bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between the True Digestibility of Dietary Calcium and Gastrointestinal Microorganisms in Goats
Authors: Liu Yuehui , Shah Ali Mujtaba , Wang Lizhi , Jin Lei , Wang Zhisheng , Xue Bai , Peng Quanhui
Published: May 2020

The current study was performed to examine the relationship between the true digestibility of calcium (TDC) in the diet and bacterial community structure in the gastrointestinal tract (GIT) of goats. Twenty-six Nubian healthy female goats were selected as experimental animals, and their TDC was determined using metabolic experiments. Eight goats were grouped into the high digestibility of Calcium (HC) phenotype, and another eight were grouped into the low digestibility of Calcium (LC) phenotype. Their bacterial 16S rRNA gene amplicons from the rumen, abomasum, jejunum, cecum, and colon contents were sequenced using next-generation high-throughput sequencing technology. In the rumen, 239 genera belonging to 23 phyla, 319 genera belonging to 30 phyla in the abomasum, 248 genera belonging to 36 phyla in the jejunum, 248 genera belonging to 25 phyla in the colon and 246 genera belonging to 23 phyla in the cecum were detected. In addition, there was a significant correlation between the TDC and the relative abundance of Candidatus_Saccharimonas, Christensenellaceae_R-7_group, Mogibacterium, Prevotella_1, Prevotella_UCG_004, Ruminococcus_2, Saccharibacteria in the rumen, Eubacterium_coprostanoligens_group, Lachnospiraceae_ND3007_group, Lachnospiraceae_NK3A20_group, p-1088-a5_gut_group, and Planctomycetes in the abomasum, Butyrivibrio in the cecum, and Fibrobacter in the cecum were observed. This study suggests an association of GIT microbial communities as a factor influencing TDC in goats.
Molecular Typing, Characterization of Antimicrobial Resistance, Virulence Profiling and Analysis of Whole-Genome Sequence of Clinical Klebsiella pneumoniae Isolates
Authors: Shelenkov Andrey , Mikhaylova Yulia , Yanushevich Yuri , Samoilov Andrei , Petrova Lyudmila , Fomina Valeria , Gusarov Vitaly , Zamyatin Mikhail , Shagin Dmitriy , Akimkin Vasiliy
Published: May 2020

Klebsiella pneumoniae is one of the most important pathogens concerned with multidrug resistance in healthcare-associated infections. The treating of infections caused by this bacterium is complicated due to the emergence and rapid spreading of carbapenem-resistant strains, which are associated with high mortality rates. Recently, several hypervirulent and carbapenemase-producing isolates were reported that make the situation even more complicated. In order to better understand the resistance and virulence mechanisms, and, in turn, to develop effective treatment strategies for the infections caused by multidrug-resistant K. pneumoniae, more comprehensive genomic and phenotypic data are required. Here, we present the first detailed molecular epidemiology report based on second and third generation (long-read) sequencing for the clinical isolates of K. pneumoniae in the Russian Federation. The data include three schemes of molecular typing, phenotypic and genotypic antibiotic resistance determination, as well as the virulence and plasmid profiling for 36 K. pneumoniae isolates. We have revealed 2 new multilocus sequence typing (MLST)-based sequence types, 32 multidrug-resistant (MDR) isolates and 5 colistin-resistant isolates in our samples. Three MDR isolates belonged to a very rare ST377 type. The whole genome sequences and additional data obtained will greatly facilitate further investigations in the field of antimicrobial resistance studies.
A Novel and Potentially Multifaceted Dehydroascorbate Reductase Increasing the Antioxidant Systems is Induced by Beauvericin in Tomato
Authors: Loi Martina , De Leonardis Silvana , Mulè Giuseppina , Logrieco Antonio F. , Paciolla Costantino
Published: May 2020

Dehydroascorbate reductases (DHARs) are important enzymes that reconvert the dehydroascorbic acid (DHA) into ascorbic acid (ASC). They are involved in the plant response to oxidative stress, such as that induced by the mycotoxin beauvericin (BEA). Tomato plants were treated with 50 µM of BEA; the main antioxidant compounds and enzymes were evaluated. DHARs were analyzed in the presence of different electron donors by native and denaturing electrophoresis as well as by western blot and mass spectrometry to identify a novel induced protein with DHAR activity. Kinetic parameters for dehydroascorbate (DHA) and glutathione (GSH) were also determined. The novel DHAR was induced after BEA treatment. It was GSH-dependent and possessed lower affinity to DHA and GSH than the classical DHARs. Interestingly, the mass spectrometry analysis of the main band appearing on sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) revealed a chloroplast sedoheptulose 1,7-bisphosphatase, a key enzyme of the Calvin cycle, and a chloroplast mRNA-binding protein, suggesting that the DHA reducing capacity could be a side activity or the novel DHAR could be part of a protein complex. These results shed new light on the ascorbate-glutathione regulation network under oxidative stress and may represent a new way to increase the plant antioxidant defense system, plant nutraceutical value, and the health benefits of plant consumption.
Antioxidant Properties of Agri-Food Byproducts and Specific Boosting Effects of Hydrolytic Treatments
Authors: Moccia Federica , Agustin-Salazar Sarai , Verotta Luisella , Caneva Enrico , Giovando Samuele , D’Errico Gerardino , Panzella Lucia , d’Ischia Marco , Napolitano Alessandra
Published: May 2020

