bluuebunny/crossref_metadata_2025 huggingface dataset:
Restoration of HCV-Specific Immune Responses with Antiviral Therapy: A Case for DAA Treatment in Acute HCV Infection
Authors: Casey Julia L. , Feld Jordan J. , MacParland Sonya A.
Published: April 2019

Worldwide, 71 million individuals are chronically infected with Hepatitis C Virus (HCV). Chronic HCV infection can lead to potentially fatal outcomes including liver cirrhosis and hepatocellular carcinoma. HCV-specific immune responses play a major role in viral control and may explain why approximately 20% of infections are spontaneously cleared before the establishment of chronicity. Chronic infection, associated with prolonged antigen exposure, leads to immune exhaustion of HCV-specific T cells. These exhausted T cells are unable to control the viral infection. Before the introduction of direct acting antivirals (DAAs), interferon (IFN)-based therapies demonstrated successful clearance of viral infection in approximately 50% of treated patients. New effective and well-tolerated DAAs lead to a sustained virological response (SVR) in more than 95% of patients regardless of viral genotype. Researchers have investigated whether treatment, and the subsequent elimination of HCV antigen, can reverse this HCV-induced exhausted phenotype. Here we review literature exploring the restoration of HCV-specific immune responses following antiviral therapy, both IFN and DAA-based regimens. IFN treatment during acute HCV infection results in greater immune restoration than IFN treatment of chronically infected patients. Immune restoration data following DAA treatment in chronically HCV infected patients shows varied results but suggests that DAA treatment may lead to partial restoration that could be improved with earlier administration. Future research should investigate immune restoration following DAA therapies administered during acute HCV infection.
Apolipoprotein A-IV: A Multifunctional Protein Involved in Protection against Atherosclerosis and Diabetes
Authors: Qu Jie , Ko Chih-Wei , Tso Patrick , Bhargava Aditi
Published: April 2019

Apolipoprotein A-IV (apoA-IV) is a lipid-binding protein, which is primarily synthesized in the small intestine, packaged into chylomicrons, and secreted into intestinal lymph during fat absorption. In the circulation, apoA-IV is present on chylomicron remnants, high-density lipoproteins, and also in lipid-free form. ApoA-IV is involved in a myriad of physiological processes such as lipid absorption and metabolism, anti-atherosclerosis, platelet aggregation and thrombosis, glucose homeostasis, and food intake. ApoA-IV deficiency is associated with atherosclerosis and diabetes, which renders it as a potential therapeutic target for treatment of these diseases. While much has been learned about the physiological functions of apoA-IV using rodent models, the action of apoA-IV at the cellular and molecular levels is less understood, let alone apoA-IV-interacting partners. In this review, we will summarize the findings on the molecular function of apoA-IV and apoA-IV-interacting proteins. The information will shed light on the discovery of apoA-IV receptors and the understanding of the molecular mechanism underlying its mode of action.
On the Impact of the Dynamics of Heat Transfer of the Thermal Machine Working Fluid and Heat Sources on the Shape of the Boundary of the Set of Realizable Regimes
Authors: Zaeva Margarita A. , Tsirlin Anatoly M. , Didina Olga V.
Published: April 2019

From the point of view of finite time thermodynamics, the performance boundaries of thermal machines are considered, taking into account the irreversibility of the heat exchange processes of the working fluid with hot and cold sources. We show how the dynamics of heat exchange affects the shape of the optimal cycle of a heat engine and its performance, in particular, energy conversion efficiency in the maximum power mode. This energy conversion efficiency can depend only on the ratio of the heat transfer coefficients to the sources, or not depend on them at all. A class of dynamic functions corresponding to “natural” requirements is introduced and it is shown that, for any dynamics from this class, the optimal cycle consists of two isotherms and two adiabats, not only for the maximum power problem, but also for the problem of maximum energy conversion efficiency at a given power. Examples are given for calculating the parameters of the optimal cycle for the cases when the heat transfer coefficient to the cold source is arbitrarily large, and for dynamics in the form of a linear phenomenological (Fourier heat transfer) law.
An Analytical Cost-Optimal Cloudlet Placement Framework over Fiber-Wireless Networks with Quasi-Convex Latency Constraint
Authors: Mondal Sourav , Das Goutam , Wong Elaine
Published: April 2019

To meet the low-latency constraints arising from future smart mobile devices, Internet-of-Things, and 5G applications, major interest is currently given to the integration of centralized cloud computing and distributed edge computing infrastructures to deliver higher performance and reliability to edge devices in accessing mobile cloud services. The three-tier network architecture arising from cloud, cloudlet, and edge-devices can handle miscellaneous latency requirements for both latency-sensitive and latency-tolerant applications more efficiently than conventional two-tier networks. In this paper, we primarily focus on the static cloudlet network planning problem and propose an analytical hybrid cost-optimization framework for optimal cloudlet placement. We formulate this problem as a convex optimization problem and solve by using Karush-Kuhn-Tucker (KKT) conditions, and show that this framework can be evaluated without any scalability issues observed with integer programming based frameworks for large datasets. Moreover, we derive user-friendly closed form expressions that provide a first-hand estimation of cloudlet deployment cost depending on a few important network parameters like split-ratio, population density, and network bandwidth. Finally, we also show that the optimal solution of this analytical framework can be considered as a tight lower bound of the optimal solutions of integer programming based frameworks and makes a better cloudlet installation cost estimation compared to other existing frameworks.
Experimental Study of the Effect of Intake Oxygen Concentration on Engine Combustion Process and Hydrocarbon Emissions with N-Butanol-Diesel Blended Fuel
Authors: Tian Wei , Chu Yunlu , Han Zhiqiang , Wang Xiang , Yu Wenbin , Wu Xueshun
Published: April 2019

