bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Empirically Derived Classification of Individuals with Subjective Cognitive Complaints Predict Dementia?
Authors: Picón Eduardo , Juncos-Rabadán Onésimo , Lojo-Seoane Cristina , Campos-Magdaleno María , Mallo Sabela C. , Nieto-Vietes Ana , Pereiro Arturo X. , Facal David
Published: November 2019

(1) Background: Early identification of mild cognitive impairment (MCI) in people reporting subjective cognitive complaints (SCC) and the study of progression of cognitive decline are important issues in dementia research. This paper examines whether empirically derived procedures predict progression from MCI to dementia. (2) Methods: At baseline, 192 participants with SCC were diagnosed according to clinical criteria as cognitively unimpaired (70), single-domain amnestic MCI (65), multiple-domain amnestic MCI (33) and multiple-domain non-amnestic MCI (24). A two-stage hierarchical cluster analysis was performed for empirical classification. Categorical regression analysis was then used to assess the predictive value of the clusters obtained. Participants were re-assessed after 36 months. (3) Results: Participants were grouped into four empirically derived clusters: Cluster 1, similar to multiple-domain amnestic MCI; Cluster 2, characterized by subjective cognitive decline (SCD) but with low scores in language and working memory; Cluster 3, with specific deterioration in episodic memory, similar to single-domain amnestic MCI; and Cluster 4, with SCD but with scores above the mean in all domains. The majority of participants who progressed to dementia were included in Cluster 1. (4) Conclusions: Cluster analysis differentiated between MCI and SCD in a sample of people with SCC and empirical criteria were more closely associated with progression to dementia than standard criteria.
The Architecture of Built Pedagogy for Active Learning—A Case Study of a University Campus in Hong Kong
Authors: Lam Edmond W.M. , Chan Daniel W.M. , Wong Irene
Published: November 2019

Traditional teaching modes are engaged with teachers delivering knowledge to students with minimum feedback. Teaching is conducted in lecture theaters and classrooms, which are sometimes designed with minimum flexibility for university education. However, the rapid development of information and communication technologies has altered the teaching pedagogy from traditionally teacher-centered to more collaborative learning between teachers and students. Learning spaces should be designed to be interactive and collaborative with suitable physical movement and social engagement among teachers and students. This paper aims to examine the relationships between modern technology and pedagogical shift, and to identify and discuss the essential design principles for effective active learning through built pedagogy. A recent renovation project of The Hong Kong Polytechnic University in converting conventional classrooms and lecture theaters to active learning spaces was adopted as a case study to illustrate and validate the design principles and their actual implementation. Feedback and responses from 410 end-user students on the impact of the renovated classrooms and lecture theaters on teaching and learning effectiveness were gleaned through empirical survey questionnaires dispatched face-to-face to students after attending classes in the renovated classrooms and lecture theaters. The results of factor analysis indicated that the 15 variables of key design criteria for active learning spaces were consolidated under six underlying clustered factor groups: (1) Versatility of learning space; (2) interior design of learning environment; (3) modern information technology / audio and video (IT/AV) technologies; (4) interior lighting; (5) comfortable furniture and acoustic design; and (6) interior temperature. The survey findings can serve as good references and useful insights for architects in designing new learning spaces and facilities that assist active and collaborative learning for university students in future.
The Prognostic Role of CD8+ T Lymphocytes in Childhood Adrenocortical Carcinomas Compared to Ki-67, PD-1, PD-L1, and the Weiss Score
Authors: Parise Ivy Zortéa S. , Parise Guilherme A. , Noronha Lúcia , Surakhy Mirvat , Woiski Thiago Demetrius , Silva Denise B. , Costa Tatiana EI-Jaick B. , Del-Valle Maria Helena C. P. , Komechen Heloisa , Rosati Roberto , Ribeiro Melyssa Grignet , Nascimento Marilza Leal , Souza José Antônio de , Andrade Diancarlos P. , Paraizo Mariana M. , Galvão Marjorana Martini R. , Barbosa José Renato S. , Barbosa Miriam Lacerda , Custódio Gislaine C. , Figueiredo Mirna M. O. , Fabro Ana Luiza M. R. , Bond Gareth , Volante Marco , Lalli Enzo , Figueiredo Bonald C.
Published: November 2019

Adrenocortical carcinoma (ACC) is a rare disease among children. Our goal was to identify prognostic biomarkers in 48 primary ACCs from children (2.83 ± 2.3 y; mean age ± SD) by evaluating the tumor stage and outcome for an age of diagnosis before or after 3 years, and association with ACC cluster of differentiation 8 positive (CD8+) cytotoxic T lymphocytes (CD8+-CTL) and Ki-67 immunohistochemical expression (IHC). Programmed death 1(PD-1)/Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in ACC was analyzed in a second, partially overlapping cohort (N = 19) with a similar mean age. All patients and control children were carriers of the germline TP53 R337H mutation. Survival without recurrence for less than 3 years and death unrelated to disease were excluded. Higher counts of CD8+-CTL were associated with patients diagnosed with ACC at a younger age and stage I, whereas a higher percentage of the Ki-67 labeling index (LI) and Weiss scores did not differentiate disease free survival (DFS) in children younger than 3 years old. No PD-1 staining was observed, whereas weakly PD-L1-positive immune cells were found in 4/19 (21%) of the ACC samples studied. A high CD8+-CTL count in ACC of surviving children is compelling evidence of an immune response against the disease. A better understanding of the options for enhancement of targets for CD8+ T cell recognition may provide insights for future pre-clinical studies.
Enriching Personalized Endometrial Cancer Research with the Harmonization of Biobanking Standards
Authors: Adishesh Meera , Hapangama Dharani K.
Published: November 2019

