bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asexual Propagation of a Virulent Clone Complex in a Human and Feline Outbreak of Sporotrichosis
Authors: Teixeira Marcus de Melo , Rodrigues Anderson Messias , Tsui Clement K. M. , de Almeida Luiz Gonzaga Paulo , Van Diepeningen Anne D. , van den Ende Bert Gerrits , Fernandes Geisa Ferreira , Kano Rui , Hamelin Richard C. , Lopes-Bezerra Leila Maria , Vasconcelos Ana Tereza Ribeiro , de Hoog Sybren , de Camargo Zoilo Pires , Felipe Maria Sueli Soares 
Published: December 2014

ABSTRACT

Sporotrichosis is one of the most frequent subcutaneous fungal infections in humans and animals caused by members of the plant-associated, dimorphic genus
Sporothrix
. Three of the four medically important
Sporothrix
species found in Brazil have been considered asexual as no sexual stage has ever been reported in
Sporothrix schenckii
,
Sporothrix brasiliensis
, or
Sporothrix globosa
. We have identified the mating type (
MAT
) loci in the
S. schenckii
(strain 1099-18/ATCC MYA-4821) and
S. brasiliensis
(strain 5110/ATCC MYA-4823) genomes by using comparative genomic approaches to determine the mating type ratio in these pathogen populations. Our analysis revealed the presence of a
MAT1-1
locus in
S. schenckii
while a
MAT1-2
locus was found in
S. brasiliensis
representing genomic synteny to other
Sordariomycetes
. Furthermore, the components of the mitogen-activated protein kinase (MAPK)-pheromone pathway, pheromone processing enzymes, and meiotic regulators have also been identified in the two pathogens, suggesting the potential for sexual reproduction. The ratio of
MAT1-1
to
MAT1-2
was not significantly different from 1:1 for all three
Sporothrix
species, but the population of
S. brasiliensis
in the outbreaks originated from a single mating type. We also explored the population genetic structure of these pathogens using sequence data of two loci to improve our knowledge of the pattern of geographic distribution, genetic variation, and virulence phenotypes. Population genetics data showed significant population differentiation and clonality with a low level of haplotype diversity in
S. brasiliensis
isolates from different regions of sporotrichosis outbreaks in Brazil. In contrast,
S. schenckii
isolates demonstrated a high degree of genetic variability without significant geographic differentiation, indicating the presence of recombination. This study demonstrated that two species causing the same disease have contrasting reproductive strategies and genetic variability patterns.
An Arginine-Glycine-Rich RNA Binding Protein Impacts the Abundance of Specific mRNAs in the Mitochondria of Trypanosoma brucei
Authors: McAdams Natalie M. , Ammerman Michelle L. , Nanduri Julee , Lott Kaylen , Fisk John C. , Read Laurie K. 
Published: December 2014

ABSTRACT

In kinetoplastid parasites, regulation of mitochondrial gene expression occurs posttranscriptionally via RNA stability and RNA editing. In addition to the 20S editosome that contains the enzymes required for RNA editing, a dynamic complex called the mitochondrial RNA binding 1 (MRB1) complex is also essential for editing.
Trypanosoma brucei
RGG3 (TbRGG3) was originally identified through its interaction with the guide RNA-associated proteins 1 and 2 (GAP1/2), components of the MRB1 complex. Both the arginine-glycine-rich character of TbRGG3, which suggests a function in RNA binding, and its interaction with MRB1 implicate TbRGG3 in mitochondrial gene regulation. Here, we report an
in vitro
and
in vivo
characterization of TbRGG3 function in
T. brucei
mitochondria. We show that
in vitro
TbRGG3 binds RNA with broad sequence specificity and has the capacity to modulate RNA-RNA interactions.
In vivo
, inducible RNA interference (RNAi) studies demonstrate that TbRGG3 is essential for proliferation of insect vector stage
T. brucei
. TbRGG3 ablation does not cause a defect in RNA editing but, rather, specifically affects the abundance of two preedited transcripts as well as their edited counterparts. Protein-protein interaction studies show that TbRGG3 associates with GAP1/2 apart from the remainder of the MRB1 complex, as well as with several non-MRB1 proteins that are required for mitochondrial RNA editing and/or stability. Together, these studies demonstrate that TbRGG3 is an essential mitochondrial gene regulatory factor that impacts the stabilities of specific RNAs.
Dynamics of Lewis b Binding and Sequence Variation of the
babA
Adhesin Gene during Chronic Helicobacter pylori Infection in Humans
Authors: Nell Sandra , Kennemann Lynn , Schwarz Sandra , Josenhans Christine , Suerbaum Sebastian 
Published: December 2014

