bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis
Authors: van den Ende Tom , ter Veer Emil , Mali Rosa M. A. , van Berge Henegouwen Mark I. , Hulshof Maarten C. C. M. , van Oijen Martijn G. H. , van Laarhoven Hanneke W. M.
Published: April 2019

Background: An overview of promising prognostic variables and predictive subgroups concerning the curative treatment of esophageal and gastric cancer from randomized controlled trials (RCTs) is lacking. Therefore, we conducted a systematic review and meta-analysis. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to March 2019 for RCTs on the curative treatment of esophageal or gastric cancer with data on prognostic and/or predictive factors for overall survival. Prognostic factors were deemed potentially clinically relevant according to the following criteria; (1) statistically significant (p < 0.05) in a multivariate analysis, (2) reported in at least 250 patients, and (3) p < 0.05, in ≥33% of the total number of patients in RCTs reporting this factor. Predictive factors were potentially clinically-relevant if (1) the p-value for interaction between subgroups was <0.20 and (2) the hazard ratio in one of the subgroups was significant (p < 0.05). Results: For gastric cancer, 39 RCTs were identified (n = 13,530 patients) and, for esophageal cancer, 33 RCTs were identified (n = 8618 patients). In total, we identified 23 potentially clinically relevant prognostic factors for gastric cancer and 16 for esophageal cancer. There were 15 potentially clinically relevant predictive factors for gastric cancer and 10 for esophageal cancer. Conclusion: The identified prognostic and predictive factors can be included and analyzed in future RCTs and be of guidance for nomograms. Further validation should be performed in large patient cohorts.
The Evolving Landscape of Cancer Stem Cells and Ways to Overcome Cancer Heterogeneity
Authors: Taniguchi Hiroaki , Suzuki Yasunori , Natori Yukikazu
Published: April 2019

Cancer stem cells (CSCs) with therapeutic resistance and plasticity can be found in various types of tumors and are recognized as attractive targets for treatments. As CSCs are derived from tissue stem or progenitor cells, and/or dedifferentiated mature cells, their signal transduction pathways are critical in the regulation of CSCs; chronic inflammation causes the accumulation of genetic mutations and aberrant epigenetic changes in these cells, potentially leading to the production of CSCs. However, the nature of CSCs appears to be stronger than the treatments of the past. To improve the treatments targeting CSCs, it is important to inhibit several molecules on the signaling cascades in CSCs simultaneously, and to overcome cancer heterogeneity caused by the plasticity. To select suitable target molecules for CSCs, we have to explore the landscape of CSCs from the perspective of cancer stemness and signaling systems, based on the curated databases of cancer-related genes. We have been studying the integration of a broad range of knowledge and experiences from cancer biology, and also from other interdisciplinary basic sciences. In this review, we have introduced the concept of developing novel strategies targeting CSCs.
Next-Generation Hedgehog/GLI Pathway Inhibitors for Cancer Therapy
Authors: Peer Elisabeth , Tesanovic Suzana , Aberger Fritz
Published: April 2019

The Hedgehog/Glioma-associated oncogene homolog (HH/GLI) signaling pathway regulates self-renewal of rare and highly malignant cancer stem cells (CSC), which have been shown to account for the initiation and maintenance of tumor growth as well as for drug resistance, metastatic spread and relapse. Efficacious therapeutic approaches targeting CSC pathways, such as HH/GLI signaling in combination with chemo, radiation or immunotherapy are, therefore, of high medical need. Pharmacological inhibition of HH/GLI pathway activity represents a promising approach to eliminate malignant CSC. Clinically approved HH/GLI pathway inhibitors target the essential pathway effector Smoothened (SMO) with striking therapeutic efficacy in skin and brain cancer patients. However, multiple genetic and molecular mechanisms resulting in de novo and acquired resistance to SMO inhibitors pose major limitations to anti-HH/GLI therapies and, thus, the eradication of CSC. In this review, we summarize reasons for clinical failure of SMO inhibitors, including mechanisms caused by genetic alterations in HH pathway effectors or triggered by additional oncogenic signals activating GLI transcription factors in a noncanonical manner. We then discuss emerging novel and rationale-based approaches to overcome SMO-inhibitor resistance, focusing on pharmacological perturbations of enzymatic modifiers of GLI activity and on compounds either directly targeting oncogenic GLI factors or interfering with synergistic crosstalk signals known to boost the oncogenicity of HH/GLI signaling.
18F-FDG-PET Can Predict Microvessel Density in Head and Neck Squamous Cell Carcinoma
Authors: Surov Alexey , Meyer Hans Jonas , Höhn Anne-Kathrin , Wienke Andreas , Sabri Osama , Purz Sandra
Published: April 2019

