bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperoxia does not affect oxygen delivery in healthy volunteers while causing a decrease in sublingual perfusion
Authors: Smit Bob , Smulders Yvo M. , Eringa Etto C. , Gelissen Harry P. M. M. , Girbes Armand R. J. , de Grooth Harm‐Jan S. , Schotman Hans H. M. , Scheffer Peter G. , Oudemans‐van Straaten Heleen M. , Spoelstra‐de Man Angelique M. E. 
Published: December 2017

AbstractObjectiveTo determine the human dose‐response relationship between a stepwise increase in arterial oxygen tension and its associated changes in DO2 and sublingual microcirculatory perfusion.MethodsFifteen healthy volunteers breathed increasing oxygen fractions for 10 minutes to reach arterial oxygen tensions of baseline (breathing air), 20, 40, 60 kPa, and max kPa (breathing oxygen). Systemic hemodynamics were measured continuously by the volume‐clamp method. At the end of each period, the sublingual microcirculation was assessed by SDF.ResultsSystemic DO2 was unchanged throughout the study (Pslope = .8). PVD decreased in a sigmoidal fashion (max −15% while breathing oxygen, SD18, Pslope = .001). CI decreased linearly (max −10%, SD10, Pslope < .001) due to a reduction in HR (max −10%, SD7, Pslope = .009). There were no changes in stroke volume or MAP. Most changes became apparent above an arterial oxygen tension of 20 kPa.ConclusionsIn healthy volunteers, supraphysiological arterial oxygen tensions have no effect on systemic DO2. Sublingual microcirculatory PVD decreased in a dose‐dependent fashion. All hemodynamic changes appear negligible up to an arterial oxygen tension of 20 kPa.
Sex‐related differences in the postmolt distribution of Weddell seals (Leptonychotes weddellii) in the southern Weddell Sea
Authors: Langley Izzy , Fedak Mike , Nicholls Keith , Boehme Lars 
Published: December 2017

AbstractThe population of Weddell seals (Leptonychotes weddellii) in the southern Weddell Sea is in a unique position on the continental shelf edge, with vast shelf waters to the south, and deep Southern Ocean to the north. We describe sex‐related differences in the winter distribution of this population, from data collected by 20 conductivity‐temperature‐depth satellite relay data loggers deployed in February 2011 at the end of the annual molt. The regional daily speed was calculated, and a state‐space model was used to estimate behavioral states to positions along individuals’ tracks. GLMMs estimated that males and smaller individuals, diving in shallower water, traveled less far per day of deployment (males 14.6 ± 2.26 km/d, females 18.9 ± 2.42 km/d), and males were estimated to dive in shallower water (males 604 ± 382 m, females 1,875 ± 1,458 m). Males and smaller individuals were also estimated to be more resident; males spent an average 83.4% ± 7.7% of their time in a resident behavioral state, compared to females at 74.1% ± 7.1%. This evidence that male and female Weddell seals in the southern Weddell Sea are adopting different strategies has not been shown elsewhere along their circumpolar distribution.
Outcome in patients with left common pulmonary vein after cryoablation with second‐generation cryoballoon
Authors: Beiert Thomas , Lodde Pia C. , Linneborn Lutz P.T. , Werner Jessica , Prinz Lisa , Stöckigt Florian , Linhart Markus , Lickfett Lars , Nickenig Georg , Schrickel Jan W. , Andrié René P. 
Published: December 2017

AbstractBackgroundPulmonary vein isolation (PVI) has become a widely accepted therapy in patients suffering from symptomatic atrial fibrillation (AF).HypothesisAF‐free survival differs in patients with left common pulmonary vein (LCPV) after PVI with second‐generation cryoballoon.MethodsWe included patients scheduled for first PVI for paroxysmal or persistent AF. Symptomatic and/or documented arrhythmia episodes (>30 seconds) were defined as AF recurrence, excluding a 3‐month blanking period.ResultsWe observed a LCPV in 37 of 270 consecutive patients (13.7%). Analyses were performed in a 1:1 propensity score matched cohort of 68 patients. During a median follow‐up of 77.0 weeks, 37 patients (54.4%) had recurrent AF. The prevalence of LCPV was numerically higher in patients with AF recurrence (62.2% vs 35.5%, P = 0.051) and Kaplan‐Meier analysis showed lower AF‐free survival in patients with existence of a LCPV (P = 0.028). At 1‐year follow‐up, 70.6% of patients without versus 55.1% of patients with LCPV were free of AF. Multivariate Cox regression analysis revealed presence of a LCPV (hazard ratio [HR]: 2.996), chronic heart failure (HR: 3.423), and mitral regurgitation > I° (HR: 2.571) as predictors of AF recurrence.ConclusionPatients with LCPV had significantly reduced AF‐free survival after ablation with the second‐generation cryoballoon, despite similar acutely successful PVIs.
The poor “sociological imagination” of the rich: Explaining attitudinal divergence towards welfare, inequality, and redistribution
Authors: Edmiston Daniel 
Published: December 2017

