bluuebunny/crossref_metadata_2025 huggingface dataset:
A Palette of Efficient and Stable Far-Red and NIR Dye Lasers
Authors: Avellanal-Zaballa Edurne , Gartzia-Rivero Leire , Bañuelos Jorge , García-Moreno Inmaculada , R. Agarrabeitia Antonia , Peña-Cabrera Eduardo , Ortiz Maria Jose
Published: September 2020

The disposal of long-wavelength-emitting sources is of paramount relevance in technology and biophotonics due to the low interference with the surroundings that these kinds of far-red and near-infrared radiations hold. As a result of the continued efforts carried out during the last few years by our research group to design new boron-dipyrromethene (BODIPY) dyes with improved photonic performance, two approaches were tested to develop a new generation of organic dyes able to display efficient and long-lasting laser emission in both target spectral regions. On the one hand, the annulation of aromatic benzofuran at the dipyrrin backbone leads to conformationally restricted dyes yielding photostable and bright laser emission beyond 600 nm at the far-red spectral region. On the other hand, a more pronounced shift to longer wavelengths reaching 725 nm at the near-infrared region is feasible, while keeping a reasonably high laser efficiency and tolerance to prolonged and intense pumping, based on aza-BODIPYs bearing peripheral aryl rings. These two complementary strategies yield a library of laser-emitting compounds comprising the 600–725 nm spectral region. Moreover, their laser performance is better than the commercially available dye lasers active in this spectral window.
Multivariate Geostatistical Modeling of Lower Calorific Value in Multi-Seam Coal Deposits
Authors: Sideri Daphne , Roumpos Christos , Pavloudakis Francis , Paraskevis Nikolaos , Modis Konstantinos
Published: September 2020

The estimation of fuel characteristics and spatial variability in multi-seam coal deposits is of great significance for the optimal mine planning and exploitation, as well as for the optimization of the corresponding power plants operation. It is mainly based on the quality properties of the coal (i.e., Lower Calorific Value (LCV), ash content, CO2, and moisture). Even though critical, these properties are not always measured in practice for all available borehole samples, or, they are generally estimated by using non-parametric statistics. Therefore, spatial modeling of LCV can become problematic due to the limited number of data. Thus, the use of other available correlated attributes might be helpful. In this research, techniques of multivariate geostatistics were used to estimate and evaluate the spatial distribution of quality properties in a multi-seam coal deposit, with special reference to the LCV. More specifically, kriging, cokriging, and Principal Component Analysis (PCA) techniques were tested in a case study as estimators of the LCV, using an extensive set of borehole data from the South Field lignite mine in Ptolemais, Greece. The research outcomes show that the application of kriging with two PCA factors and the use of inverse transform result in the best LCV estimates. Moreover, cokriging with two auxiliary variables gives more accurate values for a LCV estimate, in relation to the kriging technique. The research outcomes could be considered significant for the coal mining industry, since the use of correlated quality attributes for the estimation of LCV may contribute to a reduction of the estimation uncertainty at no additional drilling cost.
Modeling Head-On Collisions: The Problem of Identifying Collision Parameters
Authors: Aleksandrowicz Piotr
Published: September 2020

The analyses performed by the experts are crucial for the settlement of court disputes, and they have legal consequences for the parties to legal proceedings. The reliability of the simulation result is crucial. First, in article, an impact simulation was performed with the use of the program default data. Next, the impact parameters were identified from a crash test, and a simulation was presented. Due to the difficulties in obtaining the data identified, the experts usually take advantage of simplifications using only default data provided by the simulation program. This article includes the original conclusions on specific reasons of simplified collision modeling in Multi Body Systems (MBS) programs and provides specific directions of development of the V-SIM4 program used in the study to enhance the models applied. This manuscript indicates a direction for crash model development in MBS programs to consider a varied 3D body space zones stiffness related to the structure of the car body and the internal car elements instead of modeling the car body as a solid with an average stiffness. Such an approach would provide an alternative to Finite Element Method (FEM) convention modeling.
CT Radiomics in Colorectal Cancer: Detection of KRAS Mutation Using Texture Analysis and Machine Learning
Authors: González-Castro Víctor , Cernadas Eva , Huelga Emilio , Fernández-Delgado Manuel , Porto Jacobo , Antunez José Ramón , Souto-Bayarri Miguel
Published: September 2020

In this work, by using descriptive techniques, the characteristics of the texture of the CT (computed tomography) image of patients with colorectal cancer were extracted and, subsequently, classified in KRAS+ or KRAS-. This was accomplished by using different classifiers, such as Support Vector Machine (SVM), Grading Boosting Machine (GBM), Neural Networks (NNET), and Random Forest (RF). Texture analysis can provide a quantitative assessment of tumour heterogeneity by analysing both the distribution and relationship between the pixels in the image. The objective of this research is to demonstrate that CT-based Radiomics can predict the presence of mutation in the KRAS gene in colorectal cancer. This is a retrospective study, with 47 patients from the University Hospital, with a confirmatory pathological analysis of KRAS mutation. The highest accuracy and kappa achieved were 83% and 64.7%, respectively, with a sensitivity of 88.9% and a specificity of 75.0%, achieved by the NNET classifier using the texture feature vectors combining wavelet transform and Haralick coefficients. The fact of being able to identify the genetic expression of a tumour without having to perform either a biopsy or a genetic test is a great advantage, because it prevents invasive procedures that involve complications and may present biases in the sample. As well, it leads towards a more personalized and effective treatment.
Managing Cloud Intelligent Systems over Digital Ecosystems: Revealing Emerging App Technology in the Time of the COVID19 Pandemic
Authors: Susanto Heru , Leu Fang-Yie , Caesarendra Wahyu , Ibrahim Fahmi , Haghi Parastou , Khusni Uus , Glowacz Adam
Published: September 2020

