bluuebunny/crossref_metadata_2025 huggingface dataset:
Substitute Seed Nodes Mining Algorithms for Influence Maximization in Multi-Social Networks
Authors: Rao Xuli , Zhao Jiaxu , Chen Zhide , Lin Feng
Published: May 2019

Due to the growing interconnections of social networks, the problem of influence maximization has been extended from a single social network to multiple social networks. However, a critical challenge of influence maximization in multi-social networks is that some initial seed nodes may be unable to be active, which obviously leads to a low performance of influence spreading. Therefore, finding substitute nodes for mitigating the influence loss of uncooperative nodes is extremely helpful in influence maximization. In this paper, we propose three substitute mining algorithms for influence maximization in multi-social networks, namely for the Greedy-based substitute mining algorithm, pre-selected-based substitute mining algorithm, and similar-users-based substitute mining algorithm. The simulation results demonstrate that the existence of the uncooperative seed nodes leads to the range reduction of information influence. Furthermore, the viability and performance of the proposed algorithms are presented, which show that three substitute node mining algorithms can find suitable substitute nodes for multi-social networks influence maximization, thus achieves better influence.
Word Sense Disambiguation Using Cosine Similarity Collaborates with Word2vec and WordNet
Authors: Orkphol Korawit , Yang Wu
Published: May 2019

Words have different meanings (i.e., senses) depending on the context. Disambiguating the correct sense is important and a challenging task for natural language processing. An intuitive way is to select the highest similarity between the context and sense definitions provided by a large lexical database of English, WordNet. In this database, nouns, verbs, adjectives, and adverbs are grouped into sets of cognitive synonyms interlinked through conceptual semantics and lexicon relations. Traditional unsupervised approaches compute similarity by counting overlapping words between the context and sense definitions which must match exactly. Similarity should compute based on how words are related rather than overlapping by representing the context and sense definitions on a vector space model and analyzing distributional semantic relationships among them using latent semantic analysis (LSA). When a corpus of text becomes more massive, LSA consumes much more memory and is not flexible to train a huge corpus of text. A word-embedding approach has an advantage in this issue. Word2vec is a popular word-embedding approach that represents words on a fix-sized vector space model through either the skip-gram or continuous bag-of-words (CBOW) model. Word2vec is also effectively capturing semantic and syntactic word similarities from a huge corpus of text better than LSA. Our method used Word2vec to construct a context sentence vector, and sense definition vectors then give each word sense a score using cosine similarity to compute the similarity between those sentence vectors. The sense definition also expanded with sense relations retrieved from WordNet. If the score is not higher than a specific threshold, the score will be combined with the probability of that sense distribution learned from a large sense-tagged corpus, SEMCOR. The possible answer senses can be obtained from high scores. Our method shows that the result (50.9% or 48.7% without the probability of sense distribution) is higher than the baselines (i.e., original, simplified, adapted and LSA Lesk) and outperforms many unsupervised systems participating in the SENSEVAL-3 English lexical sample task.
Comparing Modeled Emissions from Wildfire and Prescribed Burning of Post-Thinning Fuel: A Case Study of the 2016 Pioneer Fire
Authors: Hyde Josh , Strand Eva K.
Published: May 2019

Prescribed fire is often used by land managers as an effective means of implementing fuel treatments to achieve a variety of goals. Smoke generated from these activities can put them at odds with air quality regulations. We set out to characterize the emission tradeoff between wildfire and prescribed fire in activity fuels from thinning in a case study of mixed conifer forest within the Boise National Forest in central Idaho. Custom fuelbeds were developed using information from the forest and emissions were modeled and compared for four scenarios, as follows: Untreated fuels burned in wildfire (UNW), prescribed fire in activity fuels left from thinning (TRX), a wildfire ignited on the post-treatment landscape (PTW), and the combined emissions from TRX followed by PTW (COM). The modeled mean total emissions from TRX were approximately 5% lower, compared to UNW, and between 2–46% lower for individual pollutants. The modeled emissions from PTW were approximately 70% lower than UNW. For the COM scenario, emissions were not significantly different from the UNW scenario for any pollutants, but for CO2. However, for the COM scenario, cumulative emissions would have been comprised of two events occurring at separate times, each with lower emissions than if they occurred at once.
Effect of the Rearing Managements Applied during Heifers’ Whole Life on Quality Traits of Five Muscles of the Beef Rib
Authors: Soulat Julien , Monteils Valérie , Picard Brigitte
Published: May 2019

The aim of this work was to study the effects of four different rearing managements applied during the heifers’ whole life period (WLP) on muscles from ribs in the chuck sale section. The characteristics of meat studied were the sensory, rheological, and color of the longissimus muscle (LM) and the rheological traits of four other muscles: complexus, infraspinatus, rhomboideus, and serratus ventralis. The main results showed that WLP rearing managements did not significantly impact the tenderness (sensory or rheological analyses) of the rib muscles. The LM had high (p ≤ 0.05) typical flavor and was appreciated when heifers received a WLP rearing management characterized by a short pasture duration during the heifers’ whole life (WLP-E). The heifers’ management characterized by a long pasture duration during their life (WLP-A) or by a diet composed mainly of hay during the growth and fattening periods (WLP-F), had lower typical flavor and were less appreciated than those with WLP-E management. Moreover, the LM color was redder for heifers of WLP-E than those of the WLP-A and WLP-F groups. This study confirmed that it is possible to obtain similar meat qualities with different rearing managements.
Natural Red Pigment Production by Monascus Purpureus in Submerged Fermentation Systems Using a Food Industry Waste: Brewer’s Spent Grain
Authors: Silbir Selim , Goksungur Yekta
Published: May 2019

