bluuebunny/crossref_metadata_2025_split huggingface dataset:
States as Gatekeepers in EU Asylum Politics: Explaining the Non‐adoption of a Refugee Quota System
Authors: Zaun Natascha 
Published: November 2017

AbstractBuilding on Moravcsik's Liberal Intergovernmentalism, I offer an explanation of the non‐decision on permanent EU refugee quotas. Some traditionally influential Member States in EU asylum politics, such as Germany, Austria and Sweden, received large numbers of refugees and faced strong domestic pressures to engage other Member States in responsibility‐sharing. Yet, governments of Member States with small application numbers (among whom several Eastern European governments were particularly vocal) had incentives to undercut responsibility‐sharing to avoid similar pressures. Having a better alternative to the potentially negotiated agreement, these governments successfully blocked the introduction of permanent refugee quotas. Besides explaining the absence of an effective response to one of the root causes of the asylum crisis (unequal strains) through asymmetrical interdependence, the article further develops Liberal Intergovernmentalist arguments and shows how national electorates influence positions taken by governments at the EU level when they are mobilized by right‐wing populist parties.
Aeromonas caviae inhibits hepatic enzymes of the phosphotransfer network in experimentally infected silver catfish: Impairment on bioenergetics
Authors: Baldissera M D , Souza C F , Verdi C M , dos Santos K L M , Da Veiga M L , da Rocha M I U M , Santos R C V , Vizzotto B S , Baldisserotto B 
Published: November 2017

AbstractSeveral studies have been demonstrated that phosphotransfer network, through the adenylate kinase (AK) and pyruvate kinase (PK) activities, allows for new perspectives leading to understanding of disease conditions associated with disturbances in energy metabolism, metabolic monitoring and signalling. In this sense, the aim of this study was to evaluate whether experimental infection by Aeromonas caviae alters hepatic AK and PK activities of silver catfish Rhamdia quelen. Hepatic AK and PK activities decreased in infected animals compared to uninfected animals, as well as the hepatic adenosine triphosphate (ATP) levels. Also, a severe hepatic damage was observed in the infected animals due to the presence of dilation and congestion of vessels, degeneration of hepatocytes and loss of liver parenchyma architecture and sinusoidal structure. Therefore, we have demonstrated, for the first time, that experimental infection by A. caviae inhibits key enzymes linked to the communication between sites of ATP generation and ATP utilization. Moreover, the absence of a reciprocal compensatory mechanism between these enzymes contributes directly to hepatic damage and for a severe energetic imbalance, which may contribute to disease pathophysiology.
The high prevalence of pathogenic Vibrio harveyi with multiple antibiotic resistance in scale drop and muscle necrosis disease of the hybrid grouper, Epinephelus fuscoguttatus (♀) × E. lanceolatus (♂), in China
Authors: Zhu Z M , Dong C F , Weng S P , He J G 
Published: November 2017

AbstractScale drop and muscle necrosis disease with high mortality widely occurred recently in the hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂), a crucial cultured marine fish species in China. In this study, 30 Harveyi clade isolates of 27 Vibrio harveyi strains were isolated from diseased hybrid groupers in the south‐east and north‐east coastal areas of China. A total of 22 V. harveyi strains were determined to be pathogenic, and most challenged fish died within 2 days of infection; surviving individuals exhibited scale drop and deep dermal lesions as naturally diseased fish. Although five typical virulence genes, including luxR, toxRVh, chiA, serine protease and vhh widely existed in V. harveyi, no obvious correlation was established between virulent strains and virulence genes harboured in them. Furthermore, multiple antibiotic resistance was widely exhibited in Harveyi clade strains, particularly for penicillins, polypeptides, lincomycins, acetylspiramycin, streptomycin, metronidazole and bacitracin. And the multiple antibiotic resistance indices were gradually decreased from southern to northern areas of China. This study demonstrated that the pathogenic V. harveyi with multiple antibiotic resistance is highly prevalent in hybrid grouper in China, which requires particular attention.
Additive effects of PNPLA3 and TM6SF2 on the histological severity of non‐alcoholic fatty liver disease
Authors: Koo Bo Kyung , Joo Sae Kyung , Kim Donghee , Bae Jeong Mo , Park Jeong Hwan , Kim Jung Ho , Kim Won 
Published: November 2017

