study was to evaluate a MST for M. bovis. A total of 58 strains isolated from tissues with lesions suggestive of bovine tuberculosis, coming from cattle herds in six Brazilian states and four standard samples of M. bovis were typified employing the MST technique. Fourteen intergenic regions were used, and four types of genetic events were reported: single nucleotide mutation (SNP), insertion, deletion, and tandem repeat (TR). Seven loci were chosen for typing. Twenty-eight type sequences (ST) were identified, indicating type sequences (ST) were identified, indicating a 92.9% HGDI (Hunter Gaston Discriminatory Index). The data were used to analyze the evolutionary patterns of these isolates and correlate them to phylogeographic lineages based on the formation of clonal complexes generated from eBURST software. Later, we associated the MST with spoligotyping technique, currently considered the gold standard for classification of M. bovis. The results support the MST as an alternative method for genotyping of M. bovis. The method has the advantage of sequencing and the availability of sequences analyzed in public databases, which can be used by professionals around the world as a tool for further analysis. This was the first study to identify the variability of isolates of M. bovis by the MST method.
The Essence of Agritourism and Its Profitability during the Coronavirus (COVID-19) Pandemic
Authors: Roman Michał , Grudzień Piotr
Published: May 2021

The article aims to present the essence of agritourism in the literature regarding the subject of its profitability during the COVID-19 pandemic. To verify the goal, data from our own research was applied. The research was conducted in 2019 and 2020 with the exploratory survey method and an interview questionnaire. Thirty-two service providers running agritourism activities in randomly selected rural communes of the Podlaskie province (communes of Mielnik, Suchowola, Giby, Płaska, and Hajnówka) participated in the study. The Ward cluster analysis method was used to group the counties of the Podlaskie Province in terms of spatial differentiation in the development of agritourism. For this purpose, data provided by the Central Statistical Authority in Poland reported for 2019 and the primary data (research by M. Roman) was applied. In the first part of the article, the authors describe and explain the basic concepts of rural tourism and agritourism based on the literature. The figures were also quoted, for example, the number of agritourism farms in Poland and other European countries. The last part of the study provides the results of our own research. The study demonstrates that in 2020 agritourism was profitable, as the owners of the farms recorded a profit. The research confirms the massive impact of the COVID-19 pandemic on agritourism. During a pandemic, many people choose places with few people (e.g., rural areas). The research also considered the importance of innovation on agritourism farms and business profitability. The issues discussed in the study relate to current events—scientific studies examining the impact of COVID-19 on agritourism concern other countries; however, the authors were not able to find studies focusing on agritourism farms in Poland. A new element of methodology in this article was to organize the concepts of agritourism and to present the impact of coronavirus pandemic on the profitability of agritourism. It was also essential to present the classification of rural tourism. According to the authors of the study, the problems covered here are new and point to new trends in the development of agritourism during the pandemic.
Influence of Nitrogen, Calcium and Nano-Fertilizer on Strawberry (Fragaria × ananassa Duch.) Fruit Inner and Outer Quality
Authors: Cvelbar Weber Nika , Koron Darinka , Jakopič Jerneja , Veberič Robert , Hudina Metka , Baša Česnik Helena
Published: May 2021

The production system, especially fertilisation has an important effect on yield and quality of strawberries. In the present study, plants were fertilized with different doses of nitrogen (0–100% recommended doses), calcium chelate, as well as nano fertilizer Lithovit. Strawberry cultivar ‘Clery’ yield and quality parameters (fruit color and firmness) including nutritional indicators (total soluble solids, sugars, organic acids, phenolic and volatile compounds) were monitored. Volatiles were identified and monitored using headspace solid phase microextraction and analysed using gas chromatograph-mass spectrometry (SPME/GC-MS) and sugars, organic acids, and phenolic compounds with high performance liquid chromatography. Organic acids and phenolic compounds were detected with mass spectrometer (HPLC/MS). Both nitrogen and calcium fertilisation had altered sugars, organic acids, volatile and phenolic contents in strawberry fruits. Fertilisation with higher doses of nitrogen and calcium increased the content of unpleasant aromas aldehydes hexanal (up to 3.8-fold) and (E)-2-hexen-1- (up to 3.7-fold). The content of fruity esters was uppermost in fruits fertilised with nano-fertiliser Lithovit (up to 2.3-fold). Fertilisation with N and Ca decreased the strength of ketone and terpenoids fruity aroma. The highest content of total phenols, as well as all individual hydroxycinnamic and hydroxybenzoic acid derivatives were obtained in the nano-fertiliser Lithovit treatment. Fertilisation, especially with nitrogen, had mostly negative impact on strawberry flavour while nano-fertilization with Lithovit improved strawberry phenolic content and aroma.
A Novel Pinkish-White Flower Color Variant Is Caused by a New Allele of Flower Color Gene W1 in Wild Soybean (Glycine soja)
Authors: Sundaramoorthy Jagadeesh , Park Gyu-Tae , Jo Hyun , Lee Jeong-Dong , Seo Hak-Soo , Song Jong-Tae
Published: May 2021