This paper studies the production of natural red pigments by Monascus purpureus CMU001 in the submerged fermentation system using a brewery waste hydrolysate, brewer’s spent grain (BSG). The chemical, structural and elemental characterization of the BSG was performed with Van-Soest method, Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS), respectively. The lignocellulosic structure of BSG was hydrolyzed with a dilute sulfuric acid solution (2% (w/v)) followed by detoxification with Ca(OH)2. Maximum red pigment production (22.25 UA500) was achieved with the following conditions: 350 rpm shake speed, 50 mL fermentation volume, initial pH of 6.5, inoculation ratio of 2% (v/v), and monosodium glutamate (MSG) as the most effective nitrogen source. Plackett–Burman design was used to assess the significance of the fermentation medium components, and MSG and ZnSO4·7H2O were found to be the significant medium variables. This study is the first study showing the compatibility of BSG hydrolysate to red pigment production by Monascus purpureus in a submerged fermentation system.
Antisense Oligonucleotide-Based Downregulation of the G56R Pathogenic Variant Causing NR2E3-Associated Autosomal Dominant Retinitis Pigmentosa
Authors: Naessens Sarah , Ruysschaert Laurien , Lefever Steve , Coppieters Frauke , De Baere Elfride
Published: May 2019

The recurrent missense variant in Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3), c.166G>A, p.(Gly56Arg) or G56R, underlies 1%–2% of cases with autosomal dominant retinitis pigmentosa (adRP), a frequent, genetically heterogeneous inherited retinal disease (IRD). The mutant NR2E3 protein has a presumed dominant negative effect (DNE) by competition for dimer formation with Cone-Rod Homeobox (CRX) but with abolishment of DNA binding, acting as a repressor in trans. Both the frequency and DNE of G56R make it an interesting target for allele-specific knock-down of the mutant allele using antisense oligonucleotides (AONs), an emerging therapeutic strategy for IRD. Here, we designed gapmer AONs with or without a locked nucleic acid modification at the site of the mutation, which were analyzed for potential off-target effects. Next, we overexpressed wild type (WT) or mutant NR2E3 in RPE-1 cells, followed by AON treatment. Transcript and protein levels of WT and mutant NR2E3 were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot respectively. All AONs showed a general knock-down of mutant and WT NR2E3 on RNA and protein level, showing the accessibility of the region for AON-induced knockdown. Further modifications are needed however to increase allele-specificity. In conclusion, we propose the first proof-of-concept for AON-mediated silencing of a single nucleotide variation with a dominant negative effect as a therapeutic approach for NR2E3-associated adRP.
Edge Detectors as Structural Imaging Tools Using Aeromagnetic Data: A Case Study of Sohag Area, Egypt
Authors: Ibraheem Ismael M. , Haggag Menna , Tezkan Bülent
Published: May 2019

The present study was designed to give a clear and comprehensive understanding of the structural situation in the Sohag region and surrounding area by applying several edge detectors to aeromagnetic data. In this research, the International Geomagnetic Reference Field (IGRF) values were removed from the aeromagnetic data and the data obtained were then reduced to the north magnetic pole (RTP). A combination of different edge detectors was applied to determine the boundaries of the magnetic sources. A good correlation was noticed between these techniques, indicating that their integration can contribute to delineating the structural framework of the area. Consequently, a detailed structural map based on the results was constructed. Generally, E-W, N45-60E, and N15-30W directions represent the main tectonic trends in the survey area. The structural map shows the existence of two main basins constituting the most probable places for hydrocarbon accumulation. The results of this study provide structural information that can constitute an invaluable contribution to the gas and oil exploration process in this promising area. They show also that the decision in choosing the location of the drilled boreholes (Balyana-1 and Gerga) was incorrect, as they were drilled in localities within an area of a thin sedimentary cover.
Effects of Rootstock/Scion Combination and Two Irrigation Water Qualities on Cherry Tomato Yield and Postharvest Fruit Quality
Authors: Abu Glion Hiam , Alkalai-Tuvia Sharon , Zaaroor-Presman Merav , Chalupowicz Daniel , Zanbar Mili , Amichai Michal , Cohen Shabtai , Shemer Tsion , Sarig Shlomo , Fallik Elazar
Published: May 2019

The aim of this research was to evaluate postharvest cherry tomato (Solanum lycopersicum (L.) Mill.) yield and fruit quality as affected by grafting and irrigation water quality in the desert region of Israel. Tomato plants (scion cv. Lorka) were grafted onto 3 commercial tomato rootstocks (Resistar, Beaufort and TRS2) and were irrigated with 2 water qualities: fresh water (electrical conductivity (EC)-1.6 dS m−1) and salty water (EC-4.0 dS m−1). Fresh water significantly increased fruit yield by an average of 17% and fruit size, regardless of plant grafting and rootstock, but there were no significant differences in fruit size between the water treatments. However, salty water, but not grafting, significantly improved several quality parameters of fruit stored for 12 d at 12 °C followed by 2 d at 20 °C in simulated sea transport of produce from Israel to Europe and marketing. Fruit harvested from plants irrigated with salty water showed higher sweetness, sourness and, especially, better general taste, and significantly reduced off-flavor, compared with those irrigated with fresh water. The combination of ‘Lorka’ on ‘Resistar’ rootstock and resulted in the best external, internal, and sensory quality parameters at the end of storability and marketing simulation, while the lowest-quality parameters were in fruit harvested from ‘Lorka’ on ‘Beaufort’ rootstock.
3-Methylcholanthrene Induces Chylous Ascites in TCDD-Inducible Poly-ADP-Ribose Polymerase (Tiparp) Knockout Mice
Authors: Cho Tiffany E. , Bott Debbie , Ahmed Shaimaa , Hutin David , Gomez Alvin , Tamblyn Laura , Zhou Angela C. , Watts Tania H. , Grant Denis M. , Matthews Jason
Published: May 2019