AbstractBackground and AimWe investigated the effects of PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7‐TMC4 rs641738 variants on metabolic phenotypes and their combined effects on the histological severity of non‐alcoholic fatty liver disease (NAFLD).MethodsWe genotyped rs738409, rs58542926, and rs641738 in biopsy‐proven NAFLD patients (n = 416) and healthy controls (n = 109). Homeostasis model assessment of insulin resistance and adipose tissue insulin resistance were calculated.ResultsThe rs738409 and rs58542926 variants, but not rs641738, were associated not only with non‐alcoholic steatohepatitis (NASH) (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.46–2.73 and OR, 1.91; 95% CI, 1.04–3.51) but also with significant fibrosis (≥ F2) (OR, 1.53; 95% CI, 1.11–2.11 and OR, 1.88; 95% CI, 1.02–3.46) in NAFLD, even after adjustment for metabolic risk factors. Of both variants, only rs738409 was associated with homeostasis model assessment of insulin resistance and adipose tissue insulin resistance even in healthy controls (P = 0.046 and 0.002, respectively) as well as in the entire study cohort (P = 0.016 and 0.048, respectively). PNPLA3 and TM6SF2 risk variants additively increased the risk of NASH and significant fibrosis (OR per risk allele, 2.03; 95% CI, 1.50–2.73 and 1.61; 95% CI, 1.19–2.17). Even in subjects with low insulin resistance, the risk of NASH or significant fibrosis increased as the number of risk alleles increased (P = 0.008 and 0.020, respectively).ConclusionsPNPLA3 and TM6SF2 determine the risk of NASH and significant fibrosis, even after adjustment for insulin resistance, and exert an additive effect on NASH and significant fibrosis.
Fatal toxoplasmosis in a southern muriqui (Brachyteles arachnoides) from São Paulo state, Brazil: Pathological, immunohistochemical, and molecular characterization
Authors: Santos Stéfanie Vanessa , Pena Hilda F.J. , Talebi Mauricio G. , Teixeira Rodrigo H.F. , Kanamura Cristina T. , Diaz‐Delgado Josué , Gennari Solange M. , Catão‐Dias José Luiz 
Published: November 2017

AbstractWe report the pathological, immunohistochemical, and molecular features of fatal acute systemic toxoplasmosis in an adult, female, free‐living southern muriqui (Brachyteles arachnoides) from São Paulo state, Brazil. PCR‐RFLP genotyping analysis identified the #21 genotype ofToxoplasma gondii. This represents the first report of acute toxoplasmosis involving this genotype in humans and animals.
The non‐peptidic δ‐opioid receptor agonist Tan‐67 mediates neuroprotection post‐ischemically and is associated with altered amyloid precursor protein expression, maturation and processing in mice
Authors: Min Jia‐Wei , Liu Yanying , Wang David , Qiao Fangfang , Wang Hongmin 
Published: November 2017

AbstractTan‐67 is a selective non‐peptidic δ‐opioid receptor (DOR) agonist that confers neuroprotection against cerebral ischemia/reperfusion (I/R)‐caused neuronal injury in pre‐treated animals. In this study, we examined whether post‐ischemic administration of Tan‐67 in stroke mice is also neuroprotective and whether the treatment affects expression, maturation and processing of the amyloid precursor protein (APP). A focal cerebral I/R model in mice was induced by middle cerebral artery occlusion for 1 h and Tan‐67 (1.5, 3 or 4.5 mg/kg) was administered via the tail vein at 1 h after reperfusion. Alternatively, naltrindole, a selective DOR antagonist (5 mg/kg), was administered 1 h before Tan‐67 treatment. Our results showed that post‐ischemic administration of Tan‐67 (3 mg/kg or 4.5 mg/kg) was neuroprotective as shown by decreased infarct volume and neuronal loss following I/R. Importantly, Tan‐67 improved animal survival and neurobehavioral outcomes. Conversely, naltrindole abolished Tan‐67 neuroprotection in infarct volume. Tan‐67 treatment also increased APP expression, maturation and processing in the ipsilateral penumbral area at 6 h but decreased APP expression and maturation in the same brain area at 24 h after I/R. Tan‐67‐induced increase in APP expression was also seen in the ischemic cortex at 24 h following I/R. Moreover, Tan‐67 attenuated BACE‐1 expression, β‐secretase activity and the BACE cleavage of APP in the ischemic cortex at 24 h after I/R, which was abolished by naltrindole. Our data suggest that Tan‐67 is a promising DOR‐dependent therapeutic agent for treating I/R‐caused disorder and that Tan‐67‐mediated neuroprotection may be mediated via modulating APP expression, maturation and processing, despite an uncertain causative relationship between the altered APP and the outcomes observed.
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The impact of shift work on intensive care nurses’ lives outside work: A cross‐sectional study
Authors: Jensen Hanne Irene , Larsen Jette West , Thomsen Tina Damgaard 
Published: November 2017