Endometrial cancer is the commonest gynecological cancer, with an incidence predicted to escalate by a further 50–100% before 2025, due to the rapid rise in risk factors such as obesity and increased life expectancy. Endometrial cancer associated mortality is also rising, depicting the need for translatable research to improve our understanding of the disease. Rapid translation of scientific discoveries will facilitate the development of new diagnostic, prognostic and therapeutic strategies. Biobanks play a vital role in providing biospecimens with accompanying clinical data for personalized translational research. Wide variation in collection, and pre-analytic variations in processing and storage of bio-specimens result in divergent and irreproducible data from multiple studies that are unsuitable for collation to formulate robust conclusions. Harmonization of biobanking standards is thus vital, in facilitating international multi-center collaborative studies with valuable outcomes to improve personalized treatments. This review will detail the pitfalls in the biobanking of biosamples from women with cancer in general, and describe the recent international harmonization project that developed standardized research tools to overcome these challenges and to enhance endometrial cancer research, which will facilitate future development of personalized novel diagnostic strategies and treatments.
Synergistic Antitumorigenic Activity of Calcitriol with Curcumin or Resveratrol is Mediated by Angiogenesis Inhibition in Triple Negative Breast Cancer Xenografts
Authors: García-Quiroz Janice , García-Becerra Rocío , Santos-Cuevas Clara , Ramírez-Nava Gerardo J. , Morales-Guadarrama Gabriela , Cárdenas-Ochoa Nohemí , Segovia-Mendoza Mariana , Prado-Garcia Heriberto , Ordaz-Rosado David , Avila Euclides , Olmos-Ortiz Andrea , López-Cisneros Sofía , Larrea Fernando , Díaz Lorenza
Published: November 2019

Calcitriol is a multitarget anticancer hormone; however, its effects on angiogenesis remain contradictory. Herein, we tested whether the antiangiogenic phytochemicals curcumin or resveratrol improved calcitriol antitumorigenic effects in vivo. Triple-negative breast cancer tumoral cells (MBCDF-T) were xenografted in nude mice, maintaining treatments for 3 weeks. Tumor onset, volume and microvessel density were significantly reduced in mice coadministered with calcitriol and curcumin (Cal+Cur). Vessel count was also reduced in mice simultaneously treated with calcitriol and resveratrol (Cal+Rsv). Cal+Cur and Cal+Rsv treatments resulted in less tumor activated endothelium, as demonstrated by decreased tumor uptake of integrin-targeted biosensors in vivo. The renal gene expression of Cyp24a1 and Cyp27b1 suggested increased calcitriol bioactivity in the combined regimens. In vitro, the phytochemicals inhibited both MBCDF-T and endothelial cells proliferation, while potentiated calcitriol’s ability to reduce MBCDF-T cell-growth and endothelial cells migration. Resveratrol induced endothelial cell death, as deduced by increased sub-G1 cells accumulation, explaining the reduced tumor vessel number in resveratrol-treated mice, which further diminished when combined with calcitriol. In conclusion, the concomitant administration of calcitriol with curcumin or resveratrol synergistically promoted anticancer effects in vitro and in vivo in human mammary tumor cells. Whereas the results suggest different mechanisms of action of the phytochemicals when coadministered with calcitriol, the converging biological effect was inhibition of tumor neoangiogenesis.
WEE1 Inhibition Enhances Anti-Apoptotic Dependency as a Result of Premature Mitotic Entry and DNA Damage
Authors: de Jong Mathilde Rikje Willemijn , Langendonk Myra , Reitsma Bart , Herbers Pien , Nijland Marcel , Huls Gerwin , van den Berg Anke , Ammatuna Emanuele , Visser Lydia , van Meerten Tom
Published: November 2019

Genomically unstable cancers are dependent on specific cell cycle checkpoints to maintain viability and prevent apoptosis. The cell cycle checkpoint protein WEE1 is highly expressed in genomically unstable cancers, including diffuse large B-cell lymphoma (DLBCL). Although WEE1 inhibition effectively induces apoptosis in cancer cells, the effect of WEE1 inhibition on anti-apoptotic dependency is not well understood. We show that inhibition of WEE1 by AZD1775 induces DNA damage and pre-mitotic entry in DLBCL, thereby enhancing dependency on BCL-2 and/or MCL-1. Combining AZD1775 with anti-apoptotic inhibitors such as venetoclax (BCL-2i) or S63845 (MCL-1i) enhanced sensitivity in a cell-specific manner. In addition, we demonstrate that both G2/M cell cycle arrest and DNA damage induction put a similar stress on DLBCL cells, thereby enhancing anti-apoptotic dependency. Therefore, genotoxic or cell cycle disrupting agents combined with specific anti-apoptotic inhibitors may be very effective in genomic unstable cancers such as DLBCL and therefore warrants further clinical evaluation.
Coexisting Germline CHEK2 and Somatic BRAFV600E Mutations in Papillary Thyroid Cancer and Their Association with Clinicopathological Features and Disease Course
Authors: Gąsior-Perczak Danuta , Kowalik Artur , Walczyk Agnieszka , Siołek Monika , Gruszczyński Krzysztof , Pałyga Iwona , Mikina Estera , Trybek Tomasz , Kopczyński Janusz , Mężyk Ryszard , Góźdź Stanisław , Kowalska Aldona
Published: November 2019