TCDD-inducible poly-ADP-ribose polymerase (TIPARP) is an aryl hydrocarbon receptor (AHR) target gene that functions as part of a negative feedback loop to repress AHR activity. Tiparp−/− mice exhibit increased sensitivity to the toxicological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), including lethal wasting syndrome. However, it is not known whether Tiparp−/− mice also exhibit increased sensitivity to other AHR ligands. In this study, we treated male Tiparp−/− or wild type (WT) mice with a single injection of 100 mg/kg 3-methylcholanthrene (3MC). Consistent with TIPARP’s role as a repressor of AHR signaling, 3MC-treated Tiparp−/− mice exhibited increased hepatic Cyp1a1 and Cyp1b1 levels compared with WT mice. No 3MC-treated Tiparp−/− mice survived beyond day 16 and the mice exhibited chylous ascites characterized by an accumulation of fluid in the peritoneal cavity. All WT mice survived the 30-day treatment and showed no signs of fluid accumulation. Treated Tiparp−/− mice also exhibited a transient and mild hepatotoxicity with inflammation. 3MC-treated WT, but not Tiparp−/− mice, developed mild hepatic steatosis. Lipid deposits accumulated on the surface of the liver and other abdominal organs in the 3MC-Tiparp−/− mice. Our study reveals that Tiparp−/− mice have increased sensitivity to 3MC-induced liver toxicity, but unlike with TCDD, lethality is due to chylous ascites rather than wasting syndrome.
Effects of the Emitted Light Spectrum of Liquid Crystal Displays on Light-Induced Retinal Photoreceptor Cell Damage
Authors: Lin Chao-Wen , Yang Chung-May , Yang Chang-Hao
Published: May 2019

Liquid crystal displays (LCDs) are used as screens in consumer electronics and are indispensable in the modern era of computing. LCDs utilize light-emitting diodes (LEDs) as backlight modules and emit high levels of blue light, which may cause retinal photoreceptor cell damage. However, traditional blue light filters may decrease the luminance of light and reduce visual quality. We adjusted the emitted light spectrum of LED backlight modules in LCDs and reduced the energy emission but maintained the luminance. The 661W photoreceptor cell line was used as the model system. We established a formula of the ocular energy exposure index (OEEI), which could be used as the indicator of LCD energy emission. Cell viability decreased and apoptosis increased significantly after exposure to LCDs with higher emitted energy. Cell damage occurred through the induction of oxidative stress and mitochondrial dysfunction. The molecular mechanisms included activation of the NF-κB pathway and upregulation of the expression of proteins associated with inflammation and apoptosis. The effect was correlated with OEEI intensity. We demonstrated that LCD exposure-induced photoreceptor damage was correlated with LCD energy emission. LCDs with lower energy emission may, therefore, serve as suitable screens to prevent light-induced retinal damage and protect consumers’ eye health.
Transcriptome Analysis of Apple Leaves in Response to Powdery Mildew (Podosphaera leucotricha) Infection
Authors: Tian Xiaomin , Zhang Li , Feng Shuaishuai , Zhao Zhengyang , Wang Xiping , Gao Hua
Published: May 2019

Apple (Malus × domestica Borkh.) is one of the most important cultivated tree fruit crops worldwide. However, sustainable apple production is threatened by powdery mildew (PM) disease, which is caused by the obligate biotrophic fungus Podosphaera leucotricha. To gain insight into the molecular basis of the PM infection and disease progression, RNA-based transcriptional profiling (RNA-seq) was used to identify differentially expressed genes (DEGs) in apples following inoculation with P. leucotricha. Four RNA-seq libraries were constructed comprising a total of 214 Gb of high-quality sequence. 1177 DEGs (661 upregulated and 629 downregulated) have been identified according to the criteria of a ratio of infection/control fold change > 2, and a false discovery rate (FDR) < 0.001. The majority of DEGs (815) were detected 12 h after inoculation, suggesting that this is an important time point in the response of the PM infection. Gene annotation analysis revealed that DEGs were predominately associated with biological processes, phenylpropanoid biosynthesis, hormone signal transduction and plant-pathogen interactions. Genes activated by infection corresponded to transcription factors (e.g., AP2/ERF, MYB, WRKY and NAC) and synthesis of defense-related metabolites, including pathogenesis-related genes, glucosidase and dehydrin. Overall, the information obtained in this study enriches the resources available for research into the molecular-genetic mechanisms of the apple/powdery mildew interactions, and provides a theoretical basis for the development of new apple varieties with resistance to PM.
GC–MS-Based Nontargeted and Targeted Metabolic Profiling Identifies Changes in the Lentinula edodes Mycelial Metabolome under High-Temperature Stress
Authors: Zhao Xu , Chen Mingjie , Zhao Yan , Zha Lei , Yang Huanling , Wu Yuejin
Published: May 2019