Aims and objectivesTo examine how shift work affects intensive care nurses’ lives outside work.BackgroundShift work is unavoidable for many nurses. When attempting to minimise negative effects of shift work, it is important to identify areas which affect nurses working shifts.DesignA cross‐sectional study.MethodsA questionnaire survey among Danish intensive care nurses concerning experiences with shift work and family life, spare time activities, sleep and health.ResultsA total of 114 nurses (88%) participated. Shift work was found to influence the opportunities for spare time activities, and about 25% of both evening‐ and night‐shift groups found that working shifts sometimes led to social isolation. A total of 58% of nurses working evening shifts sometimes to very often experienced having trouble falling asleep when working shifts. Night‐shift workers had a higher percentage of physical and mental symptoms when working shifts compared with evening‐shift workers, with mood swings and headaches being the most common. The median score for thriving on working shifts was 8 (IQR 5–9) for evening‐shift workers and 8 (IQR 7–9) for night‐shift workers (scale 0–10 with 10 being the highest level of thriving).ConclusionShift workers reported that working shifts had a negative impact on life outside work. Opportunities for participating in spare time activities and difficulties falling asleep after shifts were the main issues for evening‐shift workers, whereas physical symptoms such as headaches and mood swings were more dominant among night‐shift workers. Despite the negative effects, the participants generally thrived on working shifts.Relevance to clinical practiceBy identifying modifiable areas which negatively influence life outside work when working shifts, it will be possible subsequently to plan interventions aimed at decreasing the negative effects. Interventions may include nurses having increased influence on their work schedules and education in sleep hygiene and dietary habits.
Repeated MitraClip procedure in patients with recurrent MR after a successful first procedure: Limitations and outcome
Authors: Curio Jonathan , Reinthaler Markus , Kasner Mario , Al‐Hindwan Haitham Saleh Ali , Baeckemo‐Johansson Johan , Neumann Tim , Jacobs Stephan , Lauten Alexander , Landmesser Ulf 
Published: November 2017

ObjectivesThe present study aimed to evaluate the outcome and potential limitations of a repeated MitraClip procedure (ReClip).BackgroundThe MitraClip procedure has emerged as a treatment option in high surgical risk patients suffering from severe mitral regurgitation (MR). However, despite successful initial repair a significant number of patients develops severe recurrent MR.MethodsPatients undergoing a ReClip procedure in our institution were retrospectively identified. Baseline data and the procedural outcome were assessed to identify potential limitations of such procedures.ResultsFifteen out of 234 patients undergoing a mitral‐valve repair with the MitraClip device (Abbott Vascular) underwent a ReClip due to recurrent MR. In 11 patients, a MR reduction of at least one degree without causing mitral valve stenosis (trans‐mitral mean gradient ≥5 mmHg) was achieved by performing a ReClip. After 1 year, two patients developed severe recurrent MR again. Pulmonary artery pressures significantly decreased after the procedure in individuals with successful repair (MR reduction of at least one degree and mitral valve mean gradient <5 mmHg).ConclusionA ReClip procedure may be feasible in patients with recurrent MR but the risk benefit ratio should be carefully balanced against other treatment options.
Oral insulin delivery: existing barriers and current counter-strategies
Authors: Gedawy Ahmed , Martinez Jorge , Al-Salami Hani , Dass Crispin R 
Published: November 2017

Abstract

Objectives
The chronic and progressive nature of diabetes is usually associated with micro- and macrovascular complications where failure of pancreatic β-cell function and a general condition of hyperglycaemia is created. One possible factor is failure of the patient to comply with and adhere to the prescribed insulin due to the inconvenient administration route. This review summarizes the rationale for oral insulin administration, existing barriers and some counter-strategies trialled.

