bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruptive Technologies for Environment and Health Research: An Overview of Artificial Intelligence, Blockchain, and Internet of Things
Authors: M. Bublitz Frederico , Oetomo Arlene , S. Sahu Kirti , Kuang Amethyst , X. Fadrique Laura , E. Velmovitsky Pedro , M. Nobrega Raphael , P. Morita Plinio
Published: October 2019

The purpose of this descriptive research paper is to initiate discussions on the use of innovative technologies and their potential to support the research and development of pan-Canadian monitoring and surveillance activities associated with environmental impacts on health and within the health system. Its primary aim is to provide a review of disruptive technologies and their current uses in the environment and in healthcare. Drawing on extensive experience in population-level surveillance through the use of technology, knowledge from prior projects in the field, and conducting a review of the technologies, this paper is meant to serve as the initial steps toward a better understanding of the research area. In doing so, we hope to be able to better assess which technologies might best be leveraged to advance this unique intersection of health and environment. This paper first outlines the current use of technologies at the intersection of public health and the environment, in particular, Artificial Intelligence (AI), Blockchain, and the Internet of Things (IoT). The paper provides a description for each of these technologies, along with a summary of their current applications, and a description of the challenges one might face with adopting them. Thereafter, a high-level reference architecture, that addresses the challenges of the described technologies and could potentially be incorporated into the pan-Canadian surveillance system, is conceived and presented.
Time Varying Spillovers between the Online Search Volume and Stock Returns: Case of CESEE Markets
Authors: Škrinjarić Tihana
Published: October 2019

This research observes a time varying relationship between stock returns, volatilities and the online search volume in regard to selected CESEE (Central, Eastern and South-Eastern European) stock markets. The main hypothesis of the research assumes that a feedback relationship exists between stock returns, volatilities and the investor’s attention variable (captured by the online search volume). Moreover, the relationship is assumed to be time varying due to changing market conditions. Previous research does not deal with the time-varying multi-directional relationship. Thus, the contribution to existing research consists of estimating the aforementioned relationship between return, volatility and the search volume series for selected CESEE countries by using a novel approach of spillover indices within the VAR (Vector AutoRegression) model framework. The results indicate that the Google search volume affects the risk series more than the return series on the selected markets.
Interactions between Bus, Metro, and Taxi Use before and after the Chinese Spring Festival
Authors: Huang Jianwei , Liu Xintao , Zhao Pengxiang , Zhang Junwei , Kwan Mei-Po
Published: October 2019

Public transport plays an important role in developing sustainable cities. A better understanding of how different public transit modes (bus, metro, and taxi) interact with each other will provide better sustainable strategies to transport and urban planners. However, most existing studies are either limited to small-scale surveys or focused on the identification of general interaction patterns during times of regular traffic. Transient demographic changes in a city (i.e., many people moving out and in) can lead to significant changes in such interaction patterns and provide a useful context for better investigating the changes in these patterns. Despite that, little has been done to explore how such interaction patterns change and how they are linked to the built environment from the perspective of transient demographic changes using urban big data. In this paper, the tap-in-tap-out smart card data of bus/metro and taxi GPS trajectory data before and after the Chinese Spring Festival in Shenzhen, China, are used to explore such interaction patterns. A time-series clustering method and an elasticity change index (ECI) are adopted to detect the changing transit mode patterns and the underlying dynamics. The findings indicate that the interactions between different transit modes vary over space and time and are competitive or complementary in different parts of the city. Both ordinary least-squares (OLS) and geographically weighted regression (GWR) models with built environment variables are used to reveal the impact of changes in different transit modes on ECIs and their linkage with the built environment. The results of this study will contribute to the planning and design of multi-modal transport services.
Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles
Authors: King Jennifer R. , Wilson Melissa L. , Hetey Szabolcs , Kiraly Peter , Matsuo Koji , Castaneda Antonio V. , Toth Eszter , Krenacs Tibor , Hupuczi Petronella , Mhawech-Fauceglia Paulette , Balogh Andrea , Szilagyi Andras , Matko Janos , Papp Zoltan , Roman Lynda D. , Cortessis Victoria K. , Than Nandor Gabor
Published: October 2019

Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 × 10−6), and immune genes (OR = 1.82, p = 7.34 × 10−18), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. “Cytokine–cytokine receptor interaction” was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs.
Different Forms of TFF3 in the Human Saliva: Heterodimerization with IgG Fc Binding Protein (FCGBP)
Authors: Houben Till , Harder Sönke , Schlüter Harmut , Kalbacher Hubert , Hoffmann Werner
Published: October 2019

