bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rescue therapy within the UK Cystic Fibrosis Registry: An exploration of predictors of intravenous antibiotic use amongst adults with CF
Authors: Hoo Zhe Hui , Wildman Martin J. , Curley Rachael , Walters Stephen J. , Campbell Michael J. 
Published: September 2017

ABSTRACTBackground and objectiveIntravenous (i.v.) antibiotics are needed for rescue when preventative therapy fails to achieve stability among adults with cystic fibrosis (CF). Understanding the distribution of i.v. days can provide insight into the care that adults with CF need. We aim to determine the baseline characteristics that are associated with higher i.v. use, in particular to test the hypothesis that prior‐year i.v. use is associated with future‐year i.v. use.MethodsThis is a cross‐sectional analysis of the 2013–2014 UK CF registry data. Stepwise logistic regression was performed using current‐year i.v. days as the dependent variable, and demographic variables including prior‐year i.v. days as the covariates. Based on these results, study sample was divided into clinically meaningful subgroups using analysis similar to tree‐based method.ResultsData were available for 4269 adults in 2013 and 4644 adults in 2014. Prior‐year i.v. use was the strongest predictor for current‐year i.v. use followed by forced expiratory volume in 1 s (FEV1). Adults with high prior‐year i.v. use (>14 days) continued to require high levels of i.v., regardless of FEV1. Those with high prior‐year i.v. use and FEV1 ≥70% had higher current‐year i.v. days compared to adults with low prior‐year i.v. use and FEV1 <40% (28 days, interquartile range (IQR): 11–41 days vs 14 days, IQR: 0–28 days; Mann–Whitney P‐value <0.001 in 2013).ConclusionCF people with prior high levels of rescue often continue to need high levels of rescue even if they have good FEV1. The reasons for this require further investigations.
Father group leaders' experiences of creating an arena for father support – A qualitative study
Authors: Kerstis Birgitta , Wells Michael B. , Andersson Ewa 
Published: September 2017

BackgroundParental classes consisting of only fathers, hereafter referred to as father groups, have existed in Sweden since the mid‐1990s.ObjectiveTo describe the father group leaders' perspectives on and experiences of father groups.MethodA qualitative study was conducted using content analysis. Eleven individual interviews with father group leaders were conducted. An interview guide was used.Settings and participantsThe study was set in different parts of Sweden. The participants were eleven men who are father group leaders. They were recruited using the snowball method.FindingsThe father group leaders described how participants often have high education levels and orderly social circumstances. The leaders described that the groups increased the fathers' reflection about parenthood, which could benefit the whole family in both the short and long term. The father group leaders reported that some of the topics in the sessions directly influenced fathers to discuss issues regarding equality and their co‐parenting relationship. They also argued that participating in father groups might help convince fathers to take more parental leave and build stronger relationships with their partner and child.
Reactive oxygen species generated in chloroplasts contribute to tobacco leaf infection by the necrotrophic fungus Botrytis cinerea
Authors: Rossi Franco R. , Krapp Adriana R. , Bisaro Fabiana , Maiale Santiago J. , Pieckenstain Fernando L. , Carrillo Néstor 
Published: September 2017

SummaryReactive oxygen species (ROS) play fundamental roles in plant responses to pathogen infection, including modulation of cell death processes and defense‐related gene expression. Cell death triggered as part of the hypersensitive response enhances resistance to biotrophic pathogens, but favors the virulence of necrotrophs. Even though the involvement of ROS in the orchestration of defense responses is well established, the relative contribution of specific subcellular ROS sources to plant resistance against microorganisms with different pathogenesis strategies is not completely known. The aim of this work was to investigate the role of chloroplastic ROS in plant defense against a typical necrotrophic fungus, Botrytis cinerea. For this purpose, we used transgenic Nicotiana tabacum (tobacco) lines expressing a plastid‐targeted cyanobacterial flavodoxin (pfld lines), which accumulate lower chloroplastic ROS in response to different stresses. Tissue damage and fungal growth were significantly reduced in infected leaves of pfld plants, as compared with infected wild‐type (WT) counterparts. ROS build‐up triggered by Botrytis infection and associated with chloroplasts was significantly decreased (70–80%) in pfld leaves relative to the wild type. Phytoalexin accumulation and expression of pathogenesis‐related genes were induced to a lower degree in pfld plants than in WT siblings. The impact of fungal infection on photosynthetic activity was also lower in pfld leaves. The results indicate that chloroplast‐generated ROS play a major role in lesion development during Botrytis infection. This work demonstrates that the modulation of chloroplastic ROS levels by the expression of a heterologous antioxidant protein can provide a significant degree of protection against a canonical necrotrophic fungus.
Case report of a rare glomus jugulare tumor extended within the extracranial internal jugular vein: emphasis on initial ultrasound findings and literature review
Authors: Deng Qing , Wang Yijia , Chen Xiaoyi , Zhou Qing 
Published: September 2017

