bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients treated with first‐generation HCV protease inhibitors exhibit high ribavirin concentrations
Authors: Bodeau Sandra , Nguyen‐Khac Eric , Solas Caroline , Bennis Youssef , Capron Dominique , Duverlie Gilles , Brochot Etienne 
Published: December 2014

AbstractAnemia is a well‐known RBV‐related event in HCV therapy which is exacerbated by the addition of telaprevir and boceprevir. This retrospective study evaluated and compared ribavirin exposure and parameters able to influence hemoglobin decrease in a large population of patients treated with dual or triple therapy. Patients on triple therapy had higher ribavirin concentrations at week 12 of treatment (3460 ng/mL vs. 1843 ng/mL; P < .0001). An association was also observed between week 12 eGFR and ribavirin concentration only for patients on triple therapy (P = .002). The proportion of patients with a  >20 mL/min/1.73 m2 decrease in eGFR at week 12 was higher among patients on triple therapy: 32%, 14%, and 5% for boceprevir, telaprevir, and dual therapy, respectively (P = .025 and .026). No correlation was observed between boceprevir and telaprevir concentrations and hemoglobin or eGFR decrease. Exacerbation of anemia in patients on triple therapy is related to higher ribavirin concentrations. We provide an explanation for this increase in plasma RBV concentration. Triple therapy with PEG‐IFN, RBV, and telaprevir or boceprevir will remain the only HCV treatment option for many patients. Our data show that the RBV dose can be decreased while maintaining adequate plasma concentrations and reducing anemia.
A Brooks‐Type Theorem for the Bichromatic Number
Authors: Epple Dennis D. A. , Huang Jing 
Published: December 2014

AbstractA classical theorem of Brooks in graph coloring theory states that every connected graph G has its chromatic number less than or equal to its maximum degree , unless G is a complete graph or an odd cycle in which case is equal to . Brooks' theorem has been extended to list colorings by Erdős, Rubin, and Taylor (and, independently, by Vizing) and to some of their variants such as list T‐colorings and pair‐list colorings. The bichromatic number is a relatively new parameter arisen in the study of extremal hereditary properties of graphs. This parameter simultaneously generalizes the chromatic number and the clique covering number of a graph.In this article, we prove a theorem, akin to that of Brooks, which states that every graph G has its bichromatic number less than or equal to its bidegree , unless G belongs to a set of specified graphs in which case is equal to .
Implementation and evaluation of a rapid access palliative clinic in a New Zealand cancer centre
Authors: Casson Charlene , Round Glenys , Johnson Janet 
Published: December 2014

AbstractIntroductionPalliative patients with metastatic bone pain endure long waiting times and multiple visits to radiation therapy departments for treatment. This can prolong suffering and may be a factor in patients consenting for treatment. Rapid Access Palliative Clinics (RAPC) have been established around the world to provide a multidisciplinary approach to consultation, simulation and treatment on the same day. This paper describes the implementation and evaluation of a RAPC at Waikato Regional Cancer Centre (WRCC) by reducing the time from referral to first specialist appointment (FSA).MethodsThe structure and process for the RAPC day was outlined and the roles of staff were defined. A retrospective study was undertaken of the 261 consecutive patients seen in the RAPC from April 2009 to April 2013. Tracking sheets were created to record patient information at the initial consultation. Follow‐up telephone calls were used to assess the patient post‐treatment. Patient information was entered into a database.ResultsA total of 226 patients received radiation therapy treatment to 307 sites. All patients were seen within 1 week of referral. Sixty‐three per cent of patients were simulated and treated on the same day. The change in radiation therapy fractionation prescriptions was statistically significant (P = 0.0012). There was a statistically significant difference between initial and follow‐up pain scores (P < 0.0001).ConclusionEvaluation of the clinic has shown that it compares favourably with similar international clinics. The RAPC has decreased the referral to FSA for palliative radiation therapy and reduced the number of visits the patient has to endure due to an increase in single fraction prescriptions. This has resulted in rapid reduction in pain for the majority of patients.
Ephrins and Ephs in cochlear innervation and implications for advancing cochlear implant function
Authors: Lee Kenneth H. , Warchol Mark E. , Pawlowski Karen S. , Shao Dongmei , Koulich Elena , Zhou Constance Q. , Lee James , Henkemeyer Mark J. 
Published: December 2014

