bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Acute-Phase Protein Response Associated with the Different Pathological Forms of Bovine Paratuberculosis
Authors: Espinosa José , de la Morena Rubén , Benavides Julio , García-Pariente Carlos , Fernández Miguel , Tesouro Miguel , Arteche Noive , Vallejo Raquel , Ferreras M. Carmen , Pérez Valentín
Published: October 2020

In this study, the concentrations of two acute-phase proteins (APPs), haptoglobin (Hp) and serum amyloid A (SAA), were quantitatively assessed in serum samples from cattle naturally infected with paratuberculosis (PTB). APP profiles were compared across 190 animals classified according to the different pathological forms associated with infection: uninfected (n = 59), with focal lesions (n = 73), multifocal lesions (n = 19), and diffuse paucibacillary (n = 11) and diffuse multibacillary lesions (n = 28). Our results showed a significant increase in both APPs in infected animals compared to the control group, with differences depending on the type of lesion. Hp and SAA levels were increased significantly in all infected animals, except in cows with diffuse multibacillary lesions that showed similar values to non-infected animals. The expression pattern of both APPs was similar and negatively correlated with the antibody levels against PTB. These results indicate that the release of Hp and SAA is related to the presence of PTB lesions associated with a high cell-mediated immune response and a lower bacterial load, suggesting that the pro-inflammatory cytokines that are associated with these forms are the main stimulus for their synthesis. These molecules could show some potential to be used as putative biomarkers of PTB infection, particularly for the identification of subclinical animals showing pathological forms related to latency or resistance to the development of advanced lesions.
A Novel Corn-Expressed Phytase Improves Daily Weight Gain, Protein Efficiency Ratio and Nutrients Digestibility and Alters Fecal Microbiota in Pigs Fed with Very Low Protein Diets
Authors: Shili Cedrick N. , Broomhead Jonathan N. , Spring Shelby C. , Lanahan Mike B. , Pezeshki Adel
Published: October 2020

The objective of this study was to assess the effect of a novel corn-expressed phytase (CEP) on growth, nutrients digestibility, bone characteristics and fecal microbiota of pigs fed with very low-protein, -calcium (Ca) and -phosphorous (P) diets. Forty-eight barrows were subjected to 6 groups for 4 weeks: positive control-adequate protein (PC), negative control-reduced protein (NC), NC + low-dose CEP, i.e., 2000 FTU/kg (LD), NC + high-dose CEP, i.e., 4000 FTU/kg (HD), LD with 0.12% unit reduced Ca and 0.15% unit reduced available P (LDR), and HD with 0.12% unit reduced Ca and 0.15% unit reduced available P (HDR). Compared to NC, LD and HDR had a higher average daily gain (ADG) and gain:protein ratio (G:P), HD and HDR had greater apparent fecal digestibility of Ca and P and bone mineral density and LDR and HDR had lower serum osteocalcin. The feces of LD was enriched in Lachnospiraceae, while the HD had a higher abundance of Succinvibrio and LDR had a higher abundance of Bifidobacterium and Actinobacteria. In conclusion, supplementation of protein-restricted diets with a CEP decreased their negative effects on ADG and G:P ratio, increased the digestibility of Ca and P regardless of the levels of these minerals in the diet, improved bone characteristics and produced differential effects on fecal bacterial population.
Morphometric Characteristics of the Spermatozoa of Blue Fox (Alopex lagopus) and Silver Fox (Vulpes vulpes)
Authors: Andraszek Katarzyna , Banaszewska Dorota , Szeleszczuk Olga , Kuchta-Gładysz Marta , Grzesiakowska Anna
Published: October 2020

The results presented in this study are the first such extensive characterization of the sperm morphometry of the blue fox (Alopex lagopus) and silver fox (Vulpes vulpes), as representatives of the family Canidae. Canine spermatozoa, especially the sperm of farmed foxes, are not often described in studies on reproduction. The aim of the study was a detailed comparison of the morphometric dimensions and shape of the sperm of two fox species: silver fox and blue fox. Semen collected from 10 silver foxes and 10 blue foxes was used for the study. The specimens were stained with silver nitrate. Measurements were performed of the length, width, perimeter, and area of the head; the area of the acrosome and its coverage; the length of the midpiece and its coverage; the length of the tail; and the length of the end piece of the tail. In addition, four head shape indices were calculated: ellipticity, elongation, roughness and regularity. The following values for the morphometric parameters and shape indices were obtained for blue fox and silver fox, respectively: head length—6.72 µm and 6.33 µm; head width—4.54.µm and 4.21 µm; head perimeter—18.11 µm and 17.37 µm; head area—21.94 µm2 and 21.11 µm2; acrosome area—11.50 µm2 and 10.92 µm2; midpiece length—12.85 µm and 12.79 µm; tail end piece length—3.44 µm and 3.28 µm; tail length—65.23 µm and 65.09 µm; acrosome coverage—52.43% and 52.83%; midpiece coverage—19.71% and 19.65%; sperm length—71.95 µm and 71.42 µm; ellipticity—1.49 and 1.52; elongation—0.19 and 0.20; roughness—0.84 and 1.88; regularity—1.09 and 0.99. The significance of differences between species was verified by Tukey’s test at p ≤ 0.05. Statistically significant differences between species were found for the following parameters: head length, width, perimeter and area; acrosome area; tail, end piece, and total sperm length; roughness and regularity. The differences in the size and shape of sperm can be used to establish reference patterns for fox sperm enabling more accurate species identification.
Chemico-Biological Characterization of Torpedino Di Fondi® Tomato Fruits: A Comparison with San Marzano Cultivar at Two Ripeness Stages
Authors: Ingallina Cinzia , Maccelli Alessandro , Spano Mattia , Di Matteo Giacomo , Di Sotto Antonella , Giusti Anna Maria , Vinci Giuliana , Di Giacomo Silvia , Rapa Mattia , Ciano Salvatore , Fraschetti Caterina , Filippi Antonello , Simonetti Giovanna , Cordeiro Carlos , Silva Marta Sousa , Crestoni Maria Elisa , Sobolev Anatoly P. , Fornarini Simonetta , Mannina Luisa
Published: October 2020