AbstractQuantitative research has tended to explain attitudinal divergence towards welfare and redistribution through self‐interested rationalities. However, such an approach risks abstracting individuals from the structural determinants of resource allocation and biographical experience. With that in mind, this article draws on a qualitative study of 50 individuals experiencing relative deprivation and affluence in the United Kingdom and New Zealand to examine how lived experiences of inequality affect attitude formation towards welfare and redistribution. Scenario‐driven vignettes were used to stimulate an applied discussion of abstract principles pertaining to welfare and inequality. Use of this methodological device proffered novel insight into the phenomenological effects of material position on public attitudes and policy preferences in a comparative context. The findings suggest that affluent individuals are less likely to acknowledge systemic features shaping socioeconomic life. As a result, they exhibit a poor sociological imagination that is deployed in distinct and patterned ways to make sense of, and at times justify, economic restructuring. By contrast, those living in relative deprivation are more likely to advance accounts of intergroup relations and social location that emphasize the structuration of (dis‐)advantage. Based on the findings, policy and political implications are considered for welfare and redistribution amidst rising structural inequality.
A heuristic‐based approach to mitigating positional errors in patrol data for species distribution modeling
Authors: Zhang Guiming , Zhu A‐Xing , Huang Zhi‐Pang , Xiao Wen 
Published: December 2017

AbstractSpecies distribution modeling (SDM) at fine spatial resolutions requires species occurrence data of high positional accuracy to achieve good model performance. However, wildlife occurrences recorded by patrols in ranger‐based monitoring programs suffer from positional errors, because recorded locations represent the positions of the ranger and differ from the actual occurrence locations of wildlife (hereinafter referred to as positional errors in patrol data). This study presented an evaluation of the impact of such positional errors in patrol data on SDM and developed a heuristic‐based approach to mitigating the positional errors. The approach derives probable wildlife occurrence locations from ranger positions, utilizing heuristics based on species preferred habitat and the observer's field of view. The evaluations were conducted through a case study of SDM using patrol records of the black‐and‐white snub‐nosed monkey (Rhinopithecus bieti) in Yunnan, China. The performance of the approach was also compared against alternative sampling methods. The results showed that the positional errors inR. bietipatrol data had an adverse effect on SDM performance, and that the proposed approach can effectively mitigate the impact of the positional errors to greatly improve SDM performance.
A novel association between high red blood cell alloimmunization rates and hereditary hemorrhagic telangiectasia
Authors: Zheng Yan , Pollak Jeffrey , Henderson Katharine , Hendrickson Jeanne E. , Tormey Christopher A. 
Published: December 2017

BACKGROUNDHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder associated with multiple arteriovenous malformations. HHT patients may require red blood cell (RBC) transfusion due to spontaneous hemorrhage or surgical bleeding. Because HHT‐associated hemorrhage often occurs in submucosa we hypothesized that RBC alloimmunization rates in HHT patients may be higher than those observed in other transfused patients and investigated this in a retrospective study.STUDY DESIGN AND METHODSEighty‐five patients with HHT who were transfused at our tertiary care facility were identified. A group of randomly selected, chronically transfused patients without HHT were used as controls (n = 207). RBC transfusion and alloantibody data were extracted from medical records.RESULTSAlloimmunization rates among patients with HHT were significantly higher than those of controls (15.29% vs. 2.42%; p < 0.001), while HHT patients received fewer RBC transfusions at our institution compared to controls (4.27 units vs. 8.84 units; p < 0.0001). Anti‐E, ‐K, and ‐c were the three most common alloantibodies identified in HHT patients. There was a trend for HHT patients to make more antibodies per alloimmunized patient than controls (2.38 alloantibodies vs. 1.60 alloantibodies), although this difference was not significant (p = 0.37).CONCLUSIONTo our knowledge, this is the first study to evaluate RBC alloimmunization rates in patients with HHT. It is unclear whether the high alloimmunization rates observed are due to lifetime transfusion burden, underlying disease pathophysiology, or other variables. Additional studies are needed to evaluate the generalizability of our findings to other HHT populations and to consider the utility of prophylactic antigen matching for C/E/K.
Type 2 diabetes specifically attenuates purinergic skin vasodilatation without affecting muscarinic and nicotinic skin vasodilatation and sweating
Authors: Fujii Naoto , Meade Robert D. , McNeely Brendan D. , Nishiyasu Takeshi , Sigal Ronald J. , Kenny Glen P. 
Published: December 2017

New Findings
What is the central question of this study?
It remains to be determined whether type 2 diabetes attenuates muscarinic and nicotinic cutaneous vasodilatation and sweating as well as purinergic cutaneous vasodilatation.

What is the main finding and its importance?
We show that type 2 diabetes specifically attenuates purinergic cutaneous vasodilatation without influencing muscarinic and nicotinic cutaneous vasodilatation and sweating. Our results provide valuable new information regarding the receptor‐specific influence of type 2 diabetes on microvascular and sudomotor function.

AbstractThe present study evaluated whether type 2 diabetes (T2D) attenuates muscarinic and/or nicotinic cutaneous vasodilatation and sweating as well as purinergic cutaneous vasodilatation. Cutaneous vascular conductance and sweat rate were evaluated in 12 healthy non‐diabetic older adults (Control, 60 ± 8 years) and 13 older adults with T2D (62 ± 10 years) at three intradermal forearm skin sites perfused with the following: (i) methacholine (muscarinic receptor agonist, five doses: 0.0125, 0.25, 5, 100 and 2000 mm); (ii) nicotine (nicotinic receptor agonist, five doses: 1.2, 3.6, 11, 33 and 100 mm); or (iii) ATP (purinergic receptor agonist, five doses: 0.03, 0.3, 3, 30 and 300 mm). Each agonist was administered for 25 min per dose. At the end of the protocol, 50 mm sodium nitroprusside was administered to all skin sites to elicit maximal cutaneous vasodilatation. Cutaneous vascular conductance during methacholine and nicotine administration did not differ between groups (all P > 0.05). In contrast, cutaneous vascular conductance during administration of 30 mm (42 ± 28 versus 63 ± 26% maximum, P ≤ 0.05) and 300 mm ATP (56 ± 24 versus 71 ± 20% maximum, P ≤ 0.05) was attenuated in individuals with T2D in comparison to the Control participants. Furthermore, cutaneous vascular conductance during administration of 50 mm sodium nitroprusside was lower in individuals with T2D relative to Control subjects (P = 0.04). Methacholine‐ and nicotine‐induced sweating was similar between groups (all P > 0.05). Thus, T2D attenuates purinergic cutaneous vasodilatation without affecting muscarinic and nicotinic cutaneous vascular and sweating responses.
Ca2+ and lipid signals hold hands at endoplasmic reticulum–plasma membrane contact sites
Authors: Balla Tamas 
Published: December 2017

AbstractDiscovery of the STIM1 and Orai proteins as the principal components of store‐operated Ca2+ entry has drawn attention to contact sites between the endoplasmic reticulum (ER) and the plasma membrane (PM). Such contacts between adjacent membranes of different cellular organelles, primarily between the mitochondria and the ER, had already been known as the sites where Ca2+ released from the ER can be efficiently channelled to the mitochondria and also where phosphatidylserine synthesis and transfer takes place. Recent studies have identified contact sites between virtually every organelle and the ER and the functional importance of these small specialized membrane domains is increasingly recognized. Most recent developments have highlighted the role of phosphatidylinositol 4‐phosphate gradients as critical determinants of the non‐vesicular transport of various lipids from the ER to other organelles such as the Golgi or PM. As we learn more about membrane contact sites it becomes apparent that Ca2+ is not only transported at these sites but also controls both the dynamics and the lipid transfer efficiency of these processes. Conversely, lipids are critical for regulating the Ca2+ entry process. This review will summarize some of the most exciting recent developments in this rapidly expanding research field.
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Rapid Microarray-Based Detection of Rifampin, Isoniazid, and Fluoroquinolone Resistance in Mycobacterium tuberculosis by Use of a Single Cartridge
Authors: Havlicek Juliane , Dachsel Beatrice , Slickers Peter , Andres Sönke , Beckert Patrick , Feuerriegel Silke , Niemann Stefan , Merker Matthias , Labugger Ines 
Published: December 2017