The enzyme flavonoid 3′,5′-hydroxylase (F3′5′H) plays an important role in producing anthocyanin pigments in soybean. Loss of function of the W1 locus encoding F3′5′H always produces white flowers. However, few color variations have been reported in wild soybean. In the present study, we isolated a new color variant of wild soybean accession (IT261811) with pinkish-white flowers. We found that the flower’s pinkish-white color is caused by w1-s3, a single recessive allele of W1. The SNP detected in the mutant caused amino acid substitution (A304S) in a highly conserved SRS4 domain of F3′5′H proteins. On the basis of the results of the protein variation effect analyzer (PROVEAN) tool, we suggest that this mutation may lead to hypofunctional F3′5′H activity rather than non-functional activity, which thereby results in its pinkish-white color.
Automated Detection of Tetranychus urticae Koch in Citrus Leaves Based on Colour and VIS/NIR Hyperspectral Imaging
Authors: Gonzalez-Gonzalez María Gyomar , Blasco Jose , Cubero Sergio , Chueca Patricia
Published: May 2021

Tetranychus urticae Koch is an important citrus pest that produces chlorotic spots on the leaves and scars on the fruit of affected trees. It is detected by visual inspection of the leaves. This work studies the potential of colour and hyperspectral imaging (400–1000 nm) under laboratory conditions as a fast and automatic method to detect the damage caused by this pest. The ability of a traditional vision system to differentiate this pest from others, such as Phyllocnistis citrella, and other leaf problems such as those caused by nutritional deficiencies, has been studied and compared with a more advanced hyperspectral system. To analyse the colour images, discriminant analysis has been used to classify the pixels as belonging to either a damaged or healthy leaves. In contrast, the hyperspectral images have been analysed using PLS DA. The rate of detection of the damage caused by T. urticae with colour images reached 92.5%, while leaves that did not present any damage were all correctly identified. Other problems such as damage by P. citrella were also correctly discriminated from T. urticae. Moreover, hyperspectral imaging allowed damage caused by T. urticae to be discriminated from healthy leaves and to distinguish between recent and mature leaves, which indicates whether it is a recent or an older infestation. Furthermore, good results were achieved in the discrimination between damage caused by T. urticae, P. citrella, and nutritional deficiencies.
Pan-Resistome Insights into the Multidrug Resistance of Acinetobacter baumannii
Authors: Rodrigues Diego Lucas Neres , Morais-Rodrigues Francielly , Hurtado Raquel , dos Santos Roselane Gonçalves , Costa Daniela Camargos , Barh Debmalya , Ghosh Preetam , Alzahrani Khalid J. , Soares Siomar Castro , Ramos Rommel , Góes-Neto Aristóteles , Azevedo Vasco , Aburjaile Flávia Figueira
Published: May 2021

Acinetobacter baumannii is an important Gram-negative opportunistic pathogen that is responsible for many nosocomial infections. This etiologic agent has acquired, over the years, multiple mechanisms of resistance to a wide range of antimicrobials and the ability to survive in different environments. In this context, our study aims to elucidate the resistome from the A. baumannii strains based on phylogenetic, phylogenomic, and comparative genomics analyses. In silico analysis of the complete genomes of A. baumannii strains was carried out to identify genes involved in the resistance mechanisms and the phylogenetic relationships and grouping of the strains based on the sequence type. The presence of genomic islands containing most of the resistance gene repertoire indicated high genomic plasticity, which probably enabled the acquisition of resistance genes and the formation of a robust resistome. A. baumannii displayed an open pan-genome and revealed a still constant genetic permutation among their strains. Furthermore, the resistance genes suggest a specific profile within the species throughout its evolutionary history. Moreover, the current study performed screening and characterization of the main genes present in the resistome, which can be used in applied research to develop new therapeutic methods to control this important bacterial pathogen.
Quantification and Trends of Antimicrobial Use in Commercial Broiler Chicken Production in Pakistan
Authors: Umair Muhammad , Tahir Muhammad Farooq , Ullah Riasat Wasee , Ali Jabir , Siddique Naila , Rasheed Ayesha , Akram Muhammad , Zaheer Muhammad Usman , Mohsin Mashkoor
Published: May 2021