The peptide TFF3 is a member of a family of secretory lectins, and is typically synthesized by mucous epithelia together with mucins. It is mainly released from intestinal goblet cells as a high-molecular mass heterodimer with IgG Fc binding protein (FCGBP). Herein, we investigated human saliva by fast protein liquid chromatography (FPLC) and proteomics and identified high- and low-molecular-mass forms of TFF3. Whereas the high-molecular-mass forms represent a heterodimer with FCGBP, the low-molecular-mass forms represent homodimeric TFF3 forms. Proteomic analysis also revealed a C-terminally truncated form of TFF3. We hypothesize that salivary TFF3-FCGBP might play a role in the innate immune defense of the oral cavity and that TFF3 might also bind to microbial glycans. The known interaction of TFF3 with the agglutinin DMBT-1, a typical constituent of human saliva, further supports this protective role.
Receptor Heterodimerization and Co-Receptor Engagement in TLR2 Activation Induced by MIC1 and MIC4 from Toxoplasma gondii
Authors: Costa Mendonça-Natividade Flávia , Duque Lopes Carla , Ricci-Azevedo Rafael , Sardinha-Silva Aline , Figueiredo Pinzan Camila , Paiva Alegre-Maller Ana , L. Nohara Lilian , B. Carneiro Alan , Panunto-Castelo Ademilson , C. Almeida Igor , Roque-Barreira Maria
Published: October 2019

The microneme organelles of Toxoplasma gondii tachyzoites release protein complexes (MICs), including one composed of the transmembrane protein MIC6 plus MIC1 and MIC4. In this complex, carbohydrate recognition domains of MIC1 and MIC4 are exposed and interact with terminal sialic acid and galactose residues, respectively, of host cell glycans. Recently, we demonstrated that MIC1 and MIC4 binding to the N-glycans of Toll-like receptor (TLR) 2 and TLR4 on phagocytes triggers cell activation and pro-inflammatory cytokine production. Herein, we investigated the requirement for TLR2 heterodimerization and co-receptors in MIC-induced responses, as well as the signaling molecules involved. We used MICs to stimulate macrophages and HEK293T cells transfected with TLR2 and TLR1 or TLR6, both with or without the co-receptors CD14 and CD36. Then, the cell responses were analyzed, including nuclear factor-kappa B (NF-κB) activation and cytokine production, which showed that (1) only TLR2, among the studied factors, is crucial for MIC-induced cell activation; (2) TLR2 heterodimerization augments, but is not critical for, activation; (3) CD14 and CD36 enhance the response to MIC stimulus; and (4) MICs activate cells through a transforming growth factor beta-activated kinase 1 (TAK1)-, mammalian p38 mitogen-activated protein kinase (p38)-, and NF-κB-dependent pathway. Remarkably, among the studied factors, the interaction of MIC1 and MIC4 with TLR2 N-glycans is sufficient to induce cell activation, which promotes host protection against T. gondii infection.
TGF-β Signaling in Cellular Senescence and Aging-Related Pathology
Authors: Tominaga Kana , Suzuki Hiroshi I.
Published: October 2019

Aging is broadly defined as the functional decline that occurs in all body systems. The accumulation of senescent cells is considered a hallmark of aging and thought to contribute to the aging pathologies. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that regulates a myriad of cellular processes and has important roles in embryonic development, physiological tissue homeostasis, and various pathological conditions. TGF-β exerts potent growth inhibitory activities in various cell types, and multiple growth regulatory mechanisms have reportedly been linked to the phenotypes of cellular senescence and stem cell aging in previous studies. In addition, accumulated evidence has indicated a multifaceted association between TGF-β signaling and aging-associated disorders, including Alzheimer’s disease, muscle atrophy, and obesity. The findings regarding these diseases suggest that the impairment of TGF-β signaling in certain cell types and the upregulation of TGF-β ligands contribute to cell degeneration, tissue fibrosis, inflammation, decreased regeneration capacity, and metabolic malfunction. While the biological roles of TGF-β depend highly on cell types and cellular contexts, aging-associated changes are an important additional context which warrants further investigation to better understand the involvement in various diseases and develop therapeutic options. The present review summarizes the relationships between TGF-β signaling and cellular senescence, stem cell aging, and aging-related diseases.
Effects of Dietary Bisphenol A on the Reproductive Function of Gilthead Sea Bream (Sparus aurata) Testes
Authors: Forner-Piquer Isabel , Fakriadis Ioannis , Mylonas Constantinos C , Piscitelli Fabiana , Di Marzo Vincenzo , Maradonna Francesca , Calduch-Giner Josep , Pérez-Sánchez Jaume , Carnevali Oliana
Published: October 2019

Bisphenol A (BPA), a known endocrine disrupting chemical (EDC), was administered by diet to gilthead sea bream (Sparus aurata) in order to study its effects on the endocannabinoid system (ECS) and gonadal steroidogenesis. 2-year-old male gilthead sea bream were fed with two different concentrations of BPA (LOW at 4 and HIGH at 4000 µg/kg body weight for 21 days during the reproductive season. Exposure to 4000 µg BPA/kg bw/day (BPA HIGH) reduced sperm motility and altered the straight-line velocity (VSL) and linearity (LIN). Effects on steroidogenesis were evident, with testosterone (T) being up-regulated by both treatments and 11-ketotestosterone (11-KT) down-regulated by BPA HIGH. Plasma levels of 17β-estradiol (E2) were not affected. The Gonadosomatic Index (GSI) increased in the BPA HIGH group. Interestingly, the levels of endocannabinoids and endocannabinoid-like compounds were significantly reduced after both treatments. Unpredictably, a few changes were noticed in the expression of genes coding for ECS enzymes, while the receptors were up-regulated depending on the BPA dose. Reproductive markers in testis (leptin receptor (lepr), estrogen receptors (era, erb), progesterone receptors (pr) and the gonadotropin releasing hormone receptor (gnrhr)) were up-regulated. BPA induced the up-regulation of the hepatic genes involved in oogenesis (vitellogenin (vtg) and zona pellucida 1 (zp1)).
Insulin Receptor Trafficking: Consequences for Insulin Sensitivity and Diabetes
Authors: Chen Yang , Huang Lili , Qi Xinzhou , Chen Chen
Published: October 2019