The COVID19 pandemic has indirectly changed the landscape of the business environment system through cloud intelligence within the digital ecosystem that has as a goal increasing the access, efficiency, effectiveness, equity and quality of business processes through cloud intelligent systems. Cloud intelligent systems are becoming revolutionary in today’s world pandemic causing a complete and drastic change to a variety of industries, including, security, transportation, business, logistics and manufacturing. The main purpose of cloud intelligence systems is to facilitate the ease of access from any location and the management of practical computing resources. One of the challenges faced by cloud technology today is scheduling. The role of scheduling algorithms is very important, since tasks are executed by orders that may need more attention. Here, scheduling algorithms intended to minimize monetary cost and minimize makespan time to execute the workflow are presented. This study proposes cloud intelligent systems apps through an approach to cloud computing scheduling that may lead to great benefits and efficiency. The result is very promising. It showed that there are numerous applications of intelligent systems due to the more advanced hardware being built nowadays, plus business processes advancing to become smarter and more efficient in growing profitably over a destructive digital ecosystem during the COVID19 pandemic. The results indicate that intelligent systems over the cloud play a big role not just for interacting with the world helping businesses grow, but as well as in the advancement for a better tomorrow.
Measurements of Cloud Radiative Effect across the Southern Ocean (43° S–79° S, 63° E–158° W)
Authors: Wang Haoran , Klekociuk Andrew R. , French W. John R. , Alexander Simon P. , Warner Tom A.
Published: September 2020

The surface radiation environment over the Southern Ocean within the region bound by 42.8° S to 78.7° S and 62.6° E to 157.7° W is summarised for three austral summers. This is done using ship-based measurements with the combination of downwelling radiation sensors and a cloud imager. We focus on characterising the cloud radiative effect (CRE) under a variety of conditions, comparing observations in the open ocean with those in the sea ice zone. For comparison with our observed data, we obtained surface data from the European Centre for Medium-Range Weather Forecasts fifth reanalysis (ERA5). We found that the daily average cloud fraction was slightly lower in ERA5 compared with the observations (0.71 and 0.75, respectively). ERA5 also showed positive biases in the shortwave radiation effect and a negative bias in the longwave radiation effect. The observed mean surface CRE of −164 ± 100 Wm−2 was more negative than the mean surface CRE for ERA5 of −101 W m−2.
Temporal and Spatial Variation of PM2.5 in Xining, Northeast of the Qinghai–Xizang (Tibet) Plateau
Authors: Hu Xiaofeng , Yin Yongzheng , Duan Lian , Wang Hong , Song Weijun , Xiu Guangli
Published: September 2020

PM2.5 was sampled from January 2017 to May 2018 at an urban, suburban, industrial, and rural sites in Xining. The annual mean of PM2.5 was highest at the urban site and lowest at the rural site, with an average of 51.5 ± 48.9 and 26.4 ± 17.8 μg·m−3, respectively. The average PM2.5 concentration of the industrial and suburban sites was 42.8 ± 27.4 and 37.2 ± 23.7 μg·m−3, respectively. All sites except for the rural had concentrations above the ambient air quality standards of China (GB3095-2012). The highest concentration of PM2.5 at all sites was observed in winter, followed by spring, autumn, and summer. The concentration of major constituents showed statistically significant seasonal and spatial variation. The highest concentrations of organic carbon (OC), elemental carbon (EC), water-soluble organic carbon (WSOC), and water-soluble inorganic ions (WSIIs) were found at the urban site in winter. The average concentration of F− was higher than that in many studies, especially at the industrial site where the annual average concentration of F− was 1.5 ± 1.7 μg·m−3. The range of sulfur oxidation ratio (SOR) was 0.1–0.18 and nitrogen oxidation ratio (NOR) was 0.02–0.1 in Xining. The higher SO42−/NO3− indicates that coal combustion has greater impact than vehicle emissions. The results of the potential source contribution function (PSCF) suggest that air mass from middle- and large-scale transport from the western areas of Xining have contributed to the higher level of PM2.5. On the basis of the positive matrix factorization (PMF) model, it was found that aerosols from salt lakes and dust were the main sources of PM2.5 in Xining, accounting for 26.3% of aerosol total mass. During the sandstorms, the concentration of PM2.5 increased sharply, and the concentrations of Na+, Ca2+ and Mg2+ were 1.13–2.70, 1.68–4.41, and 1.15–5.12 times higher, respectively, than annual average concentration, implying that aerosols were mainly from dust and the largest saltwater lake, Qinghai Lake, and many other salt lakes in the province of Qinghai. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was utilized to study the surface components of PM2.5 and F− was found to be increasingly distributed from the surface to inside the particles. We determined that the extremely high PM2.5 concentration appears to be due to an episode of heavy pollution resulting from the combination of sandstorms and the burning of fireworks.
National Publication Productivity during the COVID-19 Pandemic—A Preliminary Exploratory Analysis of the 30 Countries Most Affected
Authors: Müller Simon M. , Mueller Georg F. , Navarini Alexander A. , Brandt Oliver
Published: September 2020