This paper summarizes a study based on a modified, light, single-cylinder diesel engine and the effects of the physicochemical properties for n-butanol-diesel blended fuel on the combustion process and hydrocarbon (HC) emissions in the intake at a medium speed and moderate load in, an oxygen-rich environment (Coxy = 20.9–16%), an oxygen-medium environment (Coxy = 16–12%), and an oxygen-poor environment (Coxy = 12–9%). The results show that the ignition delay period is the main factor affecting the combustion process and it has a decisive influence on HC emissions. In an oxygen-medium environment, combustion duration affected by the cetane number is the main reason for the difference in HC emissions between neat diesel fuel (B00) and diesel/n-butanol blended fuel (B20), and its influence increases as the intake oxygen concentration decreases. In an oxygen-poor environment, in-cylinder combustion temperature affected by the latent heat of vaporization is the main reason for the difference in HC emissions between B00 and B20 fuels, and its influence increases as the intake oxygen concentration decreases. By comparing B20 fuel with diesel/n-butanol/2-ethylhexyl nitrate blended fuel (B20 + EHN), the difference in the ignition delay period caused by the difference in the cetane number is the main reason for the difference in HC emissions between B20 and B20 + EHN fuels in oxygen-poor environment, and the effect of this influencing factor gradually increases as the intake oxygen concentration decreases.
Environmental Controls on the Seasonal Variation in Gas Exchange and Water Balance in a Near-Coastal Mediterranean Pinus halepensis Forest
Authors: Fotelli Mariangela N. , Korakaki Evangelia , Paparrizos Spyridon A. , Radoglou Kalliopi , Awada Tala , Matzarakis Andreas
Published: April 2019

Aleppo pine (Pinus halepensis Mill.) is widespread in most countries of the Mediterranean area. In Greece, Aleppo pine forms natural stands of high economic and ecological importance. Understanding the species’ ecophysiological traits is important in our efforts to predict its responses to ongoing climate variability and change. Therefore, the aim of this study was to assess the seasonal dynamic in Aleppo pine gas exchange and water balance on the leaf and canopy levels in response to the intra-annual variability in the abiotic environment. Specifically, we assessed needle gas exchange, water potential and δ13C ratio, as well as tree sap flow and canopy conductance in adult trees of a mature near-coastal semi-arid Aleppo pine ecosystem, over two consecutive years differing in climatic conditions, the latter being less xerothermic. Maximum photosynthesis (Amax), stomatal conductance (gs), sap flow per unit leaf area (Ql), and canopy conductance (Gs) peaked in early spring, before the start of the summer season. During summer drought, the investigated parameters were negatively affected by the increasing potential evapotranspiration (PET) rate and vapor pressure deficit (VPD). Aleppo pine displayed a water-saving, drought avoidance (isohydric) strategy via stomatal control in response to drought. The species benefited from periods of high available soil water, during the autumn and winter months, when other environmental factors were not limiting. Then, on the leaf level, air temperature had a significant effect on Amax, while on the canopy level, VPD and net radiation affected Ql. Our study demonstrates the plasticity of adult Aleppo pine in this forest ecosystem in response to the concurrent environmental conditions. These findings are important in our efforts to predict and forecast responses of the species to projected climate variability and change in the region.
The Development of Keratopathy after Surgery-Indicated Chronic Rhinosinusitis: A Population-Based Cohort Study
Authors: Hsu Hung-Jui , Lee Chia-Yi , Yang Kun-Lin , Chen Hung-Chi , Sun Chi-Chin , Huang Jing-Yang , Lin Hung-Yu , Yang Shun-Fa
Published: April 2019

The aim of the present study was to evaluate the risk of developing keratopathy in patients with surgery-indicated chronic rhinosinusitis (CRS) via the National Health Insurance Research Database in Taiwan. Patients with a diagnostic code of CRS and who received functional endoscopic sinus surgery (FESS) were considered to have surgery-indicated CRS. The exclusion criteria were legal blindness, an ocular tumor, eyeball removal or previous keratopathy, and each individual in the study group was matched to four non-CRS patients by age and sex. The outcome was set as the occurrence of keratopathy according to the diagnostic codes after the index date. Cox proportional hazard regression was used for statistical analysis. A total of 6053 patients with surgery-indicated CRS and another 24,212 non-CRS individuals were enrolled after exclusions. The age and sex distributions were identical between the two groups due to matching, while comorbidities, including hypertension, diabetes mellitus, and other cardiovascular disorders, were significantly higher in the study group. There were 231 episodes of keratopathy in the study group, and 695 episodes of keratopathy in the control group after the index date, for which study group showed a significantly higher rate of developing keratopathy with an adjusted hazard ratio of 1.208 and a higher cumulative probability. In subgroup analysis, female sex with surgery-indicated CRS showed a significantly greater risk of developing keratopathy. In conclusion, surgery-indicated CRS that needs FESS to relieve symptoms is a potential risk factor for keratopathy.
Quality of Life and Health among People Living in an Industrial Area of Poland
Authors: Szemik Szymon , Kowalska Małgorzata , Kulik Halina
Published: April 2019