Glomus jugulare tumor (GJT) is a rare benign neoplasm that is located in the skull base; it is impossible for ultrasonography to detect it in most cases. In this article, we present the case of a rare giant GJT, which extended into the internal jugular vein in the neck, initially detected by ultrasonography and confirmed by MRI and pathology. We highlight the initial ultrasonography findings and review the literature to summarize the ultrasonographic features of GJT.
Stool Culture for Diagnosis of Pulmonary Tuberculosis in Children
Authors: Walters Elisabetta , Demers Anne-Marie , van der Zalm Marieke M. , Whitelaw Andrew , Palmer Megan , Bosch Corné , Draper Heather R. , Gie Robert P. , Hesseling Anneke C. 
Published: September 2017

ABSTRACT

Bacteriological confirmation of
Mycobacterium tuberculosis
is achieved in the minority of young children with tuberculosis (TB), since specimen collection is resource intensive and respiratory secretions are mostly paucibacillary, leading to limited sensitivity of available diagnostic tests. Although molecular tests are increasingly available globally, mycobacterial culture remains the gold standard for diagnosis and determination of drug susceptibility and is more sensitive than molecular methods for paucibacillary TB. We evaluated stool culture as an alternative to respiratory specimens for the diagnosis of suspected intrathoracic TB in a subgroup of 188 children (median age, 14.4 months; 15.4% HIV infected) enrolled in a TB diagnostic study at two local hospitals in Cape Town, South Africa. One stool culture was compared to overall bacteriological confirmation by stool Xpert and by Xpert and culture of multiple respiratory specimens. After decontamination/digestion with NALC (
N
-acetyl-
l
-cysteine)-NaOH (1.25%), concentrated fluorescent smear microscopy, Xpert MTB/RIF, and liquid culture were completed for all specimens. Culture contamination of stool specimens was high at 41.5%. Seven of 90 (7.8%) children initiating TB treatment were stool culture positive for
M. tuberculosis
. Excluding contaminated cultures, the sensitivity of stool culture versus confirmed TB was 6/25 (24.0%; 95% confidence interval [CI] = 9.4 to 45.1%). In addition, stool culture detected TB in 1/93 (1.1%) children with “unconfirmed TB.” Testing the same stool by Xpert increased sensitivity to 33.3% (95% CI = 18.0 to 51.8%). In conclusion, stool culture had low sensitivity for
M. tuberculosis
detection in children with intrathoracic TB. Reducing culture contamination through improved laboratory protocols may enable more reliable estimates of its diagnostic utility.
Thinking beyond the Common Candida Species: Need for Species-Level Identification of Candida Due to the Emergence of Multidrug-Resistant Candida auris
Authors: Lockhart Shawn R. , Jackson Brendan R. , Vallabhaneni Snigdha , Ostrosky-Zeichner Luis , Pappas Peter G. , Chiller Tom 
Published: September 2017