Background: The COVID 19 pandemic increased publication productivity enormously with numerous new COVID-19-related articles appearing daily, despite the fact that many health care workers in the partially overburdened national health care systems were faced with major challenges. Methods: In a cross-sectional, observational, retrospective study we compared and correlated 17 epidemiologic, health care system-related and health-economic factors from medical databases and intergovernmental organisations potentially influencing the COVID-19 and non-COVID-19 publication productivity between 1 January and 30 April 2020 amongst the 30 countries most severely affected by the pandemic. These factors were additionally correlated with the national pre-COVID-19 publication rate for the same pre-year period to identify potential changes in the general publication behaviour. Findings: COVID-19 and non-COVID-19 publication rates correlated strongest with access to and quality of health care (ρ = 0.80 and 0.87, p < 0.0001), COVID-19 cases per capita (ρ = 0.78 and 0.72, p < 0.0001), GDP per capita (ρ = 0.69 and 0.76, p < 0.0001), health spending per capita (ρ = 0.61 and 0.73, p < 0.0001) and the pre-COVID-19 Hirsch-Index (ρ = 0.61 and 0.62, p = 0.002 and <0.0001). Ratios of publication rates for “Cancer”, “Diabetes” and “Stroke” in 2020 versus the pre-year period were 0.88 ± 0.06, 1.02 ± 0.18 and 0.9 ± 0.20, resulting in a pooled ratio of 0.93 ± 0.06 for non-COVID-19 publications. Interpretation: There are marked geographic and national differences in publication productivity during the COVID-19 pandemic. Both COVID-19- and non-COVID-19 publication productivity correlates with epidemiologic, health care system-related and healtheconomic factors, and pre-COVID publication expertise. Countries with a stable scientific infrastructure appear to maintain non-COVID-19 publication productivity nearly at the pre-year level and at the same time use their resilience to produce COVID-19 publications at high rates.
Characterization of Perionyx excavatus Development and Its Head Regeneration
Authors: Bae Yun Seon , Kim Jung , Yi Jeesoo , Park Soon Cheol , Lee Hae-Youn , Cho Sung-Jin
Published: September 2020

Regeneration is a biological process restoring lost or amputated body parts. The capability of regeneration varies among organisms and the regeneration of the central nervous system (CNS) is limited to specific animals, including the earthworm Perionyx excavatus. Thus, it is crucial to establish P. excavatus as a model system to investigate mechanisms of CNS regeneration. Here, we set up a culture system to sustain the life cycle of P. excavatus and characterize the development of P. excavatus, from embryo to juvenile, based on its morphology, myogenesis and neurogenesis. During development, embryos have EdU-positive proliferating cells throughout the whole body, whereas juveniles maintain proliferating cells exclusively in the head and tail regions, not in the trunk region. Interestingly, juveniles amputated at the trunk, which lacks proliferating cells, are able to regenerate the entire head. In this process, a group of cells, which are fully differentiated, reactivates cell proliferation. Our data suggest that P. excavatus is a model system to study CNS regeneration, which is dependent on the dedifferentiation of cells.
Hummingbird-Leaves-Reared Black Soldier Fly Prepupae: Assessment of Nutritional and Heavy Metal Compositions
Authors: Kuppusamy Giva , Kong Chee Kei , Segaran Ganeswaran Chandra , Tarmalingam Eliyarajan , Herriman Max , Ismail Mohd Fathil , Mehmood Khan Tahir , Low Liang Ee , Goh Bey-Hing
Published: September 2020

Black soldier fly (BSF) larva is an attractive animal feed replacer due to its noticeable nutritional content. However, the conventional rearing method often resulted in BSF with undesirably high heavy metal residues that are harmful to animals. In this work, putrefied Sesbania grandiflora (S. Grandiflora) leaves were employed as feed to rear BSF larvae. The resultant BSF prepupae were found to contain 43.5% protein and 16.7% fat, reflecting a comparable protein content and a 2-fold reduction in crude fat than those reared using conventional kitchen waste. Moreover, high quantities of arginine (25.4 g/kg dry matter basis (DM)), carnitine (32.9 g/kg DM), and short-chain fatty acids, including lauric (40.00%), palmitic (19.20%), and oleic (12.10%) acids, have also been noticed in the BSF prepupae. Furthermore, the BSF larvae have been recorded with 0.185 mg/kg chromium, 0.380 mg/kg selenium, and mercury below the detection limit, which is far lower than those reared using conventional kitchen and agricultural wastes (≈1.7 mg/kg chromium, 1.2 mg/kg selenium, and 0.2 mg/kg mercury). Overall, the study shows that the nutritional quality of BSF prepupae is extensively improved when using S. Grandiflora as their feed. The resultant BSF prepupae may serve as an alternative feed for animal rearing.
Different Research Approaches in Unraveling the Venom Proteome of Naja ashei
Authors: Hus Konrad Kamil , Marczak Łukasz , Petrilla Vladimír , Petrillová Monika , Legáth Jaroslav , Bocian Aleksandra
Published: September 2020

The dynamic development of venomics in recent years has resulted in a significant increase in publicly available proteomic data. The information contained therein is often used for comparisons between different datasets and to draw biological conclusions therefrom. In this article, we aimed to show the possible differences that can arise, in the final results of the proteomic experiment, while using different research workflows. We applied two software solutions (PeptideShaker and MaxQuant) to process data from shotgun LC-MS/MS analysis of Naja ashei venom and collate it with the previous report concerning this species. We were able to provide new information regarding the protein composition of this venom but also present the qualitative and quantitative limitations of currently used proteomic methods. Moreover, we reported a rapid and straightforward technique for the separation of the fraction of proteins from the three-finger toxin family. Our results underline the necessary caution in the interpretation of data based on a comparative analysis of data derived from different studies.
MicroRNAs: Diverse Mechanisms of Action and Their Potential Applications as Cancer Epi-Therapeutics
Authors: Sadakierska-Chudy Anna
Published: September 2020