ABSTRACT

The rapid and robust identification of mutations in
Mycobacterium tuberculosis
complex (MTBC) strains mediating multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes is crucial to combating the MDR tuberculosis (TB) epidemic. Currently available molecular anti-TB drug susceptibility tests either are restricted to a single target or drug (i.e., the Xpert MTB/RIF test) or present a risk of cross-contamination due to the design limitations of the open platform (i.e., line probe assays). With a good understanding of the technical and commercial boundaries, we designed a test cartridge based on an oligonucleotide array into which dried reagents are introduced and which has the ability to identify MTBC strains resistant to isoniazid, rifampin, and the fluoroquinolones. The melting curve assay interrogates 43 different mutations in the rifampin resistance-determining region (RRDR) of
rpoB
,
rpoB
codon 572,
katG
codon 315, the
inhA
promoter region, and the quinolone resistance-determining region (QRDR) of
gyrA
in a closed cartridge system within 90 min. Assay performance was evaluated with 265 clinical MTBC isolates, including MDR/XDR, non-MDR, and fully susceptible isolates, from a drug resistance survey performed in Swaziland in 2009 and 2010. In 99.5% of the cases, the results were consistent with data previously acquired utilizing Sanger sequencing. The assay, which uses a closed cartridge system in combination with a battery-powered Alere q analyzer and which has the potential to extend the current gene target panel, could serve as a rapid and robust point-of-care test in settings lacking a comprehensive molecular laboratory infrastructure to differentiate TB patients infected with MDR and non-MDR strains and to assist clinicians with their early treatment decisions.
Multicenter Evaluation of the ePlex Respiratory Pathogen Panel for the Detection of Viral and Bacterial Respiratory Tract Pathogens in Nasopharyngeal Swabs
Authors: Babady N. Esther , England Matthew R. , Jurcic Smith Kristen L. , He Taojun , Wijetunge Dona Saumya , Tang Yi-Wei , Chamberland Robin R. , Menegus Marilyn , Swierkosz Ella M. , Jerris Robert C. , Greene Wallace 
Published: December 2017

ABSTRACT

The performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus; influenza A H1 virus; influenza A 2009 H1 virus; influenza A H3 virus; influenza B virus; adenovirus; coronaviruses [HKU1, OC43, NL63, and 229E]; human rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; and respiratory syncytial virus [RSV] [RSV subtype A and RSV subtype B]) and 2 bacteria (
Mycoplasma pneumoniae
and
Chlamydia pneumoniae
) was evaluated. Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens (
n
= 2,908) were evaluated by using the ePlex RP panel, with the bioMérieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator method. Discordance analysis was performed by using target-specific PCRs and bidirectional sequencing. The reproducibility of the assay was evaluated by using reproducibility panels comprised of 6 pathogens. The overall agreement between the ePlex RP and BioFire RP results was >95% for all targets. Positive percent agreement with the BioFire RP result for viruses ranged from 85.1% (95% confidence interval [CI], 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%), while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to 99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of samples tested. Reproducibility was 100% for all targets tested, with the exception of adenovirus, for which reproducibilities were 91.6% at low virus concentrations and 100% at moderate virus concentrations. The ePlex RP panel offers a new, rapid, and sensitive “sample-to-answer” multiplex panel for the detection of the most common viral and bacterial respiratory pathogens.
The Heptad Repeat C Domain of the Respiratory Syncytial Virus Fusion Protein Plays a Key Role in Membrane Fusion
Authors: Bermingham Imogen M. , Chappell Keith J. , Watterson Daniel , Young Paul R. 
Published: December 2017