Torpedino di Fondi (TF) is a hybrid tomato landrace developed in Sicily and recently introduced in the south Lazio area along with the classical San Marzano (SM) cultivar. The present study aimed at characterizing TF tomatoes at both pink and red ripening stages, and at comparing them with traditional SM tomatoes. A multidisciplinary approach consisting of morphological, chemical (FT-ICR MS, NMR, HPLC, and spectrophotometric methods), and biological (antioxidant and antifungal in vitro activity) analyses was applied. Morphological analysis confirmed the mini-San Marzano nature and the peculiar crunchy and solid consistency of TF fruits. Pink TF tomatoes displayed the highest content of hydrophilic antioxidants, like total polyphenols (0.192 mg/g), tannins (0.013 mg/g), flavonoids (0.204 mg/g), and chlorophylls a (0.344 mg/g) and b (0.161 mg/g), whereas red TF fruits were characterized by the highest levels of fructose (3000 mg/100 g), glucose (2000 mg/100 g), tryptophan (2.7 mg/100 g), phenylalanine (13 mg/100 g), alanine (25 mg/100 g), and total tri-unsaturated fatty acids (13% mol). Red SM fruits revealed the greatest content of lipophilic antioxidants, with 1234 mg/g of total carotenoids. In agreement with phenolics content, TF cultivar showed the greatest antioxidant activity. Lastly, red TF inhibited Candida species (albicans, glabrata and krusei) growth.
Offensive and Defensive Plus–Minus Player Ratings for Soccer
Authors: Hvattum Lars Magnus
Published: October 2020

Rating systems play an important part in professional sports, for example, as a source of entertainment for fans, by influencing decisions regarding tournament seedings, by acting as qualification criteria, or as decision support for bookmakers and gamblers. Creating good ratings at a team level is challenging, but even more so is the task of creating ratings for individual players of a team. This paper considers a plus–minus rating for individual players in soccer, where a mathematical model is used to distribute credit for the performance of a team as a whole onto the individual players appearing for the team. The main aim of the work is to examine whether the individual ratings obtained can be split into offensive and defensive contributions, thereby addressing the lack of defensive metrics for soccer players. As a result, insights are gained into how elements such as the effect of player age, the effect of player dismissals, and the home field advantage can be broken down into offensive and defensive consequences.
Development of Attached Cavitation at Very Low Reynolds Numbers from Partial to Super-Cavitation
Authors: Ravelet Florent , Danlos Amélie , Bakir Farid , Croci Kilian , Khelladi Sofiane , Sarraf Christophe
Published: October 2020

The present study focuses on the inception, the growth, and the potential unsteady dynamics of attached vapor cavities into laminar separation bubbles. A viscous silicon oil has been used in a Venturi geometry to explore the flow for Reynolds numbers ranging from Re=800 to Re=2000. Special care has been taken to extract the maximum amount of dissolved air. At the lowest Reynolds numbers the cavities are steady and grow regularly with decreasing ambient pressure. A transition takes place between Re=1200 and Re=1400 for which different dynamical regimes are identified: a steady regime for tiny cavities, a periodical regime of attached cavity shrinking characterized by a very small Strouhal number for cavities of intermediate sizes, the bursting of aperiodical cavitational vortices which further lower the pressure, and finally steady super-cavitating sheets observed at the lowest of pressures. The growth of the cavity with the decrease of the cavitation number also becomes steeper. This scenario is then well established and similar for Reynolds numbers between Re=1400 and Re=2000.
Microstructure and Properties of AA6061/SiCp Composites Sintered under Ultra High-Pressure
Authors: Xu Lei , Yang Erkuo , Wang Yasong , Li Changyun , Chen Zhiru , Mi Guofa
Published: October 2020

Ultra high-pressure sintering (UHPS) was used to prepare AA6061/SiCp composites with different contents and the effect of sintering temperatures on microstructure and mechanical properties was investigated in this study. The results showed that a uniform distribution of nano-SiC particles (N-SiCp) is obtained by the UHPS method. With the increase in N-SiCp contents, the higher hardness and better wear resistance could be inspected. The interfacial reactions and Al4C3 phase appeared above 550 °C. The relative density of composites first increased and then decreased; with the temperature raising it reached 99.58% at 600 °C. The hardness and wear property showed the same trend with the hardness reaching 52 HRA and wear rate being 1.0 × 10−6 g/m at 600 °C. Besides, the wear mechanism of the composites is mainly composed of abrasive wear and adhesive wear.
Effect of Wing Corrugation on the Aerodynamic Efficiency of Two-Dimensional Flapping Wings
Authors: Dao Thanh Tien , Loan Au Thi Kim , Park Soo Hyung , Park Hoon Cheol
Published: October 2020