BRAFV600E is the most common somatic mutation in papillary thyroid carcinoma (PTC) and the majority of evidence indicates that it is associated with an aggressive clinical course. Germline mutations of the CHEK2 gene impair the DNA damage repair process and increase the risk of PTC. Coexistence of both mutations is expected to be associated with poorer clinical course. We evaluated the prevalence of concomitant CHEK2 and BRAFV600E mutations and their associations with clinicopathological features, treatment response, and disease course in PTC patients. The study included 427 unselected PTC patients (377 women and 50 men) from one center. Relationships among clinicopathological features, mutation status, treatment response, and disease outcomes were assessed. Mean follow-up was 10 years. CHEK2 mutations were detected in 15.2% and BRAFV600E mutations in 64.2% patients. Neither mutation was present in 31.4% cases and both BRAFV600E and CHEK2 mutations coexisted in 10.8% patients. No significant differences in clinicopathological features, initial risk, treatment response, or disease outcome were detected among these patient groups. CHEK2 mutations were significantly associated with older age, while BRAFV600E was significantly associated with older age and extrathyroidal extension. The coexistence of both mutations was not associated with more aggressive clinicopathological features of PTC, poorer treatment response, or disease outcome.
Targeting Epithelial Mesenchymal Plasticity in Pancreatic Cancer: A Compendium of Preclinical Discovery in a Heterogeneous Disease
Authors: Monkman James H. , Thompson Erik W. , Nagaraj Shivashankar H.
Published: November 2019

Pancreatic Ductal Adenocarcinoma (PDAC) is a particularly insidious and aggressive disease that causes significant mortality worldwide. The direct correlation between PDAC incidence, disease progression, and mortality highlights the critical need to understand the mechanisms by which PDAC cells rapidly progress to drive metastatic disease in order to identify actionable vulnerabilities. One such proposed vulnerability is epithelial mesenchymal plasticity (EMP), a process whereby neoplastic epithelial cells delaminate from their neighbours, either collectively or individually, allowing for their subsequent invasion into host tissue. This disruption of tissue homeostasis, particularly in PDAC, further promotes cellular transformation by inducing inflammatory interactions with the stromal compartment, which in turn contributes to intratumoural heterogeneity. This review describes the role of EMP in PDAC, and the preclinical target discovery that has been conducted to identify the molecular regulators and effectors of this EMP program. While inhibition of individual targets may provide therapeutic insights, a single ‘master-key’ remains elusive, making their collective interactions of greater importance in controlling the behaviours’ of heterogeneous tumour cell populations. Much work has been undertaken to understand key transcriptional programs that drive EMP in certain contexts, however, a collaborative appreciation for the subtle, context-dependent programs governing EMP regulation is needed in order to design therapeutic strategies to curb PDAC mortality.
[18F] Clofarabine for PET Imaging of Hepatocellular Carcinoma
Authors: Sergeeva Olga , Kepe Vladimir , Zhang Yifan , Miller-Atkins Galen A. , Keynon Jonathan D. , Iyer Renuka , Sexton Sandra , Awadallah Amad , Xin Wei , Saunthararajah Yogen , Chan E. Ricky , Lee Zhenghong
Published: November 2019

Clinical diagnosis of hepatocellular carcinoma (HCC) relies heavily on radiological imaging. However, information pertaining to liver cancer treatment such as the proliferation status is lacking. Imaging tumor proliferation can be valuable in patient management. This study investigated 18F-labeled clofarabine ([18F]CFA) targeting deoxycytidine kinase (dCK) for PET imaging of dCK-dependent proliferation in HCC. Since clinical PET scans showed a high liver background uptake of [18F]CFA, the aim of this study was to reduce this liver background uptake. A clinically relevant animal model of spontaneously developed HCC in the woodchucks was used for imaging experiments. Several modifiers were tested and compared with the baseline PET scan: Forodesine, probenecid, and cold clofarabine, all applied before the hot [18F]CFA injection to evaluate the reduction in liver background uptake. Application of forodesine before hot [18F]CFA injection did not reduce the background uptake. Instead, it increased the background by 11.6–36.3%. Application of probenecid also increased the liver background uptake by 16.6–32.1%. Cold CFA application did reduce the liver background uptake of [18F]CFA, comparing to the baseline scan. Combining cold CFA with [18F]CFA for PET imaging of liver cancers is a promising strategy, worthy of further clinical evaluation.
Post-Surgery Circulating Tumor Cells and AXL Overexpression as New Poor Prognostic Biomarkers in Resected Lung Adenocarcinoma
Authors: de Miguel-Pérez Diego , Bayarri-Lara Clara Isabel , Ortega Francisco Gabriel , Russo Alessandro , Moyano Rodriguez María José , Alvarez-Cubero Maria Jesus , Maza Serrano Elizabeth , Lorente José Antonio , Rolfo Christian , Serrano María José
Published: November 2019