ABSTRACT

Respiratory syncytial virus (RSV) mediates host cell entry through the fusion (F) protein, which undergoes a conformational change to facilitate the merger of viral and host lipid membrane envelopes. The RSV F protein comprises a trimer of disulfide-bonded F
1
and F
2
subunits that is present on the virion surface in a metastable prefusion state. This prefusion form is readily triggered to undergo refolding to bring two heptad repeats (heptad repeat A [HRA] and HRB) into close proximity to form a six-helix bundle that stabilizes the postfusion form and provides the free energy required for membrane fusion. This process can be triggered independently of other proteins. Here, we have performed a comprehensive analysis of a third heptad repeat region, HRC (amino acids 75 to 97), an amphipathic α-helix that lies at the interface of the prefusion F trimer and is a major structural feature of the F
2
subunit. We performed alanine scanning mutagenesis from Lys-75 to Met-97 and assessed all mutations in transient cell culture for expression, proteolytic processing, cell surface localization, protein conformation, and membrane fusion. Functional characterization revealed a striking distribution of activity in which fusion-increasing mutations localized to one side of the helical face, while fusion-decreasing mutations clustered on the opposing face. Here, we propose a model in which HRC plays a stabilizing role within the globular head for the prefusion F trimer and is potentially involved in the early events of triggering, prompting fusion peptide release and transition into the postfusion state.

IMPORTANCE
RSV is recognized as the most important viral pathogen among pediatric populations worldwide, yet no vaccine or widely available therapeutic treatment is available. The F protein is critical for the viral replication process and is the major target for neutralizing antibodies. Recent years have seen the development of prefusion stabilized F protein-based approaches to vaccine design. A detailed understanding of the specific domains and residues that contribute to protein stability and fusion function is fundamental to such efforts. Here, we present a comprehensive mutagenesis-based study of a region of the RSV F
2
subunit (amino acids 75 to 97), referred to as HRC, and propose a role for this helical region in maintaining the delicate stability of the prefusion form.
The Cellular Chaperone Heat Shock Protein 90 Is Required for Foot-and-Mouth Disease Virus Capsid Precursor Processing and Assembly of Capsid Pentamers
Authors: Newman Joseph , Asfor Amin S. , Berryman Stephen , Jackson Terry , Curry Stephen , Tuthill Tobias J. 
Published: December 2017

ABSTRACT
Productive picornavirus infection requires the hijacking of host cell pathways to aid with the different stages of virus entry, synthesis of the viral polyprotein, and viral genome replication. Many picornaviruses, including foot-and-mouth disease virus (FMDV), assemble capsids via the multimerization of several copies of a single capsid precursor protein into a pentameric subunit which further encapsidates the RNA. Pentamer formation is preceded by co- and posttranslational modification of the capsid precursor (P1-2A) by viral and cellular enzymes and the subsequent rearrangement of P1-2A into a structure amenable to pentamer formation. We have developed a cell-free system to study FMDV pentamer assembly using recombinantly expressed FMDV capsid precursor and 3C protease. Using this assay, we have shown that two structurally different inhibitors of the cellular chaperone heat shock protein 90 (hsp90) impeded FMDV capsid precursor processing and subsequent pentamer formation. Treatment of FMDV permissive cells with the hsp90 inhibitor prior to infection reduced the endpoint titer by more than 10-fold while not affecting the activity of a subgenomic replicon, indicating that translation and replication of viral RNA were unaffected by the drug.

IMPORTANCE
FMDV of the
Picornaviridae
family is a pathogen of huge economic importance to the livestock industry due to its effect on the restriction of livestock movement and necessary control measures required following an outbreak. The study of FMDV capsid assembly, and picornavirus capsid assembly more generally, has tended to be focused upon the formation of capsids from pentameric intermediates or the immediate cotranslational modification of the capsid precursor protein. Here, we describe a system to analyze the early stages of FMDV pentameric capsid intermediate assembly and demonstrate a novel requirement for the cellular chaperone hsp90 in the formation of these pentameric intermediates. We show the added complexity involved for this process to occur, which could be the basis for a novel antiviral control mechanism for FMDV.