bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Lack of Maturation of Ebola Virus-Infected Dendritic Cells Results from the Cooperative Effect of at Least Two Viral Domains
Authors: Lubaki Ndongala M. , Ilinykh Philipp , Pietzsch Colette , Tigabu Bersabeh , Freiberg Alexander N. , Koup Richard A. , Bukreyev Alexander 
Published: April 2013

ABSTRACTEbola virus (EBOV) infections are characterized by deficient T lymphocyte responses, T lymphocyte apoptosis, and lymphopenia in the absence of direct infection of T lymphocytes. In contrast, dendritic cells (DC) are infected but fail to mature appropriately, thereby impairing the T cell response. We investigated the contributions of EBOV proteins in modulating DC maturation by generating recombinant viruses expressing enhanced green fluorescent protein and carrying mutations affecting several potentially immunomodulating domains. They included envelope glycoprotein (GP) domains, as well as innate response antagonist domains (IRADs) previously identified in the VP24 and VP35 proteins. GP expressed by an unrelated vector, but not the wild-type EBOV, was found to strongly induce DC maturation, and infections with recombinant EBOV carrying mutations disabling GP functional domains did not restore DC maturation. In contrast, each of the viruses carrying mutations disabling any IRAD in VP35 induced a dramatic upregulation of DC maturation markers. This was dependent on infection, but not interaction with GP. Disabling of IRADs also resulted in up to a several hundredfold increase in secretion of cytokines and chemokines. Furthermore, these mutations induced formation of homotypic DC clusters, which represent close correlates of their maturation and presumably facilitate transfer of antigen from migratory DC to lymph node DC. Thus, an individual IRAD is insufficient to suppress DC maturation; rather, the suppression of DC maturation and the “immune paralysis” observed during EBOV infections results from a cooperative effect of two or more individual IRADs.
The VP8* Domain of Neonatal Rotavirus Strain G10P[11] Binds to Type II Precursor Glycans
Authors: Ramani Sasirekha , Cortes-Penfield Nicolas W. , Hu Liya , Crawford Sue E. , Czako Rita , Smith David F. , Kang Gagandeep , Ramig Robert F. , Le Pendu Jacques , Prasad B. V. Venkataram , Estes Mary K. 
Published: April 2013

ABSTRACT
Naturally occurring bovine-human reassortant rotaviruses with a P[11] VP4 genotype exhibit a tropism for neonates. Interaction of the VP8* domain of the spike protein VP4 with sialic acid was thought to be the key mediator for rotavirus infectivity. However, recent studies have indicated a role for nonsialylated glycoconjugates, including histo-blood group antigens (HBGAs), in the infectivity of human rotaviruses. We sought to determine if the bovine rotavirus-derived VP8* of a reassortant neonatal G10P[11] virus interacts with hitherto uncharacterized glycans. In an array screen of >600 glycans, VP8* P[11] showed specific binding to glycans with the Galβ1-4GlcNAc motif, which forms the core structure of type II glycans and is the precursor of H type II HBGA. The specificity of glycan binding was confirmed through hemagglutination assays; GST-VP8* P[11] hemagglutinates type O, A, and B red blood cells as well as pooled umbilical cord blood erythrocytes. Further, G10P[11] infectivity was significantly enhanced by the expression of H type II HBGA in CHO cells. The bovine-origin VP4 was confirmed to be essential for this increased infectivity, using laboratory-derived reassortant viruses generated from sialic acid binding rotavirus SA11-4F and a bovine G10P[11] rotavirus, B223. The binding to a core glycan unit has not been reported for any rotavirus VP4. Core glycan synthesis is constitutive in most cell types, and modification of these glycans is thought to be developmentally regulated. These studies provide the first molecular basis for understanding neonatal rotavirus infections, indicating that glycan modification during neonatal development may mediate the age-restricted infectivity of neonatal viruses.
Coronary revascularisation in stable patients after an acute coronary syndrome: a propensity analysis of early invasive versus conservative management in a register-based cohort study
Authors: Bugiardini Raffaele , Eskola Markku , Huhtala Heini , Niemelä Kari , Karhunen Pekka , Miglio Rossella , Manfrini Olivia , Pizzi Carmine , Nikus Kjell 
Published: April 2013

