bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sofosbuvir as treatment against dengue?
Authors: Gan Chye Sheng , Lim See Khai , Chee Chin Fei , Yusof Rohana , Heh Choon Han 
Published: August 2017

Dengvaxia® (CTD‐TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD‐TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti‐HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS‐461203) was predicted to bind to the catalytic motif (Gly‐Asp‐Asp) of dengue viral polymerase with binding affinity of −6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC90 of 0.4 μm. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS‐461203 to exert its antidengue potential. All in all, sofosbuvir should be subjected to in‐depth studies to provide information of its efficacy toward dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue.
Lipopolysaccharide suppresses IgE‐mast cell‐mediated reactions
Authors: Wang N. , McKell M. , Dang A. , Yamani A. , Waggoner L. , Vanoni S. , Noah T. , Wu D. , Kordowski A. , Köhl J. , Hoebe K. , Divanovic S. , Hogan S. P. 
Published: August 2017

SummaryBackgroundClinical and experimental analyses have identified a central role for IgE/FcεRI/mast cells in promoting IgE‐mediated anaphylaxis. Recent data from human studies suggest that bacterial infections can alter susceptibility to anaphylaxis.ObjectiveWe examined the effect of LPS exposure on the induction of IgE‐mast cell (MC) mediated reactions in mice.MethodsC57BL/6 WT, tlr4−/− and IL10−/− mice were exposed to LPS, and serum cytokines (TNF and IL‐10) were measured. Mice were subsequently treated with anti‐IgE, and the symptoms of passive IgE‐mediated anaphylaxis, MC activation, Ca2+‐mobilization and the expression of FcεRI on peritoneal MCs were quantitated.ResultsWe show that LPS exposure of C57BL/6 WT mice constraints IgE‐MC–mediated reactions. LPS‐induced suppression of IgE‐MC–mediated responses was TLR‐4‐dependent and associated with increased systemic IL‐10 levels, decreased surface expression of FcεRI on MCs and loss of sensitivity to IgE activation. Notably, LPS‐induced desensitization of MCs was short term with MC sensitivity to IgE reconstituted within 48 hours, which was associated with recapitulation of FcεRI expression on the MCs. Mechanistic analyses revealed a requirement for IL‐10 in LPS‐mediated decrease in MC FcεRI surface expression.Conclusions & Clinical RelevanceCollectively, these studies suggest that LPS‐induced IL‐10 promotes the down‐regulation of MC surface FcεRI expression and leads to desensitization of mice to IgE‐mediated reactions. These studies indicate that targeting of the LPS‐TLR‐4‐IL‐10 pathway may be used as a therapeutic approach to prevent adverse IgE‐mediated reactions.
Founder‐CEOs and corporate turnaround among declining firms
Authors: Abebe Michael A. , Tangpong Chanchai 
Published: August 2017

AbstractManuscript TypeEmpiricalResearch Question/IssueDespite the growing interest in leaders' role in the turnaround process, there is a paucity of research on founder‐CEOs' role in achieving successful turnaround among declining firms. In this study, using insights from the organizational identification literature, we argue that founder‐CEOs play an important role in turnaround attempts due to their strong organizational commitment and psychological attachment to the declining firm as well as the relative absence of agency problem issues common among their non‐founder counterparts.Research Findings/InsightsUsing data from a matched pair sample of 142 US firms that experienced performance decline, we found that founder‐CEO leadership significantly increases turnaround success in declining firms. We also found that, among turnaround firms, those led by founder‐CEOs tend to put more emphasis on market‐based turnaround strategies, such as new product introductions, and less emphasis on retrenchment actions, such as divestments.Theoretical/Academic ImplicationsOur findings contribute to corporate turnaround research by providing a more nuanced view of leaders' role in the turnaround process by specifically exploring the effect of founder CEO leadership. Furthermore, this study contributes to the turnaround literature by highlighting the strategic choices of founder‐CEO‐led firms and how these choices influence successful turnaround. Finally, by introducing organizational identification perspective, this study provides additional theoretical explanation of leadership antecedents of successful turnarounds.Practitioner/Policy ImplicationsThe findings of this study suggest that boards of directors, shareholders, and consultants who often participate in turnaround management should carefully consider retaining founder‐CEOs and endorsing their leadership during the turnaround process. Further, the findings provide turnaround specialists and other stakeholders with further understanding of not only the importance of product market strategies in the turnaround process but also founder‐CEOs' role in fostering such strategies.
HbA1c variability is associated with increased mortality and earlier hospital admission in people with Type 1 diabetes
Authors: Walker G. S. , Cunningham S. G. , Sainsbury C. A. R. , Jones G. C. 
Published: August 2017