ABSTRACT

Candida
species are one of the leading causes of nosocomial infections. Because much of the treatment for
Candida
infections is empirical, some institutions do not identify
Candida
to species level. With the worldwide emergence of the multidrug-resistant species
Candida auris
, identification of
Candida
to species level has new clinical relevance. Species should be identified for invasive candidiasis isolates, and species-level identification can be considered for selected noninvasive isolates to improve detection of
C. auris
.
Heterogeneity of the Epstein-Barr Virus (EBV) Major Internal Repeat Reveals Evolutionary Mechanisms of EBV and a Functional Defect in the Prototype EBV Strain B95-8
Authors: Ba abdullah Mohammed M. , Palermo Richard D. , Palser Anne L. , Grayson Nicholas E. , Kellam Paul , Correia Samantha , Szymula Agnieszka , White Robert E. 
Published: September 2017

ABSTRACT
Epstein-Barr virus (EBV) is a ubiquitous pathogen of humans that can cause several types of lymphoma and carcinoma. Like other herpesviruses, EBV has diversified through both coevolution with its host and genetic exchange between virus strains. Sequence analysis of the EBV genome is unusually challenging because of the large number and lengths of repeat regions within the virus. Here we describe the sequence assembly and analysis of the large internal repeat 1 of EBV (IR1; also known as the BamW repeats) for more than 70 strains. The diversity of the latency protein EBV nuclear antigen leader protein (EBNA-LP) resides predominantly within the exons downstream of IR1. The integrity of the putative BWRF1 open reading frame (ORF) is retained in over 80% of strains, and deletions truncating IR1 always spare BWRF1. Conserved regions include the IR1 latency promoter (Wp) and one zone upstream of and two within BWRF1. IR1 is heterogeneous in 70% of strains, and this heterogeneity arises from sequence exchange between strains as well as from spontaneous mutation, with interstrain recombination being more common in tumor-derived viruses. This genetic exchange often incorporates regions of <1 kb, and allelic gene conversion changes the frequency of small regions within the repeat but not close to the flanks. These observations suggest that IR1—and, by extension, EBV—diversifies through both recombination and breakpoint repair, while concerted evolution of IR1 is driven by gene conversion of small regions. Finally, the prototype EBV strain B95-8 contains four nonconsensus variants within a single IR1 repeat unit, including a stop codon in the EBNA-LP gene. Repairing IR1 improves EBNA-LP levels and the quality of transformation by the B95-8 bacterial artificial chromosome (BAC).

IMPORTANCE
Epstein-Barr virus (EBV) infects the majority of the world population but causes illness in only a small minority of people. Nevertheless, over 1% of cancers worldwide are attributable to EBV. Recent sequencing projects investigating virus diversity to see if different strains have different disease impacts have excluded regions of repeating sequence, as they are more technically challenging. Here we analyze the sequence of the largest repeat in EBV (IR1). We first characterized the variations in protein sequences encoded across IR1. In studying variations within the repeat of each strain, we identified a mutation in the main laboratory strain of EBV that impairs virus function, and we suggest that tumor-associated viruses may be more likely to contain DNA mixed from two strains. The patterns of this mixing suggest that sequences can spread between strains (and also within the repeat) by copying sequence from another strain (or repeat unit) to repair DNA damage.
Mutations in the Fusion Protein of Measles Virus That Confer Resistance to the Membrane Fusion Inhibitors Carbobenzoxy-
d
-Phe-
l
-Phe-Gly and 4-Nitro-2-Phenylacetyl Amino-Benzamide
Authors: Ha Michael N. , Delpeut Sébastien , Noyce Ryan S. , Sisson Gary , Black Karen M. , Lin Liang-Tzung , Bilimoria Darius , Plemper Richard K. , Privé Gilbert G. , Richardson Christopher D. 
Published: September 2017

