bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mucosal‐associated invariant T‐cell frequency and function in blood and liver of HCV mono‐ and HCV/HIV co‐infected patients with advanced fibrosis
Authors: Beudeker Boris J. B. , van Oord Gertine W. , Arends Joop E. , Schulze zur Wiesch Julian , van der Heide Marieke S. , de Knegt Robert J. , Verbon Annelies , Boonstra Andre , Claassen Mark A. A. 
Published: August 2017

AbstractBackground & AimsMucosal‐associated invariant T (MAIT) cells are important innate T cells with antimicrobial and immunoregulatory activity, recently found to be depleted in blood of patients with HIV and HCV mono‐infections. In this study, we assessed the impact of HIV, HCV and HCV/HIV co‐infection on circulating and intrahepatic MAIT‐cells and correlations with liver fibrosis.MethodsIn this cross‐sectional study, nine healthy subjects, nine HIV, 20 HCV and 22 HCV/HIV co‐infected patients were included. Blood and liver fine needle aspirate biopsies were studied using flowcytometry for CD3+CD161+Vα7.2+ MAIT‐cell frequency, phenotype and function in HCV mono‐infected and HCV/HIV co‐infected patients without or with mild fibrosis (Metavir‐score F0‐F1) or severe fibrosis to cirrhosis (Metavir‐score F3‐F4).ResultsCirculating MAIT‐cells were decreased in blood of HCV, HIV and HCV/HIV patients with F0‐F1. In HCV/HIV co‐infected individuals with severe fibrosis to cirrhosis, the frequency of circulating MAIT‐cells was even further depleted, whereas their function was comparable to HCV/HIV co‐infected patients with low or absent fibrosis. In contrast, in HCV mono‐infected patients, MAIT‐cell frequencies were not related to fibrosis severity; however, MAIT‐cell function was impaired in mono‐infected patients with more fibrosis. More advanced liver fibrosis in HCV or HCV/HIV‐infected patients was not reflected by increased accumulation of MAIT‐cells in the affected liver.ConclusionsSevere liver fibrosis is associated with dysfunctional MAIT‐cells in blood of HCV mono‐infected patients, and lower MAIT frequencies in blood of HCV/HIV co‐infected patients, without evidence for accumulation in the liver.
Oral oxycodone/naloxone for pain control in cirrhosis: Observational study in patients with symptomatic metastatic hepatocellular carcinoma
Authors: Tovoli Francesco , De Lorenzo Stefania , Samolsky Dekel Boaz G. , Piscaglia Fabio , Benevento Francesca , Brandi Giovanni , Bolondi Luigi 
Published: August 2017

AbstractBackground & AimsPain management in cirrhosis is a clinical challenge. Most analgesics are metabolized in the liver and cirrhosis may deeply alter their concentration, favouring the appearance of side effects. We aimed to assess the efficacy and safety of oral prolonged‐release association of oxycodone/naloxone tablets (OXN) in the treatment of moderate/severe cancer pain in cirrhotic patients with metastatic hepatocellular carcinoma (HCC).MethodsWe enrolled n = 32 HCC patients with moderate/severe cancer pain unresponsive to paracetamol alone or associated with codeine or tramadol. All patients received an initial OXN dose of 5 mg bid to be gradually increased in case of insufficient analgesia. At baseline and follow‐up visits, we evaluated: pain intensity (using the Numerical Rating Scale, NRS), patients’ autonomy in daily activities (Barthel Functioning Index); bowel dysfunction (Bowel Function Index, BFI), signs of hepatic encephalopathy (HE) and other opioid‐induced side effects.ResultsNo clinically significant adverse effects were reported (median follow‐up 122 days). No significant worsening of the BFI score was noted and no cases of HE were detected. Two patients (6.3%) discontinued treatment before T14 because of mild nausea and dizziness. The remaining n = 30 patients were assessed for efficacy. Treatment led to a significant reduction in the mean of pain scores both at T14 (−37.1 ± 16.3%, P < .001) and at T28 (−55.6 ± 21.5%, P < .001); Barthel scores showed gradual and significant increase from T0 (81.6 ± 13.0) to T14 (86.5 ± 11.4, P = .001) and to T28 (88.3 ± 13.6, P = .009).ConclusionsOXN may be considered a safe and effective option in the fragile population of cirrhotic patients.
Mutations in the novel gene FOPV are associated with familial autosomal dominant and non‐familial obliterative portal venopathy
Authors: Besmond Claude , Valla Dominique , Hubert Laurence , Poirier Karine , Grosse Brigitte , Guettier Catherine , Bernard Olivier , Gonzales Emmanuel , Jacquemin Emmanuel 
Published: August 2017

