bluuebunny/crossref_metadata_2025_split huggingface dataset:
A polybasic motif in ErbB3-binding protein 1 (EBP1) has key functions in nucleolar localization and polyphosphoinositide interaction
Authors: Karlsson Thomas , Altankhuyag Altanchimeg , Dobrovolska Olena , Turcu Diana C. , Lewis Aurélia E. 
Published: April 2016

Polyphosphoinositides (PPIns) are present in the nucleus where they participate in crucial nuclear processes, such as chromatin remodelling, transcription and mRNA processing. In a previous interactomics study, aimed to gain further insight into nuclear PPIns functions, we identified ErbB3 binding protein 1 (EBP1) as a potential nuclear PPIn-binding protein in a lipid pull-down screen. EBP1 is a ubiquitous and conserved protein, located in both the cytoplasm and nucleolus, and associated with cell proliferation and survival. In the present study, we show that EBP1 binds directly to several PPIns via two distinct PPIn-binding sites consisting of clusters of lysine residues and positioned at the N- and C-termini of the protein. Using interaction mutants, we show that the C-terminal PPIn-binding motif contributes the most to the localization of EBP1 in the nucleolus. Importantly, a K372N point mutation, located within the C-terminal motif and found in endometrial tumours, is sufficient to alter the nucleolar targeting of EBP1. Our study reveals also the presence of the class I phosphoinositide 3-kinase (PI3K) catalytic subunit p110β and its product PtdIns(3,4,5)P3 together with EBP1 in the nucleolus. Using NMR, we further demonstrate an association between EBP1 and PtdIns(3,4,5)P3 via both electrostatic and hydrophobic interactions. Taken together, these results show that EBP1 interacts directly with PPIns and associate with PtdIns(3,4,5)P3 in the nucleolus. The presence of p110β and PtdIns(3,4,5)P3 in the nucleolus indicates their potential role in regulating nucleolar processes, at least via EBP1.
Modulation of myocardial injury and collagen deposition following ischaemia–reperfusion by linagliptin and liraglutide, and both together
Authors: Wang Xianwei , Ding Zufeng , Yang Fen , Dai Yao , Chen Peng , Theus Sue , Singh Sharda , Budhiraja Madhu , Mehta Jawahar L. 
Published: April 2016

Studies have indicated that dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists reduce infarct size after myocardial ischaemia. Whether these agents modify cardiac remodelling after ischaemia is unclear. Furthermore, it is not known if combination of the two types of drugs is superior to either agent alone. We investigated the modulatory effect of the DPP-4 inhibitor linagliptin alone, the GLP-1 activator liraglutide alone, or the two agents together on myocardial infarct size, left ventricular contractile function and cardiac remodelling signals after a brief period of left coronary artery (LCA) occlusion. C57BL/6 mice were treated with vehicle, the DPP-4 inhibitor linagliptin, the GLP-1 activator liraglutide, or both agents together for 5 days, and then subjected to LCA occlusion (1 h) and reperfusion (3 h). Ischaemia–reperfusion increased reactive oxygen species (ROS) generation and expression of NADPH oxidase (p47phox, p22phox and gp91phox subtypes), collagens, fibronectin and proinflammatory cytokines (interleukin 6, tumour necrosis factor α and monocyte chemoattractant protein-1) in the LCA-supplied regions. Pre-treatment with linagliptin or liraglutide reduced infarct size, protected cardiomyocytes from injury and preserved cardiac contractile function in a similar fashion. It is interesting that profibrotic (collagen deposition) signals were expressed soon after ischaemia–reperfusion. Both linagliptin and liraglutide suppressed ROS generation, NADPH oxidase and proinflammatory signals, and reduced collagen deposition. Addition of linagliptin or liraglutide had no significant additive effect above and beyond that of liraglutide and linagliptin given alone. In conclusion, linagliptin and liraglutide can improve cardiac contractile function and indices of cardiac remodelling, which may be related to their role in inhibition of ROS production and proinflammatory cytokines after ischaemia.
Willingness of Australian health educators and health promotion officers to conduct rapid HIV testing
Authors: Santella Anthony J. , Fraser Jacquie , Prehn Angela W. , Boye‐Codjoe Eugenia 
Published: April 2016

