bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced X-ray emission from candidate Lyman continuum emitting galaxies
Authors: Bluem J , Kaaret P , Prestwich A , Brorby M 
Published: June 2019

ABSTRACT
X-ray binaries may have helped reionize the early Universe by enabling Lyman continuum escape. We analysed a set of eight local galaxies that are potential Lyman leaking galaxies, identified by a blue colour and weak emission lines, using Chandra X-ray observations. Five of the galaxies feature X-ray sources, while three galaxies are not significantly detected in X-rays. X-ray luminosities were found for the galaxies and X-ray sources. Four of the galaxies have elevated X-ray luminosity versus what would be expected based on star formation rate and metallicity. The presence of detected X-ray sources within the galaxies is found to correlate with the ratio of the star formation rate estimated from the near-ultraviolet flux to that estimated from the infrared. This implies reduced obscuration due to dust in the galaxies with X-ray sources. These results support the idea that X-ray binaries may be an important part of the process of reionziation.
X-ray dips and a complex UV/X-ray cross-correlation function in the black hole candidate MAXI J1820+070
Authors: Kajava J J E , Motta S E , Sanna A , Veledina A , Del Santo M , Segreto A 
Published: June 2019

ABSTRACT
MAXI J1820+070, a black hole candidate first detected in early 2018 March, was observed by XMM–Newton during the outburst rise. In this letter we report on the spectral and timing analysis of the XMM–Newton X-ray and UV data, as well as contemporaneous X-ray data from the Swift satellite. The X-ray spectrum is well described by a hard thermal Comptonization continuum. The XMM–Newton X-ray light curve shows a pronounced dipping interval, and spectral analysis indicates that it is caused by a moderately ionized partial covering absorber. The XMM–Newton/OM U-filter data do not reveal any signs of the 17 h orbital modulation that was seen later on during the outburst decay. The UV/X-ray cross-correlation function shows a complex shape, with a peak at positive lags of about 4 s and a precognition dip at negative lags, which is absent during the X-ray dipping episode. Such shape could arise if the UV emission comes partially from synchrotron self-Compton emission near the black hole, as well as from reprocessing of the X-rays in the colder accretion disc further out.
Rapid Evolution of Gained Essential Developmental Functions of a Young Gene via Interactions with Other Essential Genes
Authors: Lee Yuh Chwen G , Ventura Iuri M , Rice Gavin R , Chen Dong-Yuan , Colmenares Serafin U , Long Manyuan 
Published: June 2019

AbstractNew genes are of recent origin and only present in a subset of species in a phylogeny. Accumulated evidence suggests that new genes, like old genes that are conserved across species, can also take on important functions and be essential for the survival and reproductive success of organisms. Although there are detailed analyses of the mechanisms underlying new genes’ gaining fertility functions, how new genes rapidly become essential for viability remains unclear. We focused on a young retro-duplicated gene (CG7804, which we named Cocoon) in Drosophila that originated between 4 and 10 Ma. We found that, unlike its evolutionarily conserved parental gene, Cocoon has evolved under positive selection and accumulated many amino acid differences at functional sites from the parental gene. Despite its young age, Cocoon is essential for the survival of Drosophila melanogaster at multiple developmental stages, including the critical embryonic stage, and its expression is essential in different tissues from those of its parental gene. Functional genomic analyses found that Cocoon acquired unique DNA-binding sites and has a contrasting effect on gene expression to that of its parental gene. Importantly, Cocoon binding predominantly locates at genes that have other essential functions and/or have multiple gene–gene interactions, suggesting that Cocoon acquired novel essential function to survival through forming interactions that have large impacts on the gene interaction network. Our study is an important step toward deciphering the evolutionary trajectory by which new genes functionally diverge from parental genes and become essential.
Targeting the PI3K/Akt/mTOR pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases
Authors: Ippen Franziska Maria , Grosch Julia Katharina , Subramanian Megha , Kuter Benjamin Macfarlane , Liederer Bianca M , Plise Emile G , Mora Joana Liliana , Nayyar Naema , Schmidt Stephen Paul , Giobbie-Hurder Anita , Martinez-Lage Maria , Carter Scott L , Cahill Daniel P , Wakimoto Hiroaki , Brastianos Priscilla Kaliopi 
Published: June 2019