Antimicrobial resistance (AMR) is a global health challenge and antimicrobial use (AMU) in the livestock sector has been considered as one of the contributing factors towards the development of AMR in bacteria. This study summarizes the results of a point prevalence survey conducted to monitor farm-level AMU in commercial broiler chicken farms in Punjab and Khyber Pakhtunkhwa (KPK) provinces of Pakistan. A cross-sectional study was conducted to quantify AMU and to check seasonal variations of AMU in 12 commercial broiler chicken farms (six from each province) during the summer and winter seasons of the year 2020–2021. AMU was recorded using three AMU metrics: kg, mg per population correction unit (mg/PCU), and mg/kg of final flock weight. A total of 22 antimicrobial drugs (348.59 kg) were used for therapeutic or prophylactic purposes in surveyed broiler chicken farms. The total combined AMU for all the broiler chicken farms was 462.57 mg/PCU. The use of most of the antimicrobials increased during winter flocks compared to summer. The top three antimicrobial drugs used during the summer were neomycin (111.39 mg/PCU), doxycycline (91.91 mg/PCU), and tilmicosin (77.22 mg/PCU), whereas doxycycline (196.81 mg/PCU), neomycin (136.74 mg/PCU), and amoxicillin (115.04 mg/PCU) during the winter. Overall, 60% of the antibiotics used in broiler chicken were critically important antimicrobial classes (CIA) for human medicine as characterized by the World Health Organization. Our findings showed high AMU in broiler chicken production and a call for urgent actions to regulate CIA use in food animals in Pakistan. This baseline survey is critical for the design and implementation of a subsequent national level AMU surveys that can include additional farming types, animals’ species, and geographical locations over a longer period of time.
Feline Otitis Externa Caused by Methicillin-Resistant Staphylococcus aureus with Mixed Hemolytic Phenotype and Overview of Possible Genetic Backgrounds
Authors: Avberšek Jana , Papić Bojan , Kušar Darja , Erjavec Vladimira , Seme Katja , Golob Majda , Zdovc Irena
Published: May 2021

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial infections in humans, but its importance in small animal practice is increasing. Here, we present a case of feline otitis externa (OE) caused by MRSA; both hemolytic and nonhemolytic variants with a stable phenotype were recovered from the external auditory canal after infection was detected by routine otoscopy. One isolate per variant underwent antimicrobial susceptibility testing (AST) by broth microdilution method, conventional spa typing and whole-genome sequencing (WGS). The results showed that both variants were genetically related and were of sequence type (ST) 1327, SCCmec type IV and spa type t005. AST and WGS showed that both isolates were resistant to β-lactams and sensitive to all tested non-β-lactam antibiotics. Both isolates were pvl-negative, but encoded several other virulence genes (aur, hlgABC, sak, scn, seg, sei, sem, sen, seo and seu). Genetic background of the mixed hemolytic phenotype was not identified; no differences in the agr locus or other regulatory regions were detected. Three single-nucleotide polymorphisms were identified but could not be associated with hemolysis. This well-documented case of MRSA infection in companion animals adds to the reports of MRSA infections with a mixed hemolytic phenotype.
Strengthening Thermal Stability in V2O5-ZnO-BaO-B2O3-M(PO3)n Glass System (M = Al, Mg) for Laser Sealing Applications
Authors: Kim Soyoung , Han Karam , Kim Seonhoon , Kadathala Linganna , Kim Jinhyeok , Choi Juhyeon
Published: May 2021