Key findings
Oral insulin mimics the physiology of endogenous insulin secreted by pancreas. Following the intestinal absorption of oral insulin, it reaches the liver at high concentration via the portal vein. Oral insulin on the other hand has the potential to protect pancreatic β-cells from autoimmune destruction. Structural modification, targeting a particular tissue/receptor, and the use of innovative pharmaceutical formulations such as nanoparticles represent strategies introduced to improve oral insulin bioavailability. They showed promising results in overcoming the hurdles facing oral insulin delivery, although delivery is far from ideal.

Summary
The use of advanced pharmaceutical technologies and further research in particulate carrier system delivery predominantly nanoparticle utilization would offer useful tools in delivering insulin via the oral route which in turn would potentially improve diabetic patient compliance to insulin and the overall management of diabetes.
Evaluating bioequivalence of meloxicam tablets: is in-vitro dissolution test overdiscriminating?
Authors: Jin Chan , Zhao Chenyao , Shen Dachao , Dong Wenxiang , Liu Hongzhuo , He Zhonggui 
Published: November 2017

Abstract

Objectives
The aim of the study was to assess the impact of the differences in dissolution profiles of meloxicam tablets on the in-vivo bioavailability parameters after oral administration.

Methods
Compare in-vitro dissolution testing in the recommended media to evaluate in-vivo bioequivalence outcomes for the Biopharmaceutics Classification System Class II weak acidic drugs. Nine Beagle dogs received a single oral administration of each formulation (7.5 mg) in a three-way crossover design.

Key findings
The dissolution of meloxicam from both test products showed marked differences with that from the reference tablet in pH 1.0, 4.5 and 6.8 media at 50 or 75 rpm. Both formulations exhibiting slow or fast dissolution were then compared with the reference product for in-vivo bioequivalence study. Both products were bioequivalent with the reference tablet in either extent or rate of oral absorption. It indicated that the dissolution profiles which discriminated between the formulations in vitro did not accurately predict the in-vivo bioequivalence outcomes.

Conclusions
Comparative dissolution profiles using similarity factor (f2) in the recommended media should be relaxed to fulfil the requirements for the development, scale-up and postapproval changes to immediate release oral solid dosage forms of meloxicam.
Transport of valine across the small intestinal epithelium in pigs fed different valine levels and Bacillus subtilis
Authors: Blaabjerg K. , Nørgaard J. V. , Nielsen B. , Cantor M. D. , Derkx P. , Sehested J. , Poulsen H. D. 
Published: November 2017

SummaryMutants of Bacillus subtilis overproducing valine (B. subtilis VAL) could be an approach to supply pigs dietary valine (Val). In the study, 18 gilts were fed: (i) negative diet with a standardized ileal digestible (SID) Val:Lys of 0.63:1 (Neg); (ii) Neg added B. subtilis VAL (1.28 × 1011 cfu/kg as‐fed) or; (iii) Neg added L‐Val to a Val:Lys of 0.69:1. Using the Ussing chamber method, the study aimed to investigate whether (i) the diets affect intestinal transport of additions of 0, 5, 10 or 20 mmol Val/L from the mucosal to the serosal side and (ii) the B. subtilis VAL contributes to a net transport of Val produced in situ. The results showed that the Isc (ΔIscVal) and release of Val to the serosal side solution (Srel; μmol cm−2 min−1) increased with Val addition (linear and quadratic, p < .0001) but was similar for 5, 10 or 20 mmol Val/L and not affected by diet. No net transport of in situ produced Val by B. subtilis VAL was detected. In conclusion, feeding a Val‐deficient diet with or without B. subtilis VAL or a Val sufficient diet did not affect the Val transport across intestinal epithelia. No in situ Val production by B. subtilis VAL was observed in the Ussing chambers.
Quality of life in adolescents with hepatitis C treated with sofosbuvir and ribavirin
Authors: Younossi Z. M. , Stepanova M. , Schwarz K. B. , Wirth S. , Rosenthal P. , Gonzalez‐Peralta R. , Murray K. , Henry L. , Hunt S. 
Published: November 2017