AbstractBackgroundActivating mutations in the pathway of phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) occur in 43–70% of breast cancer brain metastasis patients. To date, the treatment of these patients presents an ongoing challenge, mainly because of the lack of targeted agents that are able to sufficiently penetrate the blood–brain barrier. GDC-0068 is a pan-Akt inhibitor that has shown to be effective in various preclinical tumor models as well as in clinical trials. The purpose of this study was to analyze the efficacy of GDC-0068 in a breast cancer brain metastases model.MethodsIn in vitro studies, antitumor activity of GDC-0068 was assessed in breast cancer cells of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)–mutant and PIK3CA-wildtype breast cancer cell lines using cell viability and apoptosis assays, cell cycle analysis, and western blots. In vivo, the efficacy of GDC-0068 was analyzed in a PIK3CA-mutant breast cancer brain metastasis orthotopic xenograft mouse model and evaluated by repeated bioluminescent imaging and immunohistochemistry.ResultsGDC-0068 decreased cell viability, induced apoptosis, and inhibited phosphorylation of proline rich Akt substrate 40 kDa and p70 S6 kinase in a dose-dependent manner in PIK3CA-mutant breast cancer brain metastatic cell lines compared with PIK3CA-wildtype cell lines. In vivo, treatment with GDC-0068 notably inhibited the growth of PIK3CA-mutant tumors and resulted in a significant survival benefit compared with sham, whereas no effect was detected in a PIK3CA-wildtype model.ConclusionsThis study suggests that the Akt inhibitor GDC-0068 may be an encouraging targeted treatment strategy for breast cancer brain metastasis patients with activating mutations in the PI3K pathway. These data provide a rationale to further evaluate the efficacy of GDC-0068 in patients with brain metastases.
Validation of a Prediction Rule forLegionellaPneumonia in Emergency Department Patients
Authors: Bolliger Rebekka , Neeser Olivia , Merker Meret , Vukajlovic Tanja , Felder Laetitia , Fiumefreddo Rico , Haubitz Sebastian , Koch Daniel , Hammerer-Lercher Angelika , Ottiger Cornelia , Fux Christoph A , Mueller Beat , Schuetz Philipp 
Published: June 2019

AbstractWe validated a clinical prediction rule for Legionella based on clinical parameters (dry cough, fever) and laboratory findings (C-reactive protein, lactate dehydrogenase, sodium, platelet counts) in 713 consecutive patients with community-acquired pneumonia. The Legionella Score performed well in estimating the likelihood for Legionella infection and thus may help to direct diagnostic and therapeutic decisions.
Democratisation without Coercion: Parliamentary Bodies as Democracy Promoters in the Mediterranean
Authors: Harwood Mark A 
Published: June 2019

Abstract
In an attempt to decentre the debate of democracy promotion in the Mediterranean, this article applies social constructivism to an analysis of the work undertaken by two International Parliamentary Bodies in the Mediterranean. With a focus on the European Parliament and the Parliamentary Assembly of the Mediterranean, we analyse how effective their role can be without coercion and move on to discuss whether newly formed democratic parliaments, as in Tunisia, may represent a more legitimate and viable source of parliamentary-driven democracy promotion.
CXCL13 as biomarker for histological involvement in Sjögren’s syndrome
Authors: Colafrancesco Serena , Priori Roberta , Smith Charlotte G , Minniti Antonina , Iannizzotto Valentina , Pipi Elena , Lucchesi Davide , Pontarini Elena , Nayar Saba , Campos Joana , Arienzo Francesca , Fusconi Massimo , Cerbelli Bruna , Giordano Carla , Valesini Guido , Bombardieri Michele , Fisher Benjamin A , Barone Francesca 
Published: June 2019

Abstract

Objectives
SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres’ formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres’ activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation. The aim of this study was to evaluate the potential role of CXCL13 as a biomarker of SG pathology in two independent SS cohorts.