Usually, miRNAs function post-transcriptionally, by base-pairing with the 3′UTR of target mRNAs, repressing protein synthesis in the cytoplasm. Furthermore, other regions including gene promoters, as well as coding and 5′UTR regions of mRNAs are able to interact with miRNAs. In recent years, miRNAs have emerged as important regulators of both translational and transcriptional programs. The expression of miRNA genes, similar to protein-coding genes, can be epigenetically regulated, in turn miRNA molecules (named epi-miRs) are able to regulate epigenetic enzymatic machinery. The most recent line of evidence indicates that miRNAs can influence physiological processes, such as embryonic development, cell proliferation, differentiation, and apoptosis as well as pathological processes (e.g., tumorigenesis) through epigenetic mechanisms. Some tumor types show repression of tumor-suppressor epi-miRs resulting in cancer progression and metastasis, hence these molecules have become novel therapeutic targets in the last few years. This review provides information about miRNAs involvement in the various levels of transcription and translation regulation, as well as discusses therapeutic potential of tumor-suppressor epi-miRs used in in vitro and in vivo anti-cancer therapy.
Comparative Analysis of Bacteriophytochrome Agp2 and Its Engineered Photoactivatable NIR Fluorescent Proteins PAiRFP1 and PAiRFP2
Authors: Khan Faez Iqbal , Hassan Fakhrul , Anwer Razique , Juan Feng , Lai Dakun
Published: September 2020

Two photoactivatable near infrared fluorescent proteins (NIR FPs) named “PAiRFP1” and “PAiRFP2” are formed by directed molecular evolution from Agp2, a bathy bacteriophytochrome of Agrobacterium tumefaciens C58. There are 15 and 24 amino acid substitutions in the structure of PAiRFP1 and PAiRFP2, respectively. A comprehensive molecular exploration of these bacteriophytochrome photoreceptors (BphPs) are required to understand the structure dynamics. In this study, the NIR fluorescence emission spectra for PAiRFP1 were recorded upon repeated excitation and the fluorescence intensity of PAiRFP1 tends to increase as the irradiation time was prolonged. We also predicted that mutations Q168L, V244F, and A480V in Agp2 will enhance the molecular stability and flexibility. During molecular dynamics (MD) simulations, the average root mean square deviations of Agp2, PAiRFP1, and PAiRFP2 were found to be 0.40, 0.49, and 0.48 nm, respectively. The structure of PAiRFP1 and PAiRFP2 were more deviated than Agp2 from its native conformation and the hydrophobic regions that were buried in PAiRFP1 and PAiRFP2 core exposed to solvent molecules. The eigenvalues and the trace of covariance matrix were found to be high for PAiRFP1 (597.90 nm2) and PAiRFP2 (726.74 nm2) when compared with Agp2 (535.79 nm2). It was also found that PAiRFP1 has more sharp Gibbs free energy global minima than Agp2 and PAiRFP2. This comparative analysis will help to gain deeper understanding on the structural changes during the evolution of photoactivatable NIR FPs. Further work can be carried out by combining PCR-based directed mutagenesis and spectroscopic methods to provide strategies for the rational designing of these PAiRFPs.
Loss of ADAM9 Leads to Modifications of the Extracellular Matrix Modulating Tumor Growth
Authors: Abety Anna N. , Pach Elke , Giebeler Nives , Fromme Julia E. , Aramadhaka Lavakumar Reddy , Mauch Cornelia , Fox Jay W. , Zigrino Paola
Published: September 2020

ADAM9 is a metalloproteinase strongly expressed at the tumor-stroma border by both tumor and stromal cells. We previously showed that the host deletion of ADAM9 leads to enhanced growth of grafted B16F1 melanoma cells by a mechanism mediated by TIMP1 and the TNF-α/sTNFR1 pathway. This study aimed to dissect the structural modifications in the tumor microenvironment due to the stromal expression of ADAM9 during melanoma progression. We performed proteomic analysis of peritumoral areas of ADAM9 deleted mice and identified the altered expression of several matrix proteins. These include decorin, collagen type XIV, fibronectin, and collagen type I. Analysis of these matrices in the matrix producing cells of the dermis, fibroblasts, showed that ADAM9−/− and wild type fibroblasts synthesize and secreted almost comparable amounts of decorin. Conversely, collagen type I expression was moderately, but not significantly, decreased at the transcriptional level, and the protein increased in ADAM9−/− fibroblast mono- and co-cultures with melanoma media. We show here for the first time that ADAM9 can release a collagen fragment. Still, it is not able to degrade collagen type I. However, the deletion of ADAM9 in fibroblasts resulted in reduced MMP-13 and -14 expression that may account for the reduced processing of collagen type I. Altogether, the data show that the ablation of ADAM9 in the host leads to the altered expression of peritumoral extracellular matrix proteins that generate a more favorable environment for melanoma cell growth. These data underscore the suppressive role of stromal expression of ADAM9 in tumor growth and call for a better understanding of how protease activities function in a cellular context for improved targeting.
Impedimetric Sensing of Factor V Leiden Mutation by Zip Nucleic Acid Probe and Electrochemical Array
Authors: Erdem Arzum , Eksin Ece
Published: September 2020