Today, the most common way of laser sealing is using a glass frit paste and screen printer. Laser sealing using glass frit paste has some problems, such as pores, nonuniform height, imperfect hermetic sealing, etc. In order to overcome these problems, sealing using fiber types of sealant is attractive for packaging devices. In this work, (70-x)V2O5-5ZnO-22BaO-3B2O3-xM(PO3)n glasses (mol%) incorporated with xM(PO3)n concentration (where M = Mg, Al, n = 2, 3, respectively) were fabricated and their thermal, thermomechanical, and structural properties were investigated. Most importantly, for this type of sealing, the glass should have a thermal stability (ΔT) of ≥80 °C and the coefficient of thermal expansion (CTE) between the glass and panel should be 1.0 ppm/°C. The highest thermal stability ΔT of the order of 93.2 °C and 112.9 °C was obtained for the 15 mol% of Mg(PO3)2 and Al(PO3)3 doped glasses, respectively. This reveals that the bond strength and connectivity is more strongly improved by trivalent Al(PO3)3. The CTE of a (70-x)V2O5-5ZnO-22BaO-3B2O3-xAl(PO3)3 glass system (mol%) (where x = 5–15, mol%) is in the range of 9.5–15.5 (×10−6/K), which is comparable with the CTE (9–10 (×10−6/K)) of commercial DSSC glass panels. Based on the results, the studied glass systems are considered to be suitable for laser sealing using fiber types of sealant.
Analysis of Variance of Dissimilar Cu-Al Alloy Friction Stir Welded Joints with Different Offset Conditions
Authors: Bora Bhabani , Kumar Ratnesh , Chattopadhyaya Somnath , Borucki Sebastian
Published: May 2021

In this investigation, dissimilar material AA6061-T6 and Cu B370 were joined by friction stir welding (FSW). This paper presents a feasibility study of FSW to join Al-alloy and Cu-alloy. The experiment was conducted using general full factorial design by varying the tool rotation speed, weld speed, and probe offset, and by keeping the plunge depth constant. In this research work, a statistical model was established to build a connection between the process variables and outcomes—yield strength (YS), ultimate tensile strength (UTS) and % elongation (% E). Statistical tools such as analysis of variance and scatter diagrams were employed to evaluate the suitability of the models. In addition, the impacts of the process variables on the tensile properties were investigated. From the experimental results, it can be concluded that (i) an excellent weld joint could be obtained by keeping the softer Al plate at the retreating side with a probe offset of 2.0 mm towards the softer material, and (ii) maximum tensile properties were obtained at a higher tool-rotation speed, weld speed, and with a probe offset of 2.0 mm. Further, the fractured tensile specimens were investigated using a scanning electron microscope (SEM). From the analyses, it was noted that, during the tensile test, the weld joint failed with a brittle–ductile mixed fracture mode.
Path Following and Obstacle Avoidance for Unmanned Aerial Vehicles Using a Virtual-Force-Based Guidance Law
Authors: Wang Xun , Cai Libing , Kong Longxing , Wang Binfeng , Huang Shaohua , Lin Chengdi
Published: May 2021

This paper presents a virtual-force-based guidance law (VFGL) for path following and obstacle avoidance in unmanned aerial vehicles. First, a virtual spring force and a virtual drag force are designed for straight-line following; then, the dynamic of the cross-track-error is equivalent to a spring mass system, which is easy to tune to acquire stability and non-overshoot convergence. Secondly, an additional virtual centripetal force is designed to counteract the influence of the curvature of the planned path so that the guidance law can accurately track a curve with a time-varying curvature. Thirdly, an extra virtual repulsive force is designed directly according to the sensor inputs; the virtual repulsive force pushes the vehicle away to move around obstacles. The use of artificial physics means the guidance law is founded on solid physical theory and is computationally simple. The physical meanings of the parameters are definite, and the VFGL has a large parameter adaptation. These make the guidance law easy to tune in application. Both the numerical and hardware-in-the-loop simulation results demonstrated the effectiveness of the proposed guidance law for path following and obstacle avoidance in unmanned aerial vehicles.
Quantitative Characterization of Geotrichum candidum Growth in Milk
Authors: Šipošová Petra , Koňuchová Martina , Valík Ľubomír , Trebichavská Monika , Medveďová Alžbeta
Published: May 2021

The study of microbial growth in relation to food environments provides essential knowledge for food quality control. With respect to its significance in the dairy industry, the growth of Geotrichum candidum isolate J in milk without and with 1% NaCl was investigated under isothermal conditions ranging from 6 to 37 °C. The mechanistic model by Baranyi and Roberts was used to fit the fungal counts over time and to estimate the growth parameters of the isolate. The effect of temperature on the growth of G. candidum in milk was modelled with the cardinal models, and the cardinal temperatures were calculated as Tmin = −3.8–0.0 °C, Topt = 28.0–34.6 °C, and Tmax = 35.2–37.2 °C. The growth of G. candidum J was slightly faster in milk with 1% NaCl and in temperature regions under 21 °C. However, in a temperature range that was close to the optimum, its growth was slightly inhibited by the lowered water activity level. The present study provides useful cultivation data for understanding the behaviour of G. candidum in milk and can serve as an effective tool for assessing the risk of fungal spoilage, predicting the shelf life of dairy products, or assessing the optimal conditions for its growth in relation to the operational parameters in dairy practices.
Accelerated Time and High-Resolution 3D Modeling of the Flow and Dispersion of Noxious Substances over a Gigantic Urban Area—The EMERGENCIES Project
Authors: Oldrini Olivier , Armand Patrick , Duchenne Christophe , Perdriel Sylvie , Nibart Maxime
Published: May 2021