Background: The prognosis of early stage non-small cell lung cancer (NSCLC) is quite disappointing and the benefits of adjuvant therapy are relatively small. Thus, there is an urgent need to identify novel prognostic and predictive biomarkers. Lung adenocarcinoma has distinct clinical–pathological characteristics and novel therapeutic strategies are under active evaluation in the adjuvant setting. Here, we investigated the prognostic impact of circulating tumor cells (CTCs) and gene and miRNA tissue expression in resectable NSCLC. Patients and methods: We assessed the association between CTC subpopulations and the outcome of resected early stage lung adenocarcinoma (ADC) patients at three different time-points (CTC1-3) (before surgery, after one month, and after six months) in comparison to squamous cell carcinoma (SCC). Furthermore, gene and miRNA tissue expression, immunoprofiling, and epithelial-to-mesenchymal transition (EMT) markers were correlated with outcome. Results: ADC (n = 47) and SCC (n = 50) revealed different tissue expression profiles, resulting in the presence of different CTC subpopulations. In ADC, miR-155 correlated with AXL and IL6R expression, which were related to the presence of EMT CTC1 (p = 0.014 and p = 0.004). In the multivariate analysis, CTC2 was an independent prognostic factor for relapse-free survival, and CTC3 and AXL were independent prognostic for overall survival only in ADC. Neither the surgery nor the adjuvant treatment influenced the prognosis of these patients. Conclusions: Our study elucidate the prognostic impact of tissue AXL expression and the presence of CTCs after surgery in adenocarcinoma patients. Tissue AXL expression and CTC EMT activation could potentially represent biomarkers for the stratification of ADC patients that might benefit from new adjuvant therapies.
Atomic Layer Deposition ZnO Over-Coated Cu/SiO2 Catalysts for Methanol Synthesis from CO2 Hydrogenation
Authors: Gao Jinglin , Boahene Philip Effah , Hu Yongfeng , Dalai Ajay , Wang Hui
Published: November 2019

Cu-ZnO-based catalysts are of importance for CO2 utilization to synthesize methanol. However, the mechanisms of CO2 activation, the split of the C=O double bond, and the formation of C-H and O-H bonds are still debatable. To understand this mechanism and to improve the selectivity of methanol formation, the combination of strong electronic adsorption (SEA) and atomic layer deposition (ALD) was used to form catalysts with Cu nanoparticles surrounded by a non-uniform ZnO layer, uniform atomic layer of ZnO, or multiple layers of ZnO on porous SiO2. N2 adsorption, H2 temperature-programmed reduction (H2-TPR) X-ray diffraction (XRD), transmission electron microscope (TEM), energy-dispersive X-ray spectroscopy (EDX), CO-chemisorption, CO2 temperature-programmed desorption (CO2-TPD), X-ray adsorption near edge structure (XANES), and extended X-ray absorption fine structure (EXAFS) were used to characterize the catalysts. The catalyst activity was correlated to the number of metallic sites. The catalyst of 5 wt% Cu over-coated with a single atomic layer of ZnO exhibited higher methanol selectivity. This catalyst has comparatively more metallic sites (smaller Cu particles with good distribution) and basic site (uniform ZnO layer) formation, and a stronger interaction between them, which provided necessary synergy for the CO2 activation and hydrogenation to form methanol.
Cleanup and Conversion of Biomass Liquefaction Aqueous Phase to C3–C5 Olefins over ZnxZryOz Catalyst
Authors: Davidson Stephen D. , Lopez-Ruiz Juan A. , Flake Matthew , Cooper Alan R. , Elkasabi Yaseen , Tomasi Morgano Marco , Lebarbier Dagle Vanessa , Albrecht Karl O. , Dagle Robert A.
Published: November 2019

The viability of using a ZnxZryOz mixed oxide catalyst for the direct production of C4 olefins from the aqueous phase derived from three different bio-oils was explored. The aqueous phases derived from (i) hydrothermal liquefaction of corn stover, (ii) fluidized bed fast pyrolysis of horse litter, and (iii) screw pyrolysis of wood pellets were evaluated as feedstocks. While exact compositions vary, the primary constituents for each feedstock are acetic acid and propionic acid. Continuous processing, based on liquid–liquid extraction, for the cleanup of the inorganic contaminants contained in the aqueous phase was also demonstrated. Complete conversion of the carboxylic acids was achieved over ZnxZryOz catalyst for all the feedstocks investigated. The main reaction products from each of the feedstocks include isobutene (>30% selectivity) and CO2 (>23% selectivity). Activity loss from coking was also observed, thereby rendering deactivation of the ZnxZryOz catalyst, however, complete recovery of catalyst activity was observed following regeneration. Finally, the presence of H2 in the feed was found to facilitate hydrogenation of intermediate acetone, thereby increasing propene production and, consequently, decreasing isobutene production.
Deactivation of Cu/SSZ-13 NH3-SCR Catalyst by Exposure to CO, H2, and C3H6
Authors: Auvray Xavier , Mihai Oana , Lundberg Björn , Olsson Louise
Published: November 2019

Lean nitric oxide (NOx)-trap (LNT) and selective catalytic reduction (SCR) are efficient systems for the abatement of NOx. The combination of LNT and SCR catalysts improves overall NOx removal, but there is a risk that the SCR catalyst will be exposed to high temperatures and rich exhaust during the LNTs sulfur regeneration. Therefore, the effect of exposure to various rich conditions and temperatures on the subsequent SCR activity of a Cu-exchanged chabazite catalyst was studied. CO, H2, C3H6, and the combination of CO + H2 were used to simulate rich conditions. Aging was performed at 800 °C, 700 °C, and, in the case of CO, 600 °C, in a plug-flow reactor. Investigation of the nature of Cu sites was performed with NH3-temperature-programed desorption (TPD) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFT) of probe molecules (NH3 and NO). The combination of CO and H2 was especially detrimental to SCR activity and to NH3 oxidation. Rich aging with low reductant concentrations resulted in a significantly larger deactivation compared to lean conditions. Aging in CO at 800 °C caused SCR deactivation but promoted high-temperature NH3 oxidation. Rich conditions greatly enhanced the loss of Brønsted and Lewis acid sites at 800 °C, indicating dealumination and Cu migration. However, at 700 °C, mainly Brønsted sites disappeared during aging. DRIFT spectroscopy analysis revealed that CO aging modified the Cu2+/CuOH+ ratio in favor of the monovalent CuOH+ species, as opposed to lean aging. To summarize, we propose that the reason for the increased deactivation observed for mild rich conditions is the transformation of the Cu species from Z2Cu to ZCuOH, possibly in combination with the formation of Cu clusters.
Impact of a Modified Fenton Process on the Degradation of a Component Leached from Microplastics in Bottom Sediments
Authors: Kida Małgorzata , Ziembowicz Sabina , Koszelnik Piotr
Published: November 2019

