bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climate change and its impact on water availability of large international rivers over the mainland Southeast Asia
Authors: Liu Zhaofei , Wang Rui , Yao Zhijun 
Published: October 2018

AbstractChanges in climate and the resulting hydrologic variability are of great concern in international river basins. Based on observed station data, climate change and its impact on water availability in large international rivers across mainland Southeast Asia (MSA) were investigated by a combined method of trend detection and hydrologic budget balance analysis. This method can be applied easily to other studies to evaluate impacts of climate change on run‐off and water resources at the basin scale. Precipitation showed a decreasing trend in the MSA during 1960–2016, especially in the dry season. Decreasing precipitation and increasing evapotranspiration were the main reasons for severe droughts during recent years. Climate change was the main reason for run‐off changes over the MSA. The presence of dams in the upstream region was not enough to change the annual variability of natural run‐off in the Mekong River. Run‐off and precipitation changes showed significant variances in different basins and regions, and in different periods. The overall trend of precipitation and run‐off showed a periodicity of about 35 years. Nonprecipitation effects were also significant in some regions, including increasing irrigation water demand in the Red River and increasing glacial melt in the Brahmaputra River basin. Melt increased at least 75.2 × 108 m3/10a during 1960–2003, representing 1.2% of mean annual run‐off in the Brahmaputra River. The positive effect of glacial meltwater was almost equal to the negative effect of evapotranspiration on run‐off change in the Lancang River. Increasing evapotranspiration played a dominant effect on run‐off changes in the Yarlung Zangbo River basin during 1960–2010.
Financial firm bankruptcies, international stock markets, and investor sentiment
Authors: Papakyriakou Panayiotis , Sakkas Athanasios , Taoushianis Zenon 
Published: October 2018

AbstractWe consider bankruptcy announcements of large financial institutions in the United States and examine their impact on an international sample of 66 stock market indices. Employing an event‐study methodology, we find that stock markets exhibit strong adverse reaction in the aftermath of such announcements. Further, we develop a surprise measure, based on the country‐level investor sentiment, and find that stock markets in negatively surprised countries respond quickly by sustaining significantly larger declines in the first three trading days following the announcements. Finally, we examine the reaction of stock markets, conditional on the economic classification of their home countries, and find that stock markets in developing (developed) economies are associated with substantially larger (smaller) economic losses.
Board diversity, corporate governance, corporate performance, and executive pay
Authors: Sarhan Ahmed A. , Ntim Collins G. , Al‐Najjar Basil 
Published: October 2018

AbstractDeparting from previous studies, this paper investigates the impact of corporate board diversity on corporate performance and executive pay within the context of Middle East and North African countries. Our sample includes a balanced panel of 600 firm‐year observations, consisting of 100 individual firms drawn from five Middle Eastern countries (Egypt, Jordan, Oman, Saudi Arabia, and United Arab of Emirates) over the 2009–2014 period. The findings are three‐fold. First, board diversity, as measured by director gender and nationality, has a positive effect on corporate financial performance. Second, the relationship between board diversity and corporate performance is stronger in better governed firms than their poorly governed counterparts. Finally, board diversity, as measured by director gender, ethnicity, and nationality, enhances the pay‐for‐performance sensitivity but not the actual executive pay. Our results suggest that decisions about board diversity are not merely influenced by moral values; they arise because of the cost–benefit considerations of what diversity can bring to the firm. The findings are robust to controlling for different alternatives of board diversity measures, corporate governance proxies, corporate outcomes, and types of endogeneities.
In chemico assessment of potential sensitizers: Stability and direct peptide reactivity of 24 fragrance ingredients
Authors: Avonto Cristina , Wang Yan‐Hong , Chittiboyina Amar G. , Vukmanovic Stanislav , Khan Ikhlas A. 
Published: October 2018