Background: The quality of life and health status of the population significantly depends on socio-economic factors, including working and employment conditions. Methods: This epidemiological cross-sectional study was carried out among young inhabitants aged 25–44 years living in the Silesian voivodeship in Poland. The quality of life was evaluated using the short version of the WHOQOL-BREF questionnaire. Results: A total of 905 respondents were examined. It was shown that the poor quality of life in all assessed domains was associated with a low job satisfaction level, low physical activity, and higher self-assessed health status. Furthermore, the worse self-assessed health status in the study group was mainly related to such factors as earlier diagnosed chronic disease, lower job satisfaction, and low physical activity. Additionally, diagnosed chronic disease among occupationally active respondents was correlated with health deterioration due to excessive stress, living in the vicinity of heavy road traffic, and was declared by women more frequently. Conclusions: The results of the presented study confirmed that the quality of life and health status in young inhabitants of the Silesian voivodeship significantly depends on the work characteristics, employment conditions and lifestyle factors.
Characteristics of the Family Support Network of Pregnant Adolescents and Its Association with Gestational Weight Gain and Birth Weight of Newborns
Authors: Sámano Reyna , Martínez-Rojano Hugo , Chico-Barba Gabriela , Sánchez-Jiménez Bernarda , Illescas-Zarate Daniel , Rodríguez-Ventura Ana Lilia
Published: April 2019

It has been proposed that, in the Mexican culture, family support can be a factor that contributes to protect the maternal and child health of pregnant adolescents. There may be complex associations between family support and the circumstances of a pregnancy during adolescence. The aim of the study was to analyze the association between the family support network (FSN) characteristic and the maternal and neonatal outcomes in Mexican adolescents. A cross-sectional study was conducted, and 352 pregnant adolescents participated; their FSN during pregnancy was assessed. The gestational weight gain and birth weight/length of newborns were registered. The size of the FSN was described and divided into quartiles; the main members for each quartile were identified. Then, sociodemographic and clinical variables were compared by FSN quartiles. Logistic regression models were performed to assess the association of FSN size and pregnancy and neonatal outcomes. Our results indicate that the mean age was 15 ± 1 year old. The primary support member in the FSN was the mother of the adolescent in each quartile, except for quartile 3, where the primary support was the mother-in-law. In quartile 3 there was a significantly lower gestational weight gain compared to quartile 4 (11.8 ± 5 vs. 13 ± 5 kg, p = 0.054). According to the regression model, a higher risk of small for gestational age (OR 2.99, CI 95% 1.25–7.15) newborns was found in quartile 3. We conclude that the maternal and neonatal outcomes did not differ between quartiles of FSN size, except for quartile 3. Small for gestational age newborns were observed when a non-blood relative was present in the FSN. The quality rather than the network size might be more important for improving pregnancy outcomes.
Impacts of Road Traffic Network and Socioeconomic Factors on the Diffusion of 2009 Pandemic Influenza A (H1N1) in Mainland China
Authors: Xu Bo , Tian Huaiyu , Sabel Clive Eric , Xu Bing
Published: April 2019

The 2009 pandemic influenza virus caused the majority of the influenza A virus infections in China in 2009. It arrived in several Chinese cities from imported cases and then spread as people travelled domestically by all means of transportation, among which road traffic was the most commonly used for daily commuting. Spatial variation in socioeconomic status not only accelerates migration across regions but also partly induces the differences in epidemic processes and in responses to epidemics across regions. However, the roles of both road travel and socioeconomic factors have not received the attention they deserve. Here, we constructed a national highway network for and between 333 cities in mainland China and extracted epidemiological variables and socioeconomic factors for each city. We calculated classic centrality measures for each city in the network and proposed two new measures (SumRatio and Multicenter Distance). We evaluated the correlation between the centrality measures and epidemiological features and conducted a spatial autoregression to quantify the impacts of road network and socioeconomic factors during the outbreak. The results showed that epidemics had more significant relationships with both our new measures than the classic ones. Higher population density, higher per person income, larger SumRatio and Multicenter Distance, more hospitals and college students, and lower per person GDP were associated with higher cumulative incidence. Higher population density and number of slaughtered pigs were found to advance epidemic arrival time. Higher population density, more colleges and slaughtered pigs, and lower Multicenter Distance were associated with longer epidemic duration. In conclusion, road transport and socioeconomic status had significant impacts and should be considered for the prevention and control of future pandemics.
Unhygienic Practices of Health Professionals in Brazilian Public Hospital Restaurants: An Alert to Promote New Policies and Hygiene Practices in the Hospitals
Authors: Draeger Cainara Lins , Akutsu Rita de Cassia Coelho de Almeida , de Oliveira Karin Eleonora Sávio , da Silva Izabel Cristina Rodrigues , Botelho Raquel Braz Assunção , Zandonadi Renata Puppin
Published: April 2019