Objectives/HypothesisDetermine if the neuronal pathfinding cues resulting from Eph/ephrin interaction in the inner ear play a role in establishing the tonotopic innervation of the cochlea.Study DesignProtein expression of Ephs and ephrins was evaluated in the inner ear of mice and chicks. Subsequently, in vitro, in vivo, and functional electrophysiologic studies were performed to indicate that Ephs and ephrins play a role regulating the normal innervation patterns in the mouse inner ear.MethodsEph and ephrin protein expression was identified in the inner ear by western blotting and localized by fluorescence immunohistochemistry and X‐gal staining. Eph/ephrin effects on neurite outgrowth was assessed via co‐culture with EphB2 expressing COS‐1 cells. Anatomic effects of disrupting Eph/ephrin signaling on cochlear innervation were determined with lipophilic dye tracing and functional effects with auditory brainstem response (ABR).ResultsExpression of several different Ephs and ephrins were found in the inner ear of chicks and mice. The changes in ephrin‐A2 immunoreactivity after gentamicin ototoxicity coincide with the spatio‐temporal pattern of hair cell loss and regeneration in the chick cochlea. EphB2 inhibited outgrowth of spiral ganglion cell neurites. Knockout mice with null function of EphB1, EphB2, and EphB3 demonstrated abnormal inner ear innervation and elevated ABR thresholds, indicating hearing loss.ConclusionsEphrin‐A2 may be involved in the guidance of ganglion cells to hair cells in the chick. Disruption of Eph/ephrin signaling results in abnormal innervation and hearing loss, suggesting that these proteins play a role in establishing normal innervation patterns in the mouse cochlea.Level of EvidenceNA Laryngoscope, 125:1189–1197, 2014
Postprandial triglycerides and adipose tissue storage of dietary fatty acids: Impact of menopause and estradiol
Authors: Bessesen Daniel H. , Cox‐York Kimberly A. , Hernandez Teri Lynn , Erickson Christopher B. , Wang Hong , Jackman Matt R. , Van Pelt Rachael E. 
Published: December 2014

ObjectivesPostprandial lipemia worsens after menopause, but the mechanism remains unknown. The hypothesized menopause‐related postprandial lipemia would be (1) associated with reduced storage of dietary fatty acids (FA) as triglyceride (TG) in subcutaneous adipose tissue (SAT) and (2) improved by short‐term estradiol (E2).MethodsTwenty‐three pre‐ (mean ± SD: 42 ± 4 years) and 22 postmenopausal (55 ± 4 years) women with similar total adiposity were studied. A subset of postmenopausal women (n = 12) were studied following 2 weeks of E2 (0.15 mg) and matching placebo in a random, cross‐over design. A liquid meal containing 14C‐oleic acid traced appearance of dietary FA in: serum (postprandial TG), breath (oxidation), and abdominal and femoral SAT (TG storage).ResultsCompared to premenopausal women, healthy, lean, postmenopausal women had increased postprandial glucose and insulin and trend for higher TG but had similar dietary FA oxidation and storage. Adipocytes were larger in post‐ compared to premenopausal women, particularly in femoral SAT. Short‐term E2 reduced postprandial TG and insulin but had no effect on oxidation or storage of dietary FA. E2 increased the proportion of small adipocytes in femoral (but not abdominal) SAT.ConclusionsShort‐term E2 attenuated menopause‐related increases in postprandial TG and increased femoral adipocyte hyperplasia but not through increased net storage of dietary FA.
Combination of miRNA499 and miRNA133 Exerts a Synergic Effect on Cardiac Differentiation
Authors: Pisano Federica , Altomare Claudia , Cervio Elisabetta , Barile Lucio , Rocchetti Marcella , Ciuffreda Maria Chiara , Malpasso Giuseppe , Copes Francesco , Mura Manuela , Danieli Patrizia , Viarengo Gianluca , Zaza Antonio , Gnecchi Massimiliano 
Published: December 2014