To clarify the physiological mechanism of the Lentinula edodes (L. edodes) response to high-temperature stress, two strains of L. edodes with different tolerances were tested at different durations of high temperature, and the results showed that there were significant changes in their phenotypes and physiology. To further explore the response mechanism, we established a targeted GC–MS-based metabolomics workflow comprising a standardized experimental setup for growth, treatment and sampling of L. edodes mycelia, and subsequent GC–MS analysis followed by data processing and evaluation of quality control (QC) measures using tailored statistical and bioinformatic tools. This study identified changes in the L. edodes mycelial metabolome following different time treatments at high temperature based on nontargeted metabolites with GC-MS and further adopted targeted metabolomics to verify the results of the analysis. After multiple statistical analyses were carried out using SIMCA software, 74 and 108 differential metabolites were obtained, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the metabolic pathways with significant changes included those related to the following: amino acid metabolism, the glycolysis pathway, the tricarboxylic acid (TCA) cycle, and sugar metabolism. Most amino acids and carbohydrates enriched in these metabolic pathways were upregulated in strain 18, downregulated in strain 18N44, or the synthesis in strain 18 was higher than that in strain 18N44. This result was consistent with the physiological phenotypic characteristics of the two strains under high-temperature stress and revealed the reason why strain 18N44 was more heat-sensitive. At the same time, under high temperature, the decrease of intermediate products in glycolysis and the TCA cycle resulted in carbon starvation and insufficient energy metabolism, thus inhibiting the growth of L. edodes. In addition, the results also showed that the metabolites produced by different L. edodes strains under high-temperature stress were basically the same. However, different strains had species specificity, so the changes in the content of metabolites involved in the response to high-temperature stress were different. This provides a theoretical basis for further understanding the mechanism of the L. edodes response to high temperature and can be used to establish an evaluation system of high-temperature-resistant strains and lay the foundation for molecular breeding of new L. edodes strains resistant to high temperature.
Emerging Roles of C-Myc in Cancer Stem Cell-Related Signaling and Resistance to Cancer Chemotherapy: A Potential Therapeutic Target Against Colorectal Cancer
Authors: Elbadawy Mohamed , Usui Tatsuya , Yamawaki Hideyuki , Sasaki Kazuaki
Published: May 2019

Myc is a nuclear transcription factor that mainly regulates cell growth, cell cycle, metabolism, and survival. Myc family proteins contain c-Myc, n-Myc, and l-Myc. Among them, c-Myc can become a promising therapeutic target molecule in cancer. Cancer stem cells (CSCs) are known to be responsible for the therapeutic resistance. In the previous study, we demonstrated that c-Myc mediates drug resistance of colorectal CSCs using a patient-derived primary three-dimensional (3D) organoid culture. In this review, we mainly focus on the roles of c-Myc-related signaling in the regulation of CSCs, chemotherapy resistance, and colorectal cancer organoids. Finally, we introduce the various types of c-Myc inhibitors and propose the possibility of c-Myc as a therapeutic target against colorectal cancer.
Electrical Stimulation of the Mesencephalic Locomotor Region Attenuates Neuronal Loss and Cytokine Expression in the Perifocal Region of Photothrombotic Stroke in Rats
Authors: Schuhmann Michael K. , Stoll Guido , Bohr Arne , Volkmann Jens , Fluri Felix
Published: May 2019

Deep brain stimulation of the mesencephalic locomotor region (MLR) improves the motor symptoms in Parkinson’s disease and experimental stroke by intervening in the motor cerebral network. Whether high-frequency stimulation (HFS) of the MLR is involved in non-motor processes, such as neuroprotection and inflammation in the area surrounding the photothrombotic lesion, has not been elucidated. This study evaluates whether MLR-HFS exerts an anti-apoptotic and anti-inflammatory effect on the border zone of cerebral photothrombotic stroke. Rats underwent photothrombotic stroke of the right sensorimotor cortex and the implantation of a microelectrode into the ipsilesional MLR. After intervention, either HFS or sham stimulation of the MLR was applied for 24 h. The infarct volumes were calculated from consecutive brain sections. Neuronal apoptosis was analyzed by TUNEL staining. Flow cytometry and immunohistochemistry determined the perilesional inflammatory response. Neuronal apoptosis was significantly reduced in the ischemic penumbra after MLR-HFS, whereas the infarct volumes did not differ between the groups. MLR-HFS significantly reduced the release of cytokines and chemokines within the ischemic penumbra. MLR-HFS is neuroprotective and it reduces pro-inflammatory mediators in the area that surrounds the photothrombotic stroke without changing the number of immune cells, which indicates that MLR-HFS enables the function of inflammatory cells to be altered on a molecular level.
Divergent Approaches to Virulence in C. albicans and C. glabrata: Two Sides of the Same Coin
Authors: Galocha Mónica , Pais Pedro , Cavalheiro Mafalda , Pereira Diana , Viana Romeu , Teixeira Miguel C.
Published: May 2019

Candida albicans and Candida glabrata are the two most prevalent etiologic agents of candidiasis worldwide. Although both are recognized as pathogenic, their choice of virulence traits is highly divergent. Indeed, it appears that these different approaches to fungal virulence may be equally successful in causing human candidiasis. In this review, the virulence mechanisms employed by C. albicans and C. glabrata are analyzed, with emphasis on the differences between the two systems. Pathogenesis features considered in this paper include dimorphic growth, secreted enzymes and signaling molecules, and stress resistance mechanisms. The consequences of these traits in tissue invasion, biofilm formation, immune system evasion, and macrophage escape, in a species dependent manner, are discussed. This review highlights the observation that C. albicans and C. glabrata follow different paths leading to a similar outcome. It also highlights the lack of knowledge on some of the specific mechanisms underlying C. glabrata pathogenesis, which deserve future scrutiny.
A Kriging Surrogate Model for Uncertainty Analysis of Graphene Based on a Finite Element Method
Authors: Shi Jiajia , Chu Liu , Braun Robin
Published: May 2019