This paper describes work to assess the possibility of a modified Fenton process being used to remove the hard-to-degrade plasticizer di(2-ethylhexyl) phthalate (DEHP) from the bottom sediments of a reservoir. The modifications in question entail iron(II) ions being replaced by iron(III), as well as facilitation of the process using a chelating agent. Analysis further revolved around the impact of such factors as amounts of reagents, reaction of the environment, initial contents of the contaminant, and the presence of other “competing” contaminants also of a hard-to-decompose nature. As the maximum efficiency of DEHP removal obtained did not exceed 30%, the low susceptibility to degradation is made clear, as is the need for earlier desorption of the contaminant from the matrix. The effect of the modified Fenton process on the content of organic matter and dissolved organic carbon was also considered, as was the tendency to cause selected metals and plant nutrients to leach from bottom sediments.
Hepatitis C Virus Enhances the Invasiveness of Hepatocellular Carcinoma via EGFR-Mediated Invadopodia Formation and Activation
Authors: Ninio Liat , Nissani Abraham , Meirson Tomer , Domovitz Tom , Genna Alessandro , Twafra Shams , Srikanth Kolluru D. , Dabour Roba , Avraham Erez , Davidovich Ateret , Gil-Henn Hava , Gal-Tanamy Meital
Published: November 2019

Hepatocellular carcinoma (HCC) represents the fifth most common cancer worldwide and the third cause of cancer-related mortality. Hepatitis C virus (HCV) is the leading cause of chronic hepatitis, which often results in liver fibrosis, cirrhosis, and eventually HCC. HCV is the most common risk factor for HCC in western countries and leads to a more aggressive and invasive disease with poorer patient survival rates. However, the mechanism by which the virus induces the metastatic spread of HCC tumor cells through the regulation of invadopodia, the key features of invasive cancer, is still unknown. Here, the integration of transcriptome with functional kinome screen revealed that HCV infection induced invasion and invadopodia-related gene expression combined with activation of host cell tyrosine kinases, leading to invadopodia formation and maturation and consequent cell invasiveness in vitro and in vivo. The promotion of invadopodia following HCV infection was mediated by the sustained stimulation of epidermal growth factor receptor (EGFR) via the viral NS3/4A protease that inactivates the T-cell protein tyrosine phosphatase (TC-PTP), which inhibits EGFR signaling. Characterization of an invadopodia-associated gene signature in HCV-mediated HCC tumors correlated with the invasiveness of HCC and poor patient prognosis. These findings might lead to new prognostic and therapeutic strategies for virus-mediated invasive cancer.
Hypoxia and EGF Stimulation Regulate VEGF Expression in Human Glioblastoma Multiforme (GBM) Cells by Differential Regulation of the PI3K/Rho-GTPase and MAPK Pathways
Authors: Nicolas Samer , Abdellatef Sandra , Haddad Maria Al , Fakhoury Isabelle , El-Sibai Mirvat
Published: November 2019

Glioblastoma multiforme (GBM) is one of the most common and deadly cancers of the central nervous system (CNS). It is characterized by the presence of hypoxic regions, especially in the core, leading to an increase in vascularity. This increased vascularization is driven by the expression of the major angiogenic inducer VEGF and the indirect angiogenic inducer Epidermal growth factor (EGF), which stimulates VEGF expression. In this study, we examine the regulation of VEGF by both hypoxia and the EGF signaling pathway. We also examine the involvement of pathways downstream from EGF signaling, including the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway and the Phosphatidylinositol-3-kinase/RhoA/C (PI3K/RhoA/C) pathway in this regulation. Our results show that VEGF expression and secretion levels increase following either hypoxia or EGF stimulation, with the two stimuli signaling in parallel. We also observed an increase in ERK and protein kinase B (Akt) phosphorylation, in response to EGF stimulation, with kinetics that correlated with the kinetics of the effect on VEGF. Using pharmacological inhibitors against ERK and PI3K and small interfering RNAs (siRNAs) against RhoA and RhoC, we found that both the ERK and the PI3K/RhoA/C pathways have to cooperate in order to lead to an increase in VEGF expression, downstream from EGF. In response to hypoxia, however, only ERK was involved in the regulation of VEGF. Hypoxia also led to a surprising decrease in the activation of PI3K and RhoA/C. Finally, the decrease in the activation of these Rho-GTPases was found to be mediated through a hypoxia-driven overexpression of the Rho-GTPase GTPase activating protein (GAP), StarD13. Therefore, while under normoxic conditions, EGF stimulates the activation of both the PI3K and the MAPK pathways and the induction of VEGF, in glioblastoma cells, hypoxic conditions lead to the suppression of the PI3K/RhoA/C pathway and an exclusive switch to the MAPK pathway.
Pivotal Role of STAT3 in Shaping Glioblastoma Immune Microenvironment
Authors: Piperi Christina , Papavassiliou Kostas A. , Papavassiliou Athanasios G.
Published: November 2019