Abstract
Several studies have demonstrated that miRNA are involved in cardiac development, stem cell maintenance, and differentiation. In particular, it has been shown that miRNA133, miRNA1, and miRNA499 are involved in progenitor cell differentiation into cardiomyocytes. However, it is unknown whether different miRNA may act synergistically to improve cardiac differentiation. We used mouse P19 cells as a cardiogenic differentiation model. miRNA499, miRNA1, or miRNA133 were transiently over-expressed in P19 cells individually or in different combinations. The over-expression of miRNA499 alone increased the number of beating cells and the association of miRNA499 with miRNA133 exerted a synergistic effect, further increasing the number of beating cells. Real-time polymerase chain reaction showed that the combination of miRNA499 + 133 enhanced the expression of cardiac genes compared with controls. Western blot and immunocytochemistry for connexin43 and cardiac troponin T confirmed these findings. Importantly, caffeine responsiveness, a clear functional parameter of cardiac differentiation, was increased by miRNA499 in association with miRNA133 and was directly correlated with the activation of the cardiac troponin I isoform promoter. Cyclic contractions were reversibly abolished by extracellular calcium depletion, nifedipine, ryanodine, and IP3R blockade. Finally, we demonstrated that the use of miRNA499 + 133 induced cardiac differentiation even in the absence of dimethyl sulfoxide. Our results show that the areas spontaneously contracting possess electrophysiological and pharmacological characteristics compatible with true cardiac excitation-contraction coupling. The translational relevance of our findings was reinforced by the demonstration that the over-expression of miRNA499 and miRNA133 was also able to induce the differentiation of human mesenchymal stromal cells toward the cardiac lineage. Stem Cells 2015;33:1187–1199
Deltamethrin‐induced oxidative stress and mitochondrial caspase‐dependent signaling pathways in murine splenocytes
Authors: Kumar Anoop , Sasmal D. , Bhaskar Amand , Mukhopadhyay Kunal , Thakur Aman , Sharma Neelima 
Published: December 2014

ABSTRACTDeltamethrin (DLM) is a well‐known pyrethroid insecticide used extensively in pest control. Exposure to DLM has been demonstrated to cause apoptosis in various cells. However, the immunotoxic effects of DLM on mammalian system and its mechanism is still an open question to be explored. To explore these effects, this study has been designed to first observe the interactions of DLM to immune cell receptors and its effects on the immune system. The docking score revealed that DLM has strong binding affinity toward the CD45 and CD28 receptors. In vitro study revealed that DLM induces apoptosis in murine splenocytes in a concentration‐dependent manner. The earliest markers of apoptosis such as enhanced reactive oxygen species and caspase 3 activation are evident as early as 1 h by 25 and 50 µM DLM. Western blot analysis demonstrated that p38 MAP kinase and Bax expression is increased in a concentration‐dependent manner, whereas Bcl 2 expression is significantly reduced after 3 h of DLM treatment. Glutathione depletion has been also observed at 3 and 6 h by 25 and 50 µM concentration of DLM. Flow cytometry results imply that the fraction of hypodiploid cells has gradually increased with all the concentrations of DLM at 18 h. N‐acetyl cysteine effectively reduces the percentage of apoptotic cells, which is increased by DLM. In contrast, buthionine sulfoxamine causes an elevation in the percentage of apoptotic cells. Phenotyping data imply the effect of DLM toxicity in murine splenocytes. In brief, the study demonstrates that DLM causes apoptosis through its interaction with CD45 and CD28 receptors, leading to oxidative stress and activation of the mitochondrial caspase‐dependent pathways which ultimately affects the immune functions. This study provides mechanistic information by which DLM causes toxicity in murine splenocytes. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 808–819, 2016.
MicroRNA‐155 targets cyb561d2 in zebrafish in response to fipronil exposure
Authors: Huang Hannian , Zhang Kai , Zhou Yongyong , Ding Xianfeng , Yu Liang , Zhu Guonian , Guo Jiangfeng 
Published: December 2014