Aim: Positron emission tomography (PET) with 18F-fluordeoxyglucose (18F-FDG) plays an essential role in the staging and tumor monitoring of head and neck squamous cell carcinoma (HNSCC). Microvessel density (MVD) is one of the clinically important histopathological features in HNSCC. The purpose of this study was to analyze possible associations between 18F-FDG-PET findings and MVD parameters in HNSCC. Materials and Methods: Overall, 22 patients with a mean age of 55.2 ± 11.0 and with different HNSCC were acquired. In all cases, whole-body 18F-FDG-PET was performed. For each tumor, the maximum and mean standardized uptake values (SUVmax; SUVmean) were determined. The MVD, including stained vessel area and total number of vessels, was estimated on CD105 stained specimens. All specimens were digitalized and analyzed by using ImageJ software 1.48v. Spearman’s correlation coefficient (r) was used to analyze associations between investigated parameters. p-values of <0.05 were taken to indicate statistical significance. Results: SUVmax correlated with vessel area (r = 0.532, p = 0.011) and vessel count (r = 0.434, p = 0.043). Receiver operating characteristic analysis identified a threshold SUVmax of 15 to predict tumors with high MVD with a sensitivity of 72.7% and specificity of 81.8%, with an area under the curve of 82.6%. Conclusion: 8F-FDG-PET parameters correlate statistically significantly with MVD in HNSCC. SUVmax may be used for discrimination of tumors with high tumor-related MVD.
CHI3L1, NTRK2, 1p/19q and IDH Status Predicts Prognosis in Glioma
Authors: Deluche Elise , Bessette Barbara , Durand Stephanie , Caire François , Rigau Valérie , Robert Sandrine , Chaunavel Alain , Forestier Lionel , Labrousse François , Jauberteau Marie-Odile , Durand Karine , Lalloué Fabrice
Published: April 2019

The aim of this study was to identify relevant biomarkers for the prognosis of glioma considering current molecular changes such as IDH mutation and 1p19q deletion. Gene expression profiling was performed using the TaqMan Low Density Array and hierarchical clustering using 96 selected genes in 64 patients with newly diagnosed glioma. The expression dataset was validated on a large independent cohort from The Cancer Genome Atlas (TCGA) database. A differential expression panel of 26 genes discriminated two prognostic groups regardless of grade and molecular groups of tumors: Patients having a poor prognosis with a median overall survival (OS) of 23.0 ± 9.6 months (group A) and patients having a good prognosis with a median OS of 115.0 ± 6.6 months (group B) (p = 0.007). Hierarchical clustering of the glioma TCGA cohort supported the prognostic value of these 26 genes (p < 0.0001). Among these genes, CHI3L1 and NTRK2 were identified as factors that can be associated with IDH status and 1p/19q co-deletion to distinguish between prognostic groups of glioma from the TCGA cohort. Therefore, CHI3L1 associated with NTRK2 seemed to be able to provide new information on glioma prognosis.
Effect of Organic Assistant on the Performance of Ceria-Based Catalysts for the Selective Catalytic Reduction of NO with Ammonia
Authors: Huang Xing , Li Shining , Qiu Wenge , Chen Yun , Cheng Jie , Sun Yanming , Bai Guangmei , Song Liyun , Zhang Guizhen , He Hong
Published: April 2019

In the present study, a series of CeO2/TiO2 catalysts were fabricated by dry ball milling method in the absence and presence of organic assistants, and their catalytic performances for the selective catalytic reduction (SCR) of NO by NH3 were investigated. It was found that the addition of organic assistants in the ball milling process and the calcining ambience exerted a significant influence on the catalytic performances of CeO2/TiO2 catalysts. The nitrogen sorption isotherm measurement (BET), powder X-ray diffraction (XRD), Raman spectra, high-resolution transmission electron microscopy (HR-TEM), hydrogen temperature-programmed reduction (H2-TPR), ammonia temperature-programmed desorption (NH3-TPD), sulfur dioxide temperature-programmed desorption (SO2-TPD), thermogravimetric analysis (TG), Fourier transform infrared (FT-IR) and X-ray photoelectron spectra (XPS) characterizations showed that the introduction of citric acid in the ball milling process could significantly change the decomposition process of the precursor mixture, which can lead to improved dispersion and reducibility of cerium species, surface acidity as well as the surface microstructure, all which were responsible for the high low temperature activity of CeTi-C-N in an NH3-SCR reaction. In contrast, the addition of sucrose in the milling process showed an inhibitory effect on the catalytic performance of CeO2/TiO2 catalyst in an NH3-SCR reaction, possibly due to the decrease of the crystallinity of the TiO2 support and the carbon residue covering the active sites.
Oxidative Coupling of Methane over Mn2O3-Na2WO4/SiC Catalysts
Authors: Kim Jieun , Park La-Hee , Ha Jeong-Myeong , Park Eun Duck
Published: April 2019

The oxidative coupling of methane (OCM) is operated at high temperatures and is a highly exothermic reaction; thus, hotspots form on the catalyst surface during reaction unless the produced heat is removed. It is crucial to control the heat formed because surface hotspots can degrade catalytic performance. Herein, we report the preparation of Mn2O3-Na2WO4/SiC catalysts using SiC, which has high thermal conductivity and good stability at high temperatures, and the catalyst was applied to the OCM. Two Mn2O3-Na2WO4/SiC catalysts were prepared by wet-impregnation on SiC supports having different particle sizes. For comparison, the Mn2O3-Na2WO4/SiO2 catalyst was also prepared by the same method. The catalysts were analyzed by nitrogen adsorption–desorption, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The transformation of SiC into α-cristobalite was observed for the Mn2O3-Na2WO4/SiC catalysts. Because SiC was completely converted into α-cristobalite for the nano-sized SiC-supported Mn2O3-Na2WO4 catalyst, the catalytic performance for the OCM reaction of Mn2O3-Na2WO4/n-SiC was similar to that of Mn2O3-Na2WO4/SiO2. However, only the surface layer of SiC was transformed into α-cristobalite for the micro-sized SiC (m-SiC) in Mn2O3-Na2WO4/m-SiC, resulting in a SiC@α-cristobalite core–shell structure. The Mn2O3-Na2WO4/m-SiC showed higher methane conversion and C2+ yield at 800 and 850 °C than Mn2O3-Na2WO4/SiO2.
Folding Status Is Determinant over Traffic-Competence in Defining CFTR Interactors in the Endoplasmic Reticulum
Authors: Santos João D. , Canato Sara , Carvalho Ana S. , Botelho Hugo M. , Aloria Kerman , Amaral Margarida D. , Matthiesen Rune , Falcao Andre O. , Farinha Carlos M.
Published: April 2019

