bluuebunny/crossref_metadata_2025_split huggingface dataset:
Negevirus: a Proposed New Taxon of Insect-Specific Viruses with Wide Geographic Distribution
Authors: Vasilakis Nikos , Forrester Naomi L. , Palacios Gustavo , Nasar Farooq , Savji Nazir , Rossi Shannan L. , Guzman Hilda , Wood Thomas G. , Popov Vsevolod , Gorchakov Rodion , González Ana Vázquez , Haddow Andrew D. , Watts Douglas M. , da Rosa Amelia P. A. Travassos , Weaver Scott C. , Lipkin W. Ian , Tesh Robert B. 
Published: December 2012

ABSTRACTSix novel insect-specific viruses, isolated from mosquitoes and phlebotomine sand flies collected in Brazil, Peru, the United States, Ivory Coast, Israel, and Indonesia, are described. Their genomes consist of single-stranded, positive-sense RNAs with poly(A) tails. By electron microscopy, the virions appear as spherical particles with diameters of ∼45 to 55 nm. Based on their genome organization and phylogenetic relationship, the six viruses, designated Negev, Ngewotan, Piura, Loreto, Dezidougou, and Santana, appear to form a new taxon, tentatively designated Negevirus. Their closest but still distant relatives are citrus leposis virus C (CiLV-C) and viruses in the genusCilevirus, which are mite-transmitted plant viruses. The negeviruses replicate rapidly and to high titer (up to 1010PFU/ml) in mosquito cells, producing extensive cytopathic effect and plaques, but they do not appear to replicate in mammalian cells or mice. A discussion follows on their possible biological significance and effect on mosquito vector competence for arboviruses.
Complex Alternative Cytoplasmic Protein Isoforms of the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Generated through Noncanonical Translation Initiation
Authors: Toptan Tuna , Fonseca Lidia , Kwun Hyun Jin , Chang Yuan , Moore Patrick S. 
Published: December 2012

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) protein is constitutively expressed in all KSHV-infected cells, as well as in all forms of KSHV-associated malignancies. LANA1 is a multifunctional KSHV oncoprotein containing multiple repeat sequences that is important for viral episome maintenance and the regulation of cellular and viral gene expression. We characterize here multiple LANA1 isoforms and show that ∼50% of LANA1 is naturally generated as N-terminally truncated shoulder proteins that are detected on SDS-PAGE as faster-migrating shoulder bands designated LANA1
S
. Higher-molecular-weight LANA1
S
isoforms initiate downstream at noncanonical sites within the N-terminal region, whereas lower-molecular-weight LANA1
S
isoforms initiate downstream within the central repeat 1 domain. LANA1
S
proteins lack an N-terminal nuclear localization signal motif, and some isoforms differ from full-length, canonical LANA1 by localizing to perinuclear and cytoplasmic sites. Although LANA1 has until now been assumed to be solely active in the nucleus, this finding indicates that this major KSHV oncoprotein may have cytoplasmic activities as well. KSHV overcomes its limited genetic coding capacity by generating alternatively initiated protein isoforms that may have distinct biological functions.
Use of FMEA analysis to reduce risk of errors in prescribing and administering drugs in paediatric wards: a quality improvement report
Authors: Lago Paola , Bizzarri Giancarlo , Scalzotto Francesca , Parpaiola Antonella , Amigoni Angela , Putoto Giovanni , Perilongo Giorgio 
Published: December 2012

ObjectiveAdministering medication to hospitalised infants and children is a complex process at high risk of error. Failure mode and effect analysis (FMEA) is a proactive tool used to analyse risks, identify failures before they happen and prioritise remedial measures. To examine the hazards associated with the process of drug delivery to children, we performed a proactive risk-assessment analysis.Design and settingFive multidisciplinary teams, representing different divisions of the paediatric department at Padua University Hospital, were trained to analyse the drug-delivery process, to identify possible causes of failures and their potential effects, to calculate a risk priority number (RPN) for each failure and plan changes in practices.Primary outcomeTo identify higher-priority potential failure modes as defined by RPNs and planning changes in clinical practice to reduce the risk of patients harm and improve safety in the process of medication use in children.ResultsIn all, 37 higher-priority potential failure modes and 71 associated causes and effects were identified. The highest RPNs related (>48) mainly to errors in calculating drug doses and concentrations. Many of these failure modes were found in all the five units, suggesting the presence of common targets for improvement, particularly in enhancing the safety of prescription and preparation of endovenous drugs. The introductions of new activities in the revised process of administering drugs allowed reducing the high-risk failure modes of 60%.ConclusionsFMEA is an effective proactive risk-assessment tool useful to aid multidisciplinary groups in understanding a process care and identifying errors that may occur, prioritising remedial interventions and possibly enhancing the safety of drug delivery in children.
An international measure of awareness and beliefs about cancer: development and testing of the ABC
Authors: Simon Alice E , Forbes Lindsay J L , Boniface David , Warburton Fiona , Brain Kate E , Dessaix Anita , Donnelly Michael , Haynes Kerry , Hvidberg Line , Lagerlund Magdalena , Petermann Lisa , Tishelman Carol , Vedsted Peter , Vigmostad Maria Nyre , Wardle Jane , Ramirez Amanda J 
Published: December 2012