Issue addressedRapid HIV tests were recently approved by the Australian government. This paper examines the attitudes and willingness to conduct rapid HIV testing (RHT) of Australian health educators and health promotion officers (HE/HPO) from various settings and disciplines.MethodsThe aim of the Promoting Research on Methods in Screening Expertise study was to explore knowledge of HIV, attitudes towards people living with HIV, and willingness to conduct RHT among HE/HPO in Australia; this information was attained via an online survey of HE/HPO. Descriptive statistics, c2 tests, t‐tests, and multivariate logistic regression were then conducted.ResultsData from 156 HE/HPOs were analysed. Overall, 60% of participants believed that HE/HPO should offer RHT. Additionally, 70% were personally willing to undergo training in conducting RHT. Fifty‐nine percent of participants scored as having ‘high’ HIV knowledge (at least 12 out of 13 correct answers), with 32% answering all questions correctly. Knowledge was strongly associated with willingness to be trained to conduct RHT.ConclusionsHE/HPO with advanced training in developing evidence‐based approaches to improve the health and wellbeing of marginalised and disadvantaged groups may be an appropriate workforce to train to conduct RHT and counselling.So what?As government agencies and community‐based organisations plan to expand RHT, HE/HPO, including those who work outside of sexual health, should be considered as a viable workforce to upskill.
A topologically driven glass in ring polymers
Authors: Michieletto Davide , Turner Matthew S. 
Published: April 2016

Significance
The glass transition is commonly associated with a reduction in the temperature of liquids or by an increase in density of granular materials. In this work, we propose a radically different approach to study dynamical arrest that relies on the topology of the components. We find that a concentrated solution of ring polymers can be driven to a kinetically arrested state by randomly pinning a small fraction of rings, a transition not observed in linear polymers. We attribute this jamming to topological interactions, called “threadings,” that populate solutions of rings. Our work provides the first evidence for these threadings and suggests that very long rings may be expected to be kinetically arrested even as the fraction of pinned rings approaches zero.
Justice and Health Care: When “Ordinary” is Extraordinary
Authors: McTavish James 
Published: April 2016

In some Asian countries, the poor are often denied access to health care. In the Philippines, we have thousands of Catholic doctors, Catholic nurses, even Catholic administrators, but not a Catholic, understood as “universal,” healthcare system available to all. This is a scandal and places heavy emotional and financial burdens on many families who need to pay the healthcare costs of sick loved ones. The Church teaches the principles of ordinary and extraordinary care, with only the former being morally obligatory. Extraordinary care, that involving excessive burden or cost may be foregone. Many families and healthcare professionals are uncertain about these principles and their application in practice. It would be helpful to more widely disseminate the Catholic Church teaching regarding ordinary and extraordinary care, especially in poor countries, to also avoid unnecessary or futile treatments, especially in critical or end-of-life situations. Lay Summary: The poor have limited access to health care in many countries. Even one episode of sickness often places the patient and their family under considerable financial strain. Many times they simply cannot afford even basic treatments. This is a scandal and an injustice which is the concern of us all. The Church teaches that when a treatment becomes very expensive it may be considered “extraordinary care” and not morally obligatory. It would be helpful to more widely disseminate this Catholic Church teaching, helping families to avoid unnecessary treatments especially in critical or end-of-life situations.
Effect of linker length between variable domains of single chain variable fragment antibody against daidzin on its reactivity
Authors: Yusakul Gorawit , Sakamoto Seiichi , Pongkitwitoon Benyakan , Tanaka Hiroyuki , Morimoto Satoshi 
Published: April 2016