Glioblastoma belongs to the most malignant intracranial tumors characterized by indispensable growth and aggressiveness that highly associates with dismal prognosis and therapy resistance. Tumor heterogeneity that often challenges therapeutic schemes is largely attributed to the complex interaction of neoplastic cells with tumor microenvironment (TME). Soluble immunoregulatory molecules secreted by glioma cells attract astrocytes, circulating stem cells and a range of immune cells to TME, inducing a local production of cytokines, chemokines and growth factors that reprogram immune cells to inflammatory phenotypes and manipulate host’s immune response in favor of cancer growth and metastasis. Accumulating evidence indicates that these tolerogenic properties are highly regulated by the constitutive and persistent activation of the oncogenic signal transducer and activator of transcription 3 (STAT3) protein, which impairs anti-tumor immunity and enhances tumor progression. Herein, we discuss current experimental and clinical evidence that highlights the pivotal role of STAT3 in glioma tumorigenesis and particularly in shaping tumor immune microenvironment in an effort to justify the high need of selective targeting for glioma immunotherapy.
Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing
Authors: Nováková Tereza , Macháčková Táňa , Novák Jan , Hude Petr , Godava Július , Žampachová Víta , Oppelt Jan , Zlámal Filip , Němec Petr , Bedáňová Helena , Slabý Ondřej , Bienertová-Vašků Julie , Špinarová Lenka , Krejčí Jan
Published: November 2019

Introduction: Acute cellular rejection (ACR) of heart allografts represents the most common reason for graft failure. Endomyocardial biopsies (EMB) are still subject to substantial interobserver variability. Novel biomarkers enabling precise ACR diagnostics may decrease interobserver variability. We aimed to identify a specific subset of microRNAs reflecting the presence of ACR. Patients and Methods: Monocentric retrospective study. A total of 38 patients with the anamnesis of ACR were identified and for each patient three consecutive samples of EMB (with, prior and after ACR) were collected. Sixteen trios were used for next-generation sequencing (exploratory cohort); the resting 22 trios were used for validation with qRT-PCR (validation cohort). Statistical analysis was performed using R software. Results: The analysis of the exploration cohort provided the total of 11 miRNAs that were altered during ACR, the three of which (miR-144, miR-589 and miR-182) were further validated in the validation cohort. Using the levels of all 11 miRNAs and principal component analysis, an ACR score was created with the specificity of 91% and sensitivity of 68% for detecting the presence of ACR in the EMB sample. Conclusion: We identified a set of microRNAs altered in endomyocardial biopsies during ACR and using their relative levels we created a diagnostic score that can be used for ACR diagnosis.
Trichinella spiralis Excretory–Secretory Products Stimulate Host Regulatory T Cell Differentiation through Activating Dendritic Cells
Authors: Sun Xi-Meng , Guo Kai , Hao Chun-Yue , Zhan Bin , Huang Jing-Jing , Zhu Xinping
Published: November 2019

Trichinella spiralis maintains chronic infections within its host, involving a variety of immunomodulatory properties, the mechanisms of which have not been completely elucidated. In this study, we found that T. spiralis infection induced strong regulatory T cell responses through parasite excretory–secretory (ES) products, characterized by increase of CD4+CD25+Foxp3+ and CD4+CD25−Foxp3+ Treg cells accompanied by high levels of IL-10 and TGF-β. T. spiralis adult worm excretory–secretory products (AES) and muscle larvae excretory–secretory products (MES) were both able to activate BMDCs in vitro to facilitate their maturation and to create regulatory cytokines IL-10 and TGF-β. The T. spiralis AES- and MES-pulsed dendritic cells (DCs) possessed abilities not only to present antigens to sensitized CD4+ T cell to stimulate their proliferation but also to induce naive CD4+ T cells to differentiate to Treg cells secreting IL-10 and TGF-β. The passive transfer of T. spiralis AES- and MES-pulsed bone marrow-derived dendritic cells (BMDCs) conferred the naive mice to acquire the differentiation of Treg cells. T. spiralis AES possesses a better ability to induce Treg cells than did MES, although the latter has the ability to induce CD4+CD25−Foxp3+ Treg cells. The results obtained in this study suggested that T. spiralis ES products stimulate the differentiation of host Treg cells possibly through activating dendritic cells to create a regulatory environment that benefits the survival of the parasite in the host.
Magnetic Ordering in Systems of Identical Particles with an Arbitrary Spin
Authors: Orlenko Elena , Orlenko Fedor
Published: November 2019

The Wigner–Eckart theorem is used for considering the collective effects related to ordering spins in systems of identical particles in ferro- and antiferromagnetic electronic systems, as well as magnetic effects that occur in high spin systems. The Hamiltonian, written in the spin representation in the form obtained by Heisenberg, Dirac, and van Vleck used to describe spin ordering in systems of particles with spin ½, is not appropriate for a description of particle systems with a spin different from ½. “High” spin particles in the spin representation need other forms of the Hamiltonian of the exchange interaction in the spin representation. The Hamiltonian for high-spin particles has been developed from the first principles, and the effects of magnetic ordering in systems of identical particles with arbitrary spin are considered in this review. An effect of giant negative magnetoresistance in the Indium antimonide has been interpreted from the exchange contribution of a high spin heavy holes point of view.
Tribological Properties of Mo2N Films at Elevated Temperature
Authors: Liu Chenkai , Ju Hongbo , Yu Lihua , Xu Junhua , Geng Yaoxiang , He Wenxiang , Jiao Jixuan
Published: November 2019