ABSTRACT

Helicobacter pylori
undergoes rapid microevolution during chronic infection, but very little is known about how this affects host interaction factors. The best-studied adhesin of
H. pylori
is BabA, which mediates binding to the blood group antigen Lewis b [Le(b)]. To study the dynamics of Le(b) adherence during human infection, we analyzed paired
H. pylori
isolates obtained sequentially from chronically infected individuals. A complete loss or significant reduction of Le(b) binding was observed in strains from 5 out of 23 individuals, indicating that the Le(b) binding phenotype is quite stable during chronic human infection. Sequence comparisons of
babA
identified differences due to mutation and/or recombination in 12 out of 16 strain pairs analyzed. Most amino acid changes were found in the putative N-terminal extracellular adhesion domain. One strain pair that had changed from a Le(b) binding to a nonbinding phenotype was used to study the role of distinct sequence changes in Le(b) binding. By transformations of the nonbinding strain with a
babA
gene amplified from the binding strain,
H. pylori
strains with mosaic
babA
genes were generated. Recombinants were enriched for a gain of Le(b) binding by biopanning or for BabA expression on the bacterial surface by pulldown assay. With this approach, we identified several amino acid residues affecting the strength of Le(b) binding. Additionally, the data showed that the C terminus of BabA, which is predicted to encode an outer membrane β-barrel domain, plays an essential role in the biogenesis of this protein.

IMPORTANCE
Helicobacter pylori
causes a chronic infection of the human stomach that can lead to ulcers and cancer. The bacterium can bind to gastric epithelial cells with specialized outer membrane proteins. The best-studied protein is the BabA adhesin which binds to the Lewis b blood group antigen. Since
H. pylori
is a bacterium with very high genetic variability, we asked whether
babA
evolves during chronic infection and how mutations or recombination in
babA
affect binding. We found that BabA-mediated adherence was stable in most individuals but observed a complete loss of binding or reduced binding in 22% of individuals. One strain pair in which binding was lost was used to generate
babA
sequences that were mosaics of a functional allele and a nonfunctional allele, and the mosaic sequences were used to identify amino acids critically involved in binding of BabA to Lewis b.
How equity is addressed in clinical practice guidelines: a content analysis
Authors: Shi Chunhu , Tian Jinhui , Wang Quan , Petkovic Jennifer , Ren Dan , Yang Kehu , Yang Yang 
Published: December 2014

ObjectivesConsidering equity into guidelines presents methodological challenges. This study aims to qualitatively synthesise the methods for incorporating equity in clinical practice guidelines (CPGs).SettingContent analysis of methodological publications.Eligibility criteria for selecting studiesMethodological publications were included if they provided checklists/frameworks on when, how and to what extent equity should be incorporated in CPGs.Data sourcesWe electronically searched MEDLINE, retrieved references, and browsed guideline development organisation websites from inception to January 2013. After study selection by two authors, general characteristics and checklists items/framework components from included studies were extracted. Based on the questions or items from checklists/frameworks (unit of analysis), content analysis was conducted to identify themes and questions/items were grouped into these themes.Primary outcomesThe primary outcomes were methodological themes and processes on how to address equity issues in guideline development.Results8 studies with 10 publications were included from 3405 citations. In total, a list of 87 questions/items was generated from 17 checklists/frameworks. After content analysis, questions were grouped into eight themes (‘scoping questions’, ‘searching relevant evidence’, ‘appraising evidence and recommendations’, ‘formulating recommendations’, ‘monitoring implementation’, ‘providing a flow chart to include equity in CPGs’, and ‘others: reporting of guidelines and comments from stakeholders’ for CPG developers and ‘assessing the quality of CPGs’ for CPG users). Four included studies covered more than five of these themes. We also summarised the process of guideline development based on the themes mentioned above.ConclusionsFor disadvantaged population-specific CPGs, eight important methodological issues identified in this review should be considered when including equity in CPGs under the guidance of a scientific guideline development manual.
Quantification of histochemical stains using whole slide imaging: development of a method and demonstration of its usefulness in laboratory quality control
Authors: Gray Allan , Wright Alex , Jackson Pete , Hale Mike , Treanor Darren 
Published: December 2014