Accidental or malicious releases in the atmosphere are more likely to occur in built-up areas, where flow and dispersion are complex. The EMERGENCIES project aims to demonstrate the operational feasibility of three-dimensional simulation as a support tool for emergency teams and first responders. The simulation domain covers a gigantic urban area around Paris, France, and uses high-resolution metric grids. It relies on the PMSS modeling system to model the flow and dispersion over this gigantic domain and on the Code_Saturne model to simulate both the close vicinity and the inside of several buildings of interest. The accelerated time is achieved through the parallel algorithms of the models. Calculations rely on a two-step approach: the flow is computed in advance using meteorological forecasts, and then on-demand release scenarios are performed. Results obtained with actual meteorological mesoscale data and realistic releases occurring both inside and outside of buildings are presented and discussed. They prove the feasibility of operational use by emergency teams in cases of atmospheric release of hazardous materials.
Aerosol Optical Properties around the East China Seas Based on AERONET Measurements
Authors: Tu Qianguang , Hao Zengzhou , Yan Yunwei , Tao Bangyi , Chung Chuyong , Kim Sumin
Published: May 2021

Understanding aerosols optical properties over the oceans is vital for enhancing our knowledge of aerosol effects on climate and pollutant transport between continents. In this study, the characteristics of aerosol optical thickness (AOT) at 500 nm (τ500nm), Ångström exponent for the wavelength pair 440–870 nm (α) and volume size distribution (VSD), are presented and analyzed over the East China seas based on the observations at four AERONET sites during 1999–2019. The main results are: (1) the mean τ500nm (α) value ranged from 0.31 to 0.36 (1.17–1.31); (2) the distribution of τ500nm (α) is similar to a log-normal distribution with a right-skewed long tail larger than 0.5 (closer to the normal distribution); (3) large AOT (τ500nm>0.6) was frequently observed in summer (June and July) and spring (March to May), followed by autumn and winter; (4) all aerosol types were observed, and urban/industrial aerosols and mixed types were dominant throughout the period. The atmospheric column aerosol was characterized by a bimodal lognormal size distribution with a fine mode at effective radius, Reff = 0.16 ± 0.01 μm, and coarse mode at Reff = 2.05 ± 0.1 μm.
Jasonia glutinosa (L.) DC., a Traditional Herbal Tea, Exerts Antioxidant and Neuroprotective Properties in Different In Vitro and In Vivo Systems
Authors: Les Francisco , Valero Marta Sofía , Moliner Cristina , Weinkove David , López Víctor , Gómez-Rincón Carlota
Published: May 2021

In traditional medicine, Jasonia glutinosa (L.) DC or rock tea (RT) has been mainly used to treat digestive and respiratory pathologies but also as an antimicrobial or an antidepressant herbal remedy. An ethanolic extract of RT has been demonstrated to have antioxidant and anti-inflammatory effects, which may be explained by its phytochemical profile, rich in polyphenols and pigments. The aim of this study is to investigate the neuroprotective potential of RT. For this purpose, the ethanolic extract of RT is assayed in Caenorhabditis elegans (C. elegans) as an in vivo model, and through in vitro assays using monoamine oxidase A, tyrosinase and acetylcholinesterase as enzymes. The RT extract reduces juglone-induced oxidative stress in worms and increases the lifespan and prevents paralysis of C. elegans CL4176, a model of Alzheimer’s disease; the extract is also able to inhibit enzymes such as acetylcholinesterase, monoamine oxidase A and tyrosinase in vitro. Together these results demonstrate that Jasonia glutinosa is a good candidate with antioxidant and neuroprotective potential for the development of new products with pharmaceutical interests.
Magnetic Field Alignment, a Perspective in the Engineering of Collagen-Silica Composite Biomaterials
Authors: Debons Nicolas , Matsumoto Kenta , Hirota Noriyuki , Coradin Thibaud , Ikoma Toshiyuki , Aimé Carole
Published: May 2021