AbstractBackground & AimsObliterative portal venopathy (OPV) is characterized by lesions of portal vein intrahepatic branches and is thought to be responsible for many cases of portal hypertension in the absence of cirrhosis or obstruction of large portal or hepatic veins. In most cases the cause of OPV remains unknown. The aim was to identify a candidate gene of OPV.MethodsWhole exome sequencing was performed in two families, including 6 patients with OPV. Identified mutations were confirmed by Sanger sequencing and expression of candidate gene transcript was studied by real time qPCR in human tissues.ResultsIn both families, no mutations were identified in genes previously reported to be associated with OPV. In each family, we identified a heterozygous mutation (c.1783G>A, p.Gly595Arg and c.4895C>T, p.Thr1632Ile) in a novel gene located on chromosome 4, that we called FOPV (Familial Obliterative Portal Venopathy), and having a cDNA coding for 1793 amino acids. The FOPV mutations segregated with the disease in families and the pattern of inheritance was suggestive of autosomal dominant inherited OPV, with incomplete penetrance and variable expressivity. In silico analysis predicted a deleterious effect of each mutant and mutations concerned highly conserved amino acids in mammals. A deleterious heterozygous FOPV missense mutation (c.4244T>C, p.Phe1415Ser) was also identified in a patient with non‐familial OPV. Expression study in liver veins showed that FOPV transcript was mainly expressed in intrahepatic portal vein.ConclusionsThis report suggests that FOPV mutations may have a pathogenic role in some cases of familial and non‐familial OPV.
Emotion processing in female youth: Testing the stability of the late positive potential
Authors: Bondy Erin , Stewart Jeremy G. , Hajcak Greg , Weinberg Anna , Tarlow Naomi , Mittal Vijay A. , Auerbach Randy P. 
Published: August 2017

AbstractThe Emotional Interrupt Task (EIT) has been used to probe emotion processing in healthy and clinical samples; however, research exploring the stability and reliability of behavioral measures and ERPs elicited from this task is limited. Establishing the psychometric properties of the EIT is critical, particularly as phenotypes and biological indicators may represent traitlike characteristics that underlie psychiatric illness. To address this gap, test‐retest stability and internal consistency of behavioral indices and ERPs resulting from the EIT in healthy, female youth (n = 28) were examined. At baseline, participants were administered the EIT while high‐density 128‐channel EEG data were recorded to probe the late positive potential (LPP). One month later, participants were readministered the EIT. Four principal findings emerged. First, there is evidence of an interference effect at baseline, as participants showed a slower reaction time for unpleasant and pleasant images relative to neutral images, and test‐retest of behavioral measures was relatively stable over time. Second, participants showed a potentiated LPP to unpleasant and pleasant images compared to neutral images, and these effects were stable over time. Moreover, in a test of the difference waves (unpleasant‐neutral vs. pleasant‐neutral), there was sustained positivity for unpleasant images. Third, behavioral measures and LPP demonstrated excellent internal consistency (odd/even correlations) across conditions. Fourth, highlighting important age‐related differences in LPP activity, younger age was associated with larger LPP amplitudes across conditions. Overall, these findings suggest that the LPP following emotional images is a stable and reliable marker of emotion processing in healthy youth.
Robustness of the KOF index of economic globalisation
Authors: Gozgor Giray 
Published: August 2017

AbstractThe KOF indices of globalisation are the most used globalisation measures in international economics literature, but it uses the nominal trade openness measure to construct the globalisation index. In this paper, we use real trade openness instead of nominal trade openness and recalculate the KOF economic globalisation index over the period 1970–2013. Using the panel data regressions for 146 countries, we revisit the economic globalisation–economic growth nexus to investigate the robustness of the KOF economic globalisation index. We consider several possibilities in model specifications, and the results show that using nominal trade openness measure in calculating the KOF globalisation index is statistically robust. In addition, the KOF economic globalisation index in logarithmic form introduces a more robust outlook in the panel data regressions—a lower bias is emerged by considering different trade openness measures to calculate the globalisation level.
Introduction
Authors: HICKEY RAYMOND , VAUGHAN ELAINE 
Published: August 2017

