bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Evaluation of a Molecular Diagnostic Method for Rapid Detection of Histoplasma capsulatum var. farciminosum, the Causative Agent of Epizootic Lymphangitis, in Equine Clinical Samples
Authors: Scantlebury C. E. , Pinchbeck G. L. , Loughnane P. , Aklilu N. , Ashine T. , Stringer A. P. , Gordon L. , Marshall M. , Christley R. M. , McCarthy A. J. 
Published: October 2016

ABSTRACT

Histoplasma capsulatum
var.
farciminosum
, the causative agent of epizootic lymphangitis (EZL), is endemic in parts of Africa. Diagnosis based on clinical signs and microscopy lacks specificity and is a barrier to further understanding this neglected disease. Here, a nested PCR method targeting the internal transcribed spacer (ITS) region of the rRNA operon was validated for application to equine clinical samples. Twenty-nine horses with signs of EZL from different climatic regions of Ethiopia were clinically examined. Blood samples and aspirates of pus from cutaneous nodules were taken, along with blood from a further 20 horses with no cutaneous EZL lesions. Among the 29 horses with suspected cases of EZL,
H. capsulatum
var.
farciminosum
was confirmed by extraction of DNA from pus and blood samples from 25 and 17 horses, respectively. Positive PCR results were also obtained with heat-inactivated pus (24 horses) and blood (23 horses) spotted onto Whatman FTA cards. Two positive results were obtained among blood samples from 20 horses that did not exhibit clinical signs of EZL. These are the first reports of the direct detection of
H. capsulatum
var.
farciminosum
in equine blood and at high frequency among horses exhibiting cutaneous lesions. The nested PCR outperformed conventional microscopic diagnosis, as characteristic yeast cells could be observed only in 14 pus samples. The presence of
H. capsulatum
var.
farciminosum
DNA was confirmed by sequencing the cloned PCR products, and while alignment of the ITS amplicons showed very little sequence variation, there was preliminary single nucleotide polymorphism-based evidence for the existence of two subgroups of
H. capsulatum
var.
farciminosum
. This molecular diagnostic method now permits investigation of the epidemiology of EZL.
Chlorhexidine versus Tincture of Iodine for Reduction of Blood Culture Contamination Rates: a Prospective Randomized Crossover Study
Authors: Story-Roller Elizabeth , Weinstein Melvin P. 
Published: October 2016

ABSTRACT

Blood cultures (BCs) are the standard method for diagnosis of bloodstream infections (BSIs). However, the average BC contamination rate (CR) in U.S. hospitals is 2.9%, potentially resulting in unnecessary antibiotic use and excessive therapy costs. Several studies have compared various skin antisepsis agents without a clear consensus as to which agent is most effective in reducing contamination. A prospective, randomized crossover study directly comparing blood culture contamination rates using chlorhexidine versus iodine tincture for skin antisepsis was performed at Robert Wood Johnson University Hospital (RWJUH). Eight nursing units at RWJUH were provided with blood culture kits containing either chlorhexidine (CH) or iodine tincture (IT) for skin antisepsis prior to all blood culture venipunctures, which were obtained by nurses or clinical care technicians. At quarterly intervals, the antiseptic agent used on each nursing unit was switched. Analyses of positive BCs were performed to distinguish true BSIs from contaminants. Of the 6,095 total BC sets obtained from the participating nursing units, 667 (10.94%) were positive and 238 (3.90%) were judged by the investigators to be contaminated. Of the 3,130 BCs obtained using IT, 340 (10.86%) were positive and 123 (3.93%) were contaminated. Of 2,965 BCs obtained using CH, 327 (11.03%) were positive and 115 (3.88%) were contaminated. The rates of contaminated BCs were not statistically significant between the two antiseptic agents (
P
= 1.0). We conclude that CH and IT are equivalent agents for blood culture skin antisepsis.
HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an Infected Individual
Authors: Coss Karen P. , Vasiljevic Snezana , Pritchard Laura K. , Krumm Stefanie A. , Glaze Molly , Madzorera Sharon , Moore Penny L. , Crispin Max , Doores Katie J. 
Published: October 2016

ABSTRACT
The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. The high density of glycosylation on the viral spike limits enzymatic processing, resulting in numerous underprocessed oligomannose-type glycans. This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. Together, these observations underscore the importance of glycan clustering for the generation of carbohydrate epitopes for anti-HIV bnAbs. The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies.