AbstractTwenty‐four pure fragrance ingredients of concern as potential skin sensitizers were previously subjected to degradation studies and evaluated using the high throughput with dansyl cysteamine (HTS‐DCYA) method. The experimental results showed that two‐thirds of the 24 fragrance ingredients underwent chemical degradation. In some cases, such degradation was accompanied by an increase in thio‐reactivity. These results prompted us to investigate the reactivity of the same ingredients using the direct peptide reactivity assay (DPRA). In the present work, the 24 chemicals were subjected to forced degradation for 150 days, and evaluated with both DPRA and HTS‐DCYA methods. At the end of the study, four and eight compounds remained non‐reactive in the DPRA and DCYA assay, respectively. Coumarin, benzyl salicylate, benzyl cinnamate and hexyl cinnamal were found unreactive in both assays, while cinnamal, cinnamyl alcohol, hydroxycitronellal and lilial were found negative in the DCYA but positive in the DPRA method. The incongruity in reactivity of these four compounds was attributed to a possible role of pro‐oxidants formed upon degradation, resulting in depletion of peptide without formation of apparent covalent adducts with the test chemical. To validate this hypothesis, the effect of hydrogen peroxide as model pro‐oxidant on both lysine‐ and cysteine‐heptapeptide depletion in the DPRA method was thus investigated. The obtained results showed little effect of oxidative conditions on lysine depletion, while cysteine depletion was significantly affected by concentrations above 1.1 mg/L of hydrogen peroxide. Overall, both in chemico methods confirmed chemical instability should be considered when assessing the skin sensitization potential of (un)known chemicals with alternative methods.
Prediction of clinically relevant drug‐induced liver injury from structure using machine learning
Authors: Hammann Felix , Schöning Verena , Drewe Jürgen 
Published: October 2018

AbstractDrug‐induced liver injury (DILI) is the most common cause of acute liver failure and often responsible for drug withdrawals from the market. Clinical manifestations vary, and toxicity may or may not appear dose‐dependent. We present several machine‐learning models (decision tree induction, k‐nearest neighbor, support vector machines, artificial neural networks) for the prediction of clinically relevant DILI based solely on drug structure, with data taken from published DILI cases. Our models achieved corrected classification rates of up to 89%. We also studied the association of a drug's interaction with carriers, enzymes and transporters, and the relationship of defined daily doses with hepatotoxicity. The results presented here are useful as a screening tool both in a clinical setting in the assessment of DILI as well as in the early stages of drug development to rule out potentially hepatotoxic candidates.
Analysis of polyvinyl alcohol release from commercially available daily disposable contact lenses using an in vitro eye model
Authors: Phan Chau‐Minh , Walther Hendrik , Riederer Donald , Lau Charis , Lorenz Kathrine Osborn , Subbaraman Lakshman Nagapatnam , Jones Lyndon 
Published: October 2018

AbstractThe purpose of this work was to determine the release of polyvinyl alcohol (PVA) from etafilcon A, omafilcon A, and nelfilcon A daily disposable hydrogel contact lenses using a novel in vitro model. PVA is an ocular lubricant that can be found in multiple formulations of artificial tears. Nelfilcon A innately contains PVA, so only the release of PVA from this lens was evaluated. Etafilcon A and omafilcon A lenses were incubated in a PBS solution containing PVA. The release of PVA was evaluated using a novel in vitro blink platform with Milli‐Q water and PBS under various blink conditions and flow rates. Nelfilcon A lenses significantly released more PVA than other lenses at 0.5 and 1.5 h in both PBS and Milli‐Q water (p < 0.001). For nelfilcon A, there was no statistical significance between the release profiles of PVA between the blink and no‐blink conditions, or for the various flow rates (p > 0.05). All tested groups and lenses showed a burst release within the first 4.5 h and rapidly plateaued thereafter. The current study demonstrates that releasable PVA (whether through uptake or through being inherently available from the material) is loosely bound on hydrogel lenses, and the majority is released within 4.5 h. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1662–1668, 2019.
Circulating microRNA signatures serve as potential diagnostic biomarkers for Helicobacter pylori infection
Authors: Yu Jie , Xu Qiaoxia , Zhang Xiaoyu , Zhu Miao 
Published: October 2018

AbstractHelicobacter pylor (H pylori), a Gram‐negative, microaerobic human pathogen, has been found to be involved in many gastroduodenal diseases. Accurate diagnosis of H pylori infection is a vital part of the effective management of gastroduodenal diseases. Circulating microRNAs (miRNAs) have shown the potential to be used as noninvasive biomarkers for the diagnosis of infectious diseases. The aim of this study was to explore plasma miRNAs as noninvasive biomarkers for H pylori infection. We performed a plasma miRNA expression profile using Illumina high‐throughput sequencing and validated the levels of differentially expressed miRNAs in the plasma of 63 H pylori‐infected patients and 41 healthy volunteers by quantitative real‐time polymerase chain reaction (qRT‐PCR). The sequencing results showed that 37 miRNAs were upregulated in the H pylori‐infected patients compared with that in the healthy volunteers, while six miRNAs were downregulated. qRT‐PCR and receiver operator characteristic analysis suggested that the expression of miR‐28‐3p, miR‐143‐3p, miR‐151a‐3p, and miR‐148a‐3p were closely associated with H pylori infection. Therefore, the four plasma miRNA panels mentioned above could serve as promising noninvasive biomarkers of H pylori infection.
Evaluation of STAT1 and Wnt5a gene expression in gingival tissues of patients with periodontal disease
Authors: Haftcheshmeh Saeed Mohammadian , Mohammadi Asadollah , Soltani Arash , Momtazi‐Borojeni Amir Abbas , Sattari Mandana 
Published: October 2018