AbstractAimDespite evidence of morbidity, no evidence exists on the relationship between HbA1c variability and mortality in Type 1 diabetes. We performed an observational study to investigate whether the association between HbA1c variability and mortality exists in a population of people with Type 1 diabetes. As a secondary outcome, we compared onset of first hospital admission between groups.MethodsPeople with Type 1 diabetes were identified for inclusion from the Scottish Care Information – Diabetes data set. This database includes data of all people known to have diabetes who live within Scotland. A survival analysis was carried out over a 47‐month period comparing two groups; group 1 with a HbA1c coefficient of variation (CV) above the median CV value, and group 2 with a CV below the median value. Time to death or first admission was also analysed. A Cox proportional hazard model was used to compare time to death, adjusting for appropriate covariables.ResultsSome 6048 individuals with Type 1 diabetes were included in the analysis. Median HbA1c CV was 7.9. The hazard ratio (HR) for mortality for those with an HbA1c CV above the median value is 1.5 over 47 months of follow‐up (P < 0.001). HR for survival to either the first admission to hospital or death for those with an HbA1c CV above the median value was 1.35 (95% confidence interval 1.25–1.45) over 730 days of follow‐up (P < 0.001).ConclusionOur results show that people with greater HbA1c variability have a higher rate of mortality and earlier hospital admission in Type 1 diabetes.
A novel echocardiographic hemodynamic classification of heart failure based on stroke volume index and left atrial pressure
Authors: Abbas Amr E. , Khoury Abdulla Rami , Aggrawal Anshul , Crile Jason , Lester Steven J. , Boura Judy 
Published: August 2017

Background and AimDividing patients with heart failure (HF) based solely on ejection fraction (EF) may over simplify the hemodynamic states of these patients. We describe a novel echo‐derived hemodynamic HF model based on flow (stroke volume index [SVI]) and left atrial pressure (E:E′) correlates.MethodsA retrospective analysis of patients admitted with HF with both reduced (HFrEF) and preserved EF (HFpEF). Patients were subdivided into four hemodynamic groups based on echocardiographic SVI (< or ≥35 mL/m2) and E/E′ (≥ or <15). Group A: normal flow and normal filling pressure, Group B: normal flow but high filling pressure, Group C: low flow and low filling pressure, and Group D: low flow and high filling pressure.ResultsA total of 176 patients were enrolled, 123 patients had HFrEF and 53 patients had HFpEF. Baseline characteristics were not statistically significant in both groups. In HFrEF, most patients were in group D compared to a heterogeneous distribution in HFpEF (P<.0001). In HFrEF, there was a trend toward an increase in B‐type natriuretic peptide levels with a decrease in SVI and increase in E/E′ (P=.05) but not in HFpEF. There was no difference in death, major adverse cardiac events, but a higher readmissions rate in the HFpEF group at 30 days and 18 months.ConclusionsHemodynamic subgroups differ between HFrEF and HFpEF. There is no difference in major adverse cardiovascular events between both groups with increased readmissions in HPpEF patients. Larger studies may help assess the impact of echo‐derived hemodynamic state on clinical outcome.
Distress and unmet needs during treatment and quality of life in early cancer survivorship: A longitudinal study of haematological cancer patients
Authors: Oberoi Devesh V. , White Victoria M. , Seymour John F. , Prince H. Miles , Harrison Simon , Jefford Michael , Winship Ingrid , Hill David J. , Bolton Damien , Millar Jeremy , Wong Doo Nicole , Kay Anne , Giles Graham 
Published: August 2017