The most common cystic fibrosis-causing mutation (F508del, present in ~85% of CF patients) leads to CFTR misfolding, which is recognized by the endoplasmic reticulum (ER) quality control (ERQC), resulting in ER retention and early degradation. It is known that CFTR exit from the ER is mediated by specific retention/sorting signals that include four arginine-framed tripeptide (AFT) retention motifs and a diacidic (DAD) exit code that controls the interaction with the COPII machinery. Here, we aim at obtaining a global view of the protein interactors that regulate CFTR exit from the ER. We used mass spectrometry-based interaction proteomics and bioinformatics analyses to identify and characterize proteins interacting with selected CFTR peptide motifs or full-length CFTR variants retained or bypassing these ERQC checkpoints. We conclude that these ERQC trafficking checkpoints rely on fundamental players in the secretory pathway, detecting key components of the protein folding machinery associated with the AFT recognition and of the trafficking machinery recognizing the diacidic code. Furthermore, a greater similarity in terms of interacting proteins is observed for variants sharing the same folding defect over those reaching the same cellular location, evidencing that folding status is dominant over ER escape in shaping the CFTR interactome.
NFκB- and MAP-Kinase Signaling Contribute to the Activation of Murine Myeloid Dendritic Cells by a Flagellin A: Allergen Fusion Protein
Authors: Moeller Tobias , Wolfheimer Sonja , Goretzki Alexandra , Scheurer Stephan , Schülke Stefan
Published: April 2019

Fusion proteins incorporating the TLR5-ligand flagellin are currently undergoing clinical trials as vaccine candidates for many diseases. We recently reported a flagellin:allergen fusion protein containing the TLR5-ligand flagellin A (FlaA) from Listeria monocytogenes and the major birch pollen allergen Bet v 1 (rFlaA:Betv1) to prevent allergic sensitization in an experimental mouse model. This study analyzes the signaling pathways contributing to rFlaA:Betv1-mediated pro- and anti-inflammatory cytokine secretion and cell metabolism in myeloid dendritic cells (mDCs) in vitro. The influence of mammalian target of rapamycin (mTOR)-, NFκB-, and MAP kinase (MAPK)-signaling on cytokine secretion and metabolic activity of bone marrow (BM)-derived mDCs stimulated with rFlaA:Betv1 were investigated by pre-treatment with either mTOR- (rapamycin), NFκB- (dexamethason, BMS-345541, TPCA-1, triptolide, or BAY-11) or MAPK- (SP600125, U0126, or SB202190) inhibitors, respectively. rFlaA:Betv1-mediated IL-10 secretion as well as activation of mDC metabolism, rather than pro-inflammatory cytokine secretion, were inhibited by rapamycin. Inhibition of NFκB-signaling suppressed rFlaA:Betv1-induced IL-12, while inhibition of MAPK-signaling dose-dependently suppressed rFlaA:Betv1-induced IL-10 as well as pro-inflammatory IL-6 and TNF-α production. Notably, with the exception of a partial JNK-dependency, rFlaA:Betv1-mediated effects on mDC metabolism were mostly NFκB- and MAPK-independent. Therefore, MAPK-mediated activation of both NFκB- and mTOR-signaling likely is a key pathway for the production of pro- and anti-inflammatory cytokines by flagellin fusion protein vaccines.
Development of a Matrix Based Statistical Framework to Compute Weight for Composite Hazards, Vulnerability and Risk Assessments
Authors: Kabir Rubaiya , Akter Marin , Karim Dewan Sadia , Haque Anisul , Rahman Munsur , Sakib Mohiuddin
Published: April 2019

Selection of relative weights for different indicators is a critical step during assessment of composite hazards, vulnerability, and risk. While assigning weight to an indicator, it is important to consider the influence of an individual indicator on a particular composite index. In general, the larger the weight of the indicator, the higher the importance of that indicator compared to other indicators. In this study, a new matrix based statistical framework (MSF) for weight assignment is developed that can be considered as the simplest and most accurate method for assigning weights for a large number of indicators. This method (MSF) is based on the valuation of the correlation matrix and Eigenvector associated with Eigenvalue. Relying on the inter build up methodology, MSF can fulfill some built-in gaps among other weightage methods. It can also directly give the ‘decision’ to select the relative weights that are found from the Eigenvector corresponding to the largest Eigenvalue. The new method is applied by assigning weights to 15 socio-economic indicators and assessed vulnerability and risk in the Bangladesh coast. While comparing with other weight methods, it is found that MSF gives the most acceptable physical explanation about the relative values of weights of indicators. In terms of accuracy, MSF is found to be most accurate compared to other weight methods. When large numbers of indicators are involved in an application, MSF is found to be relatively simple and easy to apply compared to other methods.
Surface Modification of Biomedical Titanium Alloy: Micromorphology, Microstructure Evolution and Biomedical Applications
Authors: Liu Wei , Liu Shifeng , Wang Liqiang
Published: April 2019