Major progress in the field of regenerative medicine is expected from the design of artificial scaffolds that mimic both the structural and functional properties of the ECM. The bionanocomposites approach is particularly well fitted to meet this challenge as it can combine ECM-based matrices and colloidal carriers of biological cues that regulate cell behavior. Here we have prepared bionanocomposites under high magnetic field from tilapia fish scale collagen and multifunctional silica nanoparticles (SiNPs). We show that scaffolding cues (collagen), multiple display of signaling peptides (SiNPs) and control over the global structuration (magnetic field) can be combined into a unique bionanocomposite for the engineering of biomaterials with improved cell performances.
Povidone-Iodine Attenuates Viral Replication in Ocular Cells: Implications for Ocular Transmission of RNA Viruses
Authors: Singh Sneha , Sawant Onkar B. , Mian Shahzad I. , Kumar Ashok
Published: May 2021

Several RNA viruses, including SARS-CoV-2, can infect or use the eye as an entry portal to cause ocular or systemic diseases. Povidone-Iodine (PVP-I) is routinely used during ocular surgeries and eye banking as a cost-effective disinfectant due to its broad-spectrum antimicrobial activity, including against viruses. However, whether PVP-I can exert antiviral activities in virus-infected cells remains elusive. In this study, using Zika (ZIKV) and Chikungunya (CHIKV) virus infection of human corneal and retinal pigment epithelial cells, we report antiviral mechanisms of PVP-I. Our data showed that PVP-I, even at the lowest concentration (0.01%), drastically reduced viral replication in corneal and retinal cells without causing cellular toxicity. Antiviral effects of PVP-I against ZIKV and CHIKV were mediated by direct viral inactivation, thus attenuating the ability of the virus to infect host cells. Moreover, one-minute PVP-I exposure of infected ocular cells drastically reduced viral replication and the production of infectious progeny virions. Furthermore, viral-induced (CHIKV) expression of inflammatory genes (TNF-α, IL-6, IL-8, and IL1β) were markedly reduced in PVP-I treated corneal epithelial cells. Together, our results demonstrate potent antiviral effects of PVP-I against ZIKV and CHIKV infection of ocular cells. Thus, a low dose of PVP-I can be used during tissue harvesting for corneal transplants to prevent potential transmission of RNA viruses via infected cells.
Synthetic Biology towards Improved Flavonoid Pharmacokinetics
Authors: Sajid Moon , Channakesavula Chaitanya N. , Stone Shane R. , Kaur Parwinder
Published: May 2021

Flavonoids are a structurally diverse class of natural products that have been found to have a range of beneficial activities in humans. However, the clinical utilisation of these molecules has been limited due to their low solubility, chemical stability, bioavailability and extensive intestinal metabolism in vivo. Recently, the view has been formed that site-specific modification of flavonoids by methylation and/or glycosylation, processes that occur in plants endogenously, can be used to improve and adapt their biophysical and pharmacokinetic properties. The traditional source of flavonoids and their modified forms is from plants and is limited due to the low amounts present in biomass, intrinsic to the nature of secondary metabolite biosynthesis. Access to greater amounts of flavonoids, and understanding of the impact of modifications, requires a rethink in terms of production, more specifically towards the adoption of plant biosynthetic pathways into ex planta synthesis approaches. Advances in synthetic biology and metabolic engineering, aided by protein engineering and machine learning methods, offer attractive and exciting avenues for ex planta flavonoid synthesis. This review seeks to explore the applications of synthetic biology towards the ex planta biosynthesis of flavonoids, and how the natural plant methylation and glycosylation pathways can be harnessed to produce modified flavonoids with more favourable biophysical and pharmacokinetic properties for clinical use. It is envisaged that the development of viable alternative production systems for the synthesis of flavonoids and their methylated and glycosylated forms will help facilitate their greater clinical application.
CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines
Authors: Trembley Janeen H. , Li Bin , Kren Betsy T. , Gravely Amy A. , Caicedo-Granados Emiro , Klein Mark A. , Ahmed Khalil
Published: May 2021