ObjectivesTo develop an internationally validated measure of cancer awareness and beliefs; the awareness and beliefs about cancer (ABC) measure.Design and settingItems modified from existing measures were assessed by a working group in six countries (Australia, Canada, Denmark, Norway, Sweden and the UK). Validation studies were completed in the UK, and cross-sectional surveys of the general population were carried out in the six participating countries.ParticipantsTesting in UK English included cognitive interviewing for face validity (N=10), calculation of content validity indexes (six assessors), and assessment of test–retest reliability (N=97). Conceptual and cultural equivalence of modified (Canadian and Australian) and translated (Danish, Norwegian, Swedish and Canadian French) ABC versions were tested quantitatively for equivalence of meaning (≥4 assessors per country) and in bilingual cognitive interviews (three interviews per translation). Response patterns were assessed in surveys of adults aged 50+ years (N≥2000) in each country.Main outcomesPsychometric properties were evaluated through tests of validity and reliability, conceptual and cultural equivalence and systematic item analysis. Test–retest reliability used weighted-κ and intraclass correlations. Construction and validation of aggregate scores was by factor analysis for (1) beliefs about cancer outcomes, (2) beliefs about barriers to symptomatic presentation, and item summation for (3) awareness of cancer symptoms and (4) awareness of cancer risk factors.ResultsThe English ABC had acceptable test–retest reliability and content validity. International assessments of equivalence identified a small number of items where wording needed adjustment. Survey response patterns showed that items performed well in terms of difficulty and discrimination across countries except for awareness of cancer outcomes in Australia. Aggregate scores had consistent factor structures across countries.ConclusionsThe ABC is a reliable and valid international measure of cancer awareness and beliefs. The methods used to validate and harmonise the ABC may serve as a methodological guide in international survey research.
Targeting XRCC1 Deficiency in Breast Cancer for Personalized Therapy
Authors: Sultana Rebeka , Abdel-Fatah Tarek , Abbotts Rachel , Hawkes Claire , Albarakati Nada , Seedhouse Claire , Ball Graham , Chan Stephen , Rakha Emad A. , Ellis Ian O. , Madhusudan Srinivasan 
Published: December 2012

Abstract
XRCC1 is a key component of DNA base excision repair, single strand break repair, and backup nonhomologous end-joining pathway. XRCC1 (X-ray repair cross-complementing gene 1) deficiency promotes genomic instability, increases cancer risk, and may have clinical application in breast cancer. We investigated XRCC1 expression in early breast cancers (n = 1,297) and validated in an independent cohort of estrogen receptor (ER)-α–negative breast cancers (n = 281). Preclinically, we evaluated XRCC1-deficient and -proficient Chinese hamster and human cancer cells for synthetic lethality application using double-strand break (DSB) repair inhibitors [KU55933 (ataxia telangectasia–mutated; ATM inhibitor) and NU7441 (DNA-PKcs inhibitor)]. In breast cancer, loss of XRCC1 (16%) was associated with high grade (P &lt; 0.0001), loss of hormone receptors (P &lt; 0.0001), triple-negative (P &lt; 0.0001), and basal-like phenotypes (P = 0.001). Loss of XRCC1 was associated with a two-fold increase in risk of death (P &lt; 0.0001) and independently with poor outcome (P &lt; 0.0001). Preclinically, KU55933 [2-(4-Morpholinyl)-6-(1-thianthrenyl)-4H-pyran-4-one] and NU7441 [8-(4-Dibenzothienyl)-2-(4-morpholinyl)-4H-1-benzopyran-4-one] were synthetically lethal in XRCC1-deficient compared with proficient cells as evidenced by hypersensitivity to DSB repair inhibitors, accumulation of DNA DSBs, G2–M cell-cycle arrest, and induction of apoptosis. This is the first study to show that XRCC1 deficiency in breast cancer results in an aggressive phenotype and that XRCC1 deficiency could also be exploited for a novel synthetic lethality application using DSB repair inhibitors. Cancer Res; 73(5); 1621–34. ©2012 AACR.
Proteomic Identification of Matrix Metalloproteinase Substrates in the Human Vasculature
Authors: Stegemann Christin , Didangelos Athanasios , Barallobre-Barreiro Javier , Langley Sarah R. , Mandal Kaushik , Jahangiri Marjan , Mayr Manuel 
Published: December 2012