Many previous studies have shown that wing corrugation of an insect wing is only structurally beneficial in enhancing the wing’s bending stiffness and does not much help to improve the aerodynamic performance of flapping wings. This study uses two-dimensional computational fluid dynamics (CFD) in aiming to identify a proper wing corrugation that can enhance the aerodynamic performance of the KUBeetle, an insect-like flapping-wing micro air vehicle (MAV), which operates at a Reynolds number of less than 13,000. For this purpose, various two-dimensional corrugated wings were numerically investigated. The two-dimensional flapping wing motion was extracted from the measured three-dimensional wing kinematics of the KUBeetle at spanwise locations of r = (0.375 and 0.75)R. The CFD analysis showed that at both spanwise locations, the corrugations placed over the entire wing were not beneficial for improving aerodynamic efficiency. However, for the two-dimensional flapping wing at the spanwise location of r = 0.375R, where the wing experiences relatively high angles of attack, three specially designed wings with leading-edge corrugation showed higher aerodynamic performance than that of the non-corrugated smooth wing. The improvement is closely related to the flow patterns formed around the wings. Therefore, the proposed leading-edge corrugation is suggested for the inboard wing of the KUBeetle to enhance aerodynamic performance. The corrugation in the inboard wing may also be structurally beneficial.
Trends and Persistence of Dry–Wet Conditions in Northeast Brazil
Authors: Alves da Silva Antonio Samuel , Cunha Filho Moacyr , Simões Cezar Menezes Rômulo , Stosic Tatijana , Stosic Borko
Published: October 2020

We analyze trend and persistence in Standardized Precipitation Index (SPI) time series derived from monthly rainfall data at 133 gauging stations in Pernambuco state, Brazil, using a suite of complementary methods to address the spatially explicit tendencies, and persistence. SPI was calculated for 1-, 3-, 6-, and 12-month time scales from 1950 to 2012. We use Mann–Kendall test and Sen’s slope to determine sign and magnitude of the trend, and detrended fluctuation analysis (DFA) method to quantify long-term correlations. For all time scales significant negative trends are obtained in the Sertão (deep inland) region, while significant positive trends are found in the Agreste (intermediate inland), and Zona da Mata (coastal) regions. The values of DFA exponents show different scaling behavior for different time scales. For short-term conditions described by SPI-1 the DFA exponent is close to 0.5 indicating weak persistency and low predictability, while for medium-term conditions (SPI-3 and SPI-6) DFA exponents are greater than 0.5 and increase with time scale indicating stronger persistency and higher predictability. For SPI-12 that describes long-term precipitation patterns, the values of DFA exponents for inland regions are around 1, indicating strong persistency, while in the shoreline the value of the DFA exponent is between 1.0 and 1.5, indicating anti-persistent fractional Brownian motion. These results should be useful for agricultural planning and water resource management in the region.
North–South Discrepancy of Interannual Sea Surface Temperature Anomalies over the South China Sea Associated with Eastern Pacific El Niño Events in the Spring
Authors: Liu Yujie , Li Shuang
Published: October 2020

This paper discovers a spatial feature of interannual sea surface temperature (SST) anomalies over the South China Sea (SCS) in the boreal spring, based on the Simple Ocean Data Assimilation (SODA) monthly data in the period from January 1958 to December 2010. The Empirical Orthogonal Function (EOF) analysis of interannual SST anomalies shows a north–south discrepant pattern of the first mode, which is characterized by higher (lower) anomalies in the northern (southern) SCS and possessing seasonal phase locking (in the boreal spring). Besides, the high correlation coefficient between the time series of the first EOF mode and the Nino 3 SST anomalies during winter reveals that this discrepant pattern is likely caused by El Niño events. The composites of SST anomalies show that this discrepant pattern appears in the eastern Pacific (EP) El Niño events, while it does not exist in the Central Pacific (CP) El Niño events. It is believed that the western North Pacific anticyclone (WNPA) plays a key role in conveying the El Niño impact on the interannual variabilities of SCS SST in the EP El Niño events. The anomalous anticyclone in the Philippine Sea weakens the northeasterly monsoon over the SCS by its southwest portion during the mature phases of the EP El Niño events. This anomalous atmospheric circulation contributes to the north–south discrepant pattern of the wind stress anomalies over the SCS in the EP El Niño mature winters, and then leads to the north–south dipole pattern of the contemporaneous latent heat flux anomalies. The latent heat flux is a major contributor to the surface net heat flux, and heat budget analysis shows that the net heat flux is the major contributor to the SCS SST anomalies during the spring for the EP El Niño events, and the north–south discrepancy of SCS SST anomalies in the succeeding spring is ultimately formed.
The Importance of Microbial Inoculants in a Climate-Changing Agriculture in Eastern Mediterranean Region
Authors: Kavadia Athanasia , Omirou Michalis , Fasoula Dionysia , Ioannides Ioannis M.
Published: October 2020