Mo2N films were synthesized using the reactive magnetron sputtering system in a mixture of argon and nitrogen, and the tribological properties were investigated at different testing temperatures against an Al2O3 counterpart. The relative intensity ratio (RIR) method was used to calculate the weight fraction of the tribo-film (MoO3) on the wear tracks of the films. The results showed that the average friction coefficient first increased from 0.30 at 25 °C to 0.53 at 200 °C, and then decreased to 0.29 at 550 °C, while the wear rate decreased from 2.1 × 10−6 mm3/Nmm at 25 °C to 5.3 × 10−7 mm3/Nmm at 200 °C and then increased to 3.1 × 10−5 mm3/Nmm at 550 °C. The weight fraction of tribo-film was mainly attributed to changes in the average friction coefficient and the wear rate. Besides this, the relative humidity also influenced the tribological properties at 25–200 °C.
Effect of Interlayer Thickness on Nano-Multilayer Coating Performance during High Speed Dry Milling of H13 Tool Steel
Authors: Chowdhury Shahereen , Bose Bipasha , Yamamoto Kenji , Veldhuis Stephen C.
Published: November 2019

The TiAlCrSiYN-based family of physical vapor deposition (PVD) coatings were systematically designed through the incorporation of TiAlCrN interlayer to increase coating adhesion and consequently the tool life for extreme conditions that arise during dry high-speed milling of hardened tool steels. The investigation in the present paper intends to explain the effect of TiAlCrN interlayer thickness on the overall coating properties and cutting performance. A comprehensive characterization of the structure and properties of the coatings has been performed using focused ion beam (FIB), scanning electron microscope (SEM), X-ray powder diffraction (XRD), nanoindentation, ramped load scratch test, repetitive load wear test, and nano-impact test. The wear test at a subcritical load of 1.5 N showed that there was a gradual improvement in coating adhesion to the substrate as the interlayer thickness increased from 100 to 500 nm. However, the wear performance, being related to the ability of the coating layer to exhibit minimal surface damage under operation, was found to be associated with micro-mechanical characteristics (such as hardness, elastic modulus). Around a 40% increase in the cutting performance with 300 nm interlayer exhibited that a substantial increase in tool life can be achieved through interlayer thickness variation, by obtaining a balance between mechanical and tribological properties of the studied coatings.
Graphene Adhesion Mechanics on Iron Substrates: Insight from Molecular Dynamic Simulations
Authors: Wang Lu , Jin Jianfeng , Yang Peijun , Zong Yaping , Peng Qing
Published: November 2019

The adhesion feature of graphene on metal substrates is important in graphene synthesis, transfer and applications, as well as for graphene-reinforced metal matrix composites. We investigate the adhesion energy of graphene nanosheets (GNs) on iron substrate using molecular dynamic (MD) simulations. Two Fe–C potentials are examined as Lennard–Jones (LJ) pair potential and embedded-atom method (EAM) potential. For LJ potential, the adhesion energies of monolayer GN are 0.47, 0.62, 0.70 and 0.74 J/m2 on the iron {110}, {111}, {112} and {100} surfaces, respectively, compared to the values of 26.83, 24.87, 25.13 and 25.01 J/m2 from EAM potential. When the number of GN layers increases from one to three, the adhesion energy from EAM potential increases. Such a trend is not captured by LJ potential. The iron {110} surface is the most adhesive surface for monolayer, bilayer and trilayer GNs from EAM potential. The results suggest that the LJ potential describes a weak bond of Fe–C, opposed to a hybrid chemical and strong bond from EAM potential. The average vertical distances between monolayer GN and four iron surfaces are 2.0–2.2 Å from LJ potential and 1.3–1.4 Å from EAM potential. These separations are nearly unchanged with an increasing number of layers. The ABA-stacked GN is likely to form on lower-index {110} and {100} surfaces, while the ABC-stacked GN is preferred on higher-index {111} surface. Our insights of the graphene adhesion mechanics might be beneficial in graphene growing, surface engineering and enhancement of iron using graphene sheets.
A Proteomic Study of Atherosclerotic Plaques in Men with Coronary Atherosclerosis
Authors: Stakhneva Ekaterina M. , Meshcheryakova Irina A. , Demidov Evgeny A. , Starostin Konstantin V. , Sadovski Evgeny V. , Peltek Sergey E. , Voevoda Michael I. , Chernyavskii Alexander M. , Volkov Alexander M. , Ragino Yuliya I.
Published: November 2019

Background: To study the changes in protein composition of atherosclerotic plaques at different stages of their development in coronary atherosclerosis using proteomics. Methods: The object of research consisted of homogenates of atherosclerotic plaques from coronary arteries at different stages of development, obtained from 15 patients. Plaque proteins were separated by two-dimensional electrophoresis. The resultant protein spots were identified by the matrix-assisted laser desorption ionization method with peptide mass mapping. Results: Groups of differentially expressed proteins, in which the amounts of proteins differed more than twofold (p < 0.05), were identified in pools of homogenates of atherosclerotic plaques at three stages of development. The amounts of the following proteins were increased in stable atherosclerotic plaques at the stage of lipidosis and fibrosis: vimentin, tropomyosin β-chain, actin, keratin, tubulin β-chain, microfibril-associated glycoprotein 4, serum amyloid P-component, and annexin 5. In plaques at the stage of fibrosis and calcification, the amounts of mimecan and fibrinogen were increased. In unstable atherosclerotic plaque of the necrotic–dystrophic type, the amounts of human serum albumin, mimecan, fibrinogen, serum amyloid P-component and annexin were increased. Conclusion: This proteomic study identifies the proteins present in atherosclerotic plaques of coronary arteries by comparing their proteomes at three different stages of plaque development during coronary atherosclerosis.
Risk Management in E-Commerce—A Fraud Study Case Using Acoustic Analysis through Its Complexity
Authors: Nascimento Diego C. , Barbosa Bruno , Perez André M. , Caires Daniel O. , Hirama Edgar , Ramos Pedro L. , Louzada Francisco
Published: November 2019