This study aimed to evaluate health professionals’ unhygienic practices and the stages of behaviour change in Brazilian public hospital restaurants. We evaluated all medium/large-sized public hospital restaurants (HRs) from the Brazilian Federal District (n = 9); a representative sample of 128 users). We evaluated the HRs’ physical structures, their consumers’ socio-demographic characteristics, their unhygienic practices, as well as the stages of behavioural change concerning unhygienic practices. All the HRs presented their menus for self-service distribution, so customers entered in lines to serve themselves. All the HRs had hand-wash sinks for customers; 77.8% offered antiseptic liquid soap; 33.3% offered alcohol gel; and 77.8% offered storage for professional accessories before serving food. Almost half (46.8%) of the customers did not sanitise their hands (with water and antiseptic soap and/or use of alcohol gel) immediately before serving, and 24.2% wore professional uniforms at HRs. Almost half (43.5%) of the customers spoke with each other in line while serving their plates and arranged the food on their plates with the serving utensils from the distribution counter. The declaration of behavioural change was inversely associated with the hygiene practices. Almost half of the individuals did not sanitize their hands; however, 90.4% declared “changed behaviour” when this contaminant practice was presented to them. We verified a high percentage of hygiene practices inconsistent with most of the customers´ answers about their stage of behaviour change. Based on the observations of this study, it is necessary for an awareness program to be developed that is focused on customers of HRs in order to reduce unhygienic practices. Also, it is important to promote new policies for proper hygiene practices in hospital restaurants.
Are Adolescent Body Image Concerns Associated with Health-Compromising Physical Activity Behaviours?
Authors: Jankauskiene Rasa , Baceviciene Migle , Pajaujiene Simona , Badau Dana
Published: April 2019

The present study aimed to assess the-prevalence of health-compromising eating and physical activity behaviours, and to test their associations with physical activity, internalisation of sociocultural attitudes towards appearance, and body image in a sample of adolescents of both genders. A total sample of 736 adolescents (437 or 59.4% were girls) participated in the study. The participants ranged in age from 16 to 19 years (x = 17.2, SD = 0.6). The sample completed a questionnaire measuring body mass index, the risk of eating disorders, body image, internalisation of sociocultural ideals of appearance, health-compromising eating behaviours (HCEB), and health-compromising weight control related to physical activity behaviours (HCPAB). Logistic regressions were used to assess the associations between the study variables and predictors of HCEB and HCPAB. The results of the study showed a relatively high prevalence of HCEB with a significantly higher prevalence in girls and participants with a higher BMI. The study also demonstrated that the prevalence of adolescent HCPAB was higher than HCEB. The internalisation of sociocultural attitudes towards appearance and body image concerns were higher in the HCEB and HCPAB groups. Female gender (OR = 1.88; 95% PI = 1.10–3.18), HCPAB (OR = 1.19; 95% PI = 1.10–1.28), a preoccupation with being overweight (OR = 3.43; 95% PI = 2.52–4.66), and body weight evaluation as too high (OR = 2.40; 95% PI = 1.57–3.68) were significant predictors of HCEB. More frequent physical activity (OR = 3.02; 95% PI = 1.76–5.17), HCEB (OR = 1.22; 95% PI = 1.11–1.32), and perceived pressures to conform to popular beauty ideals (OR = 1.51; 95% PI = 1.12–2.03) predicted higher HCPAB. HCPAB is an important variable associated with adolescents’ body image, physical activity, and weight control. The results of the present study are important for health promotion and education programs addressing adolescents’ healthy lifestyle, weight control, and body image concerns.
SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts
Authors: Wichit Sineewanlaya , Hamel Rodolphe , Zanzoni Andreas , Diop Fodé , Cribier Alexandra , Talignani Loïc , Diack Abibatou , Ferraris Pauline , Liegeois Florian , Urbach Serge , Ekchariyawat Peeraya , Merits Andres , Yssel Hans , Benkirane Monsef , Missé Dorothée
Published: April 2019

Chikungunya virus (CHIKV) and Zika virus (ZIKV) are emerging arboviruses that pose a worldwide threat to human health. Currently, neither vaccine nor antiviral treatment to control their infections is available. As the skin is a major viral entry site for arboviruses in the human host, we determined the global proteomic profile of CHIKV and ZIKV infections in human skin fibroblasts using Stable Isotope Labelling by Amino acids in Cell culture (SILAC)-based mass-spectrometry analysis. We show that the expression of the interferon-stimulated proteins MX1, IFIT1, IFIT3 and ISG15, as well as expression of defense response proteins DDX58, STAT1, OAS3, EIF2AK2 and SAMHD1 was significantly up-regulated in these cells upon infection with either virus. Exogenous expression of IFITs proteins markedly inhibited CHIKV and ZIKV replication which, accordingly, was restored following the abrogation of IFIT1 or IFIT3. Overexpression of SAMHD1 in cutaneous cells, or pretreatment of cells with the virus-like particles containing SAMHD1 restriction factor Vpx, resulted in a strong increase or inhibition, respectively, of both CHIKV and ZIKV replication. Moreover, silencing of SAMHD1 by specific SAMHD1-siRNA resulted in a marked decrease of viral RNA levels. Together, these results suggest that IFITs are involved in the restriction of replication of CHIKV and ZIKV and provide, as yet unreported, evidence for a proviral role of SAMHD1 in arbovirus infection of human skin cells.
Synthetic miR-143 Inhibits Growth of HER2-Positive Gastric Cancer Cells by Suppressing KRAS Networks Including DDX6 RNA Helicase
Authors: Tokumaru Yoshihisa , Tajirika Toshihiro , Sugito Nobuhiko , Kuranaga Yuki , Shinohara Haruka , Tsujino Takuya , Matsuhashi Nobuhisa , Futamura Manabu , Akao Yukihiro , Yoshida Kazuhiro
Published: April 2019