ObjectivesTo compare the effectiveness of in-hospital medical therapy versus coronary revascularisation added to medical therapy in patients who stabilised after an acute coronary syndrome (ACS).DesignPropensity score-matched cohort study from the database of the Tampere ACS registry.SettingA single academic hospital in Finland.Participants1149 patients with a recent ACS, but no serious coexisting conditions: recurrent ischaemic episodes despite adequate medical therapy, haemodynamic instability, overt congestive heart failure and serious ventricular arrhythmias.Primary and secondary outcome measuresThe composite endpoint of major acute cardiovascular events (MACEs): unstable angina requiring rehospitalisation, stroke, myocardial infarction and all-cause mortality, at 6-month follow-up.ResultsCompared with standard medical treatment, revascularisation was associated with a lower rate of MACEs at 6 months in patients of the first quintile (HR 0.81; 95% CI 0.66 to 0.99), but a higher rate of MACEs in the fifth quintile (HR 4.74, CI 1.36 to 16.49; p=0.014). There were no significant differences in the rates of MACEs in the remaining three quintiles. Patients of the first quintile were the oldest (79.7±8.3 years) and had a more significant (p<0.001) history of prior myocardial infarction (37%) and poor renal function (creatine, µmol/l: 114.9±70.7). They also showed the highest C reactive protein (7.3±9.5 mg/l) levels.ConclusionsOur findings suggest that in-hospital coronary revascularisation did not lead to any advantage with signal of possible harm in the great majority of patients who stabilised after an ACS. An early invasive management strategy may be best reserved for elderly patients having high-risk clinical features and biochemical evidence of a strong inflammatory activity.
Evaluating the construct of triage acuity against a set of reference vignettes developed via modified Delphi method
Authors: Twomey Michèle , Wallis Lee A , Myers Jonathan E 
Published: April 2013

ObjectiveTo evaluate the construct of triage acuity as measured by the South African Triage Scale (SATS) against a set of reference vignettes.MethodsA modified Delphi method was used to develop a set of reference vignettes. Delphi participants completed a 2-round consensus-building process, and independently assigned triage acuity ratings to 100 written vignettes unaware of the ratings given by others. Triage acuity ratings were summarised for all vignettes, and only those that reached 80% consensus during round 2 were included in the reference set. Triage ratings for the reference vignettes given by two independent experts using the SATS were compared with the ratings given by the international Delphi panel. Measures of sensitivity, specificity, associated percentages for over-triage/under-triage were used to evaluate the construct of triage acuity (as measured by the SATS) by examining the association between the ratings by the two experts and the international panel.ResultsOn completion of the Delphi process, 42 of the 100 vignettes reached 80% consensus on their acuity rating and made up the reference set. On average, over all acuity levels, sensitivity was 74% (CI 64% to 82%), specificity 92% (CI 87% to 94%), under-triage occurred 14% (CI 8% to 23%) and over-triage 12% (CI 8% to 23%) of the time.ConclusionsThe results of this study provide an alternative to evaluating triage scales against the construct of acuity as measured with the SATS. This method of using 80% consensus vignettes may, however, systematically bias the validity estimate towards better performance.
Geochemical assessment of arsenic toxicity in mine site along the proposed Mineral Tramway Project, Camborne, Cornwall
Authors: Bowell R. J. , Rees S. B. , Barnes A. , Prestia A. , Warrender R. , Dey B. M. 
Published: April 2013

Many abandoned mine sites in Cornwall, UK, are characterised by elevated concentrations of arsenic which can cause contamination of surrounding soil and water resources. Often these sites have important historical and cultural value that requires access to be maintained, despite the potential toxicity of As. In west Cornwall, the potential for As contamination has been recognized within the Industrial World Heritage site focused on the Mineral Tramway and mining sites mines in the Gwennap and Camborne mining districts. The major abandoned mine sites, arsenic calciner and milling sites along a proposed tourist route in this area have been assessed for As toxicity and bioavailability taking into account the proximity of footpaths to areas of potential contamination.
Arsenic concentrations up to 3.3% were found in soils along the proposed footpaths and exposed mine spoil, with 55% of all total As values above the UK criteria for contaminated industrial soil of 640 mg/kg in surface soil. Using a Physiologically Based Extraction Test (PBET), the maximum amount of As observed to be bioavailable varied from 4 mg/kg through to a maximum of 9,000 mg/kg with a positive correlation between total As concentrations and bioavailable As concentrations. Mineralogical and selective extraction evaluation identified that the PBET-released As is not so much associated with total As concentrations, but is positively correlated to As held within the weak ‘ionic-held’ As, strongly adsorbed As, As associated with amorphous iron and calcium oxide phases, and poorly crystallized As(V) salts. The data reported here have been used to develop a risk assessment of the sites and propose management strategies to mitigate these risks.
Using 3D seismic data to map shallow-marine geohazards: a case study from the Santos Basin, Brazil
Authors: Sharp Andy , Badalini Gianluca 
Published: April 2013