Climate change has gained importance due to its severe consequences for many aspects of life. Increasing temperature, drought and greenhouse gases affect directly or indirectly the productivity of agricultural and natural ecosystems as well as human health. The nutrient supply capacity of the soil is diminishing, while food requirements for the growing population are increasing. The ongoing application of agrochemicals results in adverse effects on ecosystem functioning and food chain. Now, more than ever, there is a need to mitigate the effects of agricultural activities on climate change using environmentally friendly techniques. The role of plant beneficial microorganisms on this global challenge is increasingly being explored, and there is strong evidence that could be important. The use of functional microbial guilds forms an alternative or even a supplementary approach to common agricultural practices, due to their ability to act as biofertilizers and promote plant growth. Application of microbial inocula has a significantly lower impact on the environment compared to chemical inputs, while the agricultural sector will financially benefit, and consumers will have access to quality products. Microbial inoculants could play an important role in agricultural stress management and ameliorate the negative impacts of climate change. This short review highlights the role of microbes in benefiting agricultural practices against climate-changing conditions. In particular, the main microbial plant growth-promoting functional traits that are related to climate change are presented and discussed. The importance of microbial inoculants’ multifunctionality is debated, while future needs and challenges are also highlighted.
Impact of the COVID-19 Outbreak on Air Quality in Korea
Authors: Seo Ji Hoon , Jeon Hyun Woo , Sung Ui Jae , Sohn Jong-Ryeul
Published: October 2020

The COVID-19 pandemic has led countries to take action, which has included practicing social distancing or lockdown. Many cities are experiencing air quality improvements due to human activity restrictions. The purpose of this study was to compare the air quality between 2020 and the previous three years, focusing on the two cities (Seoul and Daegu) where coronavirus is spreading the fastest in Korea. Significant decreases in PM2.5, PM10, CO, and NO2 were observed in both cities. In particular, compared to the same period of 2017-2019, in March 2020, PM2.5 showed remarkable reductions of 36% and 30% in Seoul and Daegu, respectively. The effects of social distancing have maximized improvements in air quality due to reduced transboundary pollutants. The PM2.5/PM10 ratio was significantly reduced after social distancing, indicating that the contribution of traffic-related PM2.5 declined. Air quality improved overall from January to July, and the most noticeable drop in the air quality index (AQI) was observed in April. These findings indicate that relatively weak social distancing measures compared to a COVID-19 lockdown can help reduce air pollutant levels. At the same time, however, changes in air quality in the neighboring countries caused by COVID-19 control action are affecting Korea.
Understanding the Pathogenesis of Spondyloarthritis
Authors: Sharip Aigul , Kunz Jeannette
Published: October 2020

Spondyloarthritis comprises a group of inflammatory diseases of the joints and spine, with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B*27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B*27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B*27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.
Synthesis and HPLC-ECD Study of Cytostatic Condensed O,N-Heterocycles Obtained from 3-Aminoflavanones
Authors: Szappanos Ádám , Mándi Attila , Gulácsi Katalin , Lisztes Erika , Tóth Balázs István , Bíró Tamás , Kónya-Ábrahám Anita , Kiss-Szikszai Attila , Bényei Attila , Antus Sándor , Kurtán Tibor
Published: October 2020

Racemic chiral O,N-heterocycles containing 2-arylchroman or 2-aryl-2H-chromene subunit condensed with morpholine, thiazole, or pyrrole moieties at the C-3-C-4 bond were synthesized with various substitution patterns of the aryl group by the cyclization of cis- or trans-3-aminoflavanone analogues. The 3-aminoflavanone precursors were obtained in a Neber rearrangement of oxime tosylates of flavanones, which provided the trans diastereomer as the major product and enabled the isolation of both the cis- and trans-diastereomers. The cis- and trans-aminoflavanones were utilized to prepare three diastereomers of 5-aryl-chromeno[4,3-b][1,4]oxazines. Antiproliferative activity of the condensed heterocycles and precursors was evaluated against A2780 and WM35 cancer cell lines. For a 3-(N-chloroacetylamino)-flavan-4-ol derivative, showing structural analogy with acyclic acid ceramidase inhibitors, 0.15 μM, 3.50 μM, and 6.06 μM IC50 values were measured against A2780, WM35, and HaCat cell lines, and apoptotic mechanism was confirmed. Low micromolar IC50 values down to 2.14 μM were identified for the thiazole- and pyrrole-condensed 2H-chromene derivatives. Enantiomers of the condensed heterocycles were separated by HPLC using chiral stationary phase, HPLC-ECD spectra were recorded and TDDFT-ECD calculations were performed to determine the absolute configuration and solution conformation. Characteristic ECD transitions of the separated enantiomers were correlated with the absolute configuration and effect of substitution pattern on the HPLC elution order was determined.
Modelling C9orf72-Related Amyotrophic Lateral Sclerosis in Zebrafish
Authors: Fortier Gabrielle , Butti Zoé , Patten Shunmoogum A.
Published: October 2020

A hexanucleotide repeat expansion within the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and its discovery has revolutionized our understanding of this devastating disease. Model systems are a valuable tool for studying ALS pathobiology and potential therapies. The zebrafish (Danio rerio) has particularly become a useful model organism to study neurological diseases, including ALS, due to high genetic and physiological homology to mammals, and sensitivity to various genetic and pharmacological manipulations. In this review we summarize the zebrafish models that have been used to study the pathology of C9orf72-related ALS. We discuss their value in providing mechanistic insights and their potential use for drug discovery.
Chronic Valproic Acid Administration Increases Plasma, Liver, and Brain Ammonia Concentration and Suppresses Glutamine Synthetase Activity
Authors: Badawy Abdelnaser A. , Elghaba Rasha , Soliman Mohamed , Hussein Abdelaziz M. , AlSadrah Sana A. , Awadalla Amira , Abulseoud Osama A.
Published: October 2020