Abstract
The peptide linker between variable domains of heavy (VH) and light (VL) chains is one of important factors that influence the characteristics of scFv, including binding activity and specificity against target antigen. The scFvs against daidzin (DZ-scFvs) with different linker lengths were constructed in the format of VH-(GGGGS)n-VL (n = 1, 3, 5, and 7). They were expressed in the hemolymph of silkworm larvae using the Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid DNA system, and their reactivity against daidzin and related compounds were evaluated using an indirect competitive enzyme-linked immunosorbent assay (icELISA), which is applicable for quantitative analysis of daidzin. The results showed that the reactivity of scFvs against daidzin was increased, whereas specificity slightly decreased when their peptide linker was lengthened. These results suggested that the linker length of DZ-scFvs contributes to its reactivity. In addition, the results emphasize that the linker length could control the reactivity of DZ-scFvs.
Location of the first plasma response to resonant magnetic perturbations in DIII-D H-mode plasmas
Authors: Xiao W.W. , Evans T.E. , Tynan G.R. , Eldon D. 
Published: April 2016

Abstract
The resonant location of the first plasma response to periodic toroidal phase flips of a resonant magnetic perturbation (RMP) field is experimentally identified in the DIII-D tokamak using phase minima of the modulated plasma density and toroidal rotation relative to the RMP field. The plasma response coincides with the q  =  3 rational surface and electron fluid velocity null, which is consistent with simulations of the plasma response to the RMP field from resistive magnetohydrodynamics (MHD) modeling. An asymmetric propagation of the particle and the momentum transport from the resonant location of the plasma response to the RMP into the core and into the plasma edge is observed.
Combenefit: an interactive platform for the analysis and visualization of drug combinations
Authors: Di Veroli Giovanni Y. , Fornari Chiara , Wang Dennis , Mollard Séverine , Bramhall Jo L. , Richards Frances M. , Jodrell Duncan I. 
Published: April 2016

Abstract
Motivation: Many drug combinations are routinely assessed to identify synergistic interactions in the attempt to develop novel treatment strategies. Appropriate software is required to analyze the results of these studies.
Results: We present Combenefit, new free software tool that enables the visualization, analysis and quantification of drug combination effects in terms of synergy and/or antagonism. Data from combinations assays can be processed using classical Synergy models (Loewe, Bliss, HSA), as single experiments or in batch for High Throughput Screens. This user-friendly tool provides laboratory scientists with an easy and systematic way to analyze their data. The companion package provides bioinformaticians with critical implementations of routines enabling the processing of combination data.
Availability and Implementation: Combenefit is provided as a Matlab package but also as standalone software for Windows (http://sourceforge.net/projects/combenefit/).
Contact: Giovanni.DiVeroli@cruk.cam.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
Terminal speed of a gaseous stratus with finite optical depth over a luminous flat source
Authors: Masuda Takao , Fukue Jun 
Published: April 2016

Abstract
We reexamine the terminal speed of a moving stratus irradiated by an infinite flat source, considering relativistic radiative transfer in the stratus. For the case of a particle, V. Icke (1989, A&A, 216, 294) analytically derived the terminal speed of $(4-\sqrt{7})c/3 \sim 0.45\,c$, whereas the terminal speed of a stratus with finite optical depth is calculated under the Eddington approximation (J. Fukue, 2014, PASJ, 66, 13), and becomes larger up to 0.7 c in the optically thin limit. In this paper, we numerically calculate radiative transfer in the stratus without the Eddington approximation, and obtain the terminal speed. In the optically thick limit the terminal speed approaches 0.47 c. In the optically thin limit, in contrast to the previous analytical study, it becomes small as the optical depth decreases, and approaches 0.26 c. This is due to the anisotropic effect of the radiation field in the optically thin regime.
Helping Basic Scientists Engage With Community Partners to Enrich and Accelerate Translational Research
Authors: Kost Rhonda G. , Leinberger-Jabari Andrea , Evering Teresa H. , Holt Peter R. , Neville-Williams Maija , Vasquez Kimberly S. , Coller Barry S. , Tobin Jonathan N. 
Published: April 2016

Problem
Engaging basic scientists in community-based translational research is challenging but has great potential for improving health.

Approach
In 2009, The Rockefeller University Center for Clinical and Translational Science partnered with Clinical Directors Network, a practice-based research network (PBRN), to create a community-engaged research navigation (CEnR-Nav) program to foster research pairing basic science and community-driven scientific aims. The program is led by an academic navigator and a PBRN navigator. Through meetings and joint activities, the program facilitates basic science–community partnerships and the development and conduct of joint research protocols.