A carbon nanofiber enriched 8-channel screen-printed electrochemical array was used for the impedimetric detection of SNP related to Factor V Leiden (FV Leiden) mutation, which is the most common inherited form of thrombophilia. FV Leiden mutation sensing was carried out in three steps: solution-phase nucleic acid hybridization between zip nucleic acid probe (Z-probe) and mutant type DNA target, followed by the immobilization of the hybrid on the working electrode area of array, and measurement by electrochemical impedance spectroscopy (EIS). The selectivity of the assay was tested against mutation-free DNA sequences and synthetic polymerase chain reaction (PCR) samples. The developed biosensor was a trustful assay for FV Leiden mutation diagnosis, which can effectively discriminate wild type and mutant type even in PCR samples.
Neuroprotective Effect of Piracetam against Cocaine-Induced Neuro Epigenetic Modification of DNA Methylation in Astrocytes
Authors: Sivalingam Kalaiselvi , Samikkannu Thangavel
Published: September 2020

Cocaine abuse is known to alter mitochondrial biogenesis and induce epigenetic modification linked with neuronal dysfunction. Cocaine-induced epigenetic modification of DNA methylation and the mitochondrial genome may affect mitochondrial DNA (mtDNA) and nuclear DNA (nDNA), as epigenetic DNA methylation is key to maintaining genomic integrity in the central nervous system (CNS). However, the impact of cocaine-mediated epigenetic changes in astrocytes has not yet been elucidated. In this study, we explored the neuroprotective effect of piracetam against cocaine-induced epigenetic changes in DNA methylation in astrocytes. To study our hypothesis, we exposed human astrocytes to cocaine alone or in combination with the nootropic drug piracetam. We examined the expression of the DNA methyltransferases (DNMTs) DNMT-1, DNMT-3A, and DNMT-3B; global DNA methylation levels of 5-methycytosine (5-mC); and induction of ten–eleven translocation (TET) enzymes in astrocytes. In addition, we analyzed mtDNA methylation by targeted next-generation bisulfite sequencing. Our data provide evidence that cocaine impairs DNMT activity and thereby has impacts on mtDNA, which might contribute to the neurodegeneration observed in cocaine users. These effects might be at least partially prevented by piracetam, allowing neuronal function to be maintained.
Exercise for Older Adults Improves the Quality of Life in Parkinson’s Disease and Potentially Enhances the Immune Response to COVID-19
Authors: Hall Mary-Frances E. , Church Frank C.
Published: September 2020

Parkinson’s disease (PD) is a progressive neurodegenerative disorder brought about due to dopaminergic neuronal cell loss in the midbrain substantia nigra pars compacta region. PD presents most commonly in older adults and is a disorder of both motor and nonmotor dysfunction. The novel SARS-CoV-2 virus is responsible for the recent COVID-19 pandemic, and older individuals, those with preexisting medical conditions, or both have an increased risk of developing COVID-19 with more severe outcomes. People-with-Parkinson’s (PwP) of advanced age can have both immune and autonomic nervous problems that potentially lead to pre-existing pulmonary dysfunction and higher infection risk, increasing the probability of contracting COVID-19. A lifestyle change involving moderate-intensity exercise has the potential to protect against SARS-CoV-2 through strengthening the immune system. In addition to a potential protective measure against SARS-CoV-2, exercise has been shown to improve quality-of-life (QoL) in PD patients. Recent studies provide evidence of exercise as both neuroprotective and neuroplastic. This article is a literature review investigating the role exercise plays in modifying the immune system, improving health outcomes in PwP, and potentially acting as a protective measure against SARS-Cov-2 infection. We conclude that exercise, when correctly performed, improves QoL and outcomes in PwP, and that the enhanced immune response from moderate-intensity exercise could potentially offer additional protection against COVID-19.
Effect of Polycyclic Aromatic Hydrocarbons Exposure on Cognitive Development in 5 Years Old Children
Authors: Blazkova Barbora , Pastorkova Anna , Solansky Ivo , Veleminsky Milos , Veleminsky Milos , Urbancova Katerina , Vondraskova Veronika , Hajslova Jana , Pulkrabova Jana , Sram Radim J.
Published: September 2020

Objectives: To analyze the impact of polycyclic aromatic hydrocarbons (PAHs) in ambient air at the time of delivery and five years of age on cognitive development in five year old children. Materials and Methods: Two cohorts of children born in the years 2013 and 2014 from Karvina (Northern Moravia, n = 70) and Ceske Budejovice (Southern Bohemia, n = 99) were studied at the age of five years for their cognitive development related to the exposure to PAHs, determined in the ambient air as the concentration of benzo[a]pyrene (B[a]P) and OH–PAH (hydroxy-PAH) metabolites in urine of the newborns at the time of delivery. As psychological tests, the Bender Visual Motor Gestalt Test (BG test) and the Raven Colored Progressive Matrices (RCPM test) were used. Results: Concentrations of B[a]P in the third trimester of mother’s pregnancies were 6.1 ± 4.53 ng/m3 in Karvina, and 1.19 ± 1.28 ng/m3 (p < 0.001) in Ceske Budejovice. Neither the outcome of the RCPM test nor the BG test differed between children in Karvina vs. Ceske Budejovice, or boys vs. girls. Cognitive development in five year old children was affected by the higher exposure to PM2.5 during the third trimester in girls in Karvina. Conclusions: We did not observe any significant effect of prenatal PAH exposure on psychological cognitive tests in five year old children.
Brain Structural and Functional Alterations in Mice Prenatally Exposed to LPS Are Only Partially Rescued by Anti-Inflammatory Treatment
Authors: Aria Francesca , Bonini Sara A. , Cattaneo Valentina , Premoli Marika , Mastinu Andrea , Maccarinelli Giuseppina , Memo Maurizio
Published: September 2020