Due to the inevitable presence of random defects, unpredictable grain boundaries in macroscopic samples, stress concentration at clamping points, and unknown load distribution in the investigation of graphene sheets, uncertainties are crucial and challenging issues that require more exploration. The application of the Kriging surrogate model in vibration analysis of graphene sheets is proposed in this study. The Latin hypercube sampling method effectively propagates the uncertainties in geometrical and material properties of the finite element model. The accuracy and convergence of the Kriging surrogate model are confirmed by a comparison with the reported references. The uncertainty analysis for both Zigzag and Armchair graphene sheets are compared and discussed.
P-element Somatic Inhibitor Protein Binding a Target Sequence in dsx Pre-mRNA Conserved in Bombyx mori and Spodoptera litura
Authors: Wang Yao , Zhao Qin , Wan Qiu-Xing , Wang Kai-Xuan , Zha Xing-Fu
Published: May 2019

Bombyx mori doublesex (Bmdsx) functions as a double-switch gene in the final step of the sex-determination cascade in the silkworm Bombyx mori. The P-element somatic inhibitor (PSI) protein in B. mori interacts with Bmdsx pre-mRNA in CE1 as an exonic splicing silencer to promote male-specific splicing of Bmdsx. However, the character of the interaction between BmPSI and Bmdsx pre-mRNA remains unclear. Electrophoretic mobility shift assay (EMSA) results showed that the four KH_1 motifs in BmPSI are all essential for the binding, especially the former two KH_1 motifs. Three active sites (I116, L127, and IGGI) in the KH_1 motif were found to be necessary for the binding through EMSA, circular dichroism (CD) spectroscopy, and isothermal titration calorimetry (ITC). The PSI homologous protein in S. litura (SlPSI) was purified and the binding of SlPSI and CE1 was verified. Compared with BmPSI, the mutant SlPSI proteins of I116 and IGGI lost their ability to bind to CE1. In conclusion, the binding of PSI and dsx pre-mRNA are generally conserved in both B. mori and S. litura. These findings provide clues for sex determination in Lepidoptera.
Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor
Authors: Conte Carmela , Arcuri Cataldo , Cataldi Samuela , Mecca Carmen , Codini Michela , Ceccarini Maria Rachele , Patria Federica Filomena , Beccari Tommaso , Albi Elisabetta
Published: May 2019

Sphingomyelinase (SMase) is responsible for the breakdown of sphingomyelin (SM) with production of ceramide. The absence of acid sphingomyelinase (aSMase) causes abnormal synapse formation in Niemann-Pick type A (NPA) disease. Because high levels of ceramide in the NPA brain were demonstrated, the involvement of other SMases were supposed. In the present study we focused the attention on the neurogenic niches in the hippocampal gyrus dentatus (GD), a brain structure essential for forming cohesive memory. We demonstrated for the first time the increase of (Sex determining region Y)-box 2 (SOX2), and the down-regulation of glial fibrillary acidic protein (GFAP) NPA mice GD. Moreover, we found that the expression of Toll like receptors (TLRs), was increased in NPA mice, particularly TLR2, TLR7, TLR8 and TLR9 members. Although no significant change in neutral sphingomyelinase (nSMase) gene expression was detected in the NPA mice hippocampus of, protein levels were enhanced, probably because of the slower protein degradation rate in this area. Many studies demonstrated that vitamin D receptor (VDR) is expressed in the hippocampus GD. Unexpectedly, we showed that NPA mice exhibited VDR gene and protein expression up-regulation. In summary, our study suggests a relation between hippocampal cell differentiation defect, nSMase and VDR increase in NPA mice.
25-Hydroxyvitamin D Inhibits Hepatitis C Virus Production in Hepatocellular Carcinoma Cell Line by a Vitamin D Receptor-Independent Mechanism
Authors: Ravid Amiram , Rapaport Noa , Issachar Assaf , Erman Arie , Bachmetov Larisa , Tur-Kaspa Ran , Zemel Romy
Published: May 2019

Previously, we have reported that the active vitamin D metabolite, calcitriol and vitamin D3 (cholecalciferol), both remarkably inhibit hepatitis C virus production. The mechanism by which vitamin D3 exerts its effect is puzzling due to the low levels of calcitriol produced in vitamin D3-treated Huh7.5 cells. In this study, we aimed to explore the mechanism of vitamin D3 anti-hepatitis C virus effect. We show that vitamin D3 activity is not mediated by its metabolic conversion to calcitriol, but may be due to its primary metabolic product 25(OH)D3. This is inferred from the findings that 25(OH)D3 could inhibit hepatitis C virus production in our system, and that adequate concentrations needed to exert this effect are produced in Huh7.5 cells treated with vitamin D3. Using the CRISPR-Cas9 editing technology to knockout the vitamin D receptor, we found that the antiviral activity of vitamin D3 and 25(OH)D3 was not impaired in the vitamin D receptor knockout cells. This result indicates that 25(OH)D3 anti-hepatitis C virus effect is exerted by a vitamin D receptor-independent mode of action. The possibility that vitamin D3 and 25(OH)D3, being 3β-hydroxysteroids, affect hepatitis C virus production by direct inhibition of the Hedgehog pathway in a vitamin D receptor-independent manner was ruled out. Taken together, this study proposes a novel mode of action for the anti-hepatitis C virus activity of vitamin D3 that is mediated by 25(OH)D3 in a vitamin D receptor-independent mechanism.
Detection of Yellow Fever Virus in Sylvatic Mosquitoes during Disease Outbreaks of 2017–2018 in Minas Gerais State, Brazil
Authors: Pinheiro Guilherme Garcia , Rocha Marcele Neves , de Oliveira Maria Angélica , Moreira Luciano Andrade , Andrade Filho José Dilermando
Published: May 2019