ABSTRACTMicroRNAs (miRNAs), which are a class of small noncoding RNAs, can modulate the expression of many protein‐coding genes when an organism is exposed to an environmental chemical. We previously demonstrated that miR‐155 was significantly downregulated in adult zebrafish (Danio rerio) in response to fipronil (5‐amino‐1‐[2,6‐dichloro‐4‐(trifluoromethyl) phenyl]‐4‐[(trifluoromethyl) sulphinyl]‐1H‐pyrazole‐3‐carbonitrile) exposure. However, the regulation of this miRNA's predicted target gene cyb561d2, which is a member of the cytochrome b561 (cyt b561) family involved in electron transfer, cell defence, and chemical stress, has not been experimentally validated to date. In this study, we evaluated the effects of fipronil on miR‐155 and cyb561d2 in zebrafish. The expression of miR‐155 was downregulated, whereas cyb561d2 was upregulated in both mRNA and protein level in a dose‐dependent manner upon stimulation of fipronil. The dual luciferase report assay demonstrated that miR‐155 interacted with cyb561d2 3′‐untranslated regions (3′‐UTR). The expression of cyb561d2 was reduced in both mRNA and protein levels when ZF4 cells were transfected with an miR‐155 mimic, whereas its expression levels of both mRNA and protein were increased when endogenous miR‐155 was inhibited by transfection with an miR‐155 inhibitor. The results improved our understanding of molecular mechanism of toxicity upon fipronil exposure, and presents miR‐155 as a potential novel toxicological biomarker for chemical exposure. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 877–886, 2016.
Metabolic and endocrine changes induced by chronic heatexposure in broiler chickens : biological and endocrinological variables
Authors: Geraert P. A. , Padilha J. C. F. , Guillaumin S. 
Published: December 2014

Abstract:The present study was designed to investigate the effect of chronic heat exposure (32° constant) on plasma metabolites and hormone concentrations in broiler chickens. At 2 and 4 weeks of age, fifty-four male Shaver broiler chickens were allocated to one of three treatments: 22° ad lib. feeding (22AL), 32°ad lib. feeding (32AL) and 22°,pair-feeding with the 32AL group (22PF). Ambient temperature was kept constant at either 22 or 32° for 2 weeks. Plasma glucose, triacylglycerols, phospholipids, non-esterified fatty acids (NEFA), individual amino acids, uric acid, insulin, triiodothyronine (T3), thyroxine, corticosterone were determined. Sensitivity to exogenous insulin was also measured at 7 weeks of age. At 4 and 6 weeks of age, i.e. after 2 weeks at high ambient temperature, fasted 32AL chickens displayed similar concentrations of glucose and triacylglycerols to those of 22AL birds. When fed, 32AL chickens exhibited higher plasma levels of glucose and decreased concentrations of NEFAand amino acids. Feed restriction resulted in intermediate values. Concentrations of all plasmafree amino acids were decreased under heat exposure except for aspartic acid, glutamic acid andphenylalanine. At 6 weeks of age, plasma T3 was reduced irrespective of the nutritional state, while plasma corticosterone concentrations were increased in 32AL birds compared with 22AL birds. Heat exposure did not change plasma insulin concentration in either fasted or fed chickens. The 32AL chickens displayed significantly reduced sensitivity to exogenous insulin when fasted,but an enhanced response to insulin when fed, compared with both 22° groups. Such endocrinological changes could stimulate lipid accumulation through increased de novo lipogenesis, reduced lipolysis and enhanced amino acid catabolism under chronic heat exposure.
Partition of oleic acid between the lymph and portal blood in rats having a diverted bile-pancreatic duct
Authors: Mathieu Y. , Caselli C. , Bernard A. , Carlier H. 
Published: December 2014

AbstractThe present study examines the suggestion that in the absence of adequate bile and pancreatic juice, which support the absorption from the gut of long-chain fatty acidsinto lymph, the fatty acids are absorbed directly into the portal blood. Oleic acid (18:l) partitioning between lymph and portal blood was investigated in intact and bile- and pancreatic juice-diverted rats. In a first set of experiments, 18: 1 absorption from the gut into lymph and blood was studied by continuous recovery of the mesenteric lymph for 6 h and mesenteric portal venous blood for 1 h. In a second set of experiments, esterification processes were investigated by study of the mucosal distribution of labelled lipids and by mono- and diacylglycerol acyltransferase (EC 2.3.1.22 and EC 2.3.1.20 respectively) specific activities. In the bile- and pancreatic juice-diverted rats the absorption of labelled 18:l into lymph was significantly reduced during the first 3 h of intraluminal infusion of this substrate. In such rats a compensatory absorption of labelled 18: 1 into mesenteric portal blood was not observed. At 6 h after micellar lipid- mixture infusion, the overload of lipids both in free form and as triacylglycerols persisting in the mucosa paralleled the lower acyltransferase specific activities observed in bile- and pancreatic juice-diverted rats. These studies demonstrate the absence of a previously proposed compensatory absorption of 18: 1 into portal blood when absorption into lymph is impaired by an inadequate supply of bile and pancreatic juice.
One-Week versus 2-Day Ventilator Circuit Change in Neonates with Prolonged Ventilation: Cost-Effectiveness and Impact on Ventilator-Associated Pneumonia
Authors: Chu Shih-Ming , Yang Mei-Chin , Hsiao Hsiu-Feng , Hsu Jen-Fu , Lien Reyin , Chiang Ming-Chou , Fu Ren-Huei , Huang Hsuan-Rong , Hsu Kuang-Hung , Tsai Ming-Horng 
Published: December 2014