Insulin receptor (INSR) has been extensively studied in the area of cell proliferation and energy metabolism. Impaired INSR activities lead to insulin resistance, the key factor in the pathology of metabolic disorders including type 2 diabetes mellitus (T2DM). The mainstream opinion is that insulin resistance begins at a post-receptor level. The role of INSR activities and trafficking in insulin resistance pathogenesis has been largely ignored. Ligand-activated INSR is internalized and trafficked to early endosome (EE), where INSR is dephosphorylated and sorted. INSR can be subsequently conducted to lysosome for degradation or recycled back to the plasma membrane. The metabolic fate of INSR in cellular events implies the profound influence of INSR on insulin signaling pathways. Disruption of INSR-coupled activities has been identified in a wide range of insulin resistance-related diseases such as T2DM. Accumulating evidence suggests that alterations in INSR trafficking may lead to severe insulin resistance. However, there is very little understanding of how altered INSR activities undermine complex signaling pathways to the development of insulin resistance and T2DM. Here, we focus this review on summarizing previous findings on the molecular pathways of INSR trafficking in normal and diseased states. Through this review, we provide insights into the mechanistic role of INSR intracellular processes and activities in the development of insulin resistance and diabetes.
Methotrexate an Old Drug with New Tricks
Authors: Bedoui Yosra , Guillot Xavier , Sélambarom Jimmy , Guiraud Pascale , Giry Claude , Jaffar-Bandjee Marie Christine , Ralandison Stéphane , Gasque Philippe
Published: October 2019

Methotrexate (MTX) is the first line drug for the treatment of a number of rheumatic and non-rheumatic disorders. It is currently used as an anchor disease, modifying anti-rheumatic drug in the treatment of rheumatoid arthritis (RA). Despite the development of numerous new targeted therapies, MTX remains the backbone of RA therapy due to its potent efficacy and tolerability. There has been also a growing interest in the use of MTX in the treatment of chronic viral mediated arthritis. Many viruses—including old world alphaviruses, Parvovirus B19, hepatitis B/C virus, and human immunodeficiency virus—have been associated with arthritogenic diseases and reminiscent of RA. MTX may provide benefits although with the potential risk of attenuating patients’ immune surveillance capacities. In this review, we describe the emerging mechanisms of action of MTX as an anti-inflammatory drug and complementing its well-established immunomodulatory activity. The mechanisms involve adenosine signaling modulation, alteration of cytokine networks, generation of reactive oxygen species and HMGB1 alarmin suppression. We also provide a comprehensive understanding of the mechanisms of MTX toxic effects. Lastly, we discussed the efficacy, as well as the safety, of MTX used in the management of viral-related rheumatic syndromes.
Andrographolide Ameliorates Rheumatoid Arthritis by Regulating the Apoptosis–NETosis Balance of Neutrophils
Authors: Li Xiaohong , Yuan Kai , Zhu Qingqing , Lu Qingyi , Jiang Haixu , Zhu Mengmeng , Huang Guangrui , Xu Anlong
Published: October 2019

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis with swelling and pain at synovial joints. In RA patients, delayed neutrophil apoptosis amplifies the inflammatory response and massively released neutrophil extracellular traps (NETs) induce tissue damage and provide self-antigens. Andrographolide (AD) is the major active labdane diterpenoid derived from Andrographis paniculata, which has multiple pharmacological effects, including hepatoprotection, anti-angiogenesis, anti-thrombosis, and anti-inflammation. In the present study, we investigated the effect of AD on an adjuvant-induced arthritis (AA) murine model of RA and found that AD alleviated murine arthritis by reducing neutrophil infiltration and NETosis in the ankle joints and relieved the systematic inflammation. In vitro experiments showed that AD accelerated the apoptosis of lipopolysaccharide-activated neutrophils and inhibited autophagy-dependent extracellular traps formation of neutrophils. These findings suggest that AD has considerable potential for RA therapy.
Species-Specific Glucose-6-Phosphatase Activity in the Small Intestine—Studies in Three Different Mammalian Models
Authors: Varga Viola , Murányi Zsófia , Kurucz Anita , Marcolongo Paola , Benedetti Angelo , Bánhegyi Gábor , Margittai Éva
Published: October 2019