Background—
Matrix metalloproteinases (MMPs) play a key role in cardiovascular disease, in particular aneurysm formation and plaque rupture. Surprisingly, little is known about MMP substrates in the vasculature.

Methods and Results—
We used a proteomics approach to identify vascular substrates for 3 MMPs, 1 of each of the 3 major classes of MMPs: Human arteries were incubated with MMP-3 (a member of stromelysins), MMP-9 (considered a gelatinase), and MMP-14 (considered a member of the collagenases and of the membrane-bound MMPs). Candidate substrates were identified by mass spectrometry based on increased release from the arterial tissue on digestion, spectral evidence for proteolytic degradation after gel separation, and identification of nontryptic cleavage sites. Using this approach, novel candidates were identified, including extracellular matrix proteins associated with the basement membrane, elastic fibers (emilin-1), and other extracellular proteins (periostin, tenascin-X). Seventy-four nontryptic cleavage sites were detected, many of which were shared among different MMPs. The proteomics findings were validated by immunoblotting and by digesting recombinant/purified proteins with exogenous MMPs. As proof-of-principle, results were related to in vivo pathology by searching for corresponding degradation products in human aortic tissue with different levels of endogenous MMP-9.

Conclusions—
The application of proteomics to identify MMP targets is a new frontier in cardiovascular research. Our current classification of MMPs based on few substrates is an oversimplification of a complex area of biology. This study provides a more comprehensive assessment of potential MMP substrates in the vasculature and represents a valuable resource for future investigations.
Formin Homology 2 Domain Containing 3 Variants Associated With Hypertrophic Cardiomyopathy
Authors: Wooten Eric C. , Hebl Virginia B. , Wolf Matthew J. , Greytak Sarah R. , Orr Nicole M. , Draper Isabelle , Calvino Jenna E. , Kapur Navin K. , Maron Martin S. , Kullo Iftikhar J. , Ommen Steve R. , Bos J. Martijn , Ackerman Michael J. , Huggins Gordon S. 
Published: December 2012

Background—
Incomplete penetrance and variable expression of hypertrophic cardiomyopathy (HCM) is well appreciated. Common genetic polymorphisms variants that may affect HCM penetrance and expression have been predicted but are not well established.

Methods and Results—

We performed a case-control genomewide association study to identify common HCM-associated genetic polymorphisms and then asked whether such common variants were more represented in HCM or could explain the heterogeneity of HCM phenotypes. We identified an intronic
FHOD3
variant (rs516514) associated with HCM (odds ratio, 2.45; 95% confidence interval, 1.76–3.41;
P
=1.25×10
−7
) and validated this finding in an independent cohort. Next, we tested FHOD3-V1151I (rs2303510), a nonsynonymous variant in partial linkage disequilibrium with rs516514, and we detected an even stronger association with HCM (
P
=1.76×10
−9
). Although HCM patients were more likely to carry these, FHOD3 allele subjects homozygous for FHOD3-1151I had similar HCM phenotypes as carriers of the V1151 allele. FHOD3 expression is increased in the setting of HCM, and both alleles of FHOD3-V1151I were detected in HCM myectomy tissue. Previously, FHOD3 was found to be required for formation of the sarcomere, and here we demonstrate that its fly homolog
fhos
is required for normal adult heart systolic contraction.