With the increasing demand for bone implant therapy, titanium alloy has been widely used in the biomedical field. However, various potential applications of titanium alloy implants are easily hampered by their biological inertia. In fact, the interaction of the implant with tissue is critical to the success of the implant. Thus, the implant surface is modified before implantation frequently, which can not only improve the mechanical properties of the implant, but also polish up bioactivity and osseoconductivity on a cellular level. This paper aims at reviewing titanium surface modification techniques for biomedical applications. Additionally, several other significant aspects are described in detail in this article, for example, micromorphology, microstructure evolution that determines mechanical properties, as well as a number of issues concerning about practical application of biomedical implants.
Diffusiophoresis of a Colloidal Cylinder at Small Finite Péclet Numbers
Authors: Chang Yu C. , Keh Huan J.
Published: April 2019

The diffusiophoretic migration of a circular cylindrical particle in a nonelectrolyte solution with a solute concentration gradient normal to its axis is analytically studied for a small but finite Péclet number P e . The interfacial layer of interaction between the solute molecules and the particle is taken to be thin, but the polarization of its mobile molecules is allowed. Using a method of matched asymptotic expansions, we solve the governing equations of conservation of the system and obtain an explicit formula for the diffusiophoretic velocity of the cylinder correct to the order P e 2 . It is found that the perturbed solute concentration and fluid velocity distributions have the order P e , but the leading correction to the particle velocity has the higher order P e 2 ln P e . The correction to the particle velocity to the order P e 2 can be either positive or negative depending on the polarization parameter of the thin interfacial layer, establishing that the solute convection effect is complicated and can enhance or retard the diffusiophoretic motion. The particle velocity at P e = 0.6 can be about 17% smaller or 0.2% greater than that at P e = 0 . Under practical conditions, the solute convection effect on the diffusiophoretic velocity is much greater for a cylindrical particle than for a spherical particle, whose leading correction has the order P e 2 .
Visible Light Communication System Based on Software Defined Radio: Performance Study of Intelligent Transportation and Indoor Applications
Authors: Martinek Radek , Danys Lukas , Jaros Rene
Published: April 2019

In this paper, our first attempt at visible light communication system, based on software defined radio (SDR) and implemented in LabVIEW is introduced. This paper mainly focuses on two most commonly used types of LED lights, ceiling lights and LED car lamps/tail-lights. The primary focus of this study is to determine the basic parameters of real implementation of visible light communication (VLC) system, such as transmit speed, communication errors (bit-error ratio, error vector magnitude, energy per bit to noise power spectral density ratio) and highest reachable distance. This work focuses on testing various multistate quadrature amplitude modulation (M-QAM). We have used Skoda Octavia III tail-light and Phillips indoor ceiling light as transmitters and SI PIN Thorlabs photodetector as receiver. Testing method for each light was different. When testing ceiling light, we have focused on reachable distance for each M-QAM variant. On the other side, Octavia tail-light was tested in variable nature conditions (such as thermal turbulence, rain, fog) simulated in special testing box. This work will present our solution, measured parameters and possible weak spots, which will be adjusted in the future.
Observer-Based Sliding Mode Control to Improve Stability of Three-Phase LCL-Filtered Grid-Connected VSIs
Authors: Huang Min , Li Han , Wu Weimin , Blaabjerg Frede
Published: April 2019

Grid-connected voltage source inverters (VSIs) with LCL filters have been widely used for distributed generation systems (DGs). Various control methods have been studied to achieve good performance. Among them, sliding mode control has been applied to LCL-filtered grid-connected VSIs for its fast, dynamic response and strong robustness. However, LCL networks can easily cause instability problems under weak grid conditions such as grid impedance variation. At the same time, the stability design of sliding mode control applied for LCL-filtered grid-connected inverters are important, but they lack detailed parameters design in recent papers. In this paper, a design of observer-based sliding mode control to improve the stability of three-phase LCL-filtered grid-connected VSIs was proposed. The theoretical stability analysis was developed to consider the effect of the system discretization and grid impedance variations. Finally, a 3-kW, 110-V, 50-Hz experimental setup has been built to demonstrate the validation of the proposed method.
Fractional Order Fuzzy PID Control of Automotive PEM Fuel Cell Air Feed System Using Neural Network Optimization Algorithm
Authors: AbouOmar Mahmoud S. , Zhang Hua-Jun , Su Yi-Xin
Published: April 2019

The air feeding system is one of the most important systems in the proton exchange membrane fuel cell (PEMFC) stack, which has a great impact on the stack performance. The main control objective is to design an optimal controller for the air feeding system to regulate oxygen excess at the required level to prevent oxygen starvation and obtain the maximum net power output from the PEMFC stack at different disturbance conditions. This paper proposes a fractional order fuzzy PID controller as an efficient controller for the PEMFC air feed system. The proposed controller was then employed to achieve maximum power point tracking for the PEMFC stack. The proposed controller was optimized using the neural network algorithm (NNA), which is a new metaheuristic optimization algorithm inspired by the structure and operations of the artificial neural networks (ANNs). This paper is the first application of the fractional order fuzzy PID controller to the PEMFC air feed system. The NNA algorithm was also applied for the first time for the optimization of the controllers tested in this paper. Simulation results showed the effectiveness of the proposed controller by improving the transient response providing a better set point tracking and disturbance rejection with better time domain performance indices. Sensitivity analyses were carried-out to test the robustness of the proposed controller under different uncertainty conditions. Simulation results showed that the proposed controller had good robustness against parameter uncertainty in the system.
New Estimates for Exponentially Convex Functions via Conformable Fractional Operator
Authors: Rashid Saima , Noor Muhammad Aslam , Noor Khalida Inayat
Published: April 2019