AbstractPeriodontal disease is a common chronic inflammatory disease of the oral cavity. This disease occurs as a consequence of uncontrolled inflammatory immune responses against periodontopathic bacteria. Several studies have documented the proinflammatory roles of the Signal Transducer and Activator of Transcription 1 (STAT1) and Wnt5a in inflammatory diseases. However, there has been no detailed investigation of STAT1 and Wnt5a genes expression in periodontal disease. So, we aimed to evaluate the expressions of STAT1 and Wnt5a in patients with chronic and aggressive periodontitis and determine their correlation with clinical parameters. Three groups of subjects were enrolled including control (20 healthy individuals), chronic (25 patients), and aggressive periodontitis patients (25 patients). The expressions of STAT1 and Wnt5a were evaluated in gingival tissue samples using a Real‐time polymerase chain reactions assay. The expressions of STAT1 and Wnt5a were significantly upregulated in chronic and aggressive periodontitis compared with the healthy control. We also found that the expressions of STAT1 and Wnt5a increased in aggressive periodontitis compared with chronic periodontitis. In addition, there was the linear relationship between the expression of STAT1 and Wnt5a and the clinical parameters, including clinical attachment loss and periodontal pocket depth. A linear relationship between the expressions of Wnt5a and the clinical parameters was also identified. Taken together, our findings highlight the roles of STAT1 and Wnt5a in the pathogenesis of the periodontal inflammation, suggesting these molecules as valuable therapeutic targets.
Retracted: Advanced glycation end‐products induce oxidative stress through the Sirt1/Nrf2 axis by interacting with the receptor of AGEs under diabetic conditions
Authors: Chen Xiao‐Jun , Wu Wen‐Jun , Zhou Qi , Jie Jin‐Ping , Chen Xiong , Wang Fang , Gong Xiao‐Hua 
Published: October 2018

AbstractDespite the administration of exogenous insulin and other medications used to control many aspects of diabetes mellitus (DM), increased oxidative stress has been increasingly acknowledged in DM development and complications. Therefore, this study aims to investigate the role of advanced glycation end‐products (AGEs) in oxidative stress (OS) of thyroid cells in patients with DM. Patients with DM with or without thyroid dysfunction (TD) were enrolled. Thyroid toxic damage was induced by adding AGE‐modified bovine serum albumin (AGE‐BSA) to normal human thyroid follicular epithelial cells. The cell viability, cell cycle, and cell apoptosis, as well as the content of reactive oxygen species (ROS), catalase (CAT), and malondialdehyde (MDA) in cells were measured. Thyroid hormones, T3, T4, FT3, and FT4 levels were measured by enzyme‐linked immunosorbent assay. Receptor for advanced glycation end products (RAGE), sirtuin1 ( Sirt1), and NF‐E2‐related factor 2 ( Nrf2) expressions were detected, and the mitochondrial membrane potential was measured. We found increased AGEs in the serum of DM patients with TD. By increasing AGE‐BSA concentration, cell viability; the thyroid hormones T3, T4, FT3, and FT4 levels; and mitochondrial membrane potential all significantly decreased. However, the increase in AGE‐BSA concentration led to an increase in cell apoptosis, RAGE, and nuclear factor‐κB expressions but produced the opposite effect on Sirt1, Nrf2, and heme oxygenase‐1 expressions, as well as a decrease in antioxidant response element protein levels. The AGE‐BSA increased ROS and MDA levels and reduced CAT level in normal human thyroid follicular epithelial cells on a dose independence basis. Our results demonstrated that AGEs‐mediated direct increase of RAGE produced OS in thyroid cells of DM by inactivating the Sirt1/Nrf2 axis.
Retracted: Inhibition of microRNA‐940 suppresses the migration and invasion of human osteosarcoma cells through the secreted frizzled‐related protein 1–mediated Wnt/β‐catenin signaling pathway
Authors: Lin Zun‐Wen , Zhang Wei , Jiang Si‐Ding , Wei Wen‐Bo , Li Xiao‐Feng 
Published: October 2018