Aberrant immune activity during neurodevelopment could participate in the generation of neurological dysfunctions characteristic of several neurodevelopmental disorders (NDDs). Numerous epidemiological studies have shown a link between maternal infections and NDDs risk; animal models of maternal immune activation (MIA) have confirmed this association. Activation of maternal immune system during pregnancy induces behavioral and functional alterations in offspring but the biological mechanisms at the basis of these effects are still poorly understood. In this study, we investigated the effects of prenatal lipopolysaccharide (LPS) exposure in peripheral and central inflammation, cortical cytoarchitecture and behavior of offspring (LPS-mice). LPS-mice reported a significant increase in interleukin-1β (IL-1β) serum level, glial fibrillary acidic protein (GFAP)- and ionized calcium-binding adapter molecule 1 (Iba1)-positive cells in the cortex. Furthermore, cytoarchitecture analysis in specific brain areas, showed aberrant alterations in minicolumns’ organization in LPS-mice adult brain. In addition, we demonstrated that LPS-mice presented behavioral alterations throughout life. In order to better understand biological mechanisms whereby LPS induced these alterations, dams were treated with meloxicam. We demonstrated for the first time that exposure to LPS throughout pregnancy induces structural permanent alterations in offspring brain. LPS-mice also present severe behavioral impairments. Preventive treatment with meloxicam reduced inflammation in offspring but did not rescue them from structural and behavioral alterations.
Role of Metacognition Thinking and Psychological Traits in Breast Cancer Survivorship
Authors: Ranieri Jessica , Guerra Federica , Di Giacomo Dina
Published: September 2020

Longer survivorship is possible due to advances enabling early detection and treatment. However, cancer survivors are faced with prognostic uncertainty regarding survival, long-term symptoms, surveillance, and consequences of treatment. This study aimed at investigating emotional traits of women after breast cancer (BC) diagnosis from a three-year perspective of the disease. We intended to examine the emotional trend within longer survivorship after the primary treatment for BC. A sample of 72 women diagnosed with breast cancer (age range 30–55 years) was evaluated based on metacognition (Metacognitive Questionnaire—30 test), psychological distress (Psychological Distress Inventory test), anxiety, stress, and depression (Depression, Anxiety and Stress Scale—21 test). The data analysis applied was descriptive analysis, ANOVA, MANOVA, and ANCOVA comparing MCQ-30 variables and psychological traits (PDI, DASS-21). The results indicated positive recovery after primary care despite emotional fragility in survivorship owing to negative thoughts; correlations among metacognitive factors, anxiety, and distress not only confirmed the negative emotional pattern just after primary care, but also showed women regaining a positive emotional pattern in daily life. The survivors exhibited emotional fragility during certain specific points of time during the course of their survivorship. Based on our findings, the fear of recurrence and cancer-specific psychological treatment is a better framework to boost and improve clinical practice.
Immunotherapy in Small Cell Lung Cancer
Authors: Esposito Giovanna , Palumbo Giuliano , Carillio Guido , Manzo Anna , Montanino Agnese , Sforza Vincenzo , Costanzo Raffaele , Sandomenico Claudia , La Manna Carmine , Martucci Nicola , La Rocca Antonello , De Luca Giuseppe , Piccirillo Maria Carmela , De Cecio Rossella , Botti Gerardo , Totaro Giuseppe , Muto Paolo , Picone Carmine , Normanno Nicola , Morabito Alessandro
Published: September 2020

Small-cell lung cancer (SCLC) is an aggressive tumor type with limited therapeutic options and poor prognosis. Chemotherapy regimens containing platinum represent the cornerstone of treatment for patients with extensive disease, but there has been no real progress for 30 years. The evidence that SCLC is characterized by a high mutational burden led to the development of immune-checkpoint inhibitors as single agents or in combination with chemotherapy. Randomized phase III trials demonstrated that the combination of atezolizumab (IMpower-133) or durvalumab (CASPIAN) with platinum-etoposide chemotherapy improved overall survival of patients with extensive disease. Instead, the KEYNOTE-604 study demonstrated that the addition of pembrolizumab to chemotherapy failed to significantly improve overall survival, but it prolonged progression-free survival. The safety profile of these combinations was similar with the known safety profiles of all single agents and no new adverse events were observed. Nivolumab and pembrolizumab single agents showed anti-tumor activity and acceptable safety profile in Checkmate 032 and KEYNOTE 028/158 trials, respectively, in patients with SCLC after platinum-based therapy and at least one prior line of therapy. Future challenges are the identification predictive biomarkers of response to immunotherapy in SCLC and the definition of the role of immunotherapy in patients with limited stage SCLC, in combination with radiotherapy or with other biological agents.
Influence of Intratumor Microbiome on Clinical Outcome and Immune Processes in Prostate Cancer
Authors: Ma Jiayan , Gnanasekar Aditi , Lee Abby , Li Wei Tse , Haas Martin , Wang-Rodriguez Jessica , Chang Eric Y. , Rajasekaran Mahadevan , Ongkeko Weg M.
Published: September 2020