In this paper, we derive a new Hermite–Hadamard inequality for exponentially convex functions via α-fractional integral. We also prove a new integral identity. Using this identity, we establish several Hermite–Hadamard type inequalities for exponentially convexity, which can be obtained from our results. Some special cases are also discussed.
Black Lives Matter! Nigerian Lives Matter!: Language and Why Black Performance Matters
Authors: Adelakun Abimbola A.
Published: April 2019

This essay explores performance as a language by looking at its appropriation by other cultures, and the associated history of the crafted phrases that are borrowed along. I start by noting that to create awareness of the massacres that have recently occurred in some parts of Nigeria, commentators, both in and out of the country, and activist-cum-protesters created the term “Nigerian Lives Matter.” They appropriated from “Black Lives Matter,” the American-originated advocacy movement that campaigns against violence and brutality against black people. I show that these forms of lexical interchange are possible because of non-Americans’ familiarity with America’s racial history, and black performance liberation expressivity, which they have been acculturated into as a result of their long exposure to American culture. Beyond phrases however, I argue that black performance itself is a language that has a global resonance among minorities. To illustrate this further, I do a close reading of This is Nigeria, a recent music video released by Nigerian lawyer turned artist, Folarin Falana (Falz), alongside a version of the original production, This is America, also recently released by Donald Glover (Childish Gambino). Both songs continue in the older tradition of African and African American transatlantic political relations through music, the shared understanding of the similarities of anti-black oppression, and the formation of aesthetics that mediate the advocacy of black liberation. The songs are also a pointer to how black advocacy might continue to unfold in contemporary era.
The Genome of Blue-Capped Cordon-Bleu Uncovers Hidden Diversity of LTR Retrotransposons in Zebra Finch
Authors: Boman Jesper , Frankl-Vilches Carolina , da Silva dos Santos Michelly , de Oliveira Edivaldo H. C. , Gahr Manfred , Suh Alexander
Published: April 2019

Avian genomes have perplexed researchers by being conservative in both size and rearrangements, while simultaneously holding the blueprints for a massive species radiation during the last 65 million years (My). Transposable elements (TEs) in bird genomes are relatively scarce but have been implicated as important hotspots for chromosomal inversions. In zebra finch (Taeniopygia guttata), long terminal repeat (LTR) retrotransposons have proliferated and are positively associated with chromosomal breakpoint regions. Here, we present the genome, karyotype and transposons of blue-capped cordon-bleu (Uraeginthus cyanocephalus), an African songbird that diverged from zebra finch at the root of estrildid finches 10 million years ago (Mya). This constitutes the third linked-read sequenced genome assembly and fourth in-depth curated TE library of any bird. Exploration of TE diversity on this brief evolutionary timescale constitutes a considerable increase in resolution for avian TE biology and allowed us to uncover 4.5 Mb more LTR retrotransposons in the zebra finch genome. In blue-capped cordon-bleu, we likewise observed a recent LTR accumulation indicating that this is a shared feature of Estrildidae. Curiously, we discovered 25 new endogenous retrovirus-like LTR retrotransposon families of which at least 21 are present in zebra finch but were previously undiscovered. This highlights the importance of studying close relatives of model organisms.
The Modern Gaze of Foreign Architects Travelling to Interwar Greece: Urban Planning, Archaeology, Aegean Culture, and Tourism
Authors: Athanassiou Emilia , Dima Vasiliki , Karali Konstantinia , Tournikiotis Panayotis
Published: April 2019

This paper reflects on the embrace of the Ancient world in modernity and the journey to Greece as a vehicle for their reciprocal reshaping. In the interwar period, new visual narratives emerged in Western accounts, proposing alternative contexts for Greek cultural heritage and associating regional culture with the emergence of modernism. The article investigates the mobility of modern travellers in Greece as an essential factor for the new contextualization of the country’s dominant cultural paradigm -Antiquity- as well as for the emergence of parallel narrations of the Mediterranean genius loci that examine the spatial imprint of heritage and tourism on the Greek urban, archaeological and natural environment. Western intellectuals, engineers, architects and urban planners, supported by a highly mobile network of editors, travel agencies, tourist cruises, architectural or archaeological conferences and congresses, contributed to the promotion of modern architecture and urban infrastructure in Greece. Their yet to become tourist gaze embraced the Aegean tradition, the Greek landscape and the ancient ruins as equal collocutors, initiating at the same time Greece itself into modernity. This paper traces the encounters between foreign travellers and the divergent manifestations of the country’s cultural identity in the pages of printed articles, books, travel accounts, photographic material and films. Following these documentations, the paper argues that tourism mobility gave rise to an alternative, southern modernism, whose emergence and development deviates significantly from mainstream narratives propounded by the continental historiography of modernity. Vice versa, the modern mobility networks of the South promoted the development of urban infrastructure and welfare facilities in Greece, as well as the establishment of early tourism policies, thus articulating the new national narrative of interwar Greece, based equally on classical heritage, regional culture and modern progress. The present paper is part of the research program Voyage to Greece: Mobility and modern architecture in the interwar period, where E. Athanassiou, V. Dima, V.; Karali, K. contribute as post-doctoral researchers, with P. Tournikiotis, Professor NTUA as scientific supervisor. The research is co-financed by the Greek State and the European Union.
Calcium Channel Blocker-Associated Chyloperitoneum in Patients Receiving Peritoneal Dialysis: A Systematic Review
Authors: Kim Seungyeon , Yu Yun Mi , Kwon Jeongyoon , Yoo Hyejin , Jung Sun Hoi , Lee Euni
Published: April 2019