ObjectiveTo investigate the impact of 1-week ventilator circuit change on ventilator-associated pneumonia and its cost-effectiveness compared with a 2-day change.DesignAn observational cohort study.SettingA tertiary level neonatal intensive care unit in a university-affiliated teaching hospital in Taiwan.PatientsAll neonates in the neonatal intensive care unit receiving invasive intubation for more than 1 week from July 1, 2011, through December 31, 2013.InterventionWe investigated the impact of 2 ventilator circuit change regimens, either every 2 days or 7 days, on ventilator-associated pneumonia of our cohort.Measurements and Main ResultsA total of 361 patients were maintained on mechanical ventilators for 13,981 days. The 2 groups did not differ significantly in any demographic characteristics. The rate of ventilator-associated pneumonia was comparable between the 2-day group and the 7-day group (8.2 vs 9.5 per 1,000 ventilator-days, P=.439). The durations of mechanical ventilation and hospital stay, and rates of bloodstream infection and mortality, were also comparable between the 2 groups. Switching from a 2-day to a 7-day change policy would save our neonatal intensive care unit a yearly sum of US $29,350 and 525 working hours.ConclusionDecreasing the frequency of ventilator circuit changes from every 2 days to once per week is safe and cost-effective in neonates requiring prolonged intubation for more than 1 week.Infect Control Hosp Epidemiol 2014;00(0): 1–7
Stirring and scalar transfer by grid-generated turbulence in the presence of a mean scalar gradient
Authors: Laizet S. , Vassilicos J. C. 
Published: December 2014

AbstractThe stirring of a passive scalar by grid-generated turbulence in the presence of a mean scalar gradient is studied by direct numerical simulations (DNS) for six different grids: one fractal square grid with three fractal iterations, one fractal square grid with four fractal iterations, one fractal I grid and three different regular grids. Our results can be summarised as follows. (i) For all these grids, the turbulence intensity averaged over time and over a plane parallel to the grid takes its peak value when the streamwise position of this plane is between $0.75M_{eff}$ and $1.5M_{eff}$ where $M_{eff}$ is the effective mesh size introduced by Hurst & Vassilicos (Phys. Fluids, vol. 19, 2007, 035103). (ii) Downstream of the location of this peak, the turbulence intensity averaged in this way is greatly enhanced by the fractal grids relative to the regular grids even though the fractal grids have comparable or even lower blockage ratios. The novelty of this result lies in the fact that it concerns turbulence intensities averaged over lateral planes (as well as time). (iii) The pressure drop is about the same across grids of the same blockage ratio whether fractal or not, but the pressure recovery is longer for the fractal grids. (iv) Even so, the fractal grids enhance turbulent scalar fluxes by up to an order of magnitude in the region downstream of the aforementioned peak and they also greatly enhance the streamwise growth of the fluctuating scalar variance in that region. (v) We demonstrate on a simple planar model problem that the cause of this phenomenon lies in the fractality of the grids. (vi) The turbulence scalar flux coefficient is constant far enough downstream of all the present grids and is significantly dependent on the nature and details of the turbulence-generating grid.
Law in the semi-periphery: revisiting an ambitious theory in the light of recent Portuguese socio-legal research
Authors: Guibentif Pierre 
Published: December 2014

AbstractThere is currently no mechanism – no journal, no learned society – somehow integrating Portuguese sociology of law, despite a considerable academic production. In an attempt to appreciate globally and substantially this production, this paper takes as a starting point the theory of semi-periphery formulated by Boaventura de Sousa Santos in the 1980s, and revisits the findings of socio-legal research carried out in Portugal over the recent decades in the light of that theory. The conclusion that can be drawn from this exercise is that the theory of semi-periphery – provided it is upgraded in order to better take into account features of recent processes of globalisation – still supplies a valuable framework for the reflection on the social, economic and political conditions that favour uses of the law as a tool for human groupings to govern themselves.