This paper documents a study that used high quality, conventionally processed, speculative 3D seismic data for two specific purposes: first, to identify and avoid any health, safety, security and environmental (HSSE) issues regarding the water bottom and, secondly, to avoid shallow (<1 s below the mud line) geohazards when drilling the wells. The study integrated existing legacy well data, new 3D data from the BM-S-52 concession and a targeted programme of water-bottom grab samples from the BM-S-52 concession, Santos Basin, offshore Brazil. Two aspects of the analysis are described: the first addresses the problem and solution adopted for characterizing the water-bottom environment in this area; the second addresses the interpretation of the data for shallow geohazards.
The results of this case study have been accepted by the regulatory authorities as representing sufficient evidence of risk evaluation that no further dedicated site-survey data acquisition is required. This has led to savings in time and in costs which would otherwise have been expended on deep-water site-survey campaigns. Furthermore, the use of 3D seismic data for well-location planning brings benefits in improved imaging of the near-mud-line geology, full coverage over the whole concession, operational flexibility for changing well location and timely availability of data. The analysis workflow may also be applicable in other, similar deep-water areas.
Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors
Authors: Morris Erick J. , Jha Sharda , Restaino Clifford R. , Dayananth Priya , Zhu Hugh , Cooper Alan , Carr Donna , Deng Yongi , Jin Weihong , Black Stuart , Long Brian , Liu Jenny , DiNunzio Edward , Windsor William , Zhang Rumin , Zhao Shuxia , Angagaw Minilik H. , Pinheiro Elaine M. , Desai Jagdish , Xiao Li , Shipps Gerald , Hruza Alan , Wang James , Kelly Joe , Paliwal Sunil , Gao Xiaolei , Babu Boga Sobhana , Zhu Liang , Daublain Pierre , Zhang Ling , Lutterbach Bart A. , Pelletier Marc R. , Philippar Ulrike , Siliphaivanh Phieng , Witter David , Kirschmeier Paul , Bishop W. Robert , Hicklin Daniel , Gilliland D. Gary , Jayaraman Lata , Zawel Leigh , Fawell Stephen , Samatar Ahmed A. 
Published: April 2013

Abstract
The high frequency of activating RAS or BRAF mutations in cancer provides strong rationale for targeting the mitogen-activated protein kinase (MAPK) pathway. Selective BRAF and MAP-ERK kinase (MEK) inhibitors have shown clinical efficacy in patients with melanoma. However, the majority of responses are transient, and resistance is often associated with pathway reactivation of the extracellular signal-regulated kinase (ERK) signaling pathway. Here, we describe the identification and characterization of SCH772984, a novel and selective inhibitor of ERK1/2 that displays behaviors of both type I and type II kinase inhibitors. SCH772984 has nanomolar cellular potency in tumor cells with mutations in BRAF, NRAS, or KRAS and induces tumor regressions in xenograft models at tolerated doses. Importantly, SCH772984 effectively inhibited MAPK signaling and cell proliferation in BRAF or MEK inhibitor–resistant models as well as in tumor cells resistant to concurrent treatment with BRAF and MEK inhibitors. These data support the clinical development of ERK inhibitors for tumors refractory to MAPK inhibitors.
Significance: BRAF and MEK inhibitors have activity in MAPK-dependent cancers with BRAF or RAS mutations. However, resistance is associated with pathway alterations resulting in phospho-ERK reactivation. Here, we describe a novel ERK1/2 kinase inhibitor that has antitumor activity in MAPK inhibitor-naïve and MAPK inhibitor-resistant cells containing BRAF or RAS mutations. Cancer Discov; 3(7); 742–50. ©2013 AACR.
See related commentary by Nissan et al., p. 719
This article is highlighted in the In This Issue feature, p. 705
Evolution of Factor V Leiden
Authors: Levi Marcel , Middeldorp Saskia , van Mens Thijs 
Published: April 2013