Brazil has experienced several arbovirus outbreaks in recent years, among which yellow fever stands out. The state of Minas Gerais faced outbreaks of sylvatic yellow fever in 2017 and 2018, with 1002 confirmed cases and 340 deaths. This work presents the results of survey efforts to detect the yellow fever virus in mosquitoes from two conservation areas in the metropolitan region of Belo Horizonte, Brazil. A total of 867 mosquitoes of 20 species were collected between September 2017 and May 2018, the most abundant being Psorophora (Janthinosoma) ferox (von Humboldt, 1819) (31.3%), Limatus durhamii Theobald, 1901 (19.1%) and Haemagogus (Haemagogus) janthinomys Dyar, 1921 (18.2%). Total RNA was extracted from the mosquitoes for real-time PCR analysis for yellow fever, chikungunya, mayaro, Zika and dengue viruses. The yellow fever infection rate was 8.2% for Hg. janthinomys (13 mosquitoes), which is the main vector of sylvatic yellow fever in Brazil. In addition to surveying the mosquito fauna of these conservation units, this work demonstrates the importance of monitoring the circulation of viruses near large urban centers.
Ethyl Pyruvate Directly Attenuates Active Secretion of HMGB1 in Proximal Tubular Cells via Induction of Heme Oxygenase-1
Authors: Seo Min Suk , Kim Hye Jung , Kim Hwajin , Park Sang Won
Published: May 2019

Renal ischemia reperfusion (IR) is a main cause of acute kidney injury leading to high morbidity and mortality during postoperative periods. This study investigated whether ethyl pyruvate (EP) protects the kidney against renal IR injury. Male C57BL/6 mice were treated with vehicle or EP (40 mg/kg) 1 h before ischemia and the plasma creatinine (Cr) levels and tubular damage were evaluated after reperfusion. EP attenuated the IR-induced plasma Cr levels, renal inflammation and apoptotic cell death, but the effect of EP was abolished by pretreating Zinc protoporphyrin (ZnPP), a heme oxygenase (HO)-1 inhibitor. HO-1 is a stress-induced protein and protects the kidney against IR injury. EP increased significantly HO-1 expression in the proximal tubular cells in vivo and HK-2 cells in vitro. Inhibition of PI3K/Akt pathway and knockdown of Nrf2 blocked HO-1 induction by EP. High mobility group box 1 (HMGB1) secretion was assessed as an early mediator of IR injury; plasma HMGB1 were significantly elevated as early as 2 h to 24 h after reperfusion and these were attenuated by EP, but the effect of EP was abolished by ZnPP. EP also reduced HMGB1 secretion stimulated by TNF-α in HK-2 cells, and the inhibition of PI3K/Akt and knockdown of HO-1 blocked the effect of EP. Conclusively, EP inhibits the active secretion of HMGB1 from proximal tubular cells during IR injury by inducing HO-1 via activation of PI3K/Akt and Nrf2 pathway.
Prevalence and Risk Factors for Positive Nasal Methicillin-Resistant Staphylococcus aureus Carriage among Orthopedic Patients in Korea
Authors: Choi Sung-Woo , Lee Jae Chul , Kim Jahyung , Kim Ji Eun , Baek Min Jung , Park Se Yoon , Park Suyeon , Shin Byung-Joon
Published: May 2019

Methicillin-resistant Staphylococcus aureus (MRSA) causes purulent skin and soft tissue infections as well as other life-threatening diseases. Recent guidelines recommend screening for MRSA at the time of admission. However, few studies have been conducted to determine the prevalence and risk factors for MRSA colonization. A prospective data collection and retrospective analysis was performed. MRSA screening tests were performed using nasal swabs in patients enrolled between January 2017 and July 2018. Demographic data, socio-economic data, medical comorbidities, and other risk factors for MRSA carriage were evaluated among 1577 patients enrolled in the study. The prevalence of MRSA nasal carriage was 7.2%. Univariate regression analysis showed that colonization with MRSA at the time of hospital admission was significantly related to patient age, body mass index, smoking, alcohol, trauma, recent antibiotic use, and route of hospital admission. Multiple logistic regression analysis for the risk factors for positive MRSA nasal carriage showed that being under- or overweight, trauma diagnosis, antibiotic use one month prior to admission, and admission through an emergency department were related to MRSA colonization. This study highlights the importance of a preoperative screening test for patients scheduled to undergo surgery involving implant insertion, particularly those at risk for MRSA.
Developing a Diagnostic Decision Support System for Benign Paroxysmal Positional Vertigo Using a Deep-Learning Model
Authors: Lim Eun-Cheon , Park Jeong Hye , Jeon Han Jae , Kim Hyung-Jong , Lee Hyo-Jeong , Song Chang-Geun , Hong Sung Kwang
Published: May 2019