Gastric cancer (GC) is one of the most common cancers worldwide. In the clinical setting, the identification of HER2 overexpression in GC was a significant finding, as trastuzumab, an anti-HER2 drug, provides a survival advantage to HER2-positive GC patients. In HER2-postive GC, the dysregulation of PI3K/AKT and MAPK/ERK signaling pathways has been reported, and inhibition of these pathways is an important therapeutic strategy. MiR-143 is known to act as a tumor suppressor in several cancers, such as bladder cancer, breast cancer, colorectal cancer, and gastric cancer. In the current study, we developed a novel chemically-modified miR-143 and explored the functions of this synthetic miR-143 (syn-miR-143) in HER2-positive gastric cancer. The expression level of miR-143 was down-regulated in GC cell lines, including HER2-positive GC cell lines, MKN7, and KATO-III. The ectopic expression of miR-143 in those cell lines suppressed cell growth through systemic silencing of KRAS and its effector signaling molecules, AKT and ERK. Furthermore, syn-miR-143 indirectly down-regulated the expression of HER2, an upstream molecule of KRAS, through silencing DEAD/H-box RNA helicase 6 (DDX6), RNA helicase, which enhanced HER2 protein expression at the translational step in HER2-positive GC cells. These findings suggested that syn-miR-143 acted as a tumor suppressor through the impairment of KRAS networks including the DDX6.
Platelet-Rich Fibrin Scaffolds for Cartilage and Tendon Regenerative Medicine: From Bench to Bedside
Authors: Barbon Silvia , Stocco Elena , Macchi Veronica , Contran Martina , Grandi Francesca , Borean Alessio , Parnigotto Pier Paolo , Porzionato Andrea , De Caro Raffaele
Published: April 2019

Nowadays, research in Tissue Engineering and Regenerative Medicine is focusing on the identification of instructive scaffolds to address the requirements of both clinicians and patients to achieve prompt and adequate healing in case of injury. Among biomaterials, hemocomponents, and in particular Platelet-rich Fibrin matrices, have aroused widespread interest, acting as delivery platforms for growth factors, cytokines and immune/stem-like cells for immunomodulation; their autologous origin and ready availability are also noteworthy aspects, as safety- and cost-related factors and practical aspects make it possible to shorten surgical interventions. In fact, several authors have focused on the use of Platelet-rich Fibrin in cartilage and tendon tissue engineering, reporting an increasing number of in vitro, pre-clinical and clinical studies. This narrative review attempts to compare the relevant advances in the field, with particular reference being made to the regenerative role of platelet-derived growth factors, as well as the main pre-clinical and clinical research on Platelet-rich Fibrin in chondrogenesis and tenogenesis, thereby providing a basis for critical revision of the topic.
PGC-1α Controls Mitochondrial Biogenesis in Drug-Resistant Colorectal Cancer Cells by Regulating Endoplasmic Reticulum Stress
Authors: Yun Chul Won , Han Yong-Seok , Lee Sang Hun
Published: April 2019

Anti-cancer drug resistance is a serious issue for patients with colorectal cancer (CRC). Although recent studies have shown the mechanism by which CRC cells become drug resistant, novel strategies for overcoming this drug resistance have not yet been developed. To address this problem, we characterized 5-fluorouracil (5FU)-resistant CRC cells after treatment with 5FU, and focused on the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in these cells. In 5FU-resistant CRC cells, the 5FU did not considerably decrease the mitochondrial biogenesis or mitochondrial complex I and IV activities, and only partially decreased the antioxidant enzymatic activity, oxygen consumption ratio, and cell survival. The expression of PGC-1α was remarkably increased in the 5FU-resistant CRC cells compared with the 5FU-sensitive CRC cells. The 5FU-resistant CRC cells displayed enhanced mitochondrial biogenesis, oxidative phosphorylation, and antioxidant enzyme activities against 5FU-induced reactive oxygen species, because of the increased expression of PGC-1α. PGC-1α inhibited 5FU-induced endoplasmic reticulum (ER) stress in the 5FU-resistant CRC cells, resulting in the suppression of apoptosis. These findings reveal that PGC-1α plays an important role in drug resistance in 5FU-resistant CRC cells. Moreover, PGC-1α could serve as a novel target in patients with 5FU-resistant CRC.
Transcriptional Profile Corroborates that bml Mutant Plays likely Role in Premature Leaf Senescence of Rice (Oryza sativa L.)
Authors: Akhter Delara , Qin Ran , Nath Ujjal Kumar , Eshag Jamal , Jin Xiaoli , Shi Chunhai
Published: April 2019

Leaf senescence is the last period of leaf growth and a dynamic procedure associated with its death. The adaptability of the plants to changing environments occurs thanks to leaf senescence. Hence, transcriptional profiling is important to figure out the exact mechanisms of inducing leaf senescence in a particular crop, such as rice. From this perspective, leaf samples of two different rice genotypes, the brown midrib leaf (bml) mutant and its wild type (WT) were sampled for transcriptional profiling to identify differentially-expressed genes (DEGs). We identified 2670 DEGs, among which 1657 genes were up- and 1013 genes were down-regulated. These DEGs were enriched in binding and catalytic activity, followed by the single organism process and metabolic process through gene ontology (GO), while the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the DEGs were related to the plant hormone signal transduction and photosynthetic pathway enrichment. The expression pattern and the clustering of DEGs revealed that the WRKY and NAC family, as well as zinc finger transcription factors, had greater effects on early-senescence of leaf compared to other transcription factors. These findings will help to elucidate the precise functional role of bml rice mutant in the early-leaf senescence.
Current State and Future Directions of Technology-Based Ecological Momentary Assessment and Intervention for Major Depressive Disorder: A Systematic Review
Authors: Colombo Desirée , Fernández-Álvarez Javier , Patané Andrea , Semonella Michelle , Kwiatkowska Marta , García-Palacios Azucena , Cipresso Pietro , Riva Giuseppe , Botella Cristina
Published: April 2019