Asymptomatic valproic acid (VPA)-induced hyperammonemia in the absence of liver impairment is fairly common. However, the underlying mechanisms through which VPA causes elevation in plasma ammonia (NH4) remains under investigation. Male Sprague Dawley rats (n = 72) were randomly allocated to receive VPA 400 mg/kg, 200 mg/kg, or vehicle IP daily for either 8, 14, or 28 consecutive days. The behavioral effects of VPA were assessed. Plasma, liver, and prefrontal cortex (PFC), striatum (Str), and cerebellum (Cere) were collected 1 h post last injection and assayed for NH4 concentration and glutamine synthetase (GS) enzyme activity. Chronic VPA treatment caused attenuation of measured behavioral reflexes (p < 0.0001) and increase in plasma NH4 concentration (p < 0.0001). The liver and brain also showed significant increase in tissue NH4 concentrations (p < 0.0001 each) associated with significant reduction in GS activity (p < 0.0001 and p = 0.0003, respectively). Higher tissue NH4 concentrations correlated with reduced GS activity in the liver (r = −0.447, p = 0.0007) but not in the brain (r = −0.058, p = 0.4). Within the brain, even though NH4 concentrations increased in the PFC (p = 0.001), Str (p < 0.0001), and Cere (p = 0.01), GS activity was reduced only in the PFC (p < 0.001) and not in Str (p = 0.2) or Cere (p = 0.1). These results suggest that VPA-induced elevation in plasma NH4 concentration could be related, at least in part, to the suppression of GS activity in liver and brain tissues. However, even though GS is the primary mechanism in brain NH4 clearance, the suppression of brain GS does not seem to be the main factor in explaining the elevation in brain NH4 concentration. Further research is urgently needed to investigate brain NH4 dynamics under chronic VPA treatment and whether VPA clinical efficacy in treating seizure disorders and bipolar mania is impacted by its effect on GS activity or other NH4 metabolizing enzymes.
Exploratory Analysis of Lenvatinib Therapy in Patients with Unresectable Hepatocellular Carcinoma Who Have Failed Prior PD−1/PD-L1 Checkpoint Blockade
Authors: Aoki Tomoko , Kudo Masatoshi , Ueshima Kazuomi , Morita Masahiro , Chishina Hirokazu , Takita Masahiro , Hagiwara Satoru , Ida Hiroshi , Minami Yasunori , Tsurusaki Masakatsu , Nishida Naoshi
Published: October 2020

Although programmed cell death protein 1 (PD−1)/PD-ligand 1 (PD-L1) blockade is effective in a subset of patients with hepatocellular carcinoma (HCC), its therapeutic response is still unsatisfactory. Alternatively, the potential impact of the lenvatinib in patients who showed tumor progression on PD−1/PD-L1 blockade is unknown. In this work, we evaluated the safety and efficacy of lenvatinib administration after PD-1/PD-L1 checkpoint blockade. The outcome and safety of lenvatinib administered after PD-1/PD-L1 blockade failure was analyzed retrospectively in 36 patients. Tumor growth was assessed every 4–8 weeks using modified Response Evaluation Criteria in Solid Tumors. The mean relative dose intensity of lenvatinib was 87.6% and 77.8% in patients receiving a starting dose of 8 (interquartile range (IQR), 77.5–100.0) mg and 12 (IQR, 64.4–100.0) mg, respectively. Since lenvatinib therapy initiation, the median progression-free survival was 10 months (95% confidence interval (CI): 8.3–11.8) and the median overall survival was 15.8 months (95% CI: 8.5–23.2). The objective response rate was 55.6%, and the disease control rate was 86.1%. No particular safety concerns were observed. Lenvatinib demonstrated considerable antitumor effects with acceptable safety in patients with progressive and unresectable HCC when administered right after PD-1/PD-L1 blockade failure.
Cancer-Associated Stemness and Epithelial-to-Mesenchymal Transition Signatures Related to Breast Invasive Carcinoma Prognostic
Authors: Groza Iulia-Monica , Braicu Cornelia , Jurj Ancuta , Zanoaga Oana , Lajos Raduly , Chiroi Paul , Cojocneanu Roxana , Paun Diana , Irimie Alexandru , Korban Schuyler S. , Achimas-Cadariu Patriciu , Berindan-Neagoe Ioana
Published: October 2020

Breast cancer is one of the most common oncological diseases in women, as its incidence is rapidly growing, rendering it unpredictable and causing more harm than ever before on an annual basis. Alterations of coding and noncoding genes are related to tumorigenesis and breast cancer progression. In this study, several key genes associated with epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) features were identified. EMT and CSCs are two key mechanisms responsible for self-renewal, differentiation, and self-protection, thus contributing to drug resistance. Therefore, understanding of the relationship between these processes may identify a therapeutic vulnerability that can be further exploited in clinical practice, and evaluate its correlation with overall survival rate. To determine expression levels of altered coding and noncoding genes, The Cancer Omics Atlas (TCOA) are used, and these data are overlapped with a list of CSCs and EMT-specific genes downloaded from NCBI. As a result, it is observed that CSCs are reciprocally related to EMT, thus identifying common signatures that allow for predicting the overall survival for breast cancer genes (BRCA). In fact, common CSCs and EMT signatures, represented by ALDH1A1, SFRP1, miR-139, miR-21, and miR-200c, are deemed useful as prognostic biomarkers for BRCA. Therefore, by mapping changes in gene expression across CSCs and EMT, suggesting a cross-talk between these two processes, we have been able to identify either the most common or specific genes or miRNA markers associated with overall survival rate. Thus, a better understanding of these mechanisms will lead to more effective treatment options.
A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes
Authors: Luo Qizhan , Vögeli Thomas-Alexander
Published: October 2020