Methods
109 patients with SS were recruited at Sapienza University of Rome (Italy) (n = 60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n = 49). Both sera and matched minor SG biopsy were available. Sicca (n = 57) and healthy subjects’ (n = 19) sera were used as control.

Results
CXCL13 serum level was higher in SS patients compared with controls. Correlations between its serum levels and a series of histomorphological parameters, including size of the aggregates and the presence germinal centres', were observed.

Conclusion
Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies.
High angiopoietin-2 levels associate with arterial inflammation and long-term glucocorticoid requirement in polymyalgia rheumatica
Authors: van Sleen Yannick , Boots Annemieke M H , Abdulahad Wayel H , Bijzet Johan , Sandovici Maria , van der Geest Kornelis S M , Brouwer Elisabeth 
Published: June 2019

Abstract

Objectives
PMR frequently co-occurs with GCA. So far, a simple biomarker for detecting concomitant arterial inflammation in PMR patients is lacking. Furthermore, biomarkers predicting disease course in PMR are awaited. We here investigated the diagnostic and prognostic value of acute-phase markers (ESR, CRP, IL-6, serum amyloid A) and angiogenesis markers (VEGF, soluble Tie2, angiopoietin-1, angiopoietin-2) in isolated PMR and PMR/GCA overlap patients.

Methods
We prospectively included 39 treatment-naïve PMR patients, of whom 10 patients also showed evidence of large vessel GCA by PET-CT. Age-matched healthy controls (n = 32) and infection controls (n = 13) were included for comparison. Serum marker levels were measured by an ELISA or Luminex assay. Receiver operating characteristic and Kaplan–Meier analyses were used to asses diagnostic and prognostic accuracy, respectively.

Results
All acute-phase and angiogenesis markers, except angiopoietin-1, were higher in isolated PMR patients than in healthy controls. Angiopoietin-2, ESR and soluble Tie-2 were significantly higher in patients with PMR/GCA overlap than in isolated PMR patients. Angiopoeietin-2, but not soluble Tie2, outperformed ESR and CRP in discriminating patients with and without overlapping GCA (area under the curve: 0.90; sensitivity: 100%; specificity: 76%). Moreover, high angiopoietin-2 levels were associated with long-term glucocorticoid requirement.

Conclusion
Assessment of angiopoietin-2 at baseline may assist diagnosis of concomitant vasculitis in PMR. Moreover, high levels of angiopoietin-2 were associated with an unfavourable disease course in isolated PMR patients. These findings imply that angiopoietin-2 is an interesting diagnostic and prognostic biomarker in PMR.
Innate Immune Cells and C-Reactive Protein in Acute First-Episode Psychosis and Schizophrenia: Relationship to Psychopathology and Treatment
Authors: Steiner Johann , Frodl Thomas , Schiltz Kolja , Dobrowolny Henrik , Jacobs Roland , Fernandes Brisa S , Guest Paul C , Meyer-Lotz Gabriela , Borucki Katrin , Bahn Sabine , Bogerts Bernhard , Falkai Peter , Bernstein Hans-Gert 
Published: June 2019

Abstract
Innate immunity has been linked to initiation of Alzheimer’s disease and multiple sclerosis. Moreover, risk of first-episode psychosis (FEP) and schizophrenia (Sz) is increased after various infections in predisposed individuals. Thus, we hypothesized an analogous role of innate immunity with increased C-reactive protein (CRP) in non-affective psychosis. Differential blood count, CRP, neutrophil and monocyte–macrophage activation markers, cortisol and psychotic symptoms (Positive and Negative Syndrome Scale [PANSS]) were assessed in controls (n = 294) and acutely ill unmedicated FEP (n = 129) and Sz (n = 124) patients at baseline and after 6 weeks treatment. Neutrophils, monocytes, and CRP were increased in patients vs controls at baseline (P < .001), and neutrophil and monocyte counts correlated positively with activation markers. Eosinophils were lower at baseline in FEP (P < .001) and Sz (P = .021) vs controls. Differences in neutrophils (P = .023), eosinophils (P < .001), and CRP (P < .001) were also present when controlling for smoking and cortisol, and partially remitted after antipsychotic treatment. FEP patients with high neutrophils (P = .048) or monocytes (P = .021) had higher PANSS-P scores at baseline but similar disease course. CRP correlated with PANSS-P at baseline (ρ = 0.204, P = .012). Improvement of positive symptoms after treatment correlated with declining neutrophils (ρ = 0.186, P = .015) or CRP (ρ = 0.237, P = .002) and rising eosinophils (ρ = −0.161, P = .036). In FEP, normalization of neutrophils (ρ = −0.231, P = .029) and eosinophils (ρ = 0.209, P = .048) correlated with drug dosage. In conclusion, innate immune system activation correlated with PANSS-P, supporting the immune hypothesis of psychosis. Neutrophil and monocyte counts and CRP levels may be useful markers of disease acuity, severity, and treatment response.
Open (in)justice: privacy, open justice and human rights
Authors: Cooper Gilead 
Published: June 2019