Conclusions—

Here we demonstrate the association of a common nonsynonymous
FHOD3
genetic variant with HCM. This discovery further strengthens the potential role of gene mutations and polymorphisms that alter the amino acid sequence of sarcomere proteins and HCM.
Sexual Differentiation in Tibetan Medical and Buddhist Perspectives
Authors: Cuomu Mingji , Holmes Katia 
Published: December 2012

Abstract
Classical Tibetan medicine is closely related to Buddhist philosophy. This
article describes how the study and meaning of sexual differentiation in Tibetan
medicine is deeply rooted in Buddhist texts and philosophy. The article pays
particular attention to the Buddhist theory of mutual dependence of birth and
death and on the medical ways of explaining the determining of sex. While
Tibetan medicine approaches sexual differentiation by examining its various
determinant factors, thus aiming to improve understanding of the human body and
diseases, which manifest differently in men and women, in Buddhist philosophy
sexual differentiation is perceived as a fundamental, natural phenomenon of
human life that forms a key in Tantric practices to comprehend the nature of
mind and thence attaining the highest state of mind. The article consists of a
translation of the first chapter of a Tibetan medical book on obstetrics,
including a newly written introduction to the Buddhist interpretive frame
employed in the chapter.
Why do you think you should be the author on this manuscript? Analysis of open-ended responses of authors in a general medical journal
Authors: Malički Mario , Jerončić Ana , Marušić Matko , Marušić Ana 
Published: December 2012

Abstract

Background
To assess how authors would describe their contribution to the submitted manuscript without reference to or requirement to satisfy authorship criteria of the International Committee of Medical Journal Editors (ICMJE), we analyzed responses of authors to an open-ended question “Why do you think you should be the author on this manuscript?”.

Methods
Responses of authors (n=1425) who submitted their manuscripts (n=345) to the Croatian Medical Journal, an international general medical journal, from March 2009 until July 2010 were transcribed and matched to ICMJE criteria. Statements that could not be matched were separately categorized. Responses according to the number of authors or their byline position on the manuscript were analyzed using Mann–Whitney U test and Moses test of extreme reactions.

Results
The number of authors per manuscript ranged from 1 to 26 (median=4, IQR=3-6), with the median of 2 contributions per author (IQR=2-3). Authors’ responses could be matched to the ICMJE criteria in 1116 (87.0%) cases. Among these, only 15.6% clearly declared contributions from all 3 ICMJE criteria; however, if signing of the authorship form was taken as the fulfillment of the third ICMJE criterion, overall fraction of deserving authorship was 54.2%. Non-ICMJE contributions were declared by 98 (7.6%) authors whose other contributions could be matched to ICMJE criteria, and by 116 (13.0%) authors whose contributions could not be matched to ICMJE criteria. The most frequently reported non-ICMJE contribution was literature review. Authors on manuscripts with more than 8 authors declared more contributions than those on manuscript with 8 or fewer authors: median 2, IQR 1–4, vs. median 2, IQR 1–3, respectively (Mann Whitney U test, p=0.001; Moses Test of Extreme Reactions, p<0.001). Almost a third of single authors (n=9; 31.0%) reported contributions that could not be matched to any ICMJE criterion.

Conclusions
In cases of multi-author collaborative efforts but not in manuscripts with fewer authors open-ended authorship declaration without instructions on ICMJE criteria elicited responses from authors that were similar to responses when ICMJE criteria were explicitly required. Current authorship criteria and the practice of contribution declaration should be revised in order to capture deserving authorship in biomedical research.
Can GPs working in secure environments in England re-license using the Royal College of General Practitioners revalidation proposals?
Authors: Coomber Jane , Charlton Rodger , Thistlethwaite Jill E , England Liz 
Published: December 2012

Abstract

Background
Revalidation for UK doctors is expected to be introduced from late 2012. For general practitioners (GPs), this entails collecting supporting information to be submitted and assessed in a revalidation portfolio every five years. The aim of this study was to explore the feasibility of GPs working in secure environments to collect supporting information for the Royal College of General Practitioners’ (RCGP) proposed revalidation portfolio.

Methods
We invited GPs working in secure environments in England to submit items of supporting information collected during the previous 12 months using criteria and standards required for the proposed RCGP revalidation portfolio and complete a GP issues log. Initial focus groups and initial and follow-up semi-structured face-to-face and telephone interviews were held to explore GPs’ views of this process. Quantitative and qualitative data were analysed using descriptive statistics and identifying themes respectively.