IMPORTANCE
Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env and the susceptibility of the virus to neutralization. We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design.
The Tetherin Antagonism of the Ebola Virus Glycoprotein Requires an Intact Receptor-Binding Domain and Can Be Blocked by GP1-Specific Antibodies
Authors: Brinkmann Constantin , Nehlmeier Inga , Walendy-Gnirß Kerstin , Nehls Julia , González Hernández Mariana , Hoffmann Markus , Qiu Xiangguo , Takada Ayato , Schindler Michael , Pöhlmann Stefan 
Published: October 2016

ABSTRACT

The glycoprotein of Ebola virus (EBOV GP), a member of the family
Filoviridae
, facilitates viral entry into target cells. In addition, EBOV GP antagonizes the antiviral activity of the host cell protein tetherin, which may otherwise restrict EBOV release from infected cells. However, it is unclear how EBOV GP antagonizes tetherin, and it is unknown whether the GP of Lloviu virus (LLOV), a filovirus found in dead bats in Northern Spain, also counteracts tetherin. Here, we show that LLOV GP antagonizes tetherin, indicating that tetherin may not impede LLOV spread in human cells. Moreover, we demonstrate that appropriate processing of N-glycans in tetherin/GP-coexpressing cells is required for tetherin counteraction by EBOV GP. Furthermore, we show that an intact receptor-binding domain (RBD) in the GP1 subunit of EBOV GP is a prerequisite for tetherin counteraction. In contrast, blockade of Niemann-Pick disease type C1 (NPC1), a cellular binding partner of the RBD, did not interfere with tetherin antagonism. Finally, we provide evidence that an antibody directed against GP1, which protects mice from a lethal EBOV challenge, may block GP-dependent tetherin antagonism. Our data, in conjunction with previous reports, indicate that tetherin antagonism is conserved among the GPs of all known filoviruses and demonstrate that the GP1 subunit of EBOV GP plays a central role in tetherin antagonism.

IMPORTANCE
Filoviruses are reemerging pathogens that constitute a public health threat. Understanding how Ebola virus (EBOV), a highly pathogenic filovirus responsible for the 2013-2016 Ebola virus disease epidemic in western Africa, counteracts antiviral effectors of the innate immune system might help to define novel targets for antiviral intervention. Similarly, determining whether Lloviu virus (LLOV), a filovirus detected in bats in northern Spain, is inhibited by innate antiviral effectors in human cells might help to determine whether the virus constitutes a threat to humans. The present study shows that LLOV, like EBOV, counteracts the antiviral effector protein tetherin via its glycoprotein (GP), suggesting that tetherin does not pose a defense against LLOV spread in humans. Moreover, our work identifies the GP1 subunit of EBOV GP, in particular an intact receptor-binding domain, as critical for tetherin counteraction and provides evidence that antibodies directed against GP1 can interfere with tetherin counteraction.
Glycaemic control and antidiabetic treatment trends in primary care centres in patients with type 2 diabetes mellitus during 2007–2013 in Catalonia: a population-based study
Authors: Mata-Cases Manel , Franch-Nadal Josep , Real Jordi , Mauricio Dídac 
Published: October 2016

ObjectivesTo assess trends in prescribing practices of antidiabetic agents and glycaemic control in patients with type 2 diabetes mellitus (T2DM).DesignCross-sectional analysis using yearly clinical data and antidiabetic treatments prescribed obtained from an electronic population database.SettingPrimary healthcare centres, including the entire population attended by the Institut Català de la Salut in Catalonia, Spain, from 2007 to 2013.ParticipantsPatients aged 31–90 years with a diagnosis of T2DM.ResultsThe number of registered patients with T2DM in the database was 257 072 in 2007, increasing up to 343 969 in 2013. The proportion of patients not pharmacologically treated decreased by 9.7% (95% CI −9.48% to −9.92%), while there was an increase in the percentage of patients on monotherapy (4.4% increase; 95% CI 4.16% to 4.64%), combination therapy (2.8% increase; 95% CI 2.58% to 3.02%), and insulin alone or in combination (increasing 2.5%; 95% CI 2.2% to 2.8%). The use of metformin and dipeptidyl peptidase-IV inhibitors increased gradually, while sulfonylureas, glitazones and α-glucosidase inhibitors decreased. The use of glinides remained stable, and the use of glucagon-like peptide-1 receptor agonists was still marginal. Regarding glycaemic control, there were no relevant differences across years: mean glycated haemoglobin (HbA1c) value was around 7.2%; the percentage of patients reaching an HbA1c≤7% target ranged between 52.2% and 55.6%; and those attaining their individualised target from 72.8% to 75.7%.ConclusionsAlthough the proportion of patients under pharmacological treatment increased substantially over time and there was an increase in the use of combination therapies, there have not been relevant changes in glycaemic control during the 2007–2013 period in Catalonia.
Examination of psychosocial predictors of Chinese hospital pharmacists' intention to provide clinical pharmacy services using the theory of planned behaviour: a cross-sectional questionnaire study
Authors: He Yuan , Yang Fan , Mu Dongqin , Xing Yuan , Li Xin 
Published: October 2016