AbstractObjectiveTo examine the influence of anxiety, depression and unmet supportive care needs on future quality of life (QoL) in multiple myeloma (MM) and diffuse large B‐cell lymphoma (DLBCL) patients.MethodsMultiple myeloma and DLBCL patients recruited through the population‐based Victorian Cancer Registry. Data were collected through two telephone interviews: (T1) on average 7 months postdiagnosis, (T2) average 8 months later. QoL was examined at T2 using the Functional Assessment of Cancer Therapy (FACT‐G) scale. The Hospital Anxiety and Depression Scale measured anxiety and depression, and the Supportive Care Needs Survey measured unmet needs at T1. Multivariate linear regression examined associations between QoL subscales (physical, emotional, social and functional well‐being and overall QoL) and T1 anxiety, depression and unmet needs.ResultsExcept physical well‐being, all other QoL subscales and overall QoL were significantly associated with T1 anxiety. All QoL subscales and overall QoL were significantly associated with T1 depression. Only patient care needs were associated with physical and social well‐being and overall QoL.ConclusionAnxiety, depression and patient care unmet needs during treatment are associated with diminished physical and emotional well‐being in the following months. Psychological distress and unmet supportive care needs experienced during treatment should be addressed to maximise future QoL.
Changes in serum lipid profiles caused by three regimens of interferon‐free direct‐acting antivirals for patients infected with hepatitis C virus
Authors: Inoue Takako , Goto Takaaki , Iio Etsuko , Matsunami Kayoko , Fujiwara Kei , Shinkai Noboru , Matsuura Kentaro , Matsui Takeshi , Nojiri Shunsuke , Tanaka Yasuhito 
Published: August 2017

AimSerum low‐density lipoprotein cholesterol (LDL‐C) increases during treatment of chronic hepatitis C (CHC) with interferon‐free direct‐acting antivirals (DAAs). We sought to compare the changes of serum lipid profiles caused by three regimens.MethodsA total of 216 CHC patients were enrolled. Among 170 patients infected with hepatitis C virus (HCV) genotype 1b, 85 received daclatasvir plus asunaprevir (DCV/ASV) and 85 received sofosbuvir plus ledipasvir (SOF/LDV). Forty‐six infected with HCV genotype 2 received sofosbuvir plus ribavirin (SOF/RBV). Serum total cholesterol (TC), LDL‐C, high‐density lipoprotein cholesterol, and triglyceride were measured at baseline and 4, 8, 12 (for all regimens), and 24 weeks (for DCV/ASV) during treatment (4w, 8w, 12w, and 24w, respectively) and 12 and 24 weeks after treatment (p12w and p24w, respectively).ResultsIn 69 (81.2%) patients who received DCV/ASV and achieved a sustained virologic response at 24 weeks after the end of treatment (SVR24), TC and LDL‐C increased significantly from baseline to p24w. In 84 (98.8%) treated with SOF/LDV who achieved SVR24, TC and LDL‐C increased significantly from baseline to 8w, and TC decreased significantly from 8w to p12w. The 45 (97.8%) who received SOF/RBV and achieved SVR24 showed no significant changes. At 12w, TC and LDL‐C increased to a greater degree in patients receiving SOF/LDV than in those receiving DCV/ASV or SOF/RBV.ConclusionDuring treatment with DAAs, the serum lipid profile may reflect not only recovery from the disruption of lipid metabolism induced by HCV, but also the pharmacological effects of DAAs. Further investigations are needed to elucidate the effect of DAAs on serum lipid profiles.
Testing environmental correlates of clines in clades: an example from cassidine beetles
Authors: Simões Marianna V. P. , Lieberman Bruce S. , Soberón Jorge , Peterson A. Townsend 
Published: August 2017