Largely produced agri-food byproducts represent a sustainable and easily available source of phenolic compounds, such as lignins and tannins, endowed with potent antioxidant properties. We report herein the characterization of the antioxidant properties of nine plant-derived byproducts. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) assays indicated the superior activity of pomegranate peels and seeds, grape pomace and pecan nut shell. An increase in the antioxidant potency was observed for most of the waste materials following a hydrolytic treatment, with the exception of the condensed tannin-rich pecan nut shell and grape pomace. UV-Vis and HPLC investigation of the soluble fractions coupled with the results from IR analysis and chemical degradation approaches on the whole materials allowed to conclude that the improvement of the antioxidant properties was due not only to removal of non-active components (mainly carbohydrates), but also to structural modifications of the phenolic compounds. Parallel experiments run on natural and bioinspired model phenolic polymers suggested that these structural modifications positively impacted on the antioxidant properties of lignins and hydrolyzable tannins, whereas significant degradation of condensed tannin moieties occurred, likely responsible for the lowering of the reducing power observed for grape pomace and pecan nut shell. These results open new perspectives toward the exploitation and manipulation of agri-food byproducts for application as antioxidant additives in functional materials.
A Bibliometric Review of Publications on Oxidative Stress and Chemobrain: 1990–2019
Authors: McElroy Taylor , Allen Antiño R.
Published: May 2020

Oxidative stress is considered one of the possible mechanisms behind chemobrain or the cognitive dysfunction persistent after chemotherapy treatment. Breast cancer patients have reported chemobrain symptoms since the 1990s. In this present bibliometric review, we employed the VOSviewer tool to describe the existing landscape on literature concerning oxidative stress, breast cancer chemotherapies, and chemobrain. As of 2019, 8799 papers were listed in the Web of Science database, with more than 900 papers published each year. As expected, terms relating to oxidative stress, mitochondria, breast cancer, and antioxidants have occurred very often in the literature throughout the years. In recent years, there has been an increase in the occurrence of terms related to nanomedicine. Only within the last decade do the keywords ‘brain’, ‘blood-brain barrier’, and ‘central nervous system’ appear, reflecting an increased interest in chemobrain. China has become the most prolific producer of oxidative stress and chemotherapy related papers in the last decade followed by the USA and India. In conclusion, the subject of oxidative stress as a mechanism behind chemotherapies’ toxicities is an active area of research.
Nascent Rice Husk as an Adsorbent for Removing Cationic Dyes from Textile Wastewater
Authors: Quansah Jude Ofei , Hlaing Thandar , Lyonga Fritz Ndumbe , Kyi Phyo Phyo , Hong Seung-Hee , Lee Chang-Gu , Park Seong-Jik
Published: May 2020

We assessed the applicability of rice husk (RH) to remove cationic dyes, i.e., methylene blue (MB) and crystal violet (CV), from water. RH thermally treated at 75 °C showed a higher adsorption capacity than that at high temperatures (300–700 °C). For a suitable CV-adsorption model, a pseudo-first-order model for MB adsorption was followed by the kinetics adsorption process; however, a pseudo-second-order model was then suggested. In the qt versus t1/2 plot, the MB line passed through the origin, but that of CV did not. The Langmuir isotherm model was better than the Freundlich model for both dye adsorptions; furthermore, the adsorption capacity for MB and CV was 24.48 mg/g and 25.46 mg/g, respectively. Thermodynamically, the adsorption of both MB and CV onto the RH was found to be spontaneous and endothermic. This adsorption increased insignificantly on increasing the solution pH from 4 to 10. With an increasing dosage of the RH, there was an increase in the removal percentages of MB and CV; however, adsorption capacity per unit mass of the RH was observed to decrease. Therefore, we conclude that utilizing RH as an available and affordable adsorbent is feasible to remove MB and CV from wastewater.
Smouldering Combustion Dynamics of a Soil from a Pinus halepensis Mill. Forest. A Case Study of the Rocallaura Fires in Northeastern Spain
Authors: Xifré-Salvadó Miquel Àngel , Prat-Guitart Núria , Francos Marcos , Úbeda Xavier , Castellnou Marc
Published: May 2020

This study analyses the smouldering combustion on soils that took place during the wildfires that occurred in Rocallaura (Northeastern Spain). The smouldering combustion after the first event, 23 June, was the potential source of flaming fire re-ignition of the second event, 19 July 2016. Re-ignitions are an important challenge for the firefighting system. Budget and efforts are spent on controlling these re-ignitions that can ultimately cause the collapse of the response system if the re-ignitions happen during periods of simultaneous fire events. Our objective is to contribute to better understand the dynamics of the smouldering combustion of organic soils associated with these wildfires and the impact on the Pinus halepensis Mill. forest ecosystem. Transects were established in adjacent control and post-fire zones. Laboratory analyses were conducted to determine some physical and chemical properties of both the duff and mineral soil. Using these variables, we estimate thresholds of duff ignition probability, percentage of duff consumption and smouldering combustion spread rates. Overall, we provide a set of tools for evaluating re-ignitions in forest ecosystems. We conclude that the concept of fire persistence should be a new variable for consideration in present and future analysis of fire regimes and demonstrates the significance of introducing smouldering combustion and re-ignition within the strategic framework of the wildfire hazard and integrating these phenomena into forest planning and management.
Optimal Design of a Plenum Fan with Three-Dimensional Blades
Authors: Lee Kyung Jung , Park Il Wung , Bang Ki Suk , Kim Yeong Min , Ahn Young Chull
Published: May 2020