Besides the liver, which has always been considered the major source of endogenous glucose production in all post-absorptive situations, kidneys and intestines can also produce glucose in blood, particularly during fasting and under protein feeding. However, observations gained in different experimental animals have given ambiguous results concerning the presence of the glucose-6-phosphatase system in the small intestine. The aim of this study was to better define the species-related differences of this putative gluconeogenic organ in glucose homeostasis. The components of the glucose-6-phosphatase system (i.e., glucose-6-phosphate transporter and glucose-6-phosphatase itself) were analyzed in homogenates or microsomal fractions prepared from the small intestine mucosae and liver of rats, guinea pigs, and humans. Protein and mRNA levels, as well as glucose-6-phosphatase activities, were detected. The results showed that the glucose-6-phosphatase system is poorly represented in the small intestine of rats; on the other hand, significant expressions of glucose-6-phosphate transporter and of the glucose-6-phosphatase were found in the small intestine of guinea pigs and homo sapiens. The activity of the recently described fructose-6-phosphate transporter–intraluminal hexose isomerase pathway was also present in intestinal microsomes from these two species. The results demonstrate that the gluconeogenic role of the small intestine is highly species-specific and presumably dependent on feeding behavior (e.g., fructose consumption) and the actual state of metabolism.
Liver X Receptors Regulate Cholesterol Metabolism and Immunity in Hepatic Nonparenchymal Cells
Authors: Endo-Umeda Kaori , Makishima Makoto
Published: October 2019

Excess dietary cholesterol intake and the dysregulation of cholesterol metabolism are associated with the pathogenesis and progression of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and fibrosis. Hepatic accumulation of free cholesterol induces activation of nonparenchymal cells, including Kupffer cells, macrophages, and hepatic stellate cells, which leads to persistent inflammation and fibrosis. The nuclear receptors liver X receptor α (LXRα) and LXRβ act as negative regulators of cholesterol metabolism through the induction of hepatocyte cholesterol catabolism, excretion, and the reverse cholesterol transport pathway. Additionally, LXRs exert an anti-inflammatory effect in immune cell types, such as macrophages. LXR activation suppresses acute hepatic inflammation that is mediated by Kupffer cells/macrophages. Acute liver injury, diet-induced steatohepatitis, and fibrosis are exacerbated by significant hepatic cholesterol accumulation and inflammation in LXR-deficient mice. Therefore, LXRs regulate hepatic lipid metabolism and immunity and they are potential therapeutic targets in the treatment of hepatic inflammation that is associated with cholesterol accumulation.
Chloroplasts— Beyond Energy Capture and Carbon Fixation: Tuning of Photosynthesis in Response to Chilling Stress
Authors: Gan Ping , Liu Fang , Li Rongbai , Wang Shaokui , Luo Jijing
Published: October 2019

As organelles for photosynthesis in green plants, chloroplasts play a vital role in solar energy capture and carbon fixation. The maintenance of normal chloroplast physiological functions is essential for plant growth and development. Low temperature is an adverse environmental stress that affects crop productivity. Low temperature severely affects the growth and development of plants, especially photosynthesis. To date, many studies have reported that chloroplasts are not only just organelles of photosynthesis. Chloroplasts can also perceive chilling stress signals via membranes and photoreceptors, and they maintain their homeostasis and promote photosynthesis by regulating the state of lipid membranes, the abundance of photosynthesis-related proteins, the activity of enzymes, the redox state, and the balance of hormones and by releasing retrograde signals, thus improving plant resistance to low temperatures. This review focused on the potential functions of chloroplasts in fine tuning photosynthesis processes under low-temperature stress by perceiving stress signals, modulating the expression of photosynthesis-related genes, and scavenging excess reactive oxygen species (ROS) in chloroplasts to survive the adverse environment.
Prevalence of ABCA4 Deep-Intronic Variants and Related Phenotype in An Unsolved “One-Hit” Cohort with Stargardt Disease
Authors: Nassisi Marco , Mohand-Saïd Saddek , Andrieu Camille , Antonio Aline , Condroyer Christel , Méjécase Cécile , Varin Juliette , Wohlschlegel Juliette , Dhaenens Claire-Marie , Sahel José-Alain , Zeitz Christina , Audo Isabelle
Published: October 2019

We investigated the prevalence of reported deep-intronic variants in a French cohort of 70 patients with Stargardt disease harboring a monoallelic pathogenic variant on the exonic regions of ABCA4. Direct Sanger sequencing of selected intronic regions of ABCA4 was conducted. Complete phenotypic analysis and correlation with the genotype was performed in case a known intronic pathogenic variant was identified. All other variants found on the analyzed sequences were queried for minor allele frequency and possible pathogenicity by in silico predictions. The second mutated allele was found in 14 (20%) subjects. The three known deep-intronic variants found were c.5196+1137G>A in intron 36 (6 subjects), c.4539+2064C>T in intron 30 (4 subjects) and c.4253+43G>A in intron 28 (4 subjects). Even though the phenotype depends on the compound effect of the biallelic variants, a genotype-phenotype correlation suggests that the c.5196+1137G>A was mostly associated with a mild phenotype and the c.4539+2064C>T with a more severe one. A variable effect was instead associated with the variant c.4253+43G>A. In addition, two novel variants, c.768+508A>G and c.859-245_859-243delinsTGA never associated with Stargardt disease before, were identified and a possible splice defect was predicted in silico. Our study calls for a larger cohort analysis including targeted locus sequencing and 3D protein modeling to better understand phenotype-genotype correlations associated with deep-intronic changes and patients’ selection for clinical trials.
Extracellular Matrix in Regulation of Contractile System in Cardiomyocytes
Authors: Bildyug Natalya
Published: October 2019