AimsHistochemical staining of tissue is a fundamental technique in tissue diagnosis and research, but it suffers from significant variability. Efforts to address this include laboratory quality controls and quality assurance schemes, but these rely on subjective interpretation of stain quality, are laborious and have low reproducibility. We aimed (1) to develop a method for histochemical stain quantification using whole slide imaging and image analysis and (2) to demonstrate its usefulness in measuring staining variation.MethodsA method to quantify the individual stain components of histochemical stains on virtual slides was developed. It was evaluated for repeatability and reproducibility, then applied to control sections of an appendix to quantify H&E staining (H/E intensities and H:E ratio) between automated staining machines and to measure differences between six regional diagnostic laboratories.ResultsThe method was validated with <0.5% variation in H:E ratio measurement when using the same scanner for a batch of slides (ie, it was repeatable) but was not highly reproducible between scanners or over time, where variation of 7% was found. Application of the method showed H:E ratios between three staining machines varied from 0.69 to 0.93, H:E ratio variation over time was observed. Interlaboratory comparison demonstrated differences in H:E ratio between regional laboratories from 0.57 to 0.89.ConclusionsA simple method using whole slide imaging can be used to quantify and compare histochemical staining. This method could be deployed in routine quality assurance and quality control. Work is needed on whole slide imaging devices to improve reproducibility.
Short term outcomes following clipping and coiling of ruptured intracranial aneurysms: does some of the benefit of coiling stem from less procedural impact on deranged physiology at presentation?
Authors: Mortimer Alex M , Bradford Celia , Steinfort Brendan , Faulder Ken , Assaad Nazih , Harrington Timothy 
Published: December 2014

BackgroundEndovascular coiling (EVC) has been shown to yield superior clinical outcomes to surgical clipping (SC) in the treatment of ruptured cerebral aneurysms. The reasons for these differences remain obscure. We aimed to assess outcomes of EVC and SC relative to baseline physiological derangement.MethodsThis was an exploratory analysis of prospectively collected trial data. Physiological derangement was assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system. Other contributory variables such as age, World Federation of Neurosurgical Societies (WFNS) grade, and development of complications, including hydrocephalus and vasospasm, were included in the analysis. Clinical outcome was independently assessed at 90 days using the modified Rankin Scale (mRS). Hospital stay, ventilated days, and total norepinephrine dose were also used as secondary outcomes. Multivariate analysis was performed using binary logistic regression.ResultsEVC was performed in 69 patients and SC in 66 patients. More profound physiological derangement (APACHE II score >15) was the strongest predictor of poor outcome in the overall cohort (OR 17.80, 95% CI 4.78 to 66.21, p<0.0001). For those with more deranged physiology (APACHE II score>15; 59 patients), WFNS grade ≥4 (OR 6.74, 1.43 to 31.75) and SC (OR 6.33, 1.27 to 31.38) were significant predictors of poor outcome (p<0.05). Favorable outcome (mRS 0–2) was seen in 11% of SC patients compared with 38% of EVC patients in this subgroup. SC patients had significantly increased total norepinephrine dose, ventilated days, and hospital stay (p<0.05).ConclusionsMore profound physiological derangement at baseline is a strong predictor of eventual poor outcome, and outcomes for patients with more profound baseline physiological derangement may be improved if undergoing a coiling procedure.
Breast Cancers with aBRCA1-like DNA Copy Number Profile Recur Less Often Than Expected after High-Dose Alkylating Chemotherapy
Authors: Schouten Philip C. , Marmé Frederik , Aulmann Sebastian , Sinn Hans-Peter , van Essen Hendrik F. , Ylstra Bauke , Hauptmann Michael , Schneeweiss Andreas , Linn Sabine C. 
Published: December 2014