Background: Diagnosis of benign paroxysmal positional vertigo (BPPV) depends on the accurate interpretation of nystagmus induced by positional tests. However, difficulties in interpreting eye-movement often can arise in primary care practice or emergency room. We hypothesized that the use of machine learning would be helpful for the interpretation. Methods: From our clinical data warehouse, 91,778 nystagmus videos from 3467 patients with dizziness were obtained, in which the three-dimensional movement of nystagmus was annotated by four otologic experts. From each labeled video, 30 features changed into 255 grid images fed into the input layer of the neural network for the training dataset. For the model validation, video dataset of 3566 horizontal, 2068 vertical, and 720 torsional movements from 1005 patients with BPPV were collected. Results: The model had a sensitivity and specificity of 0.910 ± 0.036 and 0.919 ± 0.032 for horizontal nystagmus; of 0.879 ± 0.029 and 0.894 ± 0.025 for vertical nystagmus; and of 0.783 ± 0.040 and 0.799 ± 0.038 for torsional nystagmus, respectively. The affected canal was predicted with a sensitivity of 0.806 ± 0.010 and a specificity of 0.971 ± 0.003. Conclusions: As our deep-learning model had high sensitivity and specificity for the classification of nystagmus and localization of affected canal in patients with BPPV, it may have wide clinical applicability.
Innovative Modeling Techniques and 3D Printing in Patients with Left Ventricular Assist Devices: A Bridge from Bench to Clinical Practice
Authors: Thaker Rishi , Araujo-Gutierrez Raquel , Marcos-Abdala Hernan G. , Agrawal Tanushree , Fida Nadia , Kassi Mahwash
Published: May 2019

Left ventricular assist devices (LVAD) cause altered flow dynamics that may result in complications such as stroke, pump thrombosis, bleeding, or aortic regurgitation. Understanding altered flow dynamics is important in order to develop more efficient and durable pump configurations. In patients with LVAD, hemodynamic assessment is limited to imaging techniques such as echocardiography which precludes detailed assessment of fluid dynamics. In this review article, we present some innovative modeling techniques that are often used in device development or for research purposes, but have not been utilized clinically. Computational fluid dynamic (CFD) modeling is based on computer simulations and particle image velocimetry (PIV) employs ex vivo models that helps study fluid characteristics such as pressure, shear stress, and velocity. Both techniques may help elaborate our understanding of complications that occur with LVAD and could be potentially used in the future to troubleshoot LVAD-related alarms. These techniques coupled with 3D printing may also allow for patient-specific device implants, lowering the risk of complications increasing device durability.
Early Identification of Isolated Sertoli Cell Dysfunction in Prepubertal and Transition Age: Is It Time?
Authors: La Vignera Sandro , Condorelli Rosita A. , Cimino Laura , Cannarella Rossella , Giacone Filippo , Calogero Aldo E.
Published: May 2019

The male transitional phase is of fundamental importance for future fertility. This aspect is largely neglected in clinical practice. This opinion aims to shed light on these issues. The children frequently complete the transition phase with a slight reduction of testicular volume. The system of detecting testicular volume is often inadequate. These patients evidently complete puberty in an incomplete way because they do not reach an adequate testicular volume, albeit in the presence of adequate height and regular secondary sexual characteristics.
Cranio-Facial Characteristics in Children with Autism Spectrum Disorders (ASD)
Authors: Tripi Gabriele , Roux Sylvie , Matranga Domenica , Maniscalco Laura , Glorioso Pasqualino , Bonnet-Brilhault Frédérique , Roccella Michele
Published: May 2019

Background: Cranio-facial anomalies frequently occur in neurodevelopmental disorders because both face and brain are derived from neuroectoderm. The identification of differences in the facial phenotype of children with Autism Spectrum Disorders (ASD) may reflect alterations in embryologic brain development in children with ASD. Methods: we evaluated 33 caucasian children with ASD using a 2D computerized photogrammetry. Anthropometric euclidean measurements and landmarks located on the soft tissue of the face and head, were based on five cranio-facial indexes. Relationships between anthropometric z-scores and participant characteristics (i.e., age, Global IQ, severity of autistic symptoms measured using the CARS checklist) were assessed. Results: Cephalic index z-score differed significantly from 0 in our ASD group (p = 0.019). Moreover, a significant negative correlation was found between Facial Index z-score and CARS score (p = 0.003); conversely, a positive correlation was found between Interchantal Index z-score and CARS score (p = 0.028). Conclusion: our measurements shows a dolichocephalic head shape which is not correlated with autism severity. Importantly, two craniofacial markers were significantly correlated with autism severity: increased orbital hyperthelorism and decrease of height of the facial midline. These data support previous findings of craniofacial anomalies in autism spectrum disorder suggesting an “ASD facial phenotype” that could be used to improve ASD diagnoses.
Elevated CTRP1 Plasma Concentration Is Associated with Sepsis and Pre-Existing Type 2 Diabetes Mellitus in Critically Ill Patients
Authors: Yagmur Eray , Buergerhausen David , Koek Ger H. , Weiskirchen Ralf , Trautwein Christian , Koch Alexander , Tacke Frank
Published: May 2019

The adipokine family of C1q/TNF-like proteins (CTRP) plays a critical role in regulating systemic energy homeostasis and insulin sensitivity. It is involved in pathophysiological processes including inflammation and insulin-resistant obesity. Sepsis is associated with metabolic alterations and dysregulated adipokines, but the role of CTRP1 in critical illness and sepsis is unclear. We investigated CTRP1 plasma concentrations in 145 septic and 73 non-septic critically ill patients at admission to the medical intensive care unit (ICU) in comparison to 66 healthy controls. We also assessed associations of CTRP1 with clinical characteristics, adipokine levels, metabolic and inflammatory parameters. CTRP1 plasma concentration was significantly elevated in critically ill patients compared to healthy subjects. CTRP1 levels were significantly higher in ICU patients with sepsis. CTRP1 correlated strongly with markers of inflammatory response, renal function, liver damage and cholestasis. Furthermore, CTRP1 levels were higher in ICU patients with type 2 diabetes mellitus, and correlated with HbA1c and body mass index. This study demonstrates significantly elevated levels of CTRP1 in critically ill patients, particularly with sepsis, and links circulating CTRP1 to inflammatory and metabolic disturbances.
TRPV2 Calcium Channel Gene Expression and Outcomes in Gastric Cancer Patients: A Clinically Relevant Association
Authors: Zoppoli Pietro , Calice Giovanni , Laurino Simona , Ruggieri Vitalba , La Rocca Francesco , La Torre Giuseppe , Ciuffi Mario , Amendola Elena , De Vita Ferdinando , Petrillo Angelica , Napolitano Giuliana , Falco Geppino , Russi Sabino
Published: May 2019