Background: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation sites corresponding to immune-cell-associated genes were acquired. Differentially methylated sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylated sites was performed to divide the sites into several subtypes. Then, the potential mechanism of different subtypes was explored. Results: Bladder cancer patients were divided into three groups. The cluster 3 subtype had the best prognosis. Cluster 1 had the poorest prognosis. The distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN Response, Type II IFN Response, and DNAss presented significant differences among the three subgroups. The distribution of genomic alterations was also different. Conclusions: The proposed classification was accurate and stable. BC patients could be divided into three subtypes based on the immune-cell-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were varied among the three subgroups. High-level immune infiltration was correlated with high-level methylation. The lower RNAss was associated with higher immune infiltration. The study of the intratumoral immune microenvironment may provide a new perspective for BC therapy.
Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting
Authors: Dadone-Montaudié Bérengère , Laroche-Clary Audrey , Mongis Aline , Chamorey Emmanuel , Di Mauro Ilaria , Chaire Vanessa , Finetti Pascal , Schiappa Renaud , Le Loarer François , Birtwisle-Peyrottes Isabelle , Michiels Jean-François , Bertucci François , Pedeutour Florence , Italiano Antoine , Bianchini Laurence
Published: October 2020

We aimed to evaluate the therapeutic potential of the pan-FGFR inhibitor erdafitinib to treat dedifferentiated liposarcoma (DDLPS). FGFR expression and their prognostic value were assessed in a series of 694 samples of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS). The effect of erdafitinib—alone or in combination with other antagonists—on tumorigenicity was evaluated in vitro and in vivo. We detected overexpression of FGFR1 and/or FGFR4 in a subset of WDLPS and DDLPS and demonstrated correlation of this expression with poor prognosis. Erdafitinib treatment reduced cell viability, inducing apoptosis and strong inhibition of the ERK1/2 pathway. Combining erdafitinib with the MDM2 antagonist RG7388 exerted a synergistic effect on viability, apoptosis, and clonogenicity in one WDLPS and two DDLPS cell lines. Efficacy of this combination was confirmed in vivo on a DDLPS xenograft. Importantly, we report the efficacy of erdafitinib in one patient with refractory DDLPS showing disease stabilization for 12 weeks. We provide evidence that the FGFR pathway has therapeutic potential for a subset of DDLPS and that an FGFR1/FGFR4 expression might constitute a powerful biomarker to select patients for FGFR inhibitor clinical trials. In addition, we show that combining erdafitinib with RG7388 is a promising strategy for patients with DDLPS that deserves further investigation in the clinical setting.
Erratum: Ju, Z., et al. Integrative Analyses of Multilevel Omics Reveal Preneoplastic Breast to Possess a Molecular Landscape That Is Globally Shared with Invasive Basal-Like Breast Cancer (Running Title: Molecular Landscape of Basal-Like Breast Cancer Progression). Cancers 2020, 12, 722
Authors: Ju Zhenlin , Bhardwaj Anjana , Embury Matthew D. , Singh Harpreet , Gunaratne Preethi H. , Bedrosian Isabelle , Wang Jing
Published: October 2020

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Polyphenol Intake and Gastric Cancer Risk: Findings from the Stomach Cancer Pooling Project (StoP)
Authors: Vitelli-Storelli Facundo , Rossi Marta , Pelucchi Claudio , Rota Matteo , Palli Domenico , Ferraroni Monica , Lunet Nuno , Morais Samantha , López-Carrillo Lizbeth , Zaridze David Georgievich , Maximovich Dmitry , Rubín García María , Castaño-Vinyals Gemma , Aragonés Nuria , Garcia de la Hera Manuela , Hernández-Ramírez Raúl Ulises , Negri Eva , Bonzi Rossella , Ward Mary H. , Lagiou Areti , Lagiou Pagona , López-Cervantes Malaquías , Boffetta Paolo , Camargo M. Constanza , Curado Maria Paula , Zhang Zuo-Feng , Vioque Jesus , La Vecchia Carlo , Martín Sánchez Vicente
Published: October 2020

Phenolic compounds may exert a favorable effect on the risk of several cancer types, including gastric cancer (GC). However, selected polyphenol classes have not been adequately investigated in relation to GC. The aim of this study is to evaluate the association between the intake of polyphenols in relation to GC risk. We used data from the Stomach cancer Pooling (StoP) Project, including 10 studies from six countries (3471 GC cases and 8344 controls). We carried out an individual participant data pooled analysis using a two-stage approach. The summary odds ratios (ORs) of GC for each compound, and the corresponding 95% confidence intervals (95% CI), were computed by pooling study specific ORs obtained through multivariate logistic regression, using random effect models. Inverse associations with GC emerged for total polyphenols (OR = 0.67, 95% CI = 0.54–0.81, for the highest versus lowest quartile of intake), total flavonoids (OR = 0.73, 95% CI = 0.55–0.90), anthocyanidins (OR = 0.74, 95% CI = 0.56–0.92), flavanols (OR = 0.77, 95% CI = 0.66–0.88), flavanones (OR = 0.57, 95%CI = 0.44–0.69), total phenolic acids (OR = 0.75, 95%CI = 0.55–0.94), and hydroxybenzoic acids (OR = 0.73, 95%CI = 0.57–0.89). Results were consistent across strata of age, sex, social class, and smoking habit. Suggestive inverse associations were also found for flavonols (OR = 0.76, 95%CI = 0.51–1.01) and hydroxycinnamic acids (OR = 0.82, 95%CI = 0.58–1.06). Further investigations from longitudinal data are needed to confirm this association.
Circulating Tumor Cells: From the Laboratory to the Cancer Clinic
Authors: Sawabata Noriyoshi
Published: October 2020