ABSTRACTSince the 1970s there has been a burgeoning interest in Irish English, which in its development and present‐day forms yields considerable insights into language variation and change. Scholarship in the field has proceeded from an initial concern with contact and shift, and the structures they engendered, to a more usage‐based orientation, both in sociolinguistic research into contemporary varieties of Irish English and in the investigation of its specific pragmatics. The basis for this expansion has been an increase in the database for Irish English currently available in a range of corpora which provide statistics and attestations for many features and phenomena.
Genetic analysis of human and swine influenza A viruses isolated in Northern Italy during 2010–2015
Authors: Chiapponi C. , Ebranati E. , Pariani E. , Faccini S. , Luppi A. , Baioni L. , Manfredi R. , Carta V. , Merenda M. , Affanni P. , Colucci M. E. , Veronesi L. , Zehender G. , Foni E. 
Published: August 2017

SummaryInfluenza A virus (IAV) infection in swine plays an important role in the ecology of influenza viruses. The emergence of new IAVs comes through different mechanisms, with the genetic reassortment of genes between influenza viruses, also originating from different species, being common. We performed a genetic analysis on 179 IAV isolates from humans (n. 75) and pigs (n. 104) collected in Northern Italy between 2010 and 2015, to monitor the genetic exchange between human and swine IAVs. No cases of human infection with swine strains were noticed, but direct infections of swine with H1N1pdm09 strains were detected. Moreover, we pointed out a continuous circulation of H1N1pdm09 strains in swine populations evidenced by the introduction of internal genes of this subtype. These events contribute to generating new viral variants—possibly endowed with pandemic potential—and emphasize the importance of continuous surveillance at both animal and human level.
Bacterial-Chromatin Structural Proteins Regulate the Bimodal Expression of the Locus of Enterocyte Effacement (LEE) Pathogenicity Island in Enteropathogenic
Escherichia coli
Authors: Leh Hervé , Khodr Ahmad , Bouger Marie-Christine , Sclavi Bianca , Rimsky Sylvie , Bury-Moné Stéphanie 
Published: August 2017

ABSTRACT

In enteropathogenic
Escherichia coli
(EPEC), the locus of enterocyte effacement (LEE) encodes a type 3 secretion system (T3SS) essential for pathogenesis. This pathogenicity island comprises five major operons (
LEE1
to
LEE5
), with the
LEE5
operon encoding T3SS effectors involved in the intimate adherence of bacteria to enterocytes. The first operon,
LEE1
, encodes Ler (LEE-encoded regulator), an H-NS (nucleoid structuring protein) paralog that alleviates the LEE H-NS silencing. We observed that the
LEE5
and
LEE1
promoters present a bimodal expression pattern, depending on environmental stimuli. One key regulator of bimodal
LEE1
and
LEE5
expression is
ler
expression, which fluctuates in response to different growth conditions. Under conditions
in vitro
considered to be equivalent to nonoptimal conditions for virulence, the opposing regulatory effects of H-NS and Ler can lead to the emergence of two bacterial subpopulations. H-NS and Ler share nucleation binding sites in the
LEE5
promoter region, but H-NS binding results in local DNA structural modifications distinct from those generated through Ler binding, at least
in vitro
. Thus, we show how two nucleoid-binding proteins can contribute to the epigenetic regulation of bacterial virulence and lead to opposing bacterial fates. This finding implicates for the first time bacterial-chromatin structural proteins in the bimodal regulation of gene expression.

IMPORTANCE
Gene expression stochasticity is an emerging phenomenon in microbiology. In certain contexts, gene expression stochasticity can shape bacterial epigenetic regulation. In enteropathogenic
Escherichia coli
(EPEC), the interplay between H-NS (a nucleoid structuring protein) and Ler (an H-NS paralog) is required for bimodal
LEE5
and
LEE1
expression, leading to the emergence of two bacterial subpopulations (with low and high states of expression). The two proteins share mutual nucleation binding sites in the
LEE5
promoter region.
In vitro
, the binding of H-NS to the
LEE5
promoter results in local structural modifications of DNA distinct from those generated through Ler binding. Furthermore,
ler
expression is a key parameter modulating the variability of the proportions of bacterial subpopulations. Accordingly, modulating the production of Ler into a nonpathogenic
E. coli
strain reproduces the bimodal expression of
LEE5
. Finally, this study illustrates how two nucleoid-binding proteins can reshape the epigenetic regulation of bacterial virulence.
Membrane Distribution of the
Pseudomonas
Quinolone Signal Modulates Outer Membrane Vesicle Production in
Pseudomonas aeruginosa
Authors: Florez Catalina , Raab Julie E. , Cooke Adam C. , Schertzer Jeffrey W. 
Published: August 2017