Gastric cancer (GC) is characterized by poor efficacy and the modest clinical impact of current therapies. Apoptosis evasion represents a causative factor for treatment failure in GC as in other cancers. Since intracellular calcium homeostasis regulation has been found to be associated with apoptosis resistance, the aberrant expression of intracellular calcium regulator genes (CaRGs) could have a prognostic value in GC patients. We analyzed the association of the expression levels of 98 CaRGs with prognosis by the log-rank test in a collection of 1524 GC samples from four gene expression profiling datasets. We also evaluated differential gene expression in comparison with normal stomach tissue, and then we crossed results with tissue microarrays from the Human Protein Atlas. Among the investigated CaRGs, patients with high levels of TRPV2 expression were characterized by a shorter overall survival. TRPV2 expression was found to increase according to tumor stage. Both mRNA and protein levels were significantly higher in tumor than normal stomach samples. TRPV2 was also associated with poor prognosis in the Lauren’s intestinal type GC and in patients treated with adjuvant therapy. Overall, we highlighted the relevance of TRPV2 not only as a prognostic biomarker but also as a potential therapeutic target to improve GC treatment efficacy.
Maternal High Fat Diet and in-Utero Metformin Exposure Significantly Impact upon the Fetal Renal Proteome of Male Mice
Authors: Nüsken Eva , Turnwald Eva-Maria , Fink Gregor , Voggel Jenny , Yosy Christopher , Kretschmer Tobias , Handwerk Marion , Wohlfarth Maria , Weber Lutz T. , Hucklenbruch-Rother Eva , Dötsch Jörg , Nüsken Kai-Dietrich , Appel Sarah
Published: May 2019

There is accumulating evidence for fetal programming of later kidney disease by maternal obesity or associated conditions. We performed a hypothesis-generating study to identify potentially underlying mechanisms. Female mice were randomly split in two groups and fed either a standard diet (SD) or high fat diet (HFD) from weaning until mating and during pregnancy. Half of the dams from both groups were treated with metformin ((M), 380 mg/kg), resulting in four experimental groups (SD, SD-M, HFD, HFD-M). Caesarean section was performed on gestational day 18.5. Fetal kidney tissue was isolated from cryo-slices using laser microdissection methods and a proteomic screen was performed. For single proteins, a fold change ≥1.5 and q-value <0.05 were considered to be statistically significant. Interestingly, HFD versus SD had a larger effect on the proteome of fetal kidneys (56 proteins affected; interaction clusters shown for proteins concerning transcription/translation, mitochondrial processes, eicosanoid metabolism, H2S-synthesis and membrane remodeling) than metformin exposure in either SD (29 proteins affected; clusters shown for proteins involved in transcription/translation) or HFD (6 proteins affected; no cluster). By further analysis, ATP6V1G1, THY1, PRKCA and NDUFB3 were identified as the most promising candidates potentially mediating reprogramming effects of metformin in a maternal high fat diet.
Trends of Lipophilic, Antioxidant and Hematological Parameters Associated with Conventional and Electronic Smoking Habits in Middle-Age Romanians
Authors: Badea Mihaela , Gaman Laura , Delia Corina , Ilea Anca , Leașu Florin , Henríquez-Hernández Luis Alberto , Luzardo Octavio P. , Rădoi Mariana , Rogozea Liliana
Published: May 2019

It is known that cigarette smoking is correlated with medical associated inquires. New electronic cigarettes are intensively advertised as an alternative to conventional smoking, but only a few studies demonstrate their harmful potential. A cross-sectional study was designed using 150 subjects from Brasov (Romania), divided into three groups: non-smokers (NS = 58), conventional cigarettes smokers (CS = 58) and electronic cigarettes users (ECS = 34). The aim of this study was to determine levels of some plasma lipophilic and hematological components, and the total antioxidant status that could be associated with the smoking status of the subjects. Serum low density lipoproteins (LDL) cholesterol increased significantly for ECS participants versus NS group (18.9% difference) (p < 0.05). Also, the CS group is characterized by an increase of serum LDL cholesterol (7.9% difference vs. NS), but with no significant statistical difference. The variation of median values of serum very low density lipoproteins (VLDL) was in order NS < ECS < CS, with statistical difference between NS and CS groups (34.6% difference; p = 0.023). When comparing the antioxidant status of the three groups, significant differences (p < 0.05) were obtained between NS vs. CS and NS vs. ECS. Similar behavior was identified for CS and ECS. Statistically significant changes (p < 0.0001) for both vitamin A and vitamin E were identified in the blood of NS vs. CS and NS vs. ECS, and also when comparing vitamin A in the blood of the CS group versus the ECS group (p < 0.05). When all groups were compared, the difference in the white blood cell (WBC) was (p = 0.008). A slight increase in the red blood cell (RBC) count was observed, but with no statistical difference between groups. These results indicated that conventional cigarette and e-cigarette usage promotes the production of excess reactive oxygen species, involving different pathways, different antioxidants and bioactive molecules.