AbstractPurpose: Breast cancers in carriers of inactivating mutations of the BRCA1 gene carry a specific DNA copy-number signature (“BRCA1-like”). This signature is shared with cancers that inactivate BRCA1 through other mechanisms. Because BRCA1 is important in repair of DNA double-strand breaks through error-free homologous recombination, patients with a BRCA1-like tumor may benefit from high-dose alkylating (HD) chemotherapy, which induces DNA double-strand breaks.Experimental Design: We investigated a single institution cohort of high-risk patients that received tandem HD chemotherapy schedule comprising ifosfamide, epirubicin, and carboplatin or conventional chemotherapy. We classified copy-number profiles to be BRCA1-like or non–BRCA1-like and analyzed clinical associations and performed survival analysis with a treatment by biomarker interaction design.Results: BRCA1-like status associated with high-grade and triple-negative breast cancers. BRCA1-like cases benefitted from the HD compared with a conventional regimen on disease-free survival (DFS): [hazard ratio (HR), 0.05; 95% confidence interval (CI), 0.01–0.38; P = 0.003]; distant DFS (DDFS): (HR, 0.06; 95% CI, 0.01–0.43; P = 0.01); and overall survival (OS; HR, 0.15; 95% CI, 0.03–0.83; P = 0.03) after correction for prognostic factors. No such benefit was observed in the non–BRCA1-like cases on DFS (HR, 0.74; 95% CI, 0.38–1.46; P = 0.39), DDFS (HR, 0.79; 95% CI, 0.41–1.52; P = 0.47), and OS (HR, 0.93; 95% CI, 0.52–1.64; P = 0.79). The P values for interaction were 0.01 (DFS), 0.01 (DDFS), and 0.045 (OS).Conclusions: BRCA1-like tumors recurred significantly less often after HD than conventional chemotherapy. BRCA1-like copy-number profile classification may be a predictive marker for HD alkylating chemotherapy. Clin Cancer Res; 21(4); 763–70. ©2014 AACR.
Interaction of Impaired Coronary Flow Reserve and Cardiomyocyte Injury on Adverse Cardiovascular Outcomes in Patients Without Overt Coronary Artery Disease
Authors: Taqueti Viviany R. , Everett Brendan M. , Murthy Venkatesh L. , Gaber Mariya , Foster Courtney R. , Hainer Jon , Blankstein Ron , Dorbala Sharmila , Di Carli Marcelo F. 
Published: December 2014

Background—
Minimally elevated serum cardiac troponin reflects myocardial injury and is associated with increased mortality, even absent coronary artery disease (CAD). We sought to investigate the relationship between low-level troponin elevation and impaired coronary flow reserve (CFR), an integrated measure of coronary vasomotor function, and to assess their contributions to adverse outcomes in patients without overt CAD.

Methods and Results—

Consecutive patients (n=761) undergoing evaluation for suspected CAD with troponin before stress myocardial perfusion positron emission tomography were followed up (median, 2.8 years) for major adverse cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, or late revascularization. Patients with flow-limiting CAD, left ventricular ejection fraction <40%, or revascularization within 60 days of imaging were excluded. CFR was quantified from stress/rest myocardial blood flow with the use of positron emission tomography. Compared with patients with negative troponin, those with at least 1 positive troponin (n=97) had higher pretest clinical scores, more renal dysfunction, and lower left ventricular ejection fraction and CFR. In adjusted analysis, impaired CFR remained independently associated with positive troponin (odds ratio, 2.18; 95% confidence interval, 1.37–3.47;
P
=0.001), and both impaired CFR and positive troponin were independently associated with major adverse cardiovascular events (hazard ratio, 2.25; 95% confidence interval, 1.31–3.86;
P
=0.003; and hazard ratio, 2.42; 95% confidence interval, 1.34–4.40;
P
=0.004, respectively). Impaired CFR and positive troponin identified patients at highest risk of major adverse cardiovascular events (log-rank
P
<0.0001), with a significant interaction (
P
<0.007) seen between CFR and troponin.