Outcomes
From 2009–2014, 39 investigators pursued 44 preliminary projects through the CEnR-Nav program; 25 of those became 23 approved protocols and 2 substudies. They involved clinical scholar trainees, early-career physician–scientists, faculty, students, postdoctoral fellows, and others. Nineteen (of 25; 76%) identified community partners, of which 9 (47%) named them as coinvestigators. Nine (of 25; 36%) included T3–T4 translational aims. Seven (of 25; 28%) secured external funding, 11 (of 25; 44%) disseminated results through presentations or publications, and 5 (71%) of 7 projects publishing results included a community partner as a coauthor. Of projects with long-term navigator participation, 9 (of 19; 47%) incorporated T3–T4 aims and 7 (of 19; 37%) secured external funding.

Next Steps
The CEnR-Nav program provides a model for successfully engaging basic scientists with communities to advance and accelerate translational science. This model's durability and generalizability have not been determined, but it achieves valuable short-term goals and facilitates scientifically meaningful community–academic partnerships.
Population Pharmacokinetics of Prednisolone in Relation to Clinical Outcome in Children With Nephrotic Syndrome
Authors: Teeninga Nynke , Guan Zheng , Stevens Jasper , Kist-van Holthe Joana E. , Ackermans Mariëtte T. , van der Heijden Albert J. , van Schaik Ron H. N. , van Gelder Teun , Nauta Jeroen 
Published: April 2016

Background:
The relapse frequency in children with nephrotic syndrome (NS) is highly variable despite standardized prednisolone treatment regimens. Existing evidence on the relationship between prednisolone pharmacokinetics (PK) and clinical response in children with NS is scarce and limited. The aim of this study was to develop a pediatric popPK model for prednisolone based on our previous model based on healthy adults using salivary measurements in children with NS and to correlate clinical outcome with between-subject variability in prednisolone exposure.

Methods:
The pharmacokinetics of prednisolone in a well-defined, prospective cohort consisting of 104 children with NS while in remission was determined. Pharmacokinetic parameters were analyzed in relation to relapse patterns and side effects. Noninvasive salivary prednisolone measurements were performed using a sparse sampling strategy. A population pharmacokinetic approach was used to derive individual estimates of apparent clearance (CL/F) and apparent volume of distribution (V/F) from the salivary concentration–time curve, followed by calculation of the area under the curve (AUC) of free prednisolone. The individual free serum prednisolone exposure from prednisolone in saliva was derived from the salivary concentration–time curves. Genetic polymorphisms of CYP3A4, CYP3A5, ABCB1, NR1L2, and POR were explored in relation to between-subject variability of CL/F.

Results:
Moderate interindividual variability was found for CL/F (CV, 44.7%). Unexplained random between-subject variability (eta) of CL/F was lower in patients carrying 1 or 2 ABCB1 3435C>T alleles compared to wild type: median −0.04 (interquartile range, −0.17 to 0.21) and 0.00 (−0.11 to 0.16) versus 0.17 (−0.08 to 0.47), P = 0.046. Exposure to free prednisolone was not associated with frequent relapses or adverse effects.

Conclusions:
This study provides evidence for the possibility of prednisolone drug monitoring through salivary measurements and this may be of particular usefulness in pediatric patients. However, the observed variability in prednisolone exposure, in the therapeutic dose range studied, is not considered to be a major determinant of clinical outcome in children with NS.
Oxygen Uptake Attenuation at Ventilatory Threshold in Men With Coronary Artery Disease
Authors: Uliari Simone , Myers Jonathan , Bernardi Eva , Chiaranda Giorgio , Conconi Francesco , Terranova Francesco , Mazzoni Gianni , Grazzi Giovanni 
Published: April 2016

PURPOSE:
Maximal oxygen uptake (

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o
2) and ventilatory threshold (VT) are widely used to assess cardiorespiratory fitness in healthy people, as well as in patients with various clinical conditions. The aim of this study was to determine whether an attenuation of

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2 occurs above the VT in patients with stable coronary artery disease.

METHODS:
A total of 33 male patients participating in an outpatient cardiac rehabilitation/secondary prevention program underwent maximal incremental cycle ergometry at increasing pedaling cadences up to the limit of tolerance. Ventilatory gas-exchange variables were measured breath by breath while work rate was recorded continuously. Ventilatory threshold was determined by a dual linear regression model (V-slope analysis).