AbstractPhenotypic change across environmental gradients has been an important topic in evolutionary biology. Members of the tortoise beetle tribe Dorynotini are characterised by an elytral suture adorned with either a tubercle or a large, vertical spine. Overall spine height across species had previously been posited to exhibit a latitudinal gradient of increasing height and decreasing width towards the southern extreme of the tribe's range, and this pattern had been linked to environmental variation.We explore the evidence behind such a cline by testing associations between climate and morphology across the clade's geographic distribution using an approach based on ecological niche modelling (ENM) and morphological and environmental hypervolumes. The degree of overlap between the respective hypervolumes was assessed, and the correlation of matrix overlap values was quantified using Mantel tests. Degrees of niche similarity and conservatism at the genus level were also assessed using both Schoener's index and Hellinger distances.Overall, we observed that characters defining our morphological hypervolumes were informative, and capable of grouping taxa into discrete units in morphospace. In contrast, environmental hypervolumes were largely homogeneous across the tribe, with high overlap among taxa. No significant correlations were found between environmental and morphological hypervolumes.Our results indicate that morphological divergence occurs along with high levels of environmental overlap; perhaps historical biogeographic factors along with sexual selection may have promoted its diversification. Our approach based on ENM and statistical comparisons between environmental and morphological hypervolumes can provide a useful approach to testing the existence of gradients and clines.
Sensitivity of an oral health‐related quality‐of‐life questionnaire in detecting oral health impairment in preschool children
Authors: Guedes Renata S. , Ardenghi Thiago M. , Emmanuelli Bruno , Piovesan Chaiana , Mendes Fausto M. 
Published: August 2017

AimThis two‐year cohort study evaluated whether the Early Childhood Oral Health Impact Scale (ECOHIS) is responsive to detect changes related to dental caries.DesignPreschool children were examined in 2010 regarding dental caries, and their parents responded to the ECOHIS. After 2 years, 352 children (response rate = 73.6%) were re‐examined and a new ECOHIS was responded. Children were categorized according to caries increment (no new caries, 1–3 surfaces with new lesions, and four or more decayed surfaces). The outcome variables were related to the decline of quality of life as determined via ECOHIS: decline, severe decline, and differences between baseline and follow‐up scores. Effect sizes (ES) were calculated, and the associations were evaluated through Poisson regression.ResultsES was small for children with 1–3 new lesions (ES = 0.19) and moderate for children with four or more new carious lesions (ES = 0.61). Children who developed 1–3 new lesions were significantly associated with all outcome variables compared to children with no new lesions, but the associations were stronger for children with four or more new carious lesions.ConclusionsThe ECOHIS is sensitive to the deterioration of quality of life due to caries increments in preschool children.
Effects of microstructure on electrochemical reactivity and conductivity in nanostructured ceria thin films
Authors: Ding Jilai , Strelcov Evgheni , Bassiri‐Gharb Nazanin 
Published: August 2017

AbstractThe proton conductivity in functional oxides is crucial in determining electrochemistry and transport phenomena in a number of applications such as catalytic devices and fuel cells. However, single characterization techniques are usually limited in detecting the ionic dynamics at the full range of environmental conditions. In this report, we probe and uncover the links between the microstructure of nanostructured ceria (NC) and parameters that govern its electrochemical reaction and proton transport, by coupling experimental data obtained with time‐resolved Kelvin probe force microscopy (tr‐KPFM), electrochemical impedance spectroscopy (EIS), and finite element analysis. It is found that surface morphology determines the water splitting rate and proton conductivity at 25°C and wet conditions, when protons are mainly generated and transported within surface physisorbed water layers. However, at higher temperature (i.e., ≥125°C) and dry conditions, when physisorbed water evaporates, grain size, and crystallographic orientation become significant factors. Specifically, the proton generation rate is negatively correlated with the grain size, whereas proton diffusivity is facilitated by surface {111} planes and additional conduction pathways offered by cracks and open pores connected to the surface.
Molecular Phylogenetic Positions of Two New Marine Gregarines (Apicomplexa)—Paralecudina anankea n. sp. and Lecudina caspera n. sp.—from the Intestine of Lumbrineris inflata (Polychaeta) Show Patterns of Co‐evolution
Authors: Iritani Davis , Wakeman Kevin C. , Leander Brian S. 
Published: August 2017