Abstract
The principle that court hearings must be open to the public is regarded as sacrosanct. It has recently been invoked by the Court of Appeal in MN v OP as the reason for refusing an application to anonymise the approval of an arrangement under the Variation of Trusts Act 1958 Act. Yet the reasons generally given for insisting on open justice as a matter of principle are unconvincing when applied to civil cases as opposed to criminal cases or those, such as judicial review, in which the power of the state is pitted against the individual citizen. If private citizens are free to resolve their disputes privately through arbitration or mediation, why should they not be allowed to have their cases heard by the court in chambers unless there is some special feature of the case requiring publicity? Why are anonymised judgments not sufficient to ensure that justice is administered fairly and in accordance with the law? Could not more use be made of reporting restrictions? In this article, it is argued that the courts should do more to protect the privacy of litigants, and should not bow to populist demands to pry into the affairs of others (particularly the very wealthy). If they do not, those who can afford to do so will choose arbitration, or litigate in off-shore jurisdictions that are more sympathetic to their reasonable desire for privacy.
Effects of microbial phytase on standardized total tract digestibility of phosphorus in hybrid rye, barley, wheat, corn, and sorghum fed to growing pigs1
Authors: McGhee Molly L , Stein Hans H 
Published: June 2019

Abstract
An experiment was conducted to determine the apparent total tract digestibility (ATTD) and the standardized total tract digestibility (STTD) of P in three varieties of hybrid rye and in one source of barley, wheat, corn, and sorghum. The STTD of P in each cereal grain was determined both without and with addition of microbial phytase. In total, 112 growing barrows (13.7 ± 1.3 kg initial BW) were allotted to a randomized complete block design with four blocks of 28 pigs. Pigs were randomly allotted to 14 diets with two replicate pigs per diet in each block, resulting in a total of eight replicate pigs per diet for the four blocks. Each diet contained one of the cereal grains as the sole source of P. There were two diets with each cereal grain with one diet containing no microbial phytase and the other diet containing 1,000 units of microbial phytase per kilogram of diet. In each period, fecal output was collected for 5 d following a 5-d adaptation period according to the marker-to-marker procedure. Among the diets that did not include microbial phytase, one hybrid of rye had greater (P &lt; 0.05) STTD of P than wheat, corn, and sorghum, which is likely a result of the greater intrinsic phytase activity in rye than in the other cereal grains. Without microbial phytase, there was no difference in the STTD of P in the three hybrids of rye and barley. Among the diets containing microbial phytase, there was no difference in STTD of P among the three hybrids of rye, barley, and corn. The STTD of P in the three hybrids of rye with microbial phytase was 61.9%, 70.8%, and 63.0%, respectively. Overall, microbial phytase improved (P &lt; 0.05) the STTD of P in all cereal grains, although the magnitude of the increase in STTD of P differed among the grains.
Both GSK-3β/CRMP2 and CDK5/CRMP2 Pathways Participate in the Protection of Dexmedetomidine Against Propofol-Induced Learning and Memory Impairment in Neonatal Rats
Authors: Li Junhua , Guo Mingyan , Liu Yafang , Wu Guiyun , Miao Liping , Zhang Jing , Zuo Zhiyi , Li Yujuan 
Published: June 2019