AbstractOsteosarcoma (OS) is the most common malignant tumor of bone with a high potential for metastasis. This study intends to explore whether microRNA‐940 (miR‐940) affects the development of OS cells and the underlying mechanism. OS and adjacent normal tissues were collected from OS patients; the OS cell line with the highest expression of miR‐940 was selected, which was then subjected to transfection of miR‐940 mimic, miR‐940 inhibitor, siRNA‐secreted frizzled‐related protein 1 (SFRP1) or LiCl (agonists of Wnt/β‐catenin pathway) to identify regulation of miR‐940 to OS cells through SFRP1. The targeting relationship between miR‐940 and SFRP1 was verified using dual‐luciferase reporter gene assay. Reverse‐transcription quantitative polymerase chain reaction and Western blot assay were performed to determine miR‐940, SFRP1, β‐catenin, and cyclinD1 and apoptosis‐related genes Fas, Bax, and Bcl‐2. MTT (3‐(4, 5‐dimethylthiazol‐2‐Yl)‐2, 5‐diphenyltetrazolium bromide) assay, scratch test, transwell assay, and flow cytometry were carried out to detect proliferation, migration, invasion, and apoptosis, respectively. Nude mice models were established to observe the tumor formation. Higher expression of miR‐940, β‐catenin, and cyclinD1 and lower SFRP1 expression were identified in OS tissues. miR‐940 targeted and negatively regulated SFRP1 expression. Furthermore, upregulated miR‐940 expression activated the Wnt/β‐catenin signaling pathway in OS. With the treatment of miR‐940 mimic, LiCL, or siRNA‐SFRP1, OS cells showed promoted proliferation, migration, invasion, tumor formation, and impeded apoptosis (further reflected by elevated Bcl‐2 expression and reduced Fas and Bax expression). The study demonstrates that miR‐940 can promote the proliferation, migration, and invasion but suppress the apoptosis of human OS cells by downregulating SFRP1 through activating Wnt/β‐catenin signaling pathway.
In silico identification and in vitro validation of nogalamycin N‐oxide (NSC116555) as a potent anticancer compound against non–small‐cell lung cancer cells
Authors: Obounchoey Phongphat , Tabtimmai Lueacha , Suphakun Praphasri , Thongkhao Kannika , Eurtivong Chatchakorn , Gleeson Matthew Paul , Choowongkomon Kiattawee 
Published: October 2018

AbstractThe epidermal growth factor receptor (EGFR) was found to be overexpressed in several cancers, especially in lung cancers. Finding new effective drug against EGFR is the key to cancer treatment. In this study, the GOLD docking algorithm was used to virtually screen for novel human EGFR inhibitors from the NCI database. Thirty‐four hit compounds were tested for EGFR‐tyrosine kinase (TK) inhibition. Two potent compounds, 1‐amino‐4‐(4‐[4‐amino‐2‐sulfophenyl]anilino)‐9,10‐dioxoanthracene‐2‐sulfonic acid (NSC125910), and nogalamycin N‐oxide (NSC116555) were identified with IC50 values against EGFR‐TK comparable to gefitinib; 16.14 and 37.71 nM, respectively. However, only NSC116555 demonstrated cytotoxic effects against non–small‐cell lung cancer, A549, shown in the cell cytotoxicity assay with an IC50 of 0.19 + 0.01 µM, which was more potent than gefitinib. Furthermore, NSC116555 showed cytotoxicity against A549 via apoptosis in a dose‐dependent manner.
Intravenous immunoglobulin G treatment increases live birth rate in women with recurrent miscarriage and modulates regulatory and exhausted regulatory T cells frequency and function
Authors: Jafarzadeh Sara , Ahmadi Majid , Dolati Sanam , Aghebati‐Maleki Leili , Eghbal‐Fard Shadi , Kamrani Amin , Behrad Behboud , Roshangar Leila , Jadidi‐Niaragh Farhad , Yousefi Bahman , Mehdipour Mahdi , Farzadi Laya , Yousefi Mehdi 
Published: October 2018