AbstractGregarine apicomplexans are unicellular parasites commonly found in the intestines and coeloms of invertebrate hosts. Traits associated with the conspicuous feeding stage of gregarines, known as the trophozoite, have been used in combination with molecular phylogenetic data for species delimitation and the reconstruction of evolutionary history. Trophozoite morphology alone is often inadequate for inferring phylogenetic relationships and delimiting species due to frequent cases of high intraspecific variation combined with relatively low interspecific variation. The current study combined morphological data with small subunit (SSU) rDNA sequences to describe and establish two novel marine gregarine species isolated from the intestine of a polychaete host Lumbrineris inflata collected in British Columbia (Canada): Paralecudina anankea n. sp. and Lecudina caspera n. sp. The sister species to the host is Lumbrineris japonica, which can be found on the opposite side of the Pacific Ocean (Japan) and contains two different species of gregarine parasites: Paralecudina polymorpha and Lecudina longissima. Molecular phylogenetic analyses placed P. anankea n. sp. as the sister species to P. polymorpha and L. caspera n. sp. as the sister species to L. longissima. This phylogenetic pattern demonstrates a co‐evolutionary history whereby speciation of the host (Lumbrineris) corresponds with simultaneous speciation of the two different lineages of intestinal gregarines (Paralecudina and Lecudina).
Fitness consequences of a clock pollinator filter in Nicotiana attenuata flowers in nature
Authors: Yon Felipe , Kessler Danny , Joo Youngsung , Kim Sang‐Gyu , Baldwin Ian T. 
Published: August 2017

SummaryNicotiana attenuata flowers, diurnally open, emit scents and move vertically to interact with nocturnal hawkmoth and day‐active hummingbird pollinators. To examine the fitness consequences of these floral rhythms, we conducted pollination trials in the plant's native habitat with phase‐shifted flowers of plants silenced in circadian clock genes. The results revealed that some pollination benefits observed under glasshouse conditions were not reproduced under natural field conditions. Floral arrhythmicity increased pollination success by hummingbirds, while reducing those by hawkmoths in the field. Thus, floral circadian rhythms may influence a plant's fitness by filtering pollinators leading to altered seed set from outcrossed pollen.
Enhanced motivation to alcohol in transgenic mice expressing human α‐synuclein
Authors: Rotermund Carola , Reolon Gustavo K. , Leixner Sarah , Boden Cindy , Bilbao Ainhoa , Kahle Philipp J. 
Published: August 2017

Abstractα‐Synuclein (αSYN) is the neuropathological hallmark protein of Parkinson's disease (PD) and related neurodegenerative disorders. Moreover, the gene encoding αSYN (SNCA) is a major genetic contributor to PD. Interestingly, independent genome‐wide association studies also identified SNCA as the most important candidate gene for alcoholism. Furthermore, single‐nucleotide‐polymorphisms have been associated with alcohol‐craving behavior and alcohol‐craving patients showed augmented αSYN expression in blood. To investigate the effect of αSYN on the addictive properties of chronic alcohol use, we examined consumption, motivation, and seeking responses induced by environmental stimuli and relapse behavior in transgenic mice expressing the human mutant [A30P]αSYN throughout the brain. The primary reinforcing effects of alcohol under operant self‐administration conditions were increased, while consumption and the alcohol deprivation effect were not altered in the transgenic mice. The same mice were subjected to immunohistochemical measurements of immediate‐early gene inductions in brain regions involved in addiction‐related behaviors. Acute ethanol injection enhanced immunostaining for the phosphorylated form of cAMP response element binding protein in both amygdala and nucleus accumbens of αSYN transgenic mice, while in wild‐type mice no effect was visible. However, at the same time, levels of cFos remain unchanged in both genotypes. These results provide experimental confirmation of SNCA as a candidate gene for alcoholism in addition to its known link to PD.
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