Although 1 in 9 American men will receive a diagnosis of prostate cancer (PC), most men with this diagnosis will not die from it, as most PCs are indolent. However, there is a subset of patients in which the once-indolent PC becomes metastatic and eventually, fatal. In this study, we analyzed microbial compositions of intratumor bacteria in PC to determine the influence of the microbiome on metastatic growth. Using large-scale RNA-sequencing data and corresponding clinical data, we correlated the abundance of microbes to immune pathways and PC risk factors, identifying specific microbes that either significantly deter or contribute to cancer aggressiveness. Interestingly, most of the microbes we found appeared to play anti-tumor roles in PC. Since these anti-tumor microbes were overrepresented in tumor samples, we believe that microbes thrive in the tumor microenvironment, outcompete cancer cells, and directly mitigate tumor growth by recruiting immune cells. These include Listeria monocytogenes, Methylobacterium radiotolerans JCM 2831, Xanthomonas albilineans GPE PC73, and Bradyrhizobium japonicum, which are negatively correlated with Gleason score, Tumor-Node-Metastasis (TNM) stage, prostate-specific antigen (PSA) level, and Androgen Receptor (AR) expression, respectively. We also identified microbes that contribute to tumor growth and are positively correlated with genomic alterations, dysregulated immune-associated (IA) genes, and prostate cancer stem cells (PCSC) genes.
Genetic Testing and Surveillance of Young Breast Cancer Survivors and Blood Relatives: A Cluster Randomized Trial
Authors: Katapodi Maria C. , Ming Chang , Northouse Laurel L. , Duffy Sonia A. , Duquette Debra , Mendelsohn-Victor Kari E. , Milliron Kara J. , Merajver Sofia D. , Dinov Ivo D. , Janz Nancy K.
Published: September 2020

We compared a tailored and a targeted intervention designed to increase genetic testing, clinical breast exam (CBE), and mammography in young breast cancer survivors (YBCS) (diagnosed <45 years old) and their blood relatives. A two-arm cluster randomized trial recruited a random sample of YBCS from the Michigan cancer registry and up to two of their blood relatives. Participants were stratified according to race and randomly assigned as family units to the tailored (n = 637) or the targeted (n = 595) intervention. Approximately 40% of participants were Black. Based on intention-to-treat analyses, YBCS in the tailored arm reported higher self-efficacy for genetic services (p = 0.0205) at 8-months follow-up. Genetic testing increased approximately 5% for YBCS in the tailored and the targeted arm (p ≤ 0.001; p < 0.001) and for Black and White/Other YBCS (p < 0.001; p < 0.001). CBEs and mammograms increased significantly in both arms, 5% for YBCS and 10% for relatives and were similar for Blacks and White/Others. YBCS and relatives needing less support from providers reported significantly higher self-efficacy and intention for genetic testing and surveillance. Black participants reported significantly higher satisfaction and acceptability. Effects of these two low-resource interventions were comparable to previous studies. Materials are suitable for Black women at risk for hereditary breast/ovarian cancer (HBOC).
Potential Role of PDGFRβ-Associated THBS4 in Colorectal Cancer Development
Authors: Kim Min Seob , Choi Hyun Seok , Wu Moxin , Myung JiYeon , Kim Eui Joong , Kim Yong Sung , Ro Seungil , Ha Se Eun , Bartlett Allison , Wei Lai , Ryu Han-Seung , Choi Suck Chei , Park Won Cheol , Kim Keun Young , Lee Moon Young
Published: September 2020

Colorectal cancer is a significant cause of death since it frequently metastasizes to several organs such as the lung or liver. Tumor development is affected by various factors, including a tumor microenvironment, which may be an essential factor that leads to tumor growth, proliferation, invasion, and metastasis. In the tumor microenvironment, abnormal changes in various growth factors, enzymes, and cytokines can wield a strong influence on cancer. Thrombospondin-4 (THBS4), which is an extracellular matrix protein, also plays essential roles in the tumor microenvironment and mediates angiogenesis by transforming growth factor-β (TGFβ) signaling. Platelet-derived growth factor receptor β (PDGFRβ), which is a receptor tyrosine kinase and is also a downstream signal of TGFβ, is associated with invasion and metastasis in colorectal cancer. We identified that PDGFRβ and THBS4 are overexpressed in tumor tissues of colorectal cancer patients, and that PDGF-D expression increased after TGFβ treatment in the colon cancer cell line DLD-1. TGFβ and PDGF-D increased cellular THBS4 protein levels and secretion but did not increase THBS4 mRNA levels. This response was further confirmed by the inositol 1,4,5-triphosphate receptor (IP3R) and stromal interaction molecule 1 (STIM1) blockade as well as the PDGFRβ blockade. We propose that the PDGFRβ signal leads to a modification of the incomplete form of THBS4 to its complete form through IP3R, STIM1, and Ca2+-signal proteins, which further induces THBS4 secretion. Additionally, we identified that DLD-1 cell-conditioned medium stimulated with PDGF-D promotes adhesion, migration, and proliferation of colon myofibroblast CCD-18co cells, and this effect was intensified in the presence of thrombin. These findings suggest that excessive PDGFRβ signaling due to increased TGFβ and PDGF-D in colorectal tumors leads to over-secretion of THBS4 and proliferative tumor development.
Therapeutically Significant MicroRNAs in Primary and Metastatic Brain Malignancies
Authors: Balachandran Akilandeswari A. , Larcher Leon M. , Chen Suxiang , Veedu Rakesh N.
Published: September 2020