The contractile apparatus of cardiomyocytes is considered to be a stable system. However, it undergoes strong rearrangements during heart development as cells progress from their non-muscle precursors. Long-term culturing of mature cardiomyocytes is also accompanied by the reorganization of their contractile apparatus with the conversion of typical myofibrils into structures of non-muscle type. Processes of heart development as well as cell adaptation to culture conditions in cardiomyocytes both involve extracellular matrix changes, which appear to be crucial for the maturation of contractile apparatus. The aim of this review is to analyze the role of extracellular matrix in the regulation of contractile system dynamics in cardiomyocytes. Here, the remodeling of actin contractile structures and the expression of actin isoforms in cardiomyocytes during differentiation and adaptation to the culture system are described along with the extracellular matrix alterations. The data supporting the regulation of actin dynamics by extracellular matrix are highlighted and the possible mechanisms of such regulation are discussed.
Post Synthetic Defect Engineering of UiO-66 Metal–Organic Framework with An Iridium(III)-HEDTA Complex and Application in Water Oxidation Catalysis
Authors: Gatto Giordano , Macchioni Alceo , Bondi Roberto , Marmottini Fabio , Costantino Ferdinando
Published: October 2019

Clean production of renewable fuels is a great challenge of our scientific community. Iridium complexes have demonstrated a superior catalytic activity in the water oxidation (WO) reaction, which is a crucial step in water splitting process. Herein, we have used a defective zirconium metal–organic framework (MOF) with UiO-66 structure as support of a highly active Ir complex based on EDTA with the formula [Ir(HEDTA)Cl]Na. The defects are induced by the partial substitution of terephthalic acid with smaller formate groups. Anchoring of the complex occurs through a post-synthetic exchange of formate anions, coordinated at the zirconium clusters of the MOF, with the free carboxylate group of the [Ir(HEDTA)Cl]− complex. The modified material was tested as a heterogeneous catalyst for the WO reaction by using cerium ammonium nitrate (CAN) as the sacrificial agent. Although turnover frequency (TOF) and turnover number (TON) values are comparable to those of other iridium heterogenized catalysts, the MOF exhibits iridium leaching not limited at the first catalytic run, as usually observed, suggesting a lack of stability of the hybrid system under strong oxidative conditions.
GeV-Class Two-Fold CW Linac Driven by an Arc-Compressor
Authors: Bacci Alberto , Bosotti Angelo , Di Mitri Simone , Drebot Illya , Faillace Luigi , Michelato Paolo , Monaco Laura , Opromolla Michele , Paparella Rocco , Petrillo Vittoria , Rossetti Conti Marcello , Rossi Andrea Renato , Serafini Luca , Sertore Daniele
Published: October 2019

We present a study of an innovative scheme to generate high repetition rate (MHz-class) GeV electron beams by adopting a two-pass two-way acceleration in a super-conducting Linac operated in Continuous Wave (CW) mode. The beam is accelerated twice in the Linac by being re-injected, after the first pass, in opposite direction of propagation. The task of recirculating the electron beam is performed by an arc compressor composed by 14 Double Bend Achromat (DBA). In this paper, we study the main issues of the two-fold acceleration scheme, the electron beam quality parameters preservation (emittance, energy spread), together with the bunch compression performance of the arc compressor, aiming to operate an X-ray Free Electron Laser. The requested power to supply the cryogenic plant and the RF sources is also significantly reduced w.r.t a conventional one-pass SC Linac for the same final energy.
Delayed Stroke after Aneurysm Treatment with Flow Diverters in Small Cerebral Vessels: A Potentially Critical Complication Caused by Subacute Vasospasm
Authors: Schob Stefan , Richter Cindy , Scherlach Cordula , Lindner Dirk , Planitzer Uwe , Hamerla Gordian , Ziganshyna Svitlana , Werdehausen Robert , Struck Manuel Florian , Schob Bernd , Gaber Khaled , Meixensberger Jürgen , Hoffmann Karl-Titus , Quäschling Ulf
Published: October 2019

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment.
Gait Classification in Unilateral Cerebral Palsy
Authors: Tsitlakidis Stefanos , Horsch Axel , Schaefer Felix , Westhauser Fabian , Goetze Marco , Hagmann Sebastien , Klotz Matthias C. M.
Published: October 2019