We successfully designed an optimized plenum fan with a three-dimensional, smooth, curved blade. The optimized model revealed that the static pressure in the channel had been increased uniformly and stably, and the flow separation at the leading edge was significantly reduced. According to simulations, the three-dimensional blade stabilized the fluid flow, and the flow friction was reduced by suppressing the flow separation as much as possible so that both the static pressure and the static efficiency were clearly improved in comparison with those of the original model. As a result, the static efficiency was improved by 6.3% compared with that of the original model.
Optimal Design of Adaptive Robust Control for the Delta Robot with Uncertainty: Fuzzy Set-Based Approach
Authors: Wu Linlin , Zhao Ruiying , Li Yuyu , Chen Ye-Hwa
Published: May 2020

An optimal control design for the uncertain Delta robot is proposed in the paper. The uncertain factors of the Delta robot include the unknown dynamic parameters, the residual vibration disturbances and the nonlinear joints friction, which are (possibly fast) time-varying and bounded. A fuzzy set theoretic approach is creatively used to describe the system uncertainty. With the fuzzily depicted uncertainty, an adaptive robust control, based on the fuzzy dynamic model, is established. It designs an adaptation mechanism, consisting of the leakage term and the dead-zone, to estimate the uncertainty information. An optimal design is constructed for the Delta robot and solved by minimizing a fuzzy set-based performance index. Unlike the traditional fuzzy control methods (if-then rules-based), the proposed control scheme is deterministic and fuzzily optimized. It is proven that the global solution in the closed form for this optimal design always exists and is unique. This research provides the Delta parallel robot a novel optimal control to guarantee the system performance regardless of the uncertainty. The effectiveness of the proposed control is illustrated by a series of simulation experiments. The results reveal that the further applications in other robots are feasible.
Potential of Chrozophora tinctoria Seed Oil as a Biodiesel Resource
Authors: Hoseini Seyed Salar , Najafi Gholamhassan , Moazzez Armin Fattahpour , Hazrati Saeid , Ebadi Mohammad Taghi , Yusaf Talal
Published: May 2020

Biodiesel is a renewable fuel that has been widely used in recent years. There are various resources used as biodiesel feedstocks, including animal fats, waste oils, and vegetable oils. In the present study, Chrozophora tinctoria seed oil is introduced as a new biodiesel feedstock. C. tinctoria is a weed and non-edible plant. So, the primary cost of this resource is very low, and hence it can be considered as a biodiesel source. This plant can also grow in most weather conditions. In the present study, the research team tried to produce biodiesel from C. tinctoria seeds through a transesterification reaction. To intensify the transesterification reaction, an ultrasonic device was used. In order to perform the transesterification reaction, potassium hydroxide was used as a catalyst. Important parameters, such as the reaction temperature, reaction time, molar ratio of methanol, and concentration of the catalyst, were adjusted. Based on the adjusted conditions, a biodiesel yield of 84% was attained. The properties of the C. tinctoria biodiesel was compared with the American Society for Testing and Materials (ASTM) standard. The results show the properties of a biodiesel: the density, kinematic viscosity, pour point, flash point, cloud point, and acid number are 0.868 g/cm3, 3.74 mPa, −7 °C, 169 °C, 4 °C, and 0.43 mg, respectively. The specification properties of C. tinctoria biodiesel can thus pass the requirement of the ASTM standard. So, C. tinctoria seed oil can be used as a suitable fuel source instead of petroleum-derived fuels.
The Nano-Scale Modified BaTiO3 Morphology Influence on Electronic Properties and Ceramics Fractal Nature Frontiers
Authors: Mitic Vojislav V. , Lazovic Goran , Lu Chun-An , Paunovic Vesna , Radovic Ivana , Stajcic Aleksandar , Vlahovic Branislav
Published: May 2020

The BaTiO3 ceramics applications based on electronic properties have very high gradient scientific and industrial-technological interests. Our scientific research has been based on nano BaTiO3 modified with Yttrium based organometallic salt (MOD-Y). The samples have been consolidated at a sintering temperature of 1350 °C. Within the study, the new frontiers for different electronic properties between the layers of BaTiO3 grains have been introduced. The research target was grain boundary investigations and the influence on dielectric properties. After scanning electron microscopy and dielectric measurements, it has been established that modified BaTiO3 samples with larger grains showed a better compact state that led to a higher dielectric constant value. DC bias stability was also investigated and showed a connection between the grain size and capacitance stability. Analyses of functions that could approximate experimental curves were successfully employed. Practical application of fractal corrections was performed, based on surface (αs) and pore size (αp) corrections, which resulted in obtainment of the relation between the capacitance and Curie temperature. Successful introduction of fractal corrections for capacitance-Curie temperature dependence for a set of experimental data is an important step towards further miniaturization of intergranular capacitors.
Introduction to Radar Scattering Application in Remote Sensing and Diagnostics: Review
Authors: Batool Sidra , Frezza Fabrizio , Mangini Fabio , Simeoni Patrizio
Published: May 2020

The manuscript reviews the current literature on scattering applications of RADAR (Radio Detecting And Ranging) in remote sensing and diagnostics. This paper gives prime features for a variety of RADAR applications ranging from forest and climate monitoring to weather forecast, sea status, planetary information, and mapping of natural disasters such as the ones caused by earthquakes. Both the fundamental parameters involved in scattering mechanisms of RADAR applications and the factors affecting RADAR performances are also discussed.
Preliminary Study of the Effects of Pulsed Electric Field (PEF) Treatments in Wines Obtained from Early-Harvested Sangiovese Grapes
Authors: Ricci Arianna , Parpinello Giuseppina Paola , Banfi Beatrice Anna , Olivi Federico , Versari Andrea
Published: May 2020