ABSTRACT

The
Pseudomonas
quinolone signal (PQS) is an important quorum-sensing molecule in
Pseudomonas aeruginosa
that also mediates its own packaging and transport by stimulating outer membrane vesicle (OMV) formation. Because OMVs have been implicated in many virulence-associated behaviors, it is critical that we understand how they are formed. Our group proposed the bilayer-couple model for OMV biogenesis, where PQS intercalates into the outer membrane, causing expansion of the outer leaflet and consequently inducing curvature. In accordance with the model, we hypothesized that PQS must be transported from the cytoplasm to the outer membrane before it can initiate OMV formation. We initially examined two laboratory strains of
P. aeruginosa
and found significant strain-dependent differences. PQS export correlated strongly with OMV production, even though equivalent amounts of total PQS were produced by both strains. Interestingly, we discovered that poor OMV producers sequestered the majority of PQS in the inner membrane, which appeared to be the result of early saturation of the export pathway. Further analysis showed that strain-specific PQS export and OMV biogenesis patterns were stable once established but could be significantly altered by changing the growth medium. Finally, we demonstrated that the associations described for laboratory strains also held for three clinical strains. These results suggest that factors controlling the export of PQS dictate OMV biogenesis. This work provides new insight into PQS-controlled virulence in
P. aeruginosa
and provides important tools to further study signal export and OMV biogenesis.

IMPORTANCE
Bacterial secretion has been recognized as an essential facet of microbial pathogenesis and human disease. Numerous virulence factors have been found to be transported within outer membrane vesicles (OMVs), and delivery using these biological nanoparticles often results in increased potency. OMV biogenesis is an important but poorly understood process that is ubiquitous among Gram-negative organisms. Our group seeks to understand the biochemical mechanisms behind the formation of OMVs and has developed a model of small-molecule-induced membrane curvature as an important driver of this process. With this work, we demonstrate that PQS, a known small-molecule OMV inducer, must be exported to promote OMV biogenesis in both lab-adapted and clinical strains of
Pseudomonas aeruginosa
. In supporting and expanding the bilayer-couple model of OMV biogenesis, the current work lays the groundwork for studying environmental and genetic factors that modulate OMV production and, consequently, the packaging and delivery of many bacterial factors.
Access 3project protocol: young people and health system navigation in the digital age: a multifaceted, mixed methods study
Authors: Kang Melissa , Robards Fiona , Sanci Lena , Steinbeck Katharine , Jan Stephen , Hawke Catherine , Kong Marlene , Usherwood Tim 
Published: August 2017

BackgroundThe integration of digital technology into everyday lives of young people has become widespread. It is not known whether and how technology influences barriers and facilitators to healthcare, and whether and how young people navigate between face-to-face and virtual healthcare. To provide new knowledge essential to policy and practice, we designed a study that would explore health system access and navigation in the digital age. The study objectives are to: (1) describe experiences of young people accessing and navigating the health system in New South Wales (NSW), Australia; (2) identify barriers and facilitators to healthcare for young people and how these vary between groups; (3) describe health system inefficiencies, particularly for young people who are marginalised; (4) provide policy-relevant knowledge translation of the research data.Methods and analysisThis mixed methods study has four parts, including: (1) a cross-sectional survey of young people (12–24 years) residing in NSW, Australia; (2) a longitudinal, qualitative study of a subsample of marginalised young people (defined as young people who: identify as Aboriginal and/or Torres Strait Islander; are experiencing homelessness; identify as sexuality and/or gender diverse; are of refugee or vulnerable migrant background; and/or live in rural or remote NSW); (3) interviews with professionals; (4) a knowledge translation forum.Ethics and disseminationEthics approvals were sought and granted. Data collection commenced in March 2016 and will continue until June 2017. This study will gather practice and policy-relevant intelligence about contemporary experiences of young people and health services, with a unique focus on five different groups of marginalised young people, documenting their experiences over time.Access 3will explore navigation around all levels of the health system, determine whether digital technology is integrated into this, and if so how, and will translate findings into policy-relevant recommendations.
Complementary Value of Contralateral Parenchymal Enhancement on DCE-MRI to Prognostic Models and Molecular Assays in High-risk ER+/HER2− Breast Cancer
Authors: van der Velden Bas H.M. , Elias Sjoerd G. , Bismeijer Tycho , Loo Claudette E. , Viergever Max A. , Wessels Lodewyk F.A. , Gilhuijs Kenneth G.A. 
Published: August 2017