SummaryFactor V Leiden is a procoagulant mutation associated with venous and arterial thrombosis and pregnancy complications. Its high prevalence of 5% in Caucasians suggests that there are evolutionary benefits as well. Carriers are indeed reported to have various advantageous phenotypes related to haemostasis, inflammation and fertility: less acute blood loss; less menstrual blood loss; decreased risk of intracranial haemorrhage; milder phenotypes of haemophilia; higher survival in and lower susceptibility to severe sepsis; higher survival in acute respiratory distress syndrome; less severe diabetic nephropathy and higher fecundity in both men and women. Not all these associations come from high quality adequately powered studies and many have not been confirmed by further research. The evolutionary influence of the alleged associations varies and is difficult to establish, partly due to a shift over time in risk factors of the diseases concerned. For most of the phenotypes possible mechanistic explanations can be provided. The procoagulant phenotype and perhaps also certain pregnancy complications follow from activated protein C (APC) resistance. Elevated APC levels possibly mediate anti-inflammatory effects. Higher sperm counts and more successful embryo implantation seem to play a role in the increased fecundity.
Bridging the Gap between Legal and Institutional Developments within Regional Seas Frameworks
Authors: Rochette Julien , Billé Raphaël 
Published: April 2013

Abstract
The last four decades have seen a considerable development of regional environmental law, especially within the United Nations Environment Programme’s Regional Seas Programme. However, implementation remains far from satisfactory. Among the enabling conditions that would favour more systematic implementation, appropriate institutional frameworks are key. It is therefore timely to examine the various ways in which institutional developments may keep up with legal progress. This article provides an international overview of institutional arrangements set up in various regional seas frameworks, and underlines common patterns as well as the variety of options experienced. It then sheds light on the Nairobi Convention framework as a typical case of a gap between legal and institutional developments. It draws on the worldwide review to explore a number of ways by which the institutional framework in the Western Indian Ocean region could be brought up to speed with the legal framework.
Transforming an Atmospheric Science Curriculum to Meet Students' Needs
Authors: Horel John D. , Ziegenfuss Donna , Perry Kevin D. 
Published: April 2013

The Department of Meteorology (now Atmospheric Sciences) at the University of Utah faced reductions in state funding in 2008 that reduced support for nontenured instructors at the same time that the faculty were becoming increasingly successful obtaining federally supported research grants. A faculty retreat and subsequent discussions led to substantive curriculum changes to modernize the curriculum, enhance course offerings for undergraduate and graduate students, and improve the overall efficiency of the academic program. Maintaining discipline standards and existing teaching loads were important constraints on these changes.
Key features of the curriculum revisions for undergraduate majors included eliminating a very rigid course progression; shifting the emphasis from required courses to elective courses; offering many courses only every other year; and relying on half-semester short courses to survey subject areas rather than focusing in depth on fewer ones. The curriculum changes were evaluated through surveys and individual and focus group discussions of students and faculty. While the feedback suggests that the changes overall were beneficial, the transitional period during which the changes were implemented was difficult for faculty and students alike.
Faculty members have opportunities now to adjust courses based on their experiences gained teaching these courses in their new format. The feedback from students and faculty suggests that building improved relationships and interactions among co-enrolled undergraduate and graduate students is the greatest need in order to improve the classroom learning environment.
Morphometric and volumetric MRI changes in idiopathic intracranial hypertension
Authors: Hoffmann Jan , Huppertz Hans-Jürgen , Schmidt Christoph , Kunte Hagen , Harms Lutz , Klingebiel Randolf , Wiener Edzard 
Published: April 2013