Ecological momentary assessment (EMA) and ecological momentary intervention (EMI) are alternative approaches to retrospective self-reports and face-to-face treatments, and they make it possible to repeatedly assess patients in naturalistic settings and extend psychological support into real life. The increase in smartphone applications and the availability of low-cost wearable biosensors have further improved the potential of EMA and EMI, which, however, have not yet been applied in clinical practice. Here, we conducted a systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to explore the state of the art of technology-based EMA and EMI for major depressive disorder (MDD). A total of 33 articles were included (EMA = 26; EMI = 7). First, we provide a detailed analysis of the included studies from technical (sampling methods, duration, prompts), clinical (fields of application, adherence rates, dropouts, intervention effectiveness), and technological (adopted devices) perspectives. Then, we identify the advantages of using information and communications technologies (ICTs) to extend the potential of these approaches to the understanding, assessment, and intervention in depression. Furthermore, we point out the relevant issues that still need to be addressed within this field, and we discuss how EMA and EMI could benefit from the use of sensors and biosensors, along with recent advances in machine learning for affective modelling.
Epitaxial Non c-Axis Twin-Free Bi2Sr2CaCu2O8+δ Thin Films for Future THz Devices
Authors: Endo Kazuhiro , Arisawa Shunichi , Badica Petre
Published: April 2019

Thin films of (117) Bi2Sr2Ca2CuO8+δ (Bi-2212) were grown by Molecular Organic Chemical Vapor Deposition (MOCVD) on (110) SrTiO3 and (110) LaAlO3 substrates. Substrates were vicinal with off angles up to 20°. Films are 3D epitaxial and X-ray diffraction φ-ψ scans demonstrate that, while the films grown on a flat substrate are composed of twinned grains, the films on vicinal substrate are twin-free. A higher quality is obtained if growth is performed at two temperatures: Growth starts at 550–600 °C and continues at 700–750 °C. The twin-free film grown by the two-temperature method shows a zero-resistance critical temperature of 37 and 32 K when the measuring current is applied in-plane parallel and perpendicular to [001] direction of the substrate. Twin-free non c-axis thin films are promising for fabrication of novel planar THz devices.
Microstructure and Compressive Behavior of Al–Y2O3 Nanocomposites Prepared by Microwave-Assisted Mechanical Alloying
Authors: Mattli Manohar Reddy , Shakoor R. A. , Matli Penchal Reddy , Amer Mohamed Adel Mohamed
Published: April 2019

In this study, Al–Y2O3 nanocomposites were synthesized via mechanical alloying and microwave-assisted sintering. The effect of different levels of yttrium oxide on the microstructural and mechanical properties of the Al–Y2O3 nanocomposites were investigated. The density of the Al–Y2O3 nanocomposites increased with increasing Y2O3 volume fraction in the aluminum matrix, while the porosity decreased. Scanning electron microscopy analysis of the nanocomposites showed the homogeneous distribution of the Y2O3 nanoparticles in the aluminum matrix. X-ray diffraction analysis revealed the presence of yttria particles in the Al matrix. The mechanical properties of the Al–Y2O3 nanocomposites increased as the addition of yttria reached to 1.5 vol. % and thereafter decreased. The microhardness first increased from 38 Hv to 81 Hv, and then decreased to 74 ± 4 Hv for 1.5 vol. % yttria. The Al–1.5 vol. % Y2O3 nanocomposite exhibited the best ultimate compressive strength and yielded a strength of 359 ± 7 and 111 ± 5 MPa, respectively. The Al–Y2O3 nanocomposites showed higher hardness, yield strength, and compressive strength than the microwave-assisted mechanically alloyed pure Al.
Drying Enhances Signal Intensities for Global GC–MS Metabolomics
Authors: Liebeke Manuel , Puskás Erik
Published: April 2019

We report here that a straightforward change of the standard derivatization procedure for GC–MS metabolomics is leading to a strong increase in metabolite signal intensity. Drying samples between methoxymation and trimethylsilylation significantly increased signals by two- to tenfold in extracts of yeast cells, plant and animal tissue, and human urine. This easy step reduces the cost of sample material and the need for expensive new hardware.
Mineralogical and Chemical Characterization of Zr-REE-Nb Ores from Khalzan Buregtei (Mongolia)—Approaches to More Efficient Extraction of Rare Metals from Alkaline Granitoids
Authors: Gronen Lars Hans , Sindern Sven , Katzmarzyk Janet Lucja , Bormann Udo , Hellmann André , Wotruba Hermann , Meyer F. Michael
Published: April 2019