Head and neck squamous cell carcinoma (HNSCC) can be categorized into human papillomavirus (HPV) positive or negative disease. Elevated protein kinase CK2 level and activity have been historically observed in HNSCC cells. Previous studies on CK2 in HNSCC did not generally include consideration of HPV(+) and HPV(−) status. Here, we investigated the response of HPV(+) and HPV(−) HNSCC cells to CK2 targeting using CX-4945 or siRNA downregulation combined with cisplatin treatment. HNSCC cell lines were examined for CK2 expression levels and activity and response to CX-4945, with and without cisplatin. CK2 levels and NFκB p65-related activity were high in HPV(+) HNSCC cells relative to HPV(−) HNSCC cells. Treatment with CX-4945 decreased viability and cisplatin IC50 in all cell lines. Targeting of CK2 increased tumor suppressor protein levels for p21 and PDCD4 in most instances. Further study is needed to understand the role of CK2 in HPV(+) and HPV(−) HNSCC and to determine how incorporation of the CK2-targeted inhibitor CX-4945 could improve cisplatin response in HNSCC.
The Role of Extracellular Vesicles in the Development of a Cancer Stem Cell Microenvironment Niche and Potential Therapeutic Targets: A Systematic Review
Authors: Brown Thomas J. , James Victoria
Published: May 2021

Cancer stem cells (CSCs) have increasingly been shown to be a crucial element of heterogenous tumors. Although a relatively small component of the population, they increase the resistance to treatment and the likelihood of recurrence. In recent years, it has been shown, across multiple cancer types (e.g., colorectal, breast and prostate), that reciprocal communication between cancer and the microenvironment exists, which is, in part, facilitated by extracellular vesicles (EVs). However, the mechanisms of this method of communication and its influence on CSC populations is less well-understood. Therefore, the aim of this systematic review is to determine the evidence that supports the role of EVs in the manipulation of the tumor microenvironment to promote the survival of CSCs. Embase and PubMed were used to identify all studies on the topic, which were screened using PRISMA guidelines, resulting in the inclusion of 16 studies. These 16 studies reported on the EV content, pathways altered by EVs and therapeutic targeting of CSC through EV-mediated changes to the microenvironment. In conclusion, these studies demonstrated the role of EV-facilitated communication in maintaining CSCs via manipulation of the tumor microenvironment, demonstrating the potential of creating therapeutics to target CSCs. However, further works are needed to fully understand the targetable mechanisms upon which future therapeutics can be based.
fMRI Retinotopic Mapping in Patients with Brain Tumors and Space-Occupying Brain Lesions in the Area of the Occipital Lobe
Authors: Hense Katharina , Plank Tina , Wendl Christina , Dodoo-Schittko Frank , Bumes Elisabeth , Greenlee Mark W. , Schmidt Nils Ole , Proescholdt Martin , Rosengarth Katharina
Published: May 2021

Functional magnetic resonance imaging (fMRI) is a valuable tool in the clinical routine of neurosurgery when planning surgical interventions and assessing the risk of postoperative functional deficits. Here, we examined how the presence of a brain tumor or lesion in the area of the occipital lobe affects the results of fMRI retinotopic mapping. fMRI data were evaluated on a retrospectively selected sample of 12 patients with occipital brain tumors, 7 patients with brain lesions and 19 control subjects. Analyses of the cortical activation, percent signal change, cluster size of the activated voxels and functional connectivity were carried out using Statistical Parametric Mapping (SPM12) and the CONN and Marsbar toolboxes. We found similar but reduced patterns of cortical activation and functional connectivity between the two patient groups compared to a healthy control group. Here, we found that retinotopic organization was well-preserved in the patients and was comparable to that of the age-matched controls. The results also showed that, compared to the tumor patients, the lesion patients showed higher percent signal changes but lower values in the cluster sizes of the activated voxels in the calcarine fissure region. Our results suggest that the lesion patients exhibited results that were more similar to those of the control subjects in terms of the BOLD signal, whereas the extent of the activation was comparable to that of the tumor patients.
Efficacy of BRAF and MEK Inhibition in Patients with BRAF-Mutant Advanced Melanoma and Germline CDKN2A Pathogenic Variants
Authors: Spagnolo Francesco , Dalmasso Bruna , Tanda Enrica , Potrony Miriam , Puig Susana , van Doorn Remco , Kapiteijn Ellen , Queirolo Paola , Helgadottir Hildur , Ghiorzo Paola
Published: May 2021