Unlike chyloperitoneum associated with clinical conditions including cancer, cirrhosis, and traumatic surgery, calcium channel blocker (CCB)-associated chyloperitoneum is rarely discussed in comprehensive studies on chyloperitoneum. We aimed to investigate the prevalence and characteristics of CCB-associated chyloperitoneum in peritoneal dialysis (PD) patients. The MEDLINE, Embase, CENTRAL, CiNii, and RISS databases were systematically searched for clinical studies on CCB-associated chyloperitoneum in PD patients published up to 31 July 2018. A total of 17 studies (four cohort studies, one case series, and 12 case reports) were selected. Eight CCBs, namely amlodipine, benidipine, diltiazem, lercanidipine, manidipine, nifedipine, nisoldipine, and verapamil, were reported to be associated with chyloperitoneum; manidipine and lercanidipine were the most frequently reported. The average prevalence of chyloperitoneum for lercanidipine was 25.97% in three cohort studies, two of which had a moderate or high risk of bias. Most of the studies revealed chyloperitoneum development within 4 days of initiation of CCB therapy and chyloperitoneum disappearance within 24 h of CCB withdrawal. The results of this study emphasise on the need for awareness among healthcare professionals regarding CCB-associated chyloperitoneum in PD patients. Further studies elucidating the causality and clinical implication of CCB-associated chyloperitoneum are needed.
Can Primary Medical Institutions Lead to Worse Health Status for Patients with Noncommunicable Diseases Compared with High-Level Hospitals? A Follow-Up Observation Study in China
Authors: Niu Yadong , Ye Ting , Zhang Yan , Zhang Liang
Published: April 2019

The weak primary healthcare system in China brings challenges to the national strategy of primary medical institutions providing general health needs for patients with non-communicable diseases (NCDs). It is necessary to explore the potential discrepancies in health status for patients with NCDs if they go to primary medical institutions rather than high-level hospitals. Data was obtained from Surveillance of Health-seeking Behavior in Hubei Province. Respondents were investigated six times to collect information on health service utilization and health-related quality of life (HRQoL). Ninety-two hypertension patients who went to medical institutions of the same level were included. HRQoL was measured by the Chinese version of EQ-5D-3L. A multilevel growth curve model was applied to analyze whether provider level could influence HRQoL. The utility score and visual analogue scale (VAS) of patients varied insignificantly over six months (p > 0.05). A growth curve model showed that comorbidity was the only factor significantly influencing utility score (p = 0.019). Time and comorbidity were the only influencing factors of VAS (p < 0.05). Our findings indicated that the level of healthcare provider had no significant impact on the health status of patients with NCDs. As such, this study concludes that the primary healthcare system in China is qualified to be the health gatekeeper for NCDs patients.
Automatic Building Footprint Extraction from Multi-Resolution Remote Sensing Images Using a Hybrid FCN
Authors: Schuegraf Philipp , Bittner Ksenia
Published: April 2019

Recent technical developments made it possible to supply large-scale satellite image coverage. This poses the challenge of efficient discovery of imagery. One very important task in applications like urban planning and reconstruction is to automatically extract building footprints. The integration of different information, which is presently achievable due to the availability of high-resolution remote sensing data sources, makes it possible to improve the quality of the extracted building outlines. Recently, deep neural networks were extended from image-level to pixel-level labelling, allowing to densely predict semantic labels. Based on these advances, we propose an end-to-end U-shaped neural network, which efficiently merges depth and spectral information within two parallel networks combined at the late stage for binary building mask generation. Moreover, as satellites usually provide high-resolution panchromatic images, but only low-resolution multi-spectral images, we tackle this issue by using a residual neural network block. It fuses those images with different spatial resolution at the early stage, before passing the fused information to the Unet stream, responsible for processing spectral information. In a parallel stream, a stereo digital surface model (DSM) is also processed by the Unet. Additionally, we demonstrate that our method generalizes for use in cities which are not included in the training data.
Reduced T-cell Numbers and Elevated Levels of Immunomodulatory Cytokines in Metastatic Prostate Cancer Patients De Novo Resistant to Abiraterone and/or Enzalutamide Therapy
Authors: Pal Sumanta , Moreira Dayson , Won Haejung , White Seok , Duttagupta Pryanka , Lucia Marc , Jones Jeremy , Hsu JoAnn , Kortylewski Marcin
Published: April 2019