In this experiment, the effect of pulsed electric field (PEF) technology on the extractability of anthocyanins and polyphenols in early-harvested Sangiovese red grapes (16.9°Bx sugar, 3.26 pH, and 10.4 g/L titratable acidity) from Emilia Romagna (Italy) was investigated. Electric field strengths were in the range of 0.9–3 kV/cm, generated by the application of short, high-voltage pulses, and the grapes were subjected to specific energies from 10.4 to 32.5 kJ/kg immediately after crushing and destemming to produce a pre-fermentative pulsed electric field treatment on a pilot scale. Grape musts and wines were analyzed for color components and polyphenols content from pressing of juices up to 3 months from the end of the fermentation of wines. Furthermore, the freshly-fermented wines were subjected to accelerated aging conditions (i.e., warming under 40 °C for 32 days) to simulate the evolution of color parameters with time. The color intensity was generally higher in treated musts and wines compared to the control, further increased by raising the intensity of the electric field. Results suggested the potentialities of pulsed electric fields (PEFs) as a mild pre-fermentative process to assist maceration and to increase the polyphenolic content of musts obtained by early-harvested Sangiovese grapes.
Living in a Foster Home: The Single Subpolar Flagellum Fla1 of Rhodobacter sphaeroides
Authors: Camarena Laura , Dreyfus Georges
Published: May 2020

Rhodobacter sphaeroides is an α-proteobacterium that has the particularity of having two functional flagellar systems used for swimming. Under the growth conditions commonly used in the laboratory, a single subpolar flagellum that traverses the cell membrane, is assembled on the surface. This flagellum has been named Fla1. Phylogenetic analyses have suggested that this flagellar genetic system was acquired from an ancient γ-proteobacterium. It has been shown that this flagellum has components homologous to those present in other γ-proteobacteria such as the H-ring characteristic of the Vibrio species. Other features of this flagellum such as a straight hook, and a prominent HAP region have been studied and the molecular basis underlying these features has been revealed. It has also been shown that FliL, and the protein MotF, mainly found in several species of the family Rhodobacteraceae, contribute to remodel the amphipathic region of MotB, known as the plug, in order to allow flagellar rotation. In the absence of the plug region of MotB, FliL and MotF are dispensable. In this review we have covered the most relevant aspects of the Fla1 flagellum of this remarkable photosynthetic bacterium.
Low Concentration of Withaferin a Inhibits Oxidative Stress-Mediated Migration and Invasion in Oral Cancer Cells
Authors: Yu Tzu-Jung , Tang Jen-Yang , Ou-Yang Fu , Wang Yen-Yun , Yuan Shyng-Shiou F. , Tseng Kevin , Lin Li-Ching , Chang Hsueh-Wei
Published: May 2020

Withaferin A (WFA) has been reported to inhibit cancer cell proliferation based on high cytotoxic concentrations. However, the low cytotoxic effect of WFA in regulating cancer cell migration is rarely investigated. The purpose of this study is to investigate the changes in migration and mechanisms of oral cancer Ca9-22 cells after low concentrations of WFA treatment. WFA under 0.5 μM at 24 h treatment shows no cytotoxicity to oral cancer Ca9-22 cells (~95% viability). Under this condition, WFA triggers reactive oxygen species (ROS) production and inhibits 2D (wound healing) and 3D cell migration (transwell) and Matrigel invasion. Mechanically, WFA inhibits matrix metalloproteinase (MMP)-2 and MMP-9 activities but induces mRNA expression for a group of antioxidant genes, such as nuclear factor, erythroid 2-like 2 (NFE2L2), heme oxygenase 1 (HMOX1), glutathione-disulfide reductase (GSR), and NAD(P)H quinone dehydrogenase 1 (NQO1)) in Ca9-22 cells. Moreover, WFA induces mild phosphorylation of the mitogen-activated protein kinase (MAPK) family, including extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 expression. All WFA-induced changes were suppressed by the presence of ROS scavenger N-acetylcysteine (NAC). Therefore, these results suggest that low concentration of WFA retains potent ROS-mediated anti-migration and -invasion abilities for oral cancer cells.
Lifestyle Characteristics and Gene Expression Analysis of Colletotrichum camelliae Isolated from Tea Plant [Camellia sinensis (L.) O. Kuntze] Based on Transcriptome
Authors: Xiong Fei , Wang Yuchun , Lu Qinhua , Hao Xinyuan , Fang Wanping , Yang Yajun , Zhu Xujun , Wang Xinchao
Published: May 2020

Colletotrichum camelliae is one of the most serious pathogens causing anthracnose in tea plants, but the interactive relationship between C. camelliae and tea plants has not been fully elucidated. This study investigated the gene expression changes in five different growth stages of C. camelliae based on transcriptome analysis to explain the lifestyle characteristics during the infection. On the basis of gene ontology (GO) enrichment analyses of differentially expressed genes (DEGs) in comparisons of germ tube (GT)/conidium (Con), appressoria (App)/Con, and cellophane infectious hyphae (CIH)/Con groups, the cellular process in the biological process category and intracellular, intracellular part, cell, and cell part in the cellular component category were significantly enriched. Hydrolase activity, catalytic activity, and molecular_function in the molecular function category were particularly enriched in the infection leaves (IL)/Con group. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the DEGs were enriched in the genetic information processing pathway (ribosome) at the GT stage and the metabolism pathway (metabolic pathways and biosynthesis of secondary metabolism) in the rest of the stages. Interestingly, the genes associated with melanin biosynthesis and carbohydrate-active enzymes (CAZys), which are vital for penetration and cell wall degradation, were significantly upregulated at the App, CIH and IL stages. Subcellular localization results further showed that the selected non-annotated secreted proteins based on transcriptome data were majorly located in the cytoplasm and nucleus, predicted as new candidate effectors. The results of this study may establish a foundation and provide innovative ideas for subsequent research on C. camelliae.
Assessment of the Antitumor Potential of Umbelliprenin, a Naturally Occurring Sesquiterpene Coumarin
Authors: Shahzadi Iram , Ali Zain , Baek Seung Ho , Mirza Bushra , Ahn Kwang Seok
Published: May 2020