This work aimed to develop business intelligence towards fraud detection using buyer-placed information combined with the sound analysis from a confirmation purchase call. We used a dataset of 789 orders in 2018, provided by different e-commerce websites and calls fulfilled from every Brazilian state. Nine acoustic index features were used, through entropy in sound and vibration, summarizing the audio plus 6 extra features related, added by 12 customer features to compose two different classifiers (Logistic Regression and Random Forest). The acoustic indexes were, in fact, capable of providing better accuracy of the models, showing a probability associated with the voice characteristics, helping decision-making in credit card fraud.
Application of Spherical-Radial Cubature Bayesian Filtering and Smoothing in Bearings Only Passive Target Tracking
Authors: Ali Wasiq , Li Yaan , Chen Zhe , Raja Muhammad Asif Zahoor , Ahmed Nauman , Chen Xiao
Published: November 2019

In this paper, an application of spherical radial cubature Bayesian filtering and smoothing algorithms is presented to solve a typical underwater bearings only passive target tracking problem effectively. Generally, passive target tracking problems in the ocean environment are represented with the state-space model having linear system dynamics merged with nonlinear passive measurements, and the system is analyzed with nonlinear filtering algorithms. In the present scheme, an application of spherical radial cubature Bayesian filtering and smoothing is efficiently investigated for accurate state estimation of a far-field moving target in complex ocean environments. The nonlinear model of a Kalman filter based on a Spherical Radial Cubature Kalman Filter (SRCKF) and discrete-time Kalman smoother known as a Spherical Radial Cubature Rauch–Tung–Striebel (SRCRTS) smoother are applied for tracking the semi-curved and curved trajectory of a moving object. The worth of spherical radial cubature Bayesian filtering and smoothing algorithms is validated by comparing with a conventional Unscented Kalman Filter (UKF) and an Unscented Rauch–Tung–Striebel (URTS) smoother. Performance analysis of these techniques is performed for white Gaussian measured noise variations, which is a significant factor in passive target tracking, while the Bearings Only Tracking (BOT) technology is used for modeling of a passive target tracking framework. Simulations based experiments are executed for obtaining least Root Mean Square Error (RMSE) among a true and estimated position of a moving target at every time instant in Cartesian coordinates. Numerical results endorsed the validation of SRCKF and SRCRTS smoothers with better convergence and accuracy rates than that of UKF and URTS for each scenario of passive target tracking problem.
Advantages and Disadvantages of Modeling Beliefs by Single Item and Scale Models in the Context of the Theory of Planned Behavior
Authors: Heuckmann Benedikt , Hammann Marcus , Asshoff Roman
Published: November 2019

Teachers’ beliefs about science teaching vary greatly. To analyze the relationships between teachers’ beliefs and other variables related to teaching and learning, researchers can use the following two options: single item belief models or belief scales. In this study, we compared both models in the context of teachers’ beliefs regarding teaching about cancer. Although both models exhibited a good model fit, each approach had both advantages and disadvantages when we judged the modelling approaches in terms of fulfilling the requirements of common psychometric standards and adequately acknowledging the diversity of different beliefs. We discuss the predictive value of both models and their contribution to planning belief-based interventions for cancer education. We argue that researchers should combine the advantages of single item and scale models when analyzing the diversity of teachers’ beliefs.
3d Beam Reconfigurable THz Antenna with Graphene-Based High-Impedance Surface
Authors: Wang Caixia , Yao Yuan , Yu Junsheng , Chen Xiaodong
Published: November 2019

In this letter, a novel 3D multi-beam reconfigurable THz loop antenna capable of steering its main beam in the semi-sphere space (θ ϵ {0°, ±5°, ±10°}; φ ϵ {0°, 30°, 60°, 90°, 120°, 150°}) is presented. The antenna is based on a switchable circular high impedance surface (HIS) using the graphene–metal hybrid approach. The effect of gate voltage on the conductivity of graphene and the switchable reflection characteristic of the graphene-based HIS are combined in the design. Changing the chemical potential of different graphene-based HIS units can effectively adjust the beam direction. The performance of the antenna is analyzed through its reflection coefficients and gain radiation patterns, and simulated results show that the maximum gain can reach 3.23 dBi at 0.5 THz.
A New Rail-to-Rail Second Generation Voltage Conveyor
Authors: Barile Gianluca , Stornelli Vincenzo , Ferri Giuseppe , Safari Leila , D’Amico Emanuele
Published: November 2019

In this paper, a novel low voltage low power CMOS second generation voltage conveyor (VCII) with an improved voltage range at both the X and Z terminals is presented. The proposed VCII is formed by a current buffer based on a class AB regulated common-gate stage and a modified rail-to-rail voltage buffer. Spice simulation results using LFoundry 0.15 μm low-Vth CMOS technology with a ±0.9 V supply voltage are provided to demonstrate the validity of the designed circuit. Thanks to the class AB behavior, from a bias current of 10 µA, the proposed VCII is capable of driving 0.5 mA on the X terminal, with a total power consumption of 120 µW. The allowed voltage swing on the Z terminal is at least equal to ±0.83 V, while on the X terminals it is ±0.72 V. Both DC and AC voltage and current gains are provided, and time domain simulations, where the voltage conveyor is used as a transimpedance amplifier (TIA), are also presented. A final table that summarizes the main features of the circuit, comparing them with the literature, is also given.