As unilateral cerebral palsy represents a complex disorder, gait classification is difficult. Knowledge of the most frequent gait patterns and functional impairment is crucial for proper decision-making. This study analyzes the prevalence of gait patterns as well as the relation of different gait patterns and the Gross Motor Function Classification System (GMFCS). Eighty-nine patients were classified retrospectively using the GMFCS, the classification of Winters, Gage, and Hicks (WGH), and Sutherland et al. The distribution of GMFCS levels among the different gait patterns was analyzed using Chi-squared test. The most common subtypes were GMFCS level I, WGH type I, and recurvatum knee. Seventeen percent (WGH) and 59% (Sutherland) of the patients did not match any criteria. Applying both classifications complementarily reduced the number of unclassified patients significantly. There was no significant difference concerning the distribution of GMFCS levels or age among the different gait patterns. A combined use of various classification systems is beneficial for proper decision-making. Unclassified patients seem to be a heterogeneous subgroup concerning functional impairment. There is a need of further characterization of the unclassifiable gait patterns and the caused functional impairment. Instrumented gait analysis remains the gold standard and should be broadly used for future studies and in clinical practice.
The Relationship between Sleep Bruxism and Obstructive Sleep Apnea Based on Polysomnographic Findings
Authors: Martynowicz Helena , Gac Pawel , Brzecka Anna , Poreba Rafal , Wojakowska Anna , Mazur Grzegorz , Smardz Joanna , Wieckiewicz Mieszko
Published: October 2019

Obstructive sleep apnea (OSA) is the most common sleep disorder. Sleep bruxism (SB) is a masticatory muscle activity during sleep that commonly co-occurs with OSA. The presented study aimed to assess this relationship and to identify factors affecting this co-occurrence. Adult patients (n = 110) were evaluated for OSA and SB in a sleep laboratory using polysomnography. The episodes of bruxism and respiratory events were scored according to the standards of the American Academy of Sleep Medicine. The prevalence of OSA and SB was found to be 86.37% and 50%, respectively. The bruxism episode index (BEI) was increased in the group with mild and moderate OSA (apnea–hypopnea index (AHI) <30) compared to that in the group with severe OSA (AHI ≥ 30) (5.50 ± 4.58 vs. 1.62 ± 1.28, p < 0.05). A positive correlation between AHI and BEI was observed in the group with AHI < 30. Regression analysis indicated that higher AHI, male gender, and diabetes were independent predictors for the increased BEI in group with AHI < 30. The relationship between OSA and SB depends on the degree of severity of OSA. OSA is correlated with SB in mild and moderate cases of OSA in the group of patients with increased risk of OSA.
New Imaging Markers of Clinical Outcome in Asymptomatic Patients with Severe Aortic Regurgitation
Authors: Kočková Radka , Línková Hana , Hlubocká Zuzana , Pravečková Alena , Polednová Andrea , Súkupová Lucie , Bláha Martin , Malý Jiří , Honsová Eva , Sedmera David , Pěnička Martin
Published: October 2019

Background: Determining the value of new imaging markers to predict aortic valve (AV) surgery in asymptomatic patients with severe aortic regurgitation (AR) in a prospective, observational, multicenter study. Methods: Consecutive patients with chronic severe AR were enrolled between 2015–2018. Baseline examination included echocardiography (ECHO) with 2- and 3-dimensional (2D and 3D) vena contracta area (VCA), and magnetic resonance imaging (MRI) with regurgitant volume (RV) and fraction (RF) analyzed in CoreLab. Results: The mean follow-up was 587 days (interquartile range (IQR) 296–901) in a total of 104 patients. Twenty patients underwent AV surgery. Baseline clinical and laboratory data did not differ between surgically and medically treated patients. Surgically treated patients had larger left ventricular (LV) dimension, end-diastolic volume (all p < 0.05), and the LV ejection fraction was similar. The surgical group showed higher prevalence of severe AR (70% vs. 40%, p = 0.02). Out of all imaging markers 3D VCA, MRI-derived RV and RF were identified as the strongest independent predictors of AV surgery (all p < 0.001). Conclusions: Parameters related to LV morphology and function showed moderate accuracy to identify patients in need of early AV surgery at the early stage of the disease. 3D ECHO-derived VCA and MRI-derived RV and RF showed high accuracy and excellent sensitivity to identify patients in need of early surgery.
Long Term Follow-Up of 103 Untreated Adult Patients with Type 1 Gaucher Disease
Authors: Dinur Tama , Zimran Ari , Becker-Cohen Michal , Arkadir David , Cozma Claudia , Hovakimyan Marina , Oppermann Sebastian , Demuth Laura , Rolfs Arndt , Revel-Vilk Shoshana
Published: October 2019

The introduction of disease-specific therapy for patients with type I Gaucher disease (GD1) was a revolution in the management of patients, but not without cost. Thus, the management of mildly affected patients is still debated. We herein report a long-term follow-up (median (range) of 20 (5–58) years) of 103 GD1 patients who have never received enzymatic or substrate reduction therapy. The median (range) platelet count and hemoglobin levels in last assessment of all but six patients who refused therapy (although recommended and approved) were 152 (56–408) × 103/mL and 13.1 (7.6–16.8) g/dL, respectively. Most patients had mild hepatosplenomegaly. Nine patients were splenectomized. No patient developed clinical bone disease. The median (range) lyso-Gb1 levels at last visit was 108.5 (8.1–711) ng/mL; lowest for patients with R496H/other and highest for patients refusing therapy. This rather large cohort with long follow-up confirms that mildly affected patients may remain stable for many years without GD-specific therapy. The challenge for the future, when newborn screening may detect all patients, is to be able to predict which of the early diagnosed patients is at risk for disease-related complications and therefore for early treatment, and who may remain asymptomatic or minimally affected with no need for disease-specific therapy.
Revealing Associations between Diagnosis Patterns and Acupoint Prescriptions Using Medical Data Extracted from Case Reports
Authors: Kim Cheol-Han , Yoon Da-Eun , Lee Ye-Seul , Jung Won-Mo , Kim Joo-Hee , Chae Younbyoung
Published: October 2019