Inherited pathogenic variants (PVs) in the CDKN2A tumor suppressor gene are among the strongest risk factors for cutaneous melanoma. Dysregulation of the p16/RB1 pathway may intrinsically limit the activity of MAPK-directed therapy due to the interplay between the two pathways. In our study, we assessed, for the first time, whether patients with germline CDKN2A PVs achieve suboptimal results with BRAF inhibitors (BRAFi)+/−MEK inhibitors (MEKi). We compared the response rate of nineteen CDKN2A PVs carriers who received first-line treatment with BRAFi+/−MEKi with an expected rate derived from phase III trials and “real-world” studies. We observed partial response in 16/19 patients (84%), and no complete responses. The overall response rate was higher than that expected from phase III trials (66%), although not statistically significant (p-value = 0.143; 95% CI = 0.60–0.97); the difference was statistically significant (p-value = 0.019; 95% CI = 0.62–0.97) in the comparison with real-world studies (57%). The clinical activity of BRAFi+/−MEKi in patients with germline CDKN2A PV was not inferior to that of clinical trials and real-world studies, which is of primary importance for clinical management and genetic counseling of this subgroup of patients.
Trajectories of Cognitive Symptoms in Sick-Listed Cancer Survivors
Authors: Klaver Kete M. , Schagen Sanne B. , Kieffer Jacobien M. , van der Beek Allard J. , Duijts Saskia F. A.
Published: May 2021

Many non-central nervous system (CNS) cancer survivors experience cognitive symptoms, which may affect their self-perceived work ability. Little is known about trajectories of self-perceived cognitive functioning in cancer survivors in the period after work disability assessment. Therefore, we evaluated: (1) trajectories of self-reported cognitive functioning, in cancer survivors with work capacity, (2) differences in trajectories of self-reported cognitive functioning between three work disability groups, and (3) explanatory factors of trajectories of self-reported cognitive functioning. Participants (n = 206) were assessed on self-reported cognitive functioning at three time points between two and four years after first day of sick leave. A statistically significant improvement in cognitive functioning was found in the total group (β = 4.62, SE = 0.91, p < 0.001). When comparing cancer survivors in different work disability groups, similar trajectories of cognitive functioning were observed. Fatigue was the only factor found to be associated with the reported trajectory (β = −0.23, SE = 0.086, p = 0.08). Self-perceived cognitive functioning scores remained considerably lower than the mean score of the general Dutch population, indicating that cognitive symptoms are a persistent problem in sick-listed cancer survivors and that evidence-based treatment options are warranted.
Liquid Biopsies from Pleural Effusions and Plasma from Patients with Malignant Pleural Mesothelioma: A Feasibility Study
Authors: Moretti Gabriele , Aretini Paolo , Lessi Francesca , Mazzanti Chiara Maria , Ak Guntulu , Metintaş Muzaffer , Lando Cecilia , Filiberti Rosa Angela , Lucchi Marco , Bonotti Alessandra , Foddis Rudy , Cristaudo Alfonso , Bottari Andrea , Apollo Alessandro , Del Re Marzia , Danesi Romano , Mutti Luciano , Gemignani Federica , Landi Stefano
Published: May 2021

Background: Malignant pleural mesothelioma (MPM) is a fatal tumor with a poor prognosis. The recent developments of liquid biopsies could provide novel diagnostic and prognostic tools in oncology. However, there is limited information about the feasibility of this technique for MPMs. Here, we investigate whether cancer-specific DNA sequences can be detected in pleural fluids and plasma of MPM patients as free circulating tumor DNA (ctDNA). Methods: We performed whole-exome sequencing on 14 tumor biopsies from 14 patients, and we analyzed 20 patient-specific somatic mutations with digital droplet PCR (ddPCR) in pleural fluids and plasma, using them as cancer-specific tumor biomarkers. Results: Most of the selected mutations could be detected in pleural fluids (94%) and, noteworthy, in plasma (83%) with the use of ddPCR. Pleural fluids showed similar levels of somatically mutated ctDNA (median = 12.75%, average = 16.3%, standard deviation = 12.3) as those detected in solid biopsies (median = 21.95%; average = 22.21%; standard deviation = 9.57), and their paired difference was weakly statistically significant (p = 0.048). On the other hand, the paired difference between solid biopsies and ctDNA from plasma (median = 0.29%, average = 0.89%, standard deviation = 1.40) was highly statistically significant (p = 2.5 × 10−7), corresponding to the important drop of circulating somatically mutated DNA in the bloodstream. However, despite the tiny amount of ctDNA in plasma, varying from 5.57% down to 0.14%, the mutations were detectable at rates similar to those possible for other tumors. Conclusions: We found robust evidence that mutated DNA is spilled from MPMs, mostly into pleural fluids, proving the concept that liquid biopsies are feasible for MPM patients.