Cancer is one of the greatest causes of mortality worldwide. The prevalence rates of different types of cancer is increasing around the world as well. Limitations in chemotherapy and radiotherapy, owing to multiple side effects including cytotoxic effects of antitumor compounds on normal cells as well as the development of resistance to these treatment options in patients, create a serious threat to successful treatment of cancer. The use of natural compounds to prevent and treat cancers has been found to be quite effective, with fewer adverse effects found in patients. Umbelliprenin (UMB) is a naturally occurring sesquiterpene compound found in Ferula species and recently in Artemisia absinthium. Many studies have highlighted the antitumor potential of UMB in different cancer cell lines as well as in animal models. UMB exerts its anticancer actions by regulating extrinsic and intrinsic apoptotic pathways; causing inhibition of the cell cycle at the G0/G1 phase; and attenuating migration and invasion by modulating the Wnt signaling, NF-ĸB, TGFβ, and Fox3 signaling pathways. UMB also affects the key hallmarks of tumor cells by attenuating tumor growth, angiogenesis, and metastasis. This review provides an insight into the role of UMB as a potential antitumor drug for different malignancies and highlights the signaling cascades affected by UMB treatment in diverse tumor cell lines and preclinical models.
Prevalence and Incidence of Multiple Sclerosis in Russian Federation: 30 Years of Studies
Authors: Boyko Alexey , Melnikov Mikhail
Published: May 2020

In the Russian Federation, multiple sclerosis prevalence rates vary from 10 to 80 cases per 100,000, depending on region and the nationality of the population. The main characteristics of multiple sclerosis epidemiology in the XX century in this big territory are: (1) steady increase in multiple sclerosis prevalence and incidence rates, maybe because of better diagnosis and treatment, but also changes in environmental/epigenetic risk profile and/or lifestyle factors; (2) increase of the female to male ratio, increase in multiple sclerosis incidence mainly in females; (3) appearance and increasing frequency of multiple sclerosis in ethnic groups, previously free of multiple sclerosis (Northern Tribes, Yakuts and others). The latest data show that in European Russia, the multiple sclerosis prevalence varies from 30 to 80 cases, in Siberia—from 20 to 70 cases, with steady increases, especially in women.
Graphene Nanoplatelets-Based Ni-Zeolite Composite Catalysts for Heptane Hydrocracking
Authors: Saab Roba , Polychronopoulou Kyriaki , Charisiou Nikolaos , Goula Maria A. , Schiffer Andreas
Published: May 2020

This paper examines the effect of incorporating graphene nanoplatelets (GNPs) in an Ni-based/Zeolite-Y catalyst on the hydrocracking of heptane fuel at two temperatures, 350 and 400 °C. Specifically, reduced GNP/NiO-ZY and NiO-ZY catalysts, each with a 5 wt. % Ni loading, were compared in this study. The results show that the reduced GNP/NiO-ZY enhanced the conversion percentage by 31% at 350 °C and by 6% at 400 °C as compared with the reduced NiO-ZY, and the GNP/NiO-ZY also showed superior stability, reporting a less than 2% drop in conversion over 20 h of time-on-stream. The enhancement in performance is linked to the surface and texture characteristics of both catalysts. Although the calcined GNP/NiO-ZY possessed a lower Brunauer–Emmett–Teller (BET) surface area of 458 m2/g compared with 536 m2/g for the calcined NiO-ZY, it showed a more hydrophobic nature, as deduced from the water adsorption profiles, which corroborates the hypothesis that the increased affinity between the catalyst surface and heptane molecules during the reaction leads to an improved catalytic activity.
CCL2 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Shows Divergent Prognostic Potential for Bladder Cancer Patients Depending on Lymph Node Stage
Authors: Eckstein Markus , Epple Elena , Jung Rudolf , Weigelt Katrin , Lieb Verena , Sikic Danijel , Stöhr Robert , Geppert Carol , Weyerer Veronika , Bertz Simone , Kehlen Astrid , Hartmann Arndt , Wullich Bernd , Taubert Helge , Wach Sven
Published: May 2020

Bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications, markers for tumor cells and immune cells that are associated with prognosis are still needed. The chemokine CC motif ligand 2 (CCL2) could be such a marker. We analyzed the expression of CCL2 by immunohistochemistry (IHC) in 168 muscle invasive BCa samples using a tissue microarray. Application of a single cut-off for the staining status of tumor cells (TCs; positive vs. negative) and immune cells (ICs; ≤6% of ICs vs. >6% of ICs) revealed 57 cases (33.9%) and 70 cases (41.7%) with CCL2-positive TCs or ICs, respectively. IHC results were correlated with clinicopathological and survival data. Positive CCL2 staining in TCs was associated with shorter overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) (p = 0.004, p = 0.036, and p = 0.047; log rank test) and appeared to be an independent prognostic factor for OS (RR = 1.70; p = 0.007; multivariate Cox’s regression analysis). In contrast, positive CCL2 staining in the ICs was associated with longer OS, DSS, and RFS (p = 0.032, p = 0.001, and p = 0.001; log rank test) and appeared to be an independent prognostic factor for DSS (RR = 1.77; p = 0.031; multivariate Cox’s regression analysis). Most interestingly, after separating the patients according to their lymph node status (N0 vs. N1+2), CCL2 staining in the ICs was differentially associated with prognosis. In the N0 group, CCL2 positivity in the ICs was a positive independent prognostic factor for OS (RR = 1.99; p = 0.014), DSS (RR = 3.17; p = 0.002), and RFS (RR = 3.10; p = 0.002), whereas in the N1+2 group, CCL2 positivity was a negative independent factor for OS (RR = 3.44; p = 0.019)) and RFS (RR = 4.47; p = 0.010; all multivariate Cox’s regression analyses). In summary, CCL2 positivity in TCs is a negative prognostic factor for OS, and CCL2 can mark ICs that are differentially associated with prognosis depending on the nodal stage of BCa patients. Therefore, CCL2 staining of TCs and ICs is suggested as a prognostic biomarker for BCa patients.
Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1
Authors: Bosseboeuf Adrien , Mennesson Nicolas , Allain-Maillet Sophie , Tallet Anne , Piver Eric , Decaux Olivier , Moreau Caroline , Moreau Philippe , Lehours Philippe , Mégraud Francis , Salle Valéry , Bigot-Corbel Edith , Harb Jean , Hermouet Sylvie
Published: May 2020

Chronic stimulation by infectious or self-antigens initiates subsets of monoclonal gammopathies of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple myeloma (MM). Recently, glucosylsphingosine (GlcSph) was reported to be the target of one third of monoclonal immunoglobulins (Igs). In this study of 233 patients (137 MGUS, 6 SMM, 90 MM), we analyzed the GlcSph-reactivity of monoclonal Igs and non-clonal Igs. The presence of GlcSph-reactive Igs in serum was unexpectedly frequent, detected for 103/233 (44.2%) patients. However, GlcSph was targeted by the patient’s monoclonal Ig for only 37 patients (15.9%); for other patients (44 MGUS, 22 MM), the GlcSph-reactive Igs were non-clonal. Then, the characteristics of patients were examined: compared to MM with an Epstein-Barr virus EBNA-1-reactive monoclonal Ig, MM patients with a GlcSph-reactive monoclonal Ig had a mild presentation. The inflammation profiles of patients were similar except for moderately elevated levels of 4 cytokines for patients with GlcSph-reactive Igs. In summary, our study highlights the importance of analyzing clonal Igs separately from non-clonal Igs and shows that, if autoimmune responses to GlcSph are frequent in MGUS/SMM and MM, GlcSph presumably represents the initial pathogenic event for ~16% cases. Importantly, GlcSph-initiated MM appears to be a mild form of MM disease.
PIOS (Patras Immunotherapy Score) Score Is Associated with Best Overall Response, Progression-Free Survival, and Post-Immunotherapy Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC) Treated with Anti-Program Cell Death-1 (PD-1) Inhibitors
Authors: Dimitrakopoulos Foteinos-Ioannis , Nikolakopoulos Achilleas , Kottorou Anastasia , Kalofonou Fotini , Liolis Elias , Frantzi Theodora , Pyrousis Ioannis , Koutras Angelos , Makatsoris Thomas , Kalofonos Haralabos
Published: May 2020

Immunotherapy with immune checkpoint inhibitors (ICIs) has changed the therapeutic management of advanced non-small cell lung cancer (aNSCLC) over the last decade. However, there is an unmet need for clinically useful biomarkers in this patient subgroup. The aim of this study was to combine baseline clinical characteristics of aNSCLC patients, in the form of a scoring system, and to investigate its predictive and prognostic value in NSCLC patients treated with ICIs. A total of 112 patients with advanced (stages IIIA to IV) NSCLC, treated with nivolumab or pembrolizumab, were enrolled in this study. Patras Immunotherapy Score (PIOS) was developed based on four of the studied parameters (performance status (PS), body mass index (BMI), age, and lines of treatment (LOT), which were incorporated into our formula (PS × BMI/ LOT × age). PIOS score was strongly associated with best overall responses (BOR), with those patients having benefit/good response (stable disease (SD) or partial (PR) or complete response (CR), achieving a higher score compared to patients who developed progressive disease (PD) (p < 0.001). Furthermore, PIOS score was associated with progression-free survival (PFS), since high-score patients had longer PFS (p < 0.001, hazard ratio (HR) = 0.469). Moreover, PIOS was associated with post-immunotherapy overall survival (OS), with high-score patients having improved OS (log-rank p = 0.019). This study suggests that a combination of baseline parameters, which give rise to PIOS score, may predict the best response of NSCLC patients treated with anti-program cell death -1 (PD-1) monotherapy as well as it may have a potent prognostic value for PFS and post immunotherapy OS.
Evaluation of Second-Line Anti-VEGF after First-Line Anti-EGFR Based Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Multicenter “SLAVE” Study
Authors: Parisi Alessandro , Cortellini Alessio , Cannita Katia , Venditti Olga , Camarda Floriana , Calegari Maria Alessandra , Salvatore Lisa , Tortora Giampaolo , Rossini Daniele , Germani Marco Maria , Boccaccino Alessandra , Dell’Aquila Emanuela , Fulgenzi Claudia , Santini Daniele , De Tursi Michele , Tinari Nicola , Di Marino Pietro , Lombardi Pasquale , Roselló Keränen Susana , Huerta Álvaro Marisol , Zurlo Ina Valeria , Corsi Domenico Cristiano , Emiliani Alessandra , Zanaletti Nicoletta , Troiani Teresa , Vitale Pasquale , Giampieri Riccardo , Merloni Filippo , Occhipinti Mario Alberto , Marchetti Paolo , Roberto Michela , Mazzuca Federica , Ghidini Michele , Indini Alice , Garajova Ingrid , Zoratto Federica , Delle Monache Simona , Porzio Giampiero , Ficorella Corrado
Published: May 2020