Results
Of the 50 GPs who consented to participate in the study, 20 submitted a portfolio. Thirty-eight GPs participated in an initial interview, nine took part in a follow-up interview and 17 completed a GP issues log. GPs reported difficulty in collecting supporting information for valid patient feedback, full-cycle clinical audits and evidence for their extended practice role(s) as sessional practitioners in the high population turnover custodial environment. Peripatetic practitioners experienced more difficulty than their institution based counterparts collating this evidence.

Conclusions
GPs working in secure environments may experience difficulties in collecting the newer types of supporting information for the proposed RCGP revalidation portfolio primarily due to their employment status within a non-medical environment and characteristics of the detainee population. Increased support from secure environment service commissioners and employers will be a prerequisite for these practitioners to enable them to re-license using the RCGP revalidation proposals.
Converting habits of antibiotic prescribing for respiratory tract infections in German primary care – the cluster-randomized controlled CHANGE-2 trial
Authors: Altiner Attila , Berner Reinhard , Diener Annette , Feldmeier Gregor , Köchling Anna , Löffler Christin , Schröder Helmut , Siegel Achim , Wollny Anja , Kern Winfried V 
Published: December 2012

Abstract

Background
With an average prescription rate of 50%, in German primary care antibiotics are still too frequently prescribed for respiratory tract infections. The over-prescription of antibiotics is often explained by perceived patient pressure and fears of a complicated disease progression. The CHANGE-2 trial will test the effectiveness of two interventions to reduce the rate of inappropriate antibiotic prescriptions for adults and children suffering from respiratory tract infections in German primary care.

Methods/Design
The study is a three-arm cluster-randomized controlled trial that measures antibiotic prescription rates over three successive winter periods and reverts to administrative data of the German statutory health insurance company AOK. More than 30,000 patients in two regions of Germany, who visit their general practitioner or pediatrician for respiratory tract infections will be included. Interventions are: A) communication training for general practitioners and pediatricians and B) intervention A plus point-of-care testing. Both interventions are tested against usual care. Outcome measure is the physicians’ antibiotic prescription rate for respiratory tract infections derived from data of the health insurance company AOK. Secondary outcomes include reconsultation rate, complications, and hospital admissions.

Discussion
Major aim of the study is to improve the process of decision-making and to ensure that patients who are likely to benefit from antibiotics are treated accordingly. Our approach is simple to implement and might be used rapidly among general practitioners and pediatricians. We expect the results of this trial to have major impact on antibiotic prescription strategies and practices in Germany, both among general practitioners and pediatricians.

Trial registration
The study is registered at the Current Controlled Trials Ltd (ISRCTN01559032)
The relationship between retinal vessel calibre and knee cartilage and BMLs
Authors: Davies-Tuck Miranda L , Kawasaki Ryo , Wluka Anita E , Wong Tien Y , Hodgson Lauren , English Dallas R , Giles Graham G , Cicuttini Flavia 
Published: December 2012

Abstract

Background
Whether the increase in vascular disease prevalence and mortality in OA populations is a result of co-occurrence of cardiovascular disease and OA, which are both common in the older population, is due to OA treatments or to the common association with reduced physical activity and/or obesity is unclear. One way to explore this non-invasively is to examine the cross-sectional relationship between changes in retinal microvasculature, which have been shown to be markers of generalized vascular pathology, and knee structural changes in an asymptomatic community-based population.

Methods
A community sample of 289 (61% women) aged 50–79 years with no knee symptoms underwent magnetic resonance imaging (MRI) of their dominant knee in 2003. Cartilage volume and bone marrow lesions (BMLs) were determined. All subjects also had retinal photographs taken from which retinal arteriolar and venular diameters were determined and summarized as the central retinal arteriolar equivalent (CRAE) and the central retinal venular equivalent (CRVE).

Results
Retinal venular diameter was significantly wider in subjects with a BML compared with subjects without a BML (mean (SD) 214.2 (2.8) μm versus 207.5 (1.1) μm respectively independent of age, gender and BMI. A trend for decreased medial tibial cartilage with increasing CRAE was also observed (regression coefficient −2.70 μl, 95%CI-5.74, 0.5, p=0.08).

Conclusion
These findings suggest that vascular pathology, indicative of inflammatory processes, is associated with early structural knee changes. The role of micro-vascular changes in the pathogenesis of OA warrants further investigation.