SummaryChronic HCV infection has been associated with impairment of HRQL in both adults and paediatric patients. Our aim was to assess the HRQL of HCV‐positive children treated with SOF + RBV. The data for this post hoc analysis were collected in a phase 2 open‐label multinational study that evaluated safety and efficacy of SOF (400 mg/day) plus RBV (weight‐based up to 1400 mg/day) for 12 or 24 weeks in adolescents with chronic HCV (GS‐US‐334‐1112). Patients and their parents/guardians completed the PedsQL‐4.0‐SF‐15 questionnaire at baseline, at the end of treatment and in post‐treatment follow‐up. We included 50 adolescents with HCV genotype 2 and 3 without cirrhosis (14.8 ± 1.9 years; male: 58%; treatment‐naïve: 82%; vertically transmitted HCV: 70%). After treatment, 100% of patients with HCV genotype 2 and 95% with genotype 3 achieved SVR‐12. During treatment with SOF + RBV, there were no significant decrements in any of patients’ self‐reported or parent‐proxy‐reported PRO scores regardless of treatment duration (all P > .05). After treatment cessation, we recorded a statistically significant improvement in patients’ self‐reported Social Functioning score by post‐treatment week 12: on average, +4.8 points on a 0‐100 scale (P = .02). By post‐treatment week 24, parent‐proxy‐reported School Functioning score increased by, on average, +13.0 points (P = .0065). In multivariate analysis, history of abdominal pain and psychiatric disorders were predictive of impaired HRQL in adolescents with HCV (P < .05). Adolescents with HCV do not seem to experience any HRQL decrement during treatment with SOF + RBV and experience some improvement of their HRQL scores after achieving SVR.
A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization
Authors: Lee H‐R. , Cho Y. Y. , Lee G. Y. , You D‐g. , Yoo Y. D. , Kim Y. J. 
Published: November 2017

SummaryHepatitis B virus X protein (HBx) acts as a multifunctional protein that regulates intracellular signalling pathways during HBV infection. It has mainly been studied in terms of its interaction with cellular proteins. Here, we show that HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane‐mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx induced membrane permeabilization, and the region comprising the transmembrane domain and the mitochondrial‐targeting sequence was sufficient for this process. Membrane permeabilization was inhibited by nonselective channel blockers or by N‐(n‐nonyl)deoxynojirimycin (NN‐DNJ), a viroporin inhibitor. Moreover, NN‐DNJ inhibited HBx‐induced mitochondrial depolarization in Huh‐7 cells. Based on the results of this study, we can postulate that the HBx protein itself is sufficient to induce mitochondrial membrane permeabilization. Our finding provides important information for a strategy of HBx targeting during HBV treatment.
Great and rapid HBsAg decline in patients with on‐treatment hepatitis flare in early phase of potent antiviral therapy
Authors: Jeng W.‐J. , Chen Y.‐C. , Liaw Y.‐F. 
Published: November 2017

SummaryHBsAg decline during nucleos(t)ide analogue therapy in chronic hepatitis B with lower pretherapy ALT is usually small and slow. This study aimed to investigate why ~10% of such patients showed “rapid HBsAg decline” ≥0.5 log10 IU/mL by month 6 of therapy. Patients with persistent pretherapy ALT <5X ULN who had qHBsAg at baseline, months 6 and 12 of entecavir or tenofovir therapy were studied. “On‐treatment ALT elevation” was defined as >10% increase above baseline to >2X ULN during first 6 months of therapy. Of the 256 patients treated, 51 experienced transient “on‐treatment ALT elevation” [group A], including 30 (11.7%) with ALT elevation to 2‐5X ULN [group A‐1] and 21 (8.2%) flared to >5X ULN [group A‐2]. The magnitude of qHBsAg decline and rate of “rapid HBsAg decline” by month 6 was significantly greater and more frequent in group A (−0.446 vs −0.042 log10 IU/mL; 45.1 vs 8.8%, respectively, P = 0.000) than in the remaining 205 patients without on‐treatment ALT elevation (group B), being greatest in patients with hepatitis flare (group A‐2: −0.559 log10 IU/mL and 57.1%, respectively). In patients with therapy ≥2 years, patients with “on‐treatment ALT elevation” also showed significantly greater annual HBsAg decline, more frequent to <100 IU/mL and 4 times higher HBsAg seroclearance rate. “On‐treatment ALT elevation,” especially flare >5X ULN, during entecavir therapy or tenofovir therapy may enhance/accelerate HBsAg decline, suggesting the effect of immune restoration upon potent viral suppression.