Currently, there are two Food and Drug Administration (FDA)-approved drugs for androgen deprivation therapy (ADT) of metastatic castration-resistant prostate cancer (mCRPC) patients: abiraterone and enzalutamide. However, our understanding of the effect of these therapies on the immune system in mCRPC patients remains limited. Here, we examined how abiraterone and enzalutamide treatment affects levels of soluble immune mediators in plasma and in circulating immune cells of 44 mCRPC patients. We found that the baseline levels of cytokines fibroblast growth factor (FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 10 (IL-10), and IL-6 were significantly lower in ADT-sensitive compared to de novo resistant patients. In addition, resistant patients showed significantly lower T cell frequencies. When comparing the levels of cytokines over the course of treatment, we observed that the levels of proinflammatory mediators, such as interferon-γ (IFN-γ), IL-5, macrophage inflammatory protein 1 alpha (MIP-1α), and tumor necrosis factor alpha (TNFα), were significantly increased in the ADT-sensitive patients. At the same time, the abiraterone/enzalutamide therapy did not reduce the percentage of tolerogenic myeloid cell populations, such as polymorphonuclear myeloid-derived suppressor cells, which retained unaltered expression of programmed death-ligand 1 (PD-L1) and B7-H3. Overall, our results suggest that certain immune markers, such as IL-6 and the frequency of effector T cells, could be predictive of therapeutic response to ADT therapies in mCRPC patients.
Structural Insights into CB1 Receptor Biased Signaling
Authors: Al-Zoubi Rufaida , Morales Paula , Reggio Patricia H.
Published: April 2019

The endocannabinoid system has emerged as a promising target for the treatment of numerous diseases, including cancer, neurodegenerative disorders, and metabolic syndromes. Thus far, two cannabinoid receptors, CB1 and CB2, have been discovered, which are found predominantly in the central nervous system (CB1) or the immune system (CB2), among other organs and tissues. CB1 receptor ligands have been shown to induce a complex pattern of intracellular effects. The binding of a ligand induces distinct conformational changes in the receptor, which will eventually translate into distinct intracellular signaling pathways through coupling to specific intracellular effector proteins. These proteins can mediate receptor desensitization, trafficking, or signaling. Ligand specificity and selectivity, complex cellular components, and the concomitant expression of other proteins (which either regulate the CB1 receptor or are regulated by the CB1 receptor) will affect the therapeutic outcome of its targeting. With an increased interest in G protein-coupled receptors (GPCR) research, in-depth studies using mutations, biological assays, and spectroscopic techniques (such as NMR, EPR, MS, FRET, and X-ray crystallography), as well as computational modelling, have begun to reveal a set of concerted structural features in Class A GPCRs which relate to signaling pathways and the mechanisms of ligand-induced activation, deactivation, or activity modulation. This review will focus on the structural features of the CB1 receptor, mutations known to bias its signaling, and reported studies of CB1 receptor ligands to control its specific signaling.
SUMOylation in Glioblastoma: A Novel Therapeutic Target
Authors: Fox Brandon M. , Janssen Andrew , Estevez-Ordonez Dagoberto , Gessler Florian , Vicario Nunzio , Chagoya Gustavo , Elsayed Galal , Sotoudeh Houman , Stetler William , Friedman Gregory K. , Bernstock Joshua D.
Published: April 2019

Protein SUMOylation is a dynamic post-translational modification which is involved in a diverse set of physiologic processes throughout the cell. Of note, SUMOylation also plays a role in the pathobiology of a myriad of cancers, one of which is glioblastoma (GBM). Accordingly, herein, we review core aspects of SUMOylation as it relates to GBM and in so doing highlight putative methods/modalities capable of therapeutically engaging the pathway for treatment of this deadly neoplasm.
Identification and Characterization of Four Autophagy-Related Genes That Are Expressed in Response to Hypoxia in the Brain of the Oriental River Prawn (Macrobrachium nipponense)
Authors: Sun Shengming , Wu Ying , Fu Hongtuo , Ge Xianping , You Hongzheng , Wu Xugan
Published: April 2019

Autophagy is a cytoprotective mechanism triggered in response to adverse environmental conditions. Herein, we investigated the autophagy process in the oriental river prawn (Macrobrachium nipponense) following hypoxia. Full-length cDNAs encoding autophagy-related genes (ATGs) ATG3, ATG4B, ATG5, and ATG9A were cloned, and transcription following hypoxia was explored in different tissues and developmental stages. The ATG3, ATG4B, ATG5, and ATG9A cDNAs include open reading frames encoding proteins of 319, 264, 268, and 828 amino acids, respectively. The four M. nipponense proteins clustered separately from vertebrate homologs in phylogenetic analysis. All four mRNAs were expressed in various tissues, with highest levels in brain and hepatopancreas. Hypoxia up-regulated all four mRNAs in a time-dependent manner. Thus, these genes may contribute to autophagy-based responses against hypoxia in M. nipponense. Biochemical analysis revealed that hypoxia stimulated anaerobic metabolism in the brain tissue. Furthermore, in situ hybridization experiments revealed that ATG4B was mainly expressed in the secretory and astrocyte cells of the brain. Silencing of ATG4B down-regulated ATG8 and decreased cell viability in juvenile prawn brains following hypoxia. Thus, autophagy is an adaptive response protecting against hypoxia in M. nipponense and possibly other crustaceans. Recombinant MnATG4B could interact with recombinant MnATG8, but the GST protein could not bind to MnATG8. These findings provide us with a better understanding of the fundamental mechanisms of autophagy in prawns.
Cognizance of Molecular Methods for the Generation of Mutagenic Phage Display Antibody Libraries for Affinity Maturation
Authors: Lim Chia Chiu , Choong Yee Siew , Lim Theam Soon
Published: April 2019