ABSTRACT

The inhibitors carbobenzoxy (Z)-
d
-Phe-
l
-Phe-Gly (fusion inhibitor peptide [FIP]) and 4-nitro-2-phenylacetyl amino-benzamide (AS-48) have similar efficacies in blocking membrane fusion and syncytium formation mediated by measles virus (MeV). Other homologues, such as Z-
d
-Phe, are less effective but may act through the same mechanism. In an attempt to map the site of action of these inhibitors, we generated mutant viruses that were resistant to the inhibitory effects of Z-
d
-Phe-
l
-Phe-Gly. These 10 mutations were localized to the heptad repeat B (HRB) region of the fusion protein, and no changes were observed in the viral hemagglutinin, which is the receptor attachment protein. Mutations were validated in a luciferase-based membrane fusion assay, using transfected fusion and hemagglutinin expression plasmids or with syncytium-based assays in Vero, Vero-SLAM, and Vero-Nectin 4 cell lines. The changes I452T, D458N, D458G/V459A, N462K, N462H, G464E, and I483R conferred resistance to both FIP and AS-48 without compromising membrane fusion. The inhibitors did not block hemagglutinin protein-mediated binding to the target cell. Edmonston vaccine/laboratory and IC323 wild-type strains were equally affected by the inhibitors. Escape mutations were mapped upon a three-dimensional (3D) structure modeled from the published crystal structure of parainfluenzavirus 5 fusion protein. The most effective mutations were situated in a region located near the base of the globular head and its junction with the alpha-helical stalk of the prefusion protein. We hypothesize that the fusion inhibitors could interfere with the structural changes that occur between the prefusion and postfusion conformations of the fusion protein.

IMPORTANCE
Due to lapses in vaccination worldwide that have caused localized outbreaks, measles virus (MeV) has regained importance as a pathogen. Antiviral agents against measles virus are not commercially available but could be useful in conjunction with MeV eradication vaccine programs and as a safeguard in oncolytic viral therapy. Three decades ago, the small hydrophobic peptide Z-
d
-Phe-
l
-Phe-Gly (FIP) was shown to block MeV infections and syncytium formation in monkey kidney cell lines. The exact mechanism of its action has yet to be determined, but it does appear to have properties similar to those of another chemical inhibitor, AS-48, which appears to interfere with the conformational change in the viral F protein that is required to elicit membrane fusion. Escape mutations were used to map the site of action for FIP. Knowledge gained from these studies could help in the design of new inhibitors against morbilliviruses and provide additional knowledge concerning the mechanism of virus-mediated membrane fusion.
Paediatric optic neuritis: factors leading to unfavourable outcome and relapses
Authors: Averseng-Peaureaux Delphine , Mizzi Marie , Colineaux Helene , Mahieu Laurence , Pera Maria Carmela , Brassat David , Chaix Yves , Berard Emilie , Deiva Kumaran , Cheuret Emmanuel 
Published: September 2017

ObjectivesTo identify prognostic factors associated with poor visual recovery and chronic relapsing diseases, for example, multiple sclerosis (MS), in children with optic neuritis (ON) at onset.MethodsThis multicentre retrospective study included 102 children with a first ON episode between 1990 and 2012. The primary criterion was poor visual recovery determined by visual acuity, and the secondary was relapses following ON.ResultsMedian age was 11 years, 66% were girls and mean follow-up was 24 months. 58% of children were diagnosed with idiopathic isolated ON, 22% had MS, 5% had Devic’s neuromyelitis optica and 6% chronic relapsing inflammatory ON. Complete visual acuity recovery rate was 57% (95% CI=[46%-69%]) at 6 months and 71% (95% CI=[60%-81%]) at 1 and 2 years but was lower in MS (p<0.01), with recovery rate of only 27% (95% CI=[12%-54%]) at 1 year. Age ≥10 years, optic disc pallor at funduscopy and MS were the principal factors associated with poor visual recovery. Age ≥10 years, abnormal brain MRI at onset and oligoclonal banding were significantly associated with MS (p<0.01).ConclusionAge ≥10, optic disc pallor and MS were associated with poor recovery. Better identification of these patients may help to adapt treatment and lead to a prospective treatment study.
Enteric-coated mycophenolate sodium in the treatment of non-infectious intermediate uveitis: results of a prospective, controlled, randomised, open-label, early terminated multicentre trial
Authors: Deuter Christoph M E , Engelmann Katrin , Heiligenhaus Arnd , Lanzl Ines , Mackensen Friederike , Ness Thomas , Pleyer Uwe , Stuebiger Nicole , Wilhelm Barbara , Luedtke Holger , Zierhut Manfred , Doycheva Deshka 
Published: September 2017