Objective: The optimal acupoints for a particular disease can be determined by analysis of diagnosis patterns. The objective of this study was to reveal the association between such patterns and the acupoints prescribed in clinical practice using medical data extracted from case reports. Methods: This study evaluated online virtual diagnoses made by currently practicing Korean medical doctors (N = 80). The doctors were presented with 10 case reports published in Korean medical journals and were asked to diagnose the patients and prescribe acupoints accordingly. A network analysis and the term frequency-inverse document frequency (tf-idf) method were used to analyse and quantify the relationship between diagnosis patterns and prescribed acupoints. Results: The network analysis showed that ST36, LI4, LR3, and SP6 were the most frequently used acupoints across all diagnoses. The tf-idf values showed the acupoints used for specific diseases, such as BL40 for bladder disease and LU9 for lung disease. Conclusions: The associations between diagnosis patterns and prescribed acupoints were identified using an online virtual diagnosis modality. Network and text mining analyses revealed commonly applied and disease-specific acupoints in both qualitative and quantitative terms.
Polyphenol-Rich Extracts from Toona sinensis Bark and Fruit Ameliorate Free Fatty Acid-Induced Lipogenesis through AMPK and LC3 Pathways
Authors: Chen Yung-Chia , Chen Hsin-Ju , Huang Bu-Miin , Chen Yu-Chi , Chang Chi-Fen
Published: October 2019

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease found worldwide. The present study aimed to evaluate the mechanisms of inhibiting lipid accumulation in free fatty acid (FFA)-treated HepG2 cells caused by bark and fruit extracts of Toona sinensis (TSB and TSF). FFA induced lipid and triglyceride (TG) accumulation, which was attenuated by TSB and TSF. TSB and/or TSF promoted phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-coA carboxylase and peroxisome proliferator-activated receptor alpha upregulation. Furthermore, TSB and TSF suppressed FFA-induced liver X receptor, sterol regulatory element-binding transcription protein 1, fatty acid synthase, and stearoyl-CoA desaturase 1 protein expression. Moreover, TSB and/or TSF induced phosphorylation of Unc-51 like autophagy-activating kinase and microtubule-associated protein 1A/1B-light chain 3 expressions. Therefore, TSB and TSF relieve lipid accumulation by attenuating lipogenic protein expression, activating the AMPK pathway, and upregulating the autophagic flux to enhance lipid metabolism. Moreover, TSB and TSF reduced TG contents, implying the therapeutic use of TSB and TSF in NAFLD.
Life Cycle Assessment of LNG Fueled Vessel in Domestic Services
Authors: Hwang Sangsoo , Jeong Byongug , Jung Kwanghyo , Kim Mingyu , Zhou Peilin
Published: October 2019

This research was focused on a comparative analysis of using LNG as a marine fuel with a conventional marine gas oil (MGO) from an environmental point of view. A case study was performed using a 50K bulk carrier engaged in domestic services in South Korea. Considering the energy exporting market for South Korea, the fuel supply chain was designed with the two largest suppliers: Middle East (LNG-Qatar/MGO-Saudi Arabia) and U.S. The life cycle of each fuel type was categorized into three stages: Well-to-Tank (WtT), Tank-to-Wake (TtW), and Well-to-Wake (WtW). With the process modelling, the environmental impact of each stage was analyzed based on the five environmental impact categorizes: Global Warming Potential (GWP), Acidification Potential (AP), Photochemical Potential (POCP), Eutrophication Potential (EP) and Particulate Matter (PM). Analysis results reveal that emission levels for the LNG cases are significantly lower than the MGO cases in all potential impact categories. Particularly, Case 1 (LNG import to Korea from Qatar) is identified as the best option as producing the lowest emission levels per 1.0 × 107 MJ of fuel consumption: 977 tonnages of CO2 equivalent (for GWP), 1.76 tonnages of SO2 equivalent (for AP), 1.18 tonnages of N equivalent (for EP), 4.28 tonnages of NMVOC equivalent (for POCP) and 26 kg of PM 2.5 equivalent (for PM). On the other hand, the results also point out that the selection of the fuel supply routes could be an important factor contributing to emission levels since longer distances for freight transportation result in more emissions. It is worth noting that the life cycle assessment can offer us better understanding of holistic emission levels contributed by marine fuels from the cradle to the grave, which are highly believed to remedy the shortcomings of current marine emission indicators.
Robust Adaptive Heading Control for a Ray-Type Hybrid Underwater Glider with Propellers
Authors: Nguyen Ngoc-Duc , Choi Hyeung-Sik , Lee Sung-Wook
Published: October 2019