Brain cancer is one among the rare cancers with high mortality rate that affects both children and adults. The most aggressive form of primary brain tumor is glioblastoma. Secondary brain tumors most commonly metastasize from primary cancers of lung, breast, or melanoma. The five-year survival of primary and secondary brain tumors is 34% and 2.4%, respectively. Owing to poor prognosis, tumor heterogeneity, increased tumor relapse, and resistance to therapies, brain cancers have high mortality and poor survival rates compared to other cancers. Early diagnosis, effective targeted treatments, and improved prognosis have the potential to increase the survival rate of patients with primary and secondary brain malignancies. MicroRNAs (miRNAs) are short noncoding RNAs of approximately 18–22 nucleotides that play a significant role in the regulation of multiple genes. With growing interest in the development of miRNA-based therapeutics, it is crucial to understand the differential role of these miRNAs in the given cancer scenario. This review focuses on the differential expression of ten miRNAs (miR-145, miR-31, miR-451, miR-19a, miR-143, miR-125b, miR-328, miR-210, miR-146a, and miR-126) in glioblastoma and brain metastasis. These miRNAs are highly dysregulated in both primary and metastatic brain tumors, which necessitates a better understanding of their role in these cancers. In the context of the tumor microenvironment and the expression of different genes, these miRNAs possess both oncogenic and/or tumor-suppressive roles within the same cancer.
Neurotrophin Signaling in Medulloblastoma
Authors: Thomaz Amanda , Jaeger Mariane , Brunetto Algemir L. , Brunetto André T. , Gregianin Lauro , de Farias Caroline Brunetto , Ramaswamy Vijay , Nör Carolina , Taylor Michael D. , Roesler Rafael
Published: September 2020

Neurotrophins are a family of secreted proteins that act by binding to tropomyosin receptor kinase (Trk) or p75NTR receptors to regulate nervous system development and plasticity. Increasing evidence indicates that neurotrophins and their receptors in cancer cells play a role in tumor growth and resistance to treatment. In this review, we summarize evidence indicating that neurotrophin signaling influences medulloblastoma (MB), the most common type of malignant brain cancer afflicting children. We discuss the potential of neurotrophin receptors as new therapeutic targets for the treatment of MB. Overall, activation of TrkA and TrkC types of receptors seem to promote cell death, whereas TrkB might stimulate MB growth, and TrkB inhibition displays antitumor effects. Importantly, we show analyses of the gene expression profile of neurotrophins and their receptors in MB primary tumors, which indicate, among other findings, that higher levels of NTRK1 or NTRK2 are associated with reduced overall survival (OS) of patients with SHH MB tumors.
Latest Development in Multiple Myeloma
Authors: Imai Yoichi
Published: September 2020

Specialists in the field of multiple myeloma (MM) research have written a series of 12 articles (2 original articles, 10 reviews) in the Special Issue “Latest Development in Multiple Myeloma” [...]
FANCD2 Confers a Malignant Phenotype in Esophageal Squamous Cell Carcinoma by Regulating Cell Cycle Progression
Authors: Lei Lisa Chan , Yu Valen Zhuoyou , Ko Josephine Mun Yee , Ning Lvwen , Lung Maria Li
Published: September 2020

Fanconi anemia patients with germline genetic defects in FANCD2 are highly susceptible to cancers. Esophageal squamous cell carcinoma (ESCC) is a deadly cancer. Little is known about the function of FANCD2 in ESCC. For detailed molecular and mechanistic insights on the functional role of FANCD2 in ESCC, in vivo and in vitro assays and RNA sequencing approaches were used. Utilizing Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) technology, FANCD2 knockout models were established to examine the functional impact in mouse models for tumor growth and metastasis and in vitro assays for cell growth, cell cycle, and cellular localization. Our RNA sequence analyses were integrated with public datasets. FANCD2 confers a malignant phenotype in ESCC. FANCD2 is significantly upregulated in ESCC tumors, as compared to normal counterparts. Depletion of FANCD2 protein expression significantly suppresses the cancer cell proliferation and tumor colony formation and metastasis potential, as well as cell cycle progression, by involving cyclin-CDK and ATR/ATM signaling. FANCD2 translocates from the nucleus to the cytoplasm during cell cycle progression. We provide evidence of a novel role of FANCD2 in ESCC tumor progression and its potential usefulness as a biomarker for ESCC disease management.
CCAAT/Enhancer-Binding Protein Delta (C/EBPδ): A Previously Unrecognized Tumor Suppressor that Limits the Oncogenic Potential of Pancreatic Ductal Adenocarcinoma Cells
Authors: Hartl Leonie , Duitman JanWillem , Aberson Hella L. , Chen Kan , Dijk Frederike , Roelofs Joris J.T.H. , Dings Mark P.G. , Hooijer Gerrit K.J. , Hernanda Pratika Y. , Pan Qiunwei , Busch Olivier R. , Besselink Marc G.H. , Boerman Ton , Peppelenbosch Maikel P. , Bijlsma Maarten F. , Spek C. Arnold
Published: September 2020

CCAAT/enhancer-binding protein δ (C/EBPδ) is a transcription factor involved in growth arrest and differentiation, which has consequently been suggested to harbor tumor suppressive activities. However, C/EBPδ over-expression correlates with poor prognosis in glioblastoma and promotes genomic instability in cervical cancer, hinting at an oncogenic role of C/EBPδ in these contexts. Here, we explore the role of C/EBPδ in pancreatic cancer. We determined C/EBPδ expression in biopsies from pancreatic cancer patients using public gene-expression datasets and in-house tissue microarrays. We found that C/EBPδ is highly expressed in healthy pancreatic ductal cells but lost in pancreatic ductal adenocarcinoma. Furthermore, loss of C/EBPδ correlated with increased lymph node involvement and shorter overall survival in pancreatic ductal adenocarcinoma patients. In accordance with this, in vitro experiments showed reduced clonogenic capacity and proliferation of pancreatic ductal adenocarcinoma cells following C/EBPδ re-expression, concurrent with decreased sphere formation capacity in soft agar assays. We thus report a previously unrecognized but important tumor suppressor role of C/EBPδ in pancreatic ductal adenocarcinoma. This is of particular interest since only few tumor suppressors have been identified in the context of pancreatic cancer. Moreover, our findings suggest that restoration of C/EBPδ activity could hold therapeutic value in pancreatic ductal adenocarcinoma, although the latter claim needs to be substantiated in future studies.