Alkaline rocks are worldwide observed as hosts for rare metal (Zr-REE-Nb) minerals. The classification of the ore bearing rock type is challenging due to the fact that textures and mineral assemblage are obscured by post-magmatic alteration. In addition, the alteration causes fine and intricate intergrowth of the ore minerals with associated gangue. Hence, intensive comminution is necessary to liberate the ore minerals, which is one parameter hampering the economical use of this deposit type. This study provides a quantitative mineralogical investigation of the ore bearing rock suite at Khalzan Buregtei as an example of rare metal deposits. R1-R2 multication parameters are shown to be highly appropriate as quantitative mineralogical indicators based on readily available major element datasets to visualize and quantify alteration types of the ore bearing rock suite. The ore minerals were found to be associated with a cluster-forming assemblage of post-magmatic phases. Automated mineralogy was applied to quantify the textural properties of the ore mineral clusters. This finding permits efficient pre-concentration of rare metal ore at coarser particle size fraction, requiring less energy consuming comminution.
In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier
Authors: Chlebek Jakub , Korábečný Jan , Doležal Rafael , Štěpánková Šárka , Pérez Daniel I. , Hošťálková Anna , Opletal Lubomír , Cahlíková Lucie , Macáková Kateřina , Kučera Tomáš , Hrabinová Martina , Jun Daniel
Published: April 2019

In recent studies, several alkaloids acting as cholinesterase inhibitors were isolated from Corydalis cava (Papaveraceae). Inhibitory activities of (+)-thalictricavine (1) and (+)-canadine (2) on human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) were evaluated with the Ellman’s spectrophotometric method. Molecular modeling was used to inspect the binding mode of compounds into the active site pocket of hAChE. The possible permeability of 1 and 2 through the blood–brain barrier (BBB) was predicted by the parallel artificial permeation assay (PAMPA) and logBB calculation. In vitro, 1 and 2 were found to be selective hAChE inhibitors with IC50 values of 0.38 ± 0.05 µM and 0.70 ± 0.07 µM, respectively, but against hBChE were considered inactive (IC50 values > 100 µM). Furthermore, both alkaloids demonstrated a competitive-type pattern of hAChE inhibition and bind, most probably, in the same AChE sub-site as its substrate. In silico docking experiments allowed us to confirm their binding poses into the active center of hAChE. Based on the PAMPA and logBB calculation, 2 is potentially centrally active, but for 1 BBB crossing is limited. In conclusion, 1 and 2 appear as potential lead compounds for the treatment of Alzheimer’s disease.
A Loose Parts Randomized Controlled Trial to Promote Active Outdoor Play in Preschool-aged Children: Physical Literacy in the Early Years (PLEY) Project
Authors: Houser Natalie E. , Cawley Jane , Kolen Angela M. , Rainham Daniel , Rehman Laurene , Turner Joan , Kirk Sara F. L. , Stone Michelle R.
Published: April 2019

BACKGROUND: The Physical Literacy in the Early Years (PLEY) intervention is a randomized mixed-methods controlled trial focused on embedding loose parts materials into the outdoor play spaces of regulated child care centres across Nova Scotia. The aim is to evaluate the efficacy of the PLEY intervention versus standard regulated childcare practice in influencing thoughts and behaviors of children, parents, and educators. METHODS: Participating early child care centres (n = 19) were randomly assigned to intervention or control sites. Intervention sites received loose parts kits at the beginning of the project while control sites received kits upon project completion. The kits included items such as rocks, tree cookies, balls, wood planks, tubes, tires, ropes, and pulleys. Children (n = 183 at baseline) had their physical activity (accelerometers) and movement skills (TGMD-3 and PGMQ) measured before and after the intervention. All centres provided responses to environmental surveys (Go NAP SACC and Site Context Questionnaire), and educators in intervention sites participated in focus group and photovoice sessions. Educators were also provided with a full day professional development opportunity (plus ongoing mentoring) focused on physical activity, physical literacy, outdoor play, risk-taking, and loose parts. Parents participated in an interview addressing active outdoor play, physical literacy, and attitudes towards risk taking during play. DISCUSSION: This study will provide a better understanding of how integrating loose parts materials into outdoor play spaces impacts children’s health, and the impact on educator and parent attitudes, beliefs, and understanding around physical literacy, active outdoor play and risk-taking during play.
Modification of Graphene Oxide Membranes by the Incorporation of Nafion Macromolecules and Conductive Scaffolds
Authors: Concha-Guzmán Maria O. , Jaramillo-Quintero Oscar A. , Rincón Marina E.
Published: April 2019

Stable, reproducible and low-cost graphene oxide (GO)/Nafion (N) membranes were fabricated using electronically conductive carbon paper (CP) matts as a scaffold. The presence of polar groups in the Nafion molecule facilitates the strong interaction with functional groups in the GO, which increases GO dispersion and aids the retention of the composite into the CP scaffold. Distribution of GO/N was carefully characterized by X-ray diffraction work function measurements, Raman and scanning electron microscopy analyses. The performance of these membranes was tested with 1 M NaCl at standard conditions, finding 85% ion removal in the best membranes by a mixed ion rejection/retention mechanism. The Nafion provided mechanical stability and fixed negative charge to the membranes, and its micellar organization, segregation and confinement favored ion rejection in Nafion-rich areas. The good electronic conductivity of these membranes was also demonstrated, allowing for the application of a small potential bias to enhance membrane performance in future studies.
Sandwich-Structured Silver Nanowire Transparent Conductive Films with 3H Hardness and Robust Flexibility for Potential Applications in Curved Touch Screens
Authors: Chu Xikun , Tao Jingqi , Li Shuxin , Ji Shulin , Ye Changhui
Published: April 2019