Background/aimsTo evaluate the efficacy, safety and tolerability of enteric-coated mycophenolate sodium (EC-MPS) in combination with low-dose corticosteroids compared with a monotherapy with low-dose corticosteroids in subjects with non-infectious intermediate uveitis (IU).MethodsOpen-label, prospective, controlled, randomised multicentre trial. Patients were randomised in a 1:1 ratio to either the treatment group (prednisolone plus EC-MPS) or control group (prednisolone monotherapy). Patients in the control group who relapsed within 6 months changed to the crossover group (prednisolone plus EC-MPS). Maximum treatment duration was 15 months. The primary endpoint was the time to first relapse in the treatment group and control group.ResultsForty-one patients at eight sites were analysed. Twenty-two patients were allocated to the treatment group, with 19 patients in the control group. A first relapse occurred in 9 patients (40.9%) in the treatment group and 15 patients (78.9%) in the control group (p=0.03). The median time to the first relapse was >15 months for the treatment group and 2.8 months for the control group (p=0.07). The probability of relapse-free survival at month 15 was estimated to be 52.9% in the treatment group and 19.7% in the control group (p=0.01). 15 patients changed to the crossover group. Of these, only four patients developed a second relapse. No safety concerns arose during the trial. Only one patient had to discontinue EC-MPS due to increased liver enzymes.ConclusionEC-MPS can be considered an effective and well-tolerated immunosuppressive drug to prevent relapses in patients with chronic IU.Trial registration numberEUDRACT number: 2009-009998-10, Results.
Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre, randomised controlled trial: design and methodology
Authors: Gazzard Gus , Konstantakopoulou Evgenia , Garway-Heath David , Barton Keith , Wormald Richard , Morris Stephen , Hunter Rachael , Rubin Gary , Buszewicz Marta , Ambler Gareth , Bunce Catey 
Published: September 2017

PurposeThe Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT).DesignThe LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis.ConclusionsThe LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication.Trial registration numberISRCTN32038223, Pre-results.
Intramuscular tendon involvement on MRI has limited value for predicting time to return to play following acute hamstring injury
Authors: van der Made Anne D , Almusa Emad , Whiteley Rod , Hamilton Bruce , Eirale Cristiano , van Hellemondt Frank , Tol Johannes L 
Published: September 2017

BackgroundHamstring injury with intramuscular tendon involvement is regarded as a serious injury with a delay in return to play (RTP) of more than 50 days and reinjury rates up to 63%. However, this reputation is based on retrospective case series with high risk of bias.ObjectiveDetermine whether intramuscular tendon involvement is associated with delayed RTP and elevated rates of reinjury.MethodsMRI of male athletes with an acute hamstring injury was obtained within 5 days of injury. Evaluation included standardised MRI scoring and scoring of intramuscular tendon involvement. Time to RTP and reinjury rate were prospectively recorded.ResultsOut of 70 included participants, intramuscular tendon disruption was present in 29 (41.4%) injuries. Injuries without intramuscular tendon disruption had a mean time to RTP of 22.2±7.4 days. Injuries with <50%, 50%–99% and 100% disruption of tendon cross-sectional area had a mean time to RTP of 24.0±9.7, 25.3±8.6 and 31.6±10.9 days, respectively. Injuries with full-thickness disruption took longer to RTP compared with injuries without disruption (p=0.025). Longitudinal intramuscular tendon disruption was not significantly associated with time to RTP. Waviness was present in 17 (24.3%) injuries. Mean time to RTP for injuries without and with waviness was 22.6±7.5 and 30.2±10.8 days (p=0.014). There were 11 (15.7%) reinjuries within 12 months, five (17.2%) in the group with intramuscular tendon disruption and six (14.6%) in the group without intramuscular tendon disruption.ConclusionTime to RTP for injuries with full-thickness disruption of the intramuscular tendon and waviness is significantly longer (by slightly more than 1 week) compared with injuries without intramuscular tendon involvement. However, due to the considerable overlap in time to RTP between groups with and without intramuscular tendon involvement, its clinical significance for the individual athlete is limited.