Antibodies leverage on their unique architecture to bind with an array of antigens. The strength of interaction has a direct relation to the affinity of the antibodies towards the antigen. In vivo affinity maturation is performed through multiple rounds of somatic hypermutation and selection in the germinal centre. This unique process involves intricate sequence rearrangements at the gene level via molecular mechanisms. The emergence of in vitro display technologies, mainly phage display and recombinant DNA technology, has helped revolutionize the way antibody improvements are being carried out in the laboratory. The adaptation of molecular approaches in vitro to replicate the in vivo processes has allowed for improvements in the way recombinant antibodies are designed and tuned. Combinatorial libraries, consisting of a myriad of possible antibodies, are capable of replicating the diversity of the natural human antibody repertoire. The isolation of target-specific antibodies with specific affinity characteristics can also be accomplished through modification of stringent protocols. Despite the ability to screen and select for high-affinity binders, some ‘fine tuning’ may be required to enhance antibody binding in terms of its affinity. This review will provide a brief account of phage display technology used for antibody generation followed by a summary of different combinatorial library characteristics. The review will focus on available strategies, which include molecular approaches, next generation sequencing, and in silico approaches used for antibody affinity maturation in both therapeutic and diagnostic applications.
Pyridine-2,6-Dicarboxylic Acid Esters (pydicR2) as O,N,O-Pincer Ligands in CuII Complexes
Authors: Butsch Katharina , Sandleben Aaron , Dokoohaki Maryam Heydari , Zolghadr Amin Reza , Klein Axel
Published: April 2019

The pyridine-2,6-carboxylic esters pydicR2 with R = Me or Ph form the unprecedented mononuclear CuII complexes [Cu(pydicR2)Cl3]− in one-pot reactions starting from pyridine-2,6-carboxychloride pydicCl2, CuII chloride, and NEt3 in MeOH or PhOH solution under non-aqueous conditions. The triethylammonium salts (HNEt3)[Cu(pydicR2)Cl3] were isolated. The methyl derivative could be crystallized to allow a XRD structure determination. Both structures were optimized using DFT calculations in various surroundings ranging from gas phase and the non-coordinating solvent CH2Cl2 to the weakly coordinating acetone and well-coordinating solvents acetonitrile (MeCN) or dimethylformamide (DMF), while detailed calculation showed the charge distribution, dipole moments, and HOMO–LUMO gap energies changing upon solvation. According to these calculations, the ion pairs and the anionic CuII complexes were stable, which shows only Cu–Cl bond elongation and weakening of the charge transfer between the anionic complex and the cation as solvents become polar. Synthesis attempts in the presence of water yielded the CuII complexes [Cu(pydic)(OH2)2]n and [Cu(OH2)6][{Cu(pydic)}2(µ-Cl)2], which results from pydicCl2 hydrolysis. Alternatively, the new pydic(IPh)2 (IPh = 2-iodo-phenyl) ester ligand was synthesized and reacted with anhydrous CuCl2, which yields the new binuclear complex [{Cu(pydic(IPh)2)Cl}2(µ-Cl)2]. EPR spectroscopy of the solid compounds reveals typical axial spectra in line with the observed and DFT calculated geometries. Cyclic voltammetry and UV–vis absorption spectroscopy in solution are in line with un-dissociated complex species [Cu(pydicR2)Cl3]−.
Hemipteran Pests of Sugarcane in North America
Authors: Wilson Blake E.
Published: April 2019

Piercing-sucking herbivores (Insecta: Hemiptera) represent one of the greatest threats to agricultural production worldwide. Hemipteran pests directly injure plants as well as vector disease-causing plant pathogens. Production of sugarcane (Saccharum spp.) in North America is impacted by a complex of Hemiptera including the sugarcane aphid, Melanaphis sacchari Zehntner (Aphididae); yellow sugarcane aphid, Sipha flava (Forbes) (Aphididae); West Indian canefly, Saccharosydne saccharivora (Westwood) (Delphacidae); sugarcane delphacid, Perkinsiella saccharicida Kirkaldy (Delphacidae); and sugarcane lace bug, Leptodictya tabida (Herric-Schaeffer) (Tingidae). None of these pests is consistently damaging to large amounts of sugarcane acreage, but regional outbreaks are common. The biology, ecology, and pest management of these insects are discussed with emphasis on North America sugarcane production.
Repetitive Transcranial Magnetic Stimulation Therapy (rTMS) for Endometriosis Patients with Refractory Pelvic Chronic Pain: A Pilot Study
Authors: Pinot-Monange Anne , Moisset Xavier , Chauvet Pauline , Gremeau Anne-Sophie , Comptour Aurélie , Canis Michel , Pereira Bruno , Bourdel Nicolas
Published: April 2019

Endometriosis concerns more than 10% of women of reproductive age, frequently leading to chronic pelvic pain. Repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) induces an analgesic effect. This effect on chronic pelvic pain is yet to be evaluated. The objective of this study was to assess the feasibility and effect of rTMS to reduce pain and improve quality of life (QoL) in patients with chronic pelvic pain due to endometriosis. This pilot, open-labelled prospective trial examined treatment by neuronavigated rTMS over M1, one session per day for 5 consecutive days. Each session consisted of 1.500 pulses at 10 Hz. We assessed tolerance, pain change and QoL until 4 weeks post treatment with a primary endpoint at day 8. Twelve women were included. No patients experienced serious adverse effects or a significant increase in pain. Nine women reported improvement on the Patient Global Impression of Change with a reduction in both pain intensity and pain interference (5.1 ± 1.4 vs. 4.1 ± 1.6, p = 0.01 and 6.2 ± 2.1 vs. 4.2 ± 1.5, p = 0.004, respectively). rTMS appears well tolerated and might be of interest for patients suffering from chronic pelvic pain for whom other treatments have failed. A randomized controlled trial is mandatory before proposing such treatment.