Conclusions—
In patients without overt CAD, impaired CFR was independently associated with minimally elevated troponin and major adverse cardiovascular events. Impaired CFR, here reflecting microvascular dysfunction, modified the effect of a positive troponin on adverse outcomes.
Molecular phylogenetics of American snapping shrimps allied to Alpheus floridanus Kingsley, 1878 (Crustacea: Decapoda: Alpheidae)
Authors: BRACKEN-GRISSOM HEATHER D. , ROBLES RAFAEL , FELDER DARRYL L. 
Published: December 2014

Widely distributed populations of the snapping shrimp, Alpheus floridanus Kinglsey, 1878, from the eastern Pacific and western and eastern Atlantic Ocean have long been suspected to represent different species due to extreme morphological variation among conspecifics. A companion study (Bracken-Grissom & Felder 2014) contains redescriptions of two western Atlantic species (A. floridanus Kingsley 1878 sensu stricto and A. platycheirus Boone, 1927), assignments of the original syntypes for A. floridanus, descriptions of three new species from the Atlantic and eastern Pacific (A. hephaestus Bracken-Grissom & Felder, 2014; A. roblesi Bracken-Grissom & Felder, 2014; A. ulalae Bracken-Grissom & Felder, 2014), and discussion of the relationship of the eastern Atlantic A. floridanus africanus Balss, 1916. The present study underpins all these findings by application of molecular phylogenetic techniques. Analysis of partial sequences of the 16S, 12S, and COI mitochondrial genes separate species throughout the eastern Pacific and the eastern and western Atlantic. Morphological comparisons suggested that the two syntypes of A. floridanus belong to different species, and molecular results in this study confirm this separation. Genetic data suggest a strong affinity between the western Atlantic A. platycheirus and the eastern Pacific A. hephaestus. Close relationships are evident between trans-Atlantic species, A. floridanus africanus and A. floridanus, a pattern also seen for other cryptic and pseudocryptic species of Alpheus. Alpheus roblesi and A. ulalae represent early-branching lineages within the complex. In some cases, molecular phylogenetic relationships between members of the A. floridanus complex can be reconciled with postulated biogeographic history.
Virtual Exertions
Authors: Chen Karen B. , Ponto Kevin , Tredinnick Ross D. , Radwin Robert G. 
Published: December 2014

Objective: This study was a proof of concept for virtual exertions, a novel method that involves the use of body tracking and electromyography for grasping and moving projections of objects in virtual reality (VR). The user views objects in his or her hands during rehearsed co-contractions of the same agonist-antagonist muscles normally used for the desired activities to suggest exerting forces. Background: Unlike physical objects, virtual objects are images and lack mass. There is currently no practical physically demanding way to interact with virtual objects to simulate strenuous activities. Method: Eleven participants grasped and lifted similar physical and virtual objects of various weights in an immersive 3-D Cave Automatic Virtual Environment. Muscle activity, localized muscle fatigue, ratings of perceived exertions, and NASA Task Load Index were measured. Additionally, the relationship between levels of immersion (2-D vs. 3-D) was studied. Results: Although the overall magnitude of biceps activity and workload were greater in VR, muscle activity trends and fatigue patterns for varying weights within VR and physical conditions were the same. Perceived exertions for varying weights were not significantly different between VR and physical conditions. Conclusions: Perceived exertion levels and muscle activity patterns corresponded to the assigned virtual loads, which supported the hypothesis that the method evoked the perception of physical exertions and showed that the method was promising. Application: Ultimately this approach may offer opportunities for research and training individuals to perform strenuous activities under potentially safer conditions that mimic situations while seeing their own body and hands relative to the scene.