Abstract
Purpose: To determine whether markers of healthy breast stroma are able to select a subgroup of patients at low risk of death or metastasis from patients considered at high risk according to routine markers of the tumor.
Experimental Design: Patients with ER+/HER2− breast cancer were consecutively included for retrospective analysis. The contralateral parenchyma was segmented automatically on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), where upon the average of the top-10% late enhancement was calculated. This contralateral parenchymal enhancement (CPE) was analyzed with respect to routine prognostic models and molecular assays (Nottingham Prognostic Index, Dutch clinical chemotherapy-selection guidelines, 70-gene signature, and 21-gene recurrence score). CPE was split in tertiles and tested for overall and distant disease-free survival. CPE was adjusted for patient and tumor characteristics, as well as systemic therapy, using inverse probability weighting (IPW). Subanalyses were performed in patients at high risk according to prognostic models and molecular assays.
Results: Four-hundred-and-fifteen patients were included, constituting the same group in which the association between CPE and survival was discovered. Median follow-up was 85 months, 34/415(8%) patients succumbed. After IPW-adjustment for patient and tumor characteristics, patients with high CPE had significantly better overall survival than those with low CPE in groups at high risk according to the Nottingham Prognostic Index [HR (95% CI): 0.08 (0.00–0.40), P &lt; 0.001]; Dutch clinical guidelines [HR (95% CI): 0.22 (0.00–0.81), P = 0.021]; and 21-gene recurrence score [HR (95% CI): 0.14 (0.00–0.84), P = 0.030]. One group showed a trend [70-gene signature: HR (95% CI): 0.25 (0.00–1.02), P = 0.054].
Conclusions: In patients at high risk based on the tumor, subgroups at relatively low risk were identified using pretreatment enhancement of the stroma on breast DCE-MRI. Clin Cancer Res; 23(21); 6505–15. ©2017 AACR.
Structure and Maintenance Mechanism of Long-Lived Concentric Eyewalls Associated with Simulated Typhoon Bolaven (2012)
Authors: Tsujino Satoki , Tsuboki Kazuhisa , Kuo Hung-Chi 
Published: August 2017

Abstract
Typhoons with long-lived concentric eyewalls (CEs) are more intense than those with short-lived CEs. It is important for more accurate prediction of typhoon intensity to understand the maintenance mechanism of the long-lived CEs. To study the mechanism of the long-term maintenance of CEs, a numerical experiment of Typhoon Bolaven (2012) is performed using a nonhydrostatic model with full physics. Two aspects of the maintenance of simulated CEs are investigated: the maintenance of the inner eyewall and the contraction of the outer eyewall. To examine the maintenance of the inner eyewall, the equivalent potential temperature budget and air parcel trajectories of the simulated inner eyewall are calculated. The results show that the entropy supply to the inner eyewall is sufficient to maintain the inner eyewall after secondary eyewall formation (SEF). During the early period after SEF, entropy is supplied by an axisymmetric inflow, and later it is supplied by nonaxisymmetric flows of the outer eyewall. To examine the contraction of the outer eyewall, the potential vorticity (PV) budget of the outer eyewall is diagnosed. The result reveals that the negative contribution to the contraction of the outer PV peak (i.e., the outer eyewall) in the early period is the negative PV generation due to axisymmetric advection and diabatic heating just inside of the outer PV peak. In the later period, the negative PV generation due to nonaxisymmetric structure is important for the prevention of contraction. The present study reveals that the structure of the outer eyewall plays important roles in the maintenance of long-lived CEs.