ObjectivesMain study aim was as follows: (1) to explore the usefulness of the theory of planned behaviour (TPB) model in predicting Chinese hospital pharmacists' intention to provide clinical pharmacy services (CPSs), including auxiliary CPSs and core CPSs; (2) to identify the main factors affecting the Chinese hospital pharmacists' intention to provide core CPSs based on TPB quantitatively.DesignCross-sectional questionnaire study.SettingThe study was conducted in 22 general hospitals in seven cities located in the eastern and western part of China.Participants416 hospital pharmacists (292 (70.2%) female) entered and completed the study.Primary and secondary outcome measuresQuantitative responses with hospital pharmacists' intention, attitude, subjective norms (SNs) and perceived behavioural control (PBC) over provision of CPSs and their past behaviour (PB)-related CPSs.ResultsThe structural equation model analysis found that attitude (p=0.0079, β=0.12), SN (p=0.038, β=0.10) and the pharmacists' intention to provide auxiliary CPSs (p=0.0001, β=0.63) significantly predicted of their intention to provide core CPSs, accounting for 54.0% of its variance. Attitude (p=0.0001, β=0.35), PBC (p=0.0182, β=0.12) and PB (p=0.0009, β=0.15) are significant predictors of pharmacists' intention, accounting for 21% of the variance in pharmacists' intention to provide auxiliary CPSs.ConclusionsThe TPB with the addition of PB is a useful framework for predicting pharmacists' intention to provide CPSs in Chinese hospital care context. Strategies to improve hospital pharmacists' intention to provide CPSs should focus on helping the individuals related medical care see the value of CPSs, altering their perception of social pressure towards core CPSs and the removal of obstacles that impede the translation of intentions into behaviour.
An ED paradox: patients who arrive by ambulance and then leave without consulting an ED provider
Authors: Doupe Malcolm B , Day Suzanne , Palatnick Wes , Chochinov Alecs , Chateau Dan , Snider Carolyn , Lobato de Faria Ricardo , Weldon Erin , Derksen Shelley 
Published: October 2016

BackgroundScientists have called for strategies to identify ED patients with unmet needs. We identify the unique profile of ED patients who arrive by ambulance and subsequently leave without consulting a provider (ie, a paradoxical visit, PV).MethodsUsing a retrospective cohort design, administrative data from Winnipeg, Manitoba were interrogated to identify all ED patients 17+ years old as having zero, single or multiple PVs in 2012/2013. Analyses compare the sociodemographic, physical (eg, arthritis), mental (eg, substance abuse) and concurrent healthcare use profile of non-PV, single and multiple PV patients.ResultsThe study cohort consisted of 122 639 patients with 250 754 ED visits. Across all ED sites, 2.3% of patients (N=2815) made 3387 PVs, comprising 1.4% of all ED visits. Descriptively, more single versus non-PV patients lived in urban core and lowest-income areas, were frequent ED users generally, were substance abusers and had seven plus primary care physician visits. Multiple PV patients had a similar but more extreme profile versus their single PV counterparts (eg, 54.7% of multiple vs 27.4% of single PV patients had substance abuse challenges). From multivariate statistics, single versus non-PV patients are defined uniquely by their frequent ED use, by their substance abuse, as living in a core and low income area, and as having multiple visits with primary care physicians.ConclusionsPV patients have needs that do not align with the acute model of ED care. These patients may benefit from a more integrated care approach likely involving allied health professionals.
Benchmarking a large regional UK HER2 testing service against current practice guidelines
Authors: Thomas Jeremy , Loane Joseph , Matthews Richard , Maxwell Scott , Ingman Tim , Beesley Mathew , Ferrigan Lynda 
Published: October 2016