RESULTS:
Four patients were excluded from the analysis because they were unable to pedal at the increasing cadences required by the protocol. The remaining 29 patients successfully completed the test without complications or evidence of significant ST segment depression. The slope of the

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o
2/work rate relationship above the VT decreased significantly (−44.6% on average) in 23 of the 26 patients in which VT was able to be determined.

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2 at the start of

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2 attenuation (

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2
att) and at VT were highly correlated and in strong agreement (1637 ± 451 mL/min vs 1650 ± 473 mL/min, r
2 = 0.96, P < .01).

CONCLUSIONS:

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o
2att does occur and coincides with the VT in the majority of patients tested with stable coronary artery disease.
Management of Spasticity in Moderate and Severe Traumatic Brain Injury: Evaluation of Clinical Practice Guidelines
Authors: Pattuwage Loyal , Olver John , Martin Caius , Lai Francis , Piccenna Loretta , Gruen Russell , Bragge Peter 
Published: April 2016

Introduction:
Moderate to severe traumatic brain injury (TBI) can result in development of spasticity, which adversely affects function and quality of life. Given the foundation of optimal clinical practice is use of the best available evidence, we aimed to identify, describe, and evaluate methodological quality of evidence-based spasticity clinical practice guidelines (CPGs).

Methods:
A comprehensive search for CPGs encompassed electronic databases and online sources. Eligible CPGs were evaluated using the validated Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.

Results:
Five CPGs were eligible for review; 2 were specific to acquired brain injury and 1 to TBI. The 3 brain injury-specific CPGs contained 423 recommendations overall, but only 8 spasticity recommendations. On the basis of AGREE appraisals, all CPGs performed well in the areas of reporting scope and purpose; clearly presenting recommendations; including various stakeholders in the CPG development process; and reporting conflict of interest. However, only one CPG performed adequately on describing facilitators and barriers to implementation, advice, and tools on how to implement recommendations and provision of audit criteria. Intraclass correlation coefficient (ICC) for agreement between raters showed high agreement (ICC > 0.80) for most guidelines.

Conclusion:
Given the unique etiological features and treatment challenges associated with managing spasticity after TBI, more TBI-specific spasticity CPGs are required. These should incorporate information on the facilitators and barriers to implementation, advice on implementing recommendations, and audit criteria.
AN ATYPICAL CASE OF SYMPATHETIC OPHTHALMIA AFTER LIMBAL CORNEAL LACERATION
Authors: Subudhi Praveen , Kanungo Sanghamitra , Subudhi B. Nageswar Rao 
Published: April 2016

Background/Purpose:
To report a case of atypical sympathetic ophthalmia after limbal corneal laceration.

Methods and Results:
An 11-year-old child had a successful left eye corneal laceration repair at the temporal limbus with excision of exposed nonnecrotic iris tissue, resulting in good visual acuity of 20/80 and 20/25 on postoperative Days 1 and 7, respectively. The patient was prescribed 1 mg/kg oral prednisolone in a tapering dose as prophylaxis. On postoperative Day 21, the patient presented with acute onset decreased vision in both eyes. Visual acuity was counting fingers 3 feet in both eyes. On examination, anterior segment examination was quiet without any inflammation, anterior vitreous face showed 1+ cells, and dilated funduscopy revealed bilateral symmetrical serous retinal detachments along the posterior pole. Optical coherence tomography demonstrated separation and elevation of inner neurosensory layers from the outer segment marking presence of hyperreflective material along with subretinal fluid between detached surfaces. There was stippled hyperfluorescence along the posterior pole as seen in fluorescein angiography. With a diagnosis of sympathetic ophthalmia confirmed, oral prednisolone (2 mg/kg body weight) was instituted after which, there was gradual decrease in macular elevation with corresponding improvement in visual acuity with no recurrence for the last 6 months.

Conclusion:
To our knowledge, this is the first reported instance of an atypical presentation of sympathetic ophthalmia, and antecedent corticosteroid therapy would have mitigated robust anterior segment findings usually associated with the condition.