AbstractExhausted T cells and regulatory T (Treg) cells have been recently proposed to be new risk factors for recurrent miscarriage (RM). Intravenous immunoglobulin G (IVIG) treatment reported to modulate various immune cells. In this study, the effects of IVIG on the frequency and function of exhausted T cells, exhausted Tregs, and Treg cells, as well as pregnancy outcome in women with unexplained RM (URM), were investigated. Ninety‐four pregnant women with RM were enrolled. At the time of positive pregnancy, blood samples were drawn. Forty‐four patients with URM were included as IVIG receiving treated group and received 400 mg/kg of IVIG and the rest fifty patients were considered as a control group and received no IVIG administration. IVIG was given intravenously every 4 weeks during 32 weeks of gestation. Blood samples of patients were collected after the latest administration. Exhausted T cells, exhausted Tregs, and Treg cells were evaluated pre‐ and posttreatment in both groups. IVIG induced a significant decrease in the frequency of exhausted Tregs population and function as well as a significant increase in Treg cells population, however, IVIG failed to affect population and the function of exhausted T cells. Pregnancy outcome was successful in IVIG treated women (86.3%) and were significantly different (P = 0.0006) in compared with the untreated URM subjects (42%). Therefore, employing of IVIG increases Treg cells and diminishes exhausted Tregs responses in RM patients with cellular immune anomalies throughout the pregnancy. Immunemodulatory effects of IVIG are probably associated with successful pregnancy outcome.
Nicotine stimulates IL‐6 expression by activating the AP‐1 and STAT‐3 pathways in human endothelial EA.hy926 cells
Authors: Ung Trong Thuan , Nguyen Thi Thinh , Lian Sen , Li Shinan , Xia Yong , Kim Nam Ho , Jung Young Do 
Published: October 2018

AbstractInterleukin‐6 (IL‐6), a pleiotropic cytokine, plays a key role in endothelial injury and atherosclerosis. In this study, we investigated the effects of nicotine, a major psychoactive compound in cigarette smoke, on IL‐6 expression and EA.hy926 endothelial cell invasion. Nicotine stimulated IL‐6 expression via the activator protein 1 (AP‐1) transcription factor. Pharmacological inhibition and mutagenesis studies indicated that p38 mitogen‐activated protein kinase (MAPK) mediated the IL‐6‐induced upregulation of nicotine in EA.hy926 cells. Furthermore, the antioxidant compound N‐acetyl‐cysteine eliminated the nicotine‐activated production of reactive oxygen species (ROS) and inhibited signal transducer and activator of transcription 3 (STAT‐3) phosphorylation; these two mechanisms mediated the upregulation of IL‐6 expression by nicotine. In addition, the EA.hy926 cells treated with nicotine displayed markedly enhanced invasiveness due to IL‐6 upregulation. Our data demonstrate that nicotine induced IL‐6 expression, which, in turn, enhanced the invasiveness of endothelial EA.hy926 cells, via activation of the p38 MAPK/AP‐1 and ROS/STAT‐3 signaling pathways.
Flavopiridol's effects on metastasis in KRAS mutant lung adenocarcinoma cells
Authors: Dogan Turacli Irem , Demirtas Korkmaz Funda , Candar Tuba , Ekmekci Abdullah 
Published: October 2018

AbstractBackgroundThere is still no clinically approved agent for mutant KRAS, which is the most common alteration in non–small‐cell lung cancer (NSCLC). Flavopiridol is a semisynthetic flavonoid that inhibits cell growth through cyclin‐dependent kinases in G1/S or G2/M of the cell cycle and induces apoptosis. In this study, we evaluated its effect on cellular apoptosis, survival, and metastasis mechanisms on KRAS mutant A549, Calu‐1, and H2009 cell lines.MethodsThe cytotoxic effects of flavopiridol on NSCLC cells were determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide cell viability test. The cells were treated with 200 and 400 nM flavopiridol, and, then, apoptosis, survival, and metastasis‐related protein expressions were determined by Western blot analysis. The antimetastatic effects of flavopiridol were assessed by wound healing and Galectin‐3 activity assay.ResultsFlavopiridol drastically affected toxicity in all KRAS mutant NSCLC cells at nanomolar concentrations. Also, it could efficiently inhibit wound healing and Galectin‐3 activity in all the cells tested. However, the metastasis‐related protein expressions did not reflect these obvious effects on blotting. p‐Erk was activated as a cellular survival mechanism to escape apoptosis in all the cells tested.ConclusionAlthough there are many mechanisms that still need to be elucidated, flavopiridol can be used as a metastasis inhibitor and an apoptosis inducer in KRAS mutant NSCLC.