AimsTo critically evaluate HER2 testing data for 3500 consecutive cases over 28 months for a single laboratory and review these findings in the light of current UK reporting guidelines.MethodsWe have reviewed all data relating to the HER2 testing service including reagents and analytical machine, HER2 immunohistochemistry (IHC) and fluorescentin situhybridisation (FISH) scoring profiles. We have examined the place of double counting and rapid screening of FISH and when it is and is not safe to do so. This analysis has been facilitated greatly by the inclusion of custom scripts embedded in a spreadsheet used for recording the data.ResultsThere were no differences in scoring profiles in relation to testing machine or reagent batch for both HER2 IHC and FISH. There was excellent concordance in scoring by the biomedical scientists and pathologists providing the service. There is a significant difference between the proximity of scores in double-scored cases with HER2 copy number >6.0 compared with those with copy number <6.00. It is safe to single score with rapid screening of HER2 FISH following a first count with a HER2/CEP17 ratio <1.5 and a HER2 copy number <3.5.ConclusionsSingle counting of HER2 FISH supported by a second rapid screen is safe and practicable within strict parameters. Any assessment of proximity of scores in double-scored cases should take into account the HER2 copy number, with greater spreads experienced at higher copy numbers. Centralising HER2 testing in a regional centre allows detailed audit of the entire analytical process.
Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages
Authors: Kiltz U , van der Heijde D , Boonen A , Bautista-Molano W , Burgos-Vargas R , Chiowchanwisawakit P , Duruoz T , El-Zorkany B , Essers I , Gaydukova I , Géher P , Gossec L , Grazio S , Gu J , Khan M A , Kim T J , Maksymowych W P , Marzo-Ortega H , Navarro-Compán V , Olivieri I , Patrikos D , Pimentel-Santos F M , Schirmer M , van den Bosch F , Weber U , Zochling J , Braun J 
Published: October 2016

IntroductionThe Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages.MethodsTranslation and cross-cultural adaptation has been carried out following the forward–backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included.ResultsThe ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option ‘not applicable’ was added to two items of the ASAS HI to improve appropriateness.DiscussionThis study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures.
Some stochastic properties on the GCFϵ expansion when ϵ(kn) = cknτ + cknτ−1
Authors: Tang Liang , Zhong Ting 
Published: October 2016

For any [Formula: see text], let [Formula: see text] be the generalized continued fraction (GCF[Formula: see text]) expansion of [Formula: see text] with parameter [Formula: see text]. The concrete case has shown that, for different range of the parameter [Formula: see text] (when [Formula: see text] and [Formula: see text] for all [Formula: see text]), the stochastic properties of [Formula: see text] differ. In this paper, we deal with the case [Formula: see text] for [Formula: see text] and [Formula: see text], and obtain two probabilistic results as follows: [Formula: see text] [Formula: see text] Besides, we also prove the so-called “0–1” law and some other limit results when [Formula: see text] with [Formula: see text] and [Formula: see text]. These results are closely related to [Formula: see text], but independent of [Formula: see text].
Landscape of Genomic Alterations in Pituitary Adenomas
Authors: Bi Wenya Linda , Horowitz Peleg , Greenwald Noah F. , Abedalthagafi Malak , Agarwalla Pankaj K. , Gibson Wiliam J. , Mei Yu , Schumacher Steven E. , Ben-David Uri , Chevalier Aaron , Carter Scott , Tiao Grace , Brastianos Priscilla K. , Ligon Azra H. , Ducar Matthew , MacConaill Laura , Laws Edward R. , Santagata Sandro , Beroukhim Rameen , Dunn Ian F. 
Published: October 2016

AbstractPurpose: Pituitary adenomas are the second most common primary brain tumor, yet their genetic profiles are incompletely understood.Experimental Design: We performed whole-exome sequencing of 42 pituitary macroadenomas and matched normal DNA. These adenomas included hormonally active and inactive tumors, ones with typical or atypical histology, and ones that were primary or recurrent.Results: We identified mutations, insertions/deletions, and copy-number alterations. Nearly one-third of samples (29%) had chromosome arm-level copy-number alterations across large fractions of the genome. Despite such widespread genomic disruption, these tumors had few focal events, which is unusual among highly disrupted cancers. The other 71% of tumors formed a distinct molecular class, with somatic copy number alterations involving less than 6% of the genome. Among the highly disrupted group, 75% were functional adenomas or atypical null-cell adenomas, whereas 87% of the less-disrupted group were nonfunctional adenomas. We confirmed this association between functional subtype and disruption in a validation dataset of 87 pituitary adenomas. Analysis of previously published expression data from an additional 50 adenomas showed that arm-level alterations significantly impacted transcript levels, and that the disrupted samples were characterized by expression changes associated with poor outcome in other cancers. Arm-level losses of chromosomes 1, 2, 11, and 18 were significantly recurrent. No significantly recurrent mutations were identified, suggesting no genes are altered by exonic mutations across large fractions of pituitary macroadenomas.Conclusions: These data indicate that sporadic pituitary adenomas have distinct copy-number profiles that associate with hormonal and histologic subtypes and influence gene expression. Clin Cancer Res; 23(7); 1841–51. ©2016 AACR.