Objective We aimed at validating established imaging features of idiopathic intracranial hypertension (IIH) by using state-of-the-art MR imaging together with advanced post-processing techniques and correlated imaging findings to clinical scores. Methods Twenty-five IIH patients as well as age-, sex- and body mass index (BMI)-matched controls underwent high-resolution T1w and T2w MR imaging in a 1.5 T scanner, followed by assessment of optic nerve sheaths, pituitary gland, ventricles and Meckel's cave. Imaging findings were correlated with cerebrospinal fluid (CSF) opening pressures and clinical symptom scores of visual disturbances (visual field defects or enlarged blind spot), headache, tinnitus (pulsatile and non-pulsatile) and vertigo. CSF as well as ventricle volumes were determined by using an automated MRI volumetry algorithm. Results So-called ‘empty sella’ and optic nerve sheath distension were identified as reliable imaging signs in IIH. Posterior globe flattening turned out as a highly specific but not very sensitive sign. No abnormalities of the lateral ventricles were observed. These morphometric results could be confirmed using MR volumetry (VBM). Clinical symptoms did not correlate with an increase in lumbar opening pressure. Conclusions Our study results indicate that lateral ventricle size is not affected in IIH. In contrast, abnormalities of the pituitary gland and optic nerve sheath were reliable diagnostic signs for IIH.
Best practice in early psychosis intervention for Australian indigenous communities: indigenous worker consultation and service model description
Authors: Catts Stanley , O’Toole Brian , Neil Amanda , Harris Meredith , Frost Aaron , Eadie Kathy , Evans Russell , Crissman Belinda , McClay Jennifer , Shorey Travis 
Published: April 2013

Objective: The aim of this study was to identify promising elements of best practice relevant to mainstream mental health service (MHS) delivery of early psychosis intervention (EPI) to Indigenous communities. In a companion paper, a comprehensive literature review identified a promising service model with potential for delivering EPI: an Indigenous sub-team embedded within a mainstream health service. Method: This paper describes a consultation process with Indigenous Mental Health Workers (IMHWs) in south eastern Queensland. A case study of the Sunshine Coast Cultural Healing Program (CHP-SC) was carried out during the consultation process. Results: IMHWs agreed that the Australian clinical guidelines for early psychosis were relevant to improving outcomes for Indigenous patients. IMHWs unanimously identified the CHP-SC as a best practice mainstream MHS for delivering EPI. The CHP-SC, which represented an Indigenous sub-team model, was found to be associated with substantially improved engagement of Indigenous young people. Conclusions: We provisionally conclude that specialist EPI could be delivered by specialist Indigenous sub-teams (rather than specialist EPI teams) embedded in mainstream MHSs that incorporate culturally safe practice and are fully integrated with Indigenous primary care services, and recommend that the model be formally evaluated.
A systematic approach to clinical reasoning in psychiatry
Authors: Fernando Irosh , Cohen Martin , Henskens Frans 
Published: April 2013

Objective: Clinical reasoning in psychiatry may be considered to be more challenging than in other branches of medicine because of its highly subjective nature. The literature on systematic approaches to the teaching of clinical reasoning in psychiatry is lacking, and we propose an approach that may assist educators and learners. Method: A systematic approach with a theoretical underpinning in logical inferences will be proposed as a teaching and learning tool. Conclusion: This paper complements our previous paper on psychiatric case formulation and expands our model of a theoretical framework for diagnostic reasoning and case formulation in psychiatry. Our approach also serves as a tool to assist in integrating the diverse clinical knowledge base in psychiatry.
Effect of Leaflet-Based Intervention on Family Members of Terminally Ill Patients With Cancer Having Delirium
Authors: Otani Hiroyuki , Morita Tatsuya , Uno Satsuki , Yamamoto Ryo , Hirose Hikaru , Matsubara Tatsuhiro , Takigawa Chizuko , Sasaki Kazuyoshi 
Published: April 2013

Objective: We aimed to assess leaflet-based intervention effects on family-perceived distress, the need for improvements in professional care for delirium, and family knowledge of delirium causes. Methods: Leaflet-based intervention effects were assessed by comparing responses of family members given in the leaflet with those of a historical control group not receiving it. Results: Knowledge of delirium causes was significantly more likely to be correct in the intervention group, while there were no significant differences in family-perceived distress or need for improvements in professional care for delirium between the 2 groups. Conclusions: The leaflet providing information about delirium improved family knowledge of cancer delirium. To relieve family distress, a comprehensive program focused mainly on psychological aspects, in addition to educational intervention with this leaflet, is a promising strategy.