Circulating tumor cells (CTCs) are cells that are separated from the primary tumor, move through the bloodstream, and spread from the original tumor to other sites, causing cancer metastasis [...]
In Vivo Remodeling of Altered Autophagy-Lysosomal Pathway by a Phosphopeptide in Lupus
Authors: Wang Fengjuan , Tasset Inmaculada , Cuervo Ana Maria , Muller Sylviane
Published: October 2020

The phosphopeptide P140/Lupuzor, which improves the course of lupus disease in mice and patients, targets chaperone-mediated autophagy (CMA), a selective form of autophagy that is abnormally upregulated in lupus-prone MRL/lpr mice. Administered intravenously to diseased mice, P140 reduces the expression level of two major protein players of CMA, LAMP2A and HSPA8, and inhibits CMA in vitro in a cell line that stably expresses a CMA reporter. Here, we aimed to demonstrate that P140 also affects CMA in vivo and to unravel the precise cellular mechanism of how P140 interacts with the CMA process. MRL/lpr mice and CBA/J mice used as control received P140 or control peptides intravenously. Lysosome-enriched fractions of spleen or liver were prepared to examine lysosomal function. Highly purified lysosomes were further isolated and left to incubate with the CMA substrate to study at which cellular step P140 interacts with the CMA process. The data show that P140 effectively regulates CMA in vivo in MRL/lpr mice at the step of substrate lysosomal uptake and restores some alterations of defective lysosomes. For the first time, it is demonstrated that by occluding the intralysosome uptake of CMA substrates, a therapeutic molecule can attenuate excessive CMA activity in a pathological pro-inflammatory context and protect against hyperinflammation. This recovery effect of P140 on hyperactivated CMA is not only important for lupus therapy but potentially also for treating other (auto)inflammatory diseases, including neurologic and metabolic disorders, where CMA modulation would be highly beneficial.
A Systems Approach to Building Community Capacity and Resilience
Authors: Amadei Bernard
Published: October 2020

Capacity and resilience are two closely aligned concepts in human development. They both contribute to increasing the ability of societies to cope with and adapt to challenging and adverse perturbations that may affect systems the societies depend upon. A traditional approach to building capacity and resilience at the community scale is to address in a fragmented manner specific issues at play in institutional, socio-economic, environmental, and infrastructure systems that may prevent the delivery of adequate community services and meeting development goals. This compartmentalized approach, driven by a need to reach some form of satisfactory community equilibrium, fails to recognize the interactions and interconnectedness that exist among community systems, which, if addressed, could solve multiple issues more effectively. It also does not account for the complex, adaptive, and dynamic nature of communities. A resilient community is more than just a collection of well-functioning silos. This paper proposes a system dynamics approach to account for the dynamic and adaptive nature of communities when developing capacity-building strategies toward strengthening their ability to deliver services and deal with adverse events. A case study of small-scale community capacity assessment around the service of wastewater and sewage treatment published elsewhere is presented to illustrate the proposed approach.
Electrochemical and Surface Analytical Study on the Role of Poly(butylene-succinate)-l-proline during Corrosion of Mild Steel in 1 M HCl
Authors: Tsoeunyane George M. , Makhatha Elizabeth M.
Published: October 2020

The synthesis and corrosion inhibition performance of poly(butylene-succinate)-L-proline (PBSLP) prepared by solution polymerization are reported. PBSLP was characterized by FTIR, XRD, and SEM/energy dispersive X-ray (EDX). PBSLP was used to protect mild steel in 1 M hydrochloric acid. An SEM and an atomic force microscope (AFM) were used to characterize the surface morphology of the mild steel coupons. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) were used to characterize the inhibition mechanism of PBSLP, and the inhibitor was a mixed-type corrosion inhibitor with a maximum corrosion inhibition efficiency of 93.0%. Adsorption studies revealed the adsorption of PBSLP to be a monolayer process and therefore, obeyed the Langmuir isotherm model.
Synthesis of Enaminones-Based Benzo[d]imidazole Scaffold: Characterization and Molecular Insight Structure
Authors: Alshahrani Saeed , Soliman Saied M. , Alamary Abdullah Saleh , Al-Majid Abdullah Mohammed , Haukka Matti , Yousuf Sammer , Barakat Assem
Published: October 2020

(E)-1-(1H-Benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one 2 was synthesized by one-pot synthesis protocol of 2-acetyl benzo[d]imidazole with dimethylformamide dimethylacetal (DMF-DMA) in xylene at 140 °C for 8 h. Reaction of enaminone derivative 1 with acetylacetone in the presence of AcOH/NH4OAc under reflux afforded the cyclized pyridino-benzo[d]imidazole derivative 3. The latter compound was converted into the corresponding β-enaminone 4 with DMF-DMA. The single crystal X-ray diffraction technique eventually confirmed the assigned chemical structure of the N-alkyl-β-enaminone 2 and pyridino-benzo[d]imidazole derivative 3. N-alkyl-β-enaminone 2 crystallized in the monoclinic space group P21/n with unit cell parameters of a = 9.8953(3) Å, b = 5.7545(2) Å, c = 21.7891(7) Å, and β =100.627(2)°, and with one molecule per asymmetric unit. On the other hand, compound 3 crystallized in the orthorhombic crystal system and space group P212121 with unit cell parameters of a = 6.82950(10) Å, b = 8.00540(10) Å, c = 22.4779(2) Å, and also with one molecule per asymmetric unit. Based on Hirshfeld analysis, the H...H (51.3%), O...H (10.0%), N...H (10.3%), and C...H (27.6%) contacts in 2 and the H...H (46.8%), O...H (9.9%), N...H (13.0%), and C...H (21.6%) in addition to the C…C (6.7%) interactions in 3 are the most important towards crystal stability via molecular packing. The main difference is the presence of π–π interaction among the molecular units of 3 but not in 2. The calculated 1H and 13C NMR chemical shifts showed good agreements with experimental data. Electronic properties and reactivity parameters of both compounds are also calculated and compared.
Phylogenetics of Molecular Regulators Contributing to Plant Stress Tolerance
Authors: Yu Xiang , Bao Yan
Published: October 2020