This paper presents the modeling of a new ray-type hybrid underwater glider (RHUG) and an experimental approach used to robustly and adaptively control heading motion. The motions of the proposed RHUG are divided into vertical-plane motions and heading motion. Hydrodynamic coefficients in the vertical-plane dynamics are obtained using a computational fluid dynamics (CFD) method for various pitch angles. Due to the difficulty of obtaining accurate parameter values for the heading dynamics, a robust adaptive control algorithm was designed containing an adaptation law for the unknown parameters and robust action for minimizing environmental disturbances. For robust action against bounded disturbances, such as waves and ocean currents, sliding mode control was applied under the assumption that the bounds of the external disturbances are known. A direct adaptive algorithm for heading motion was applied in an experiment. Computer simulations of the proposed robust adaptive heading control are presented to demonstrate the robustness of the proposed control system in the presence of bounded disturbances. To verify the performance of the proposed controller for heading dynamics, several heading control experiments were conducted in a water tank and in the sea.
The Influence of Domestic and Foreign Shocks on Portfolio Diversification Gains and the Associated Risks
Authors: Narayan Seema
Published: October 2019

This paper evaluates the influence of foreign or domestic stock market return and return of volatility shocks on dynamic conditional correlations (DCCs) between international stock markets and correlation volatility, respectively. The correlations between markets have implications for the gains from portfolio diversification, while correlation volatilities can be seen as risks to portfolio diversification. Meanwhile, domestic shocks are sourced from the return and return volatility from 24 developed, emerging, and frontier stock markets. The US stock market is the source of foreign shocks. The domestic and foreign shocks are derived using market-based returns and under bearish market conditions. We estimate multivariate exponential generalized autoregressive conditional heteroskedasticity (E-GARCH) models using daily and monthly MSCI based stock price data of selected developed, emerging, and frontier markets over 1993:1–2014:1. Our key results are as follows. Domestic market shocks were significant drivers of gains from portfolio diversification most of the time, although the US market effects were relatively stronger. On the other hand, the US, in terms of the number of significant cases as well as the size effects of shocks, dominated as a determinant of correlation volatility (or risks to portfolio diversification). Further, under bear market conditions, adjustments in correlations and correlation volatilities are found to be mostly US-induced. Bearish shocks, rather than market return based shocks, show strong evidence of the leverage effect. Signs of persistence of shocks are mainly noticed under bearish conditions.
Surface Modification of Polyester-Fabric with Hydrogels and Silver Nanoparticles: Photochemical Versus Gamma Irradiation Methods
Authors: Montoya-Villegas Kathleen A. , Ramírez-Jiménez Alejandro , Licea-Claverie Ángel , Pérez-Sicairos Sergio , Bucio Emilio , Bernáldez-Sarabia Johanna , Licea-Navarro Alexei F.
Published: October 2019

A Gamma irradiation and photochemical crosslinking/grafting of poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(2-hydroxyethyl methacrylate-co-poly(ethylene glycol) methacrylate) (poly(HEMA-co-PEGMA)) hydrogels onto polyethyleneterephtalate fabric (PET) surfaces were evaluated, in order to obtain a hydrophilic homogeneous coating onto PET fabrics. The materials were characterized by FTIR-ATR, SEM, EDS, and thermal analysis. Furthermore, silver nanoparticles (AgNPs) were loaded by in situ reduction of AgNO3, and its antibacterial activity against Staphylococcus aureus and Escherichia coli was determined. Results showed a ticker coating of hydrogel using gamma radiation and stronger in deep modification of the fibers; however, by the photochemical method, a thin coating with good coverage of PET surface was obtained. The differences in hydrophilicity, thermal properties, and antibacterial activity of the coated fabrics by using both methods were rather small.
The Influence of Post Weld Heat Treatment Precipitation on Duplex Stainless Steels Weld Overlay towards Pitting Corrosion
Authors: Sim Bernard-Maxmillan , Hong Tang-Sai , Hanim Mohamed Arif-Azmah , Tchan Edwin-Jong Nyon , Talari Mahesh-Kumar
Published: October 2019

Duplex stainless steels (DSSs) are complex materials and they have been widely used in the marine environment and gas industries, primarily offering a better resistance of pitting corrosion and good mechanical properties. In the present work, the effects of heat treatment on duplex stainless steel (DSS) weld overlay samples that were heat treated at three different temperatures, namely 350 °C, 650 °C, and 1050 °C, and followed by air cooling and water quenching were studied. Stress relief temperature at 650 °C had induced sigma phase precipitation in between delta ferrite and austenite (δ/γ) grain boundaries, resulting in the loss of corrosion resistance in the weld metal. Interestingly, post weld heat treatment (PWHT) test samples that were reheated to solution annealing temperature had shown no weight loss. The ferrite count determination in the region of weld metal overlay increased at hydrogen relief and decreased at stress relief temperatures due to slow cooling, which is more favorable to austenite formation. The amount of ferrite in the weld metals was significantly reduced with the increment of solution anneal temperature to 1050 °C because of sufficient time for the formation of austenite and giving optimum equilibrium fraction in the welds.