Background: The optimal anti-angiogenic strategy as second-line treatment in RAS wild-type metastatic colorectal cancer (mCRC) treated with anti-EGFR (Epidermal Growth Factor Receptor) based first-line treatment is still debated. Methods: This multicenter, real-world, retrospective study is aimed at evaluating the effectiveness of second-line Bevacizumab- and Aflibercept-based treatments after an anti-EGFR based first-line regimen. Clinical outcomes measured were: objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AEs) profiles. Results: From February 2011 to October 2019, 277 consecutive mCRC patients received Bevacizumab-based (228, 82.3%) or Aflibercept-based (49, 17.7%) regimen. No significant difference was found regarding ORR. The median follow-up was 27.7 months (95%CI: 24.7–34.4). Aflibercept-treated group had a significantly shorter PFS compared to Bevacizumab-treated group (5.6 vs. 7.1 months, respectively) (HR = 1.34 (95%CI: 0.95–1.89); p = 0.0932). The median OS of the Bevacizumab-treated group and Aflibercept-treated group was 16.2 (95%CI: 15.3–18.1) and 12.7 (95%CI: 8.8–17.5) months, respectively (HR= 1.31 (95%CI: 0.89–1.93) p = 0.16). After adjusting for the key covariates (age, gender, performance status, number of metastatic sites and primary tumor side) Bevacizumab-based regimens revealed to be significantly related with a prolonged PFS (HR = 1.44 (95%CI: 1.02–2.03); p = 0.0399) compared to Aflibercept-based regimens, but not with a prolonged OS (HR = 1.47 (95%CI: 0.99–2.17); p = 0.0503). The incidence of G3/G4 VEGF inhibitors class-specific AEs was 7.5% and 26.5% in the Bevacizumab-treated group and the Aflibercept-treated group, respectively (p = 0.0001). Conclusion: Our analysis seems to reveal that Bevacizumab-based regimens have a slightly better PFS and class-specific AEs profile compared to Aflibercept-based regimen as second-line treatment of RAS wild-type mCRC patients previously treated with anti-EGFR based treatments. These results have to be taken with caution and no conclusive considerations are allowed.
Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways
Authors: Di Gilio Alessia , Catino Annamaria , Lombardi Angela , Palmisani Jolanda , Facchini Laura , Mongelli Teresa , Varesano Niccolò , Bellotti Roberto , Galetta Domenico , de Gennaro Gianluigi , Tangaro Sabina
Published: May 2020

Malignant pleural mesothelioma (MPM) is a rare neoplasm, mainly caused by asbestos exposure, with a high mortality rate. The management of patients with MPM is controversial due to a long latency period between exposure and diagnosis and because of non-specific symptoms generally appearing at advanced stage of the disease. Breath analysis, aimed at the identification of diagnostic Volatile Organic Compounds (VOCs) pattern in exhaled breath, is believed to improve early detection of MPM. Therefore, in this study, breath samples from 14 MPM patients and 20 healthy controls (HC) were collected and analyzed by Thermal Desorption-Gas Chromatography-Mass Spectrometry (TD-GC/MS). Nonparametric test allowed to identify the most weighting variables to discriminate between MPM and HC breath samples and multivariate statistics were applied. Considering that MPM is an aggressive neoplasm leading to a late diagnosis and thus the recruitment of patients is very difficult, a promising data mining approach was developed and validated in order to discriminate between MPM patients and healthy controls, even if no large population data are available. Three different machine learning algorithms were applied to perform the classification task with a leave-one-out cross-validation approach, leading to remarkable results (Area Under Curve AUC = 93%). Ten VOCs, such as ketones, alkanes and methylate derivates, as well as hydrocarbons, were able to discriminate between MPM patients and healthy controls and for each compound which resulted diagnostic for MPM, the metabolic pathway was studied in order to identify the link between VOC and the neoplasm. Moreover, five breath samples from asymptomatic asbestos-exposed persons (AEx) were exploratively analyzed, processed and tested by the validated statistical method as blinded samples in order to evaluate the performance for the early recognition of patients affected by MPM among asbestos-exposed persons. Good agreement was found between the information obtained by gold-standard diagnostic methods such as computed tomography CT and model output.
Risk Assessment by Presurgical Tractography Using Navigated TMS Maps in Patients with Highly Motor- or Language-Eloquent Brain Tumors
Authors: Sollmann Nico , Zhang Haosu , Fratini Alessia , Wildschuetz Noémie , Ille Sebastian , Schröder Axel , Zimmer Claus , Meyer Bernhard , Krieg Sandro
Published: May 2020