Genetic studies on model plants and crops in the last few decades have uncovered numerous genes that play vital roles in plant tolerance to adverse environments. These genes could be used as targets for genetic engineering to improve plant tolerance to abiotic and biotic stresses. Recent advances in CRISPR-based genome editing have accelerated modern plant breeding and wild-species domestication. However, the stress regulators in many crops and horticultural cultivars and their wild species remain largely unexplored. Thus, transferring the accumulated knowledge of these molecular regulators from model plants to a wider range of other species is critical for modern plant breeding. Phylogenetic analysis is one of the powerful strategies for studying the functional conservation and diversity of homologous gene families among different species with complete genome sequences available. In addition, many transcriptome datasets of plants under stress conditions have been publicly released, providing a useful resource for addressing the stress response of given gene families. This Special Issue aims to illustrate the phylogenetics of molecular regulators with potential in contributing to plant stress tolerance and their stress response diversity in multiple non-model plants.
Diversity and Distribution Patterns of Hard Bottom Polychaete Assemblages in the North Adriatic Sea (Mediterranean)
Authors: Mikac Barbara , Licciano Margherita , Jaklin Andrej , Iveša Ljiljana , Giangrande Adriana , Musco Luigi
Published: October 2020

The knowledge on the hard bottom polychaete assemblages in the Northern Adriatic Sea, a Mediterranean region strongly affected by environmental pressures, is scarce and outdated. The objective of this paper was to update the information on polychaete diversity and depict their patterns of natural spatial variation, in relation to changes in algal coverage at increasing depth. Hard bottom benthos was quantitatively sampled by scraping off the substrate from three stations at Sveti Ivan Island (North Adriatic) at three depths (1.5 m, 5 m and 25 m). Polychaete fauna comprised 107 taxa (the majority of them identified at species level) belonging to 22 families, with the family Syllidae ranking first in terms of number of species, followed by Sabellidae, Nereididae, Eunicidae and Serpulidae. Considering the number of polychaete species and their identity, the present data differed considerably from previous studies carried out in the area. Two alien species, Lepidonotus tenuisetosus, which represented a new record for the Adriatic Sea, and Nereis persica, were recorded. The highest mean abundance, species diversity and internal structural similarity of polychaete assemblages were found at 5 m depth, characterised by complex and heterogeneous algal habitat. The DISTLM forward analysis revealed that the distribution of several algal taxa as well as some algal functional-morphological groups significantly explained the observed distribution patterns of abundance and diversity of polychaete assemblages. The diversity of the North Adriatic hard bottom polychaete fauna is largely underestimated and needs regular updating in order to detect and monitor changes of benthic communities in the area.
Survivability of Salmonella and Escherichia coli O157:H7 Pathogens and Food Safety Concerns on Commercial Powder Milk Products
Authors: Paswan Roshan , Park Young W.
Published: October 2020

Milk and dairy products are susceptible to the incidence of foodborne illnesses by numerous pathogens, including Listeria monocytogenes, Salmonella spp., Escherichia coli, enteropathogenic Campylobacter jejuni, Yersinia enterocolitica, Cronobacter (Enterobacter sakazakii) and Staphylococcus aureus. Annually Salmonella infections cause approximately 93.8 million cases of gastroenteritis and 155,000 deaths worldwide. Including meat and poultry, dairy products are the most commonly contaminated foods by Salmonella. Studies show that Salmonella, Escherichia coli O157:H7 and Listeria monocytogenes are among the top 5 pathogens causing hospitalization and life-threatening foodborne illnesses. The U.S. Centers for Disease Control and Prevention (CDC) estimated that annually around 1.2 million foodborne illnesses with more than 23,000 hospitalizations, 450 deaths and 130 outbreaks were attributed to Salmonella infection in the U.S. The Salmonella enteric in skim milk powder survived at three months storage, with water activity as low as 0.33. With respect to Escherichia coli O157:H7, it is capable of causing disease at a low dosage, ranging from 5–50 cells. Viable cells of Escherichia coli O157:H7 reportedly survive in infant formula powder for one year at 5 °C. The survivability of Escherichia coli in powder milk was significantly reduced with the synergistic effects of storage time and temperature. The U.S. Dairy Export Council recommends that milk powder should be stored in a cool and dry place, at a temperature not to exceed 27 °C, and a relative humidity not to exceed 65%. Reports have recommended that milk powder products need to be stored in light, oxygen, and moisture-proof containers. In this article, the survival of the major foodborne pathogens including Salmonella and Escherichia coli O157:H7 in powdered milk products from common dairy species such as cow and goats are reviewed.