A sandwich-structured bottom hard-coat/silver nanowire/top hard-coat (BHC/AgNW/THC) transparent conductive film (TCF) has been prepared by embedding the functional AgNW layer between two HC layers. The BHC/AgNW/THC TCFs show high scratch resistance with a hardness of 3H due to the enhanced adhesion to the substrate. In addition, the BHC/AgNW/THC TCFs exhibit a transmittance of 90.6% and a haze of 1% at 550 nm under a sheet resistance of 72 Ω/sq. Furthermore, highly enhanced long-term stability has been guaranteed by the HC layers due to their excellent gas barrier property. The amazing fact is that hard coating has little effect on the flexibility of AgNW films especially under extreme bending conditions and negligible resistance change could be observed after bending over thousands of times. Consequently, the greatly improved performance of BHC/AgNW/THC TCFs provided by employing hard coating layers paves the way for real-world applications of flexible AgNWs in vast areas that rigid indium tin oxide is not suitable.
Adherence to Mediterranean Diet, Malnutrition, Length of Stay and Mortality in Elderly Patients Hospitalized in Internal Medicine Wards
Authors: Lo Buglio Aurelio , Bellanti Francesco , Capurso Cristiano , Paglia Annalisa , Vendemiale Gianluigi
Published: April 2019

This investigation aimed to explore the adherence to a Mediterranean Diet and its relationship with length of stay and in-hospital mortality, circulating interleukins, body composition, and frailty, in elderly patients hospitalized in internal medicine wards. Thus, a cross-sectional study in 194 acute hospitalized, community-dwelling elderly patients was performed. Adherence to a Mediterranean Diet was evaluated by the Italian Mediterranean Index (IMI). Length of stay, but not in-hospital mortality rate, was higher in patients with a low IMI score, as compared to subjects with high IMI score. Markers of systemic inflammation, as well as circulating interleukin-6 and tumor necrosis factor alpha, were higher in patients with a low IMI score, with respect to patients with high IMI score. Furthermore, patients with low IMI score had increased fat mass and reduced lean mass, together with a higher prevalence of frailty, as compared to those presenting with high IMI score. In a multivariate logistic regression model, an IMI score < 3 resulted as an independent predictor of longer length of stay. In conclusion, low adherence to a Mediterranean Diet in elderly patients hospitalized in internal medicine wards is associated with higher length of stay and related to unfavorable changes in circulating pro-inflammatory markers and body composition.
Three Polymethoxyflavones Purified from Ougan (Citrus reticulata Cv. Suavissima) Inhibited LPS-Induced NO Elevation in the Neuroglia BV-2 Cell Line via the JAK2/STAT3 Pathway
Authors: Wang Yue , Zang Wenjing , Ji Shiyu , Cao Jinping , Sun Chongde
Published: April 2019

In order to establish an efficient method for separation of polymethoxyflavones (PMFs) and explore the anti-inflammatory mechanism of PMF monomers, a citrus variety rich in PMFs, Ougan (Citrus reticulata cv. Suavissima), was selected, and three monomers, including nobiletin, tangeretin, and 5-demethylnobiletin, were purified by ultrasonic-assisted extraction, solid phase extraction, and high-speed countercurrent chromatography separation. UPLC-MS was used to identify the three monomers. UPLC determined purities of 99.87% to nobiletin, 99.76% to tangeretin, and 98.75% to 5-demethylnobiletin with the standard curve method. A lipopolysaccharide (LPS)-induced NO releasing model was performed in the mouse microglia BV-2 cell line. Results illustrated that PMF monomers inhibited the NO release and the inflammation-related cytokines, including IL-1β, IL-6, and TNFα elevation. QRT-PCR revealed that PMFs alleviated LPS-induced upregulation of iNOS, IL-6, JAK2, TNFα, IL-1β, and NF-κB and LPS-induced downregulation of IκBα, while they did not affect TLR1, TLR2, TLR4, and TLR6. STAT3 expression was repressed by tangeretin and 5-demethylnobiletin, but not by nobiletin. Western blot assay also showed a suppression of expression and phosphorylation of JAK2 by all three PMF monomers, while STAT3 phosphorylation was restrained by tangeretin and 5-demethylnobiletin. The mechanism was primarily verified by the JAK2 inhibitor Ruxolitinib and the STAT3 inhibitor Stattic.
Interpretation of Non-Clinical Data for Prediction of Human Pharmacokinetic Parameters: In Vitro-In Vivo Extrapolation and Allometric Scaling
Authors: Choi Go-Wun , Lee Yong-Bok , Cho Hea-Young
Published: April 2019

Extrapolation of pharmacokinetic (PK) parameters from in vitro or in vivo animal to human is one of the main tasks in the drug development process. Translational approaches provide evidence for go or no-go decision-making during drug discovery and the development process, and the prediction of human PKs prior to the first-in-human clinical trials. In vitro-in vivo extrapolation and allometric scaling are the choice of method for projection to human situations. Although these methods are useful tools for the estimation of PK parameters, it is a challenge to apply these methods since underlying biochemical, mathematical, physiological, and background knowledge of PKs are required. In addition, it is difficult to select an appropriate methodology depending on the data available. Therefore, this review covers the principles of PK parameters pertaining to the clearance, volume of distribution, elimination half-life, absorption rate constant, and prediction method from the original idea to recently developed models in order to introduce optimal models for the prediction of PK parameters.