Abstract
Dexmedetomidine has been reported to ameliorate propofol-induced neurotoxicity in neonatal animals. However, the underlying mechanism is still undetermined. Glycogen synthase kinase-3β (GSK-3β), cycline-dependent kinase-5 (CDK5), and Rho-kinase (RhoA) pathways play critical roles in neuronal development. The present study is to investigate whether GSK-3β, CDK5, and RhoA pathways are involved in the neuroprotection of dexmedetomidine. Seven-day-old (P7) Sprague Dawley rats were anesthetized with propofol for 6 h. Dexmedetomidine at various concentrations were administered before propofol exposure. Neuroapoptosis, the neuronal proliferation, and the level of neurotransmitter in the hippocampus were evaluated. The effects of GSK-3β inhibitor SB415286, CDK5 inhibitor roscovitine, or RhoA inhibitor Y276321 on propofol-induced neurotoxicity were assessed. Propofol-induced apoptosis in the hippocampal neurons and astrocytes, inhibited neuronal proliferation in the dentate gyrus region, down-regulated the level of γ-aminobutyric acid and glutamate in the hippocampus, and impaired long-term cognitive function. These harmful effects were reduced by pretreatment with 50 μg·kg−1 dexmedetomidine. Moreover, propofol-activated GSK-3β and CDK5 pathways, but not RhoA pathway, by reducing the phosphorylation of GSK-3β (ser 9), increasing the expression of CDK5 activator P25 and increasing the phosphorylation of their target sites on collapsin response mediator protein 2 (CRMP2) shortly after exposure. These effects were reversed by pretreatment with 50 μg·kg−1 dexmedetomidine. Furthermore, SB415286 and roscovitine, not Y276321, attenuated the propofol-induced neuroapoptosis, brain cell proliferation inhibition, γ-aminobutyric acid and glutamate downregulation, and learning and memory dysfunction. Our results indicate that dexmedetomidine reduces propofol-induced neurotoxicity and neurocognitive impairment via inhibiting activation of GSK-3β/CRMP2 and CDK5/CRMP2 pathways in the hippocampus of neonatal rats.
Hepatitis C Contamination of Medication Vials Accessed with Sterile Needles and Syringes
Authors: van Vlymen Janet M. , Magnus Julie , Jaeger Melanie , Breton Sophie , Taylor Nathan G. , Phelan Rachel , Sagan Selena M. 
Published: June 2019

Abstract

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background
Health care–associated hepatitis C virus outbreaks from contaminated medication vials continue to be reported even though most practitioners deny reusing needles or syringes. The hypothesis was that when caring for hepatitis C virus–infected patients, healthcare providers may inadvertently contaminate the medication vial diaphragm and that subsequent access with sterile needles and syringes can transfer hepatitis C virus into the medication, where it remains stable in sufficient quantities to infect subsequent patients.

Methods
A parallel-arm lab study (n = 9) was performed in which contamination of medication vials in healthcare settings was simulated using cell culture–derived hepatitis C virus. First, surface-contaminated vials were accessed with sterile needles and syringes, and then hepatitis C virus contamination was assessed in cell culture. Second, after contaminating several medications with hepatitis C virus, viral infectivity over time was assessed. Last, surface-contaminated vial diaphragms were disinfected with 70% isopropyl alcohol to determine whether disinfection of the vial surface was sufficient to eliminate hepatitis C virus infectivity.

Results
Contamination of medication vials with hepatitis C virus and subsequent access with sterile needles and syringes resulted in contamination of the vial contents in sufficient quantities to initiate an infection in cell culture. Hepatitis C virus remained viable for several days in several commonly used medications. Finally, a single or 2- to 3-s wipe of the vial diaphragm with 70% isopropyl alcohol was not sufficient to eliminate hepatitis C virus infectivity.

Conclusions
Hepatitis C virus can be transferred into commonly used medications when using sterile single-use needles and syringes where it remains viable for several days. Furthermore, cleaning the vial diaphragm with 70% isopropyl alcohol is not sufficient to eliminate the risk of hepatitis C virus infectivity. This highlights the potential risks associated with sharing medications between patients.