Patients with functionally eloquent brain lesions are at risk of functional decline in the course of resection. Given tumor-related plastic reshaping and reallocation of function, individual data are needed for patient counseling and risk assessment prior to surgery. This study evaluates the utility of mapping by navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging fiber tracking (DTI FT) for individual risk evaluation of surgery-related decline of motor or language function in the clinical setting. In total, 250 preoperative nTMS mappings (100 language and 150 motor mappings) derived from 216 patients (mean age: 57.0 ± 15.5 years, 58.8% males; glioma World Health Organization (WHO) grade I & II: 4.2%, glioma WHO grade III & IV: 83.4%, arteriovenous malformations: 1.9%, cavernoma: 2.3%, metastasis: 8.2%) were included. Deterministic tractography based on nTMS motor or language maps as seed regions was performed with 25%, 50%, and 75% of the individual fractional anisotropy threshold (FAT). Lesion-to-tract distances (LTDs) were measured between the tumor mass and the corticospinal tract (CST), arcuate fascicle (AF), or other closest language-related tracts. LTDs were compared between patients and correlated to the functional status (no/transient/permanent surgery-related paresis or aphasia). Significant differences were found between patients with no or transient surgery-related deficits and patients with permanent surgery-related deficits regarding LTDs in relation to the CST (p < 0.0001), AF (p ≤ 0.0491), or other closest language-related tracts (p ≤ 0.0435). The cut-off values for surgery-related paresis or aphasia were ≤ 12 mm (LTD—CST) and ≤ 16 mm (LTD—AF) or ≤25 mm (LTD—other closest language-related tract), respectively. Moreover, there were significant associations between the status of surgery-related deficits and the LTD when considering the CST (range r: −0.3994 to −0.3910, p < 0.0001) or AF (range r: −0.2918 to −0.2592, p = 0.0135 and p = 0.0473 for 25% and 50% FAT). In conclusion, this is the largest study evaluating the application of both preoperative functional mapping and function-based tractography for motor and language function for risk stratification in patients with functionally eloquent tumors. The LTD may qualify as a viable marker that can be seamlessly assessed in the clinical neurooncological setup.
Proteomic Tissue-Based Classifier for Early Prediction of Prostate Cancer Progression
Authors: Gao Yuqian , Wang Yi-Ting , Chen Yongmei , Wang Hui , Young Denise , Shi Tujin , Song Yingjie , Schepmoes Athena A. , Kuo Claire , Fillmore Thomas L. , Qian Wei-Jun , Smith Richard D. , Srivastava Sudhir , Kagan Jacob , Dobi Albert , Sesterhenn Isabell A. , Rosner Inger L. , Petrovics Gyorgy , Rodland Karin D. , Srivastava Shiv , Cullen Jennifer , Liu Tao
Published: May 2020

Although ~40% of screen-detected prostate cancers (PCa) are indolent, advanced-stage PCa is a lethal disease with 5-year survival rates around 29%. Identification of biomarkers for early detection of aggressive disease is a key challenge. Starting with 52 candidate biomarkers, selected from existing PCa genomics datasets and known PCa driver genes, we used targeted mass spectrometry to quantify proteins that significantly differed in primary tumors from PCa patients treated with radical prostatectomy (RP) across three study outcomes: (i) metastasis ≥1-year post-RP, (ii) biochemical recurrence ≥1-year post-RP, and (iii) no progression after ≥10 years post-RP. Sixteen proteins that differed significantly in an initial set of 105 samples were evaluated in the entire cohort (n = 338). A five-protein classifier which combined FOLH1, KLK3, TGFB1, SPARC, and CAMKK2 with existing clinical and pathological standard of care variables demonstrated significant improvement in predicting distant metastasis, achieving an area under the receiver-operating characteristic curve of 0.92 (0.86, 0.99, p = 0.001) and a negative predictive value of 92% in the training/testing analysis. This classifier has the potential to stratify patients based on risk of aggressive, metastatic PCa that will require early intervention compared to low risk patients who could be managed through active surveillance.
Serological Biomarkers for Early Detection of Hepatocellular Carcinoma: A Focus on Autoantibodies against Tumor-Associated Antigens Encoded by Cancer Driver Genes
Authors: Wang Keyan , Li Miao , Qin Jiejie , Sun Guiying , Dai Liping , Wang Peng , Ye Hua , Shi Jianxiang , Cheng Lin , Yang Qian , Qiu Cuipeng , Jiang Di , Wang Xiao , Zhang Jianying
Published: May 2020

Substantial evidence manifests the occurrence of autoantibodies to tumor-associated antigens (TAAs) in the early stage of hepatocellular carcinoma (HCC), and previous studies have mainly focused on known TAAs. In the present study, protein microarrays based on cancer driver genes were customized to screen TAAs. Subsequently, autoantibodies against selected TAAs in sera were tested by enzyme-linked immunosorbent assays (ELISA) in 1175 subjects of three independent datasets (verification dataset, training dataset, and validation dataset). The verification dataset was used to verify the results from the microarrays. A logistic regression model was constructed within the training dataset; seven TAAs were included in the model and yielded an area under the receiver operating characteristic curve (AUC) of 0.831. The validation dataset further evaluated the model, exhibiting an AUC of 0.789. Remarkably, as the aggravation of HCC increased, the prediction probability (PP) of the model tended to decrease, the trend of which was contrary to alpha-fetoprotein (AFP). For AFP-negative HCC patients, the positive rate of this model reached 67.3% in the training dataset and 50.9% in the validation dataset. Screening TAAs with protein microarrays based on cancer driver genes is the latest, fast, and effective method for finding indicators of HCC. The identified anti-TAA autoantibodies can be potential biomarkers in the early detection of HCC.