bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tetraspanin CD82 interaction with cholesterol promotes extracellular vesicle–mediated release of ezrin to inhibit tumour cell movement
Authors: Huang Chao , Hays Franklin A. , Tomasek James J. , Benyajati Siribhinya , Zhang Xin A. 
Published: November 2019

ABSTRACTTumour metastasis suppressor KAI1/CD82 inhibits tumour cell movement. As a transmembrane protein, tetraspanin CD82 bridges the interactions between membrane microdomains of lipid rafts and tetraspanin‐enriched microdomains (TEMs). In this study, we found that CD82 and other tetraspanins contain cholesterol recognition/interaction amino‐acid consensus (CRAC) sequences in their transmembrane domains and revealed that cholesterol binding of CD82 determines its interaction with lipid rafts but not with TEMs. Functionally, CD82 needs cholesterol binding to inhibit solitary migration, collective migration, invasion and infiltrative outgrowth of tumour cells. Importantly, CD82–cholesterol/–lipid raft interaction not only promotes extracellular release of lipid raft components such as cholesterol and gangliosides but also facilitates extracellular vesicle (EV)–mediated release of ezrin–radixin–moesin (ERM) protein Ezrin. Since ERM proteins link actin cytoskeleton to the plasma membrane, we show for the first time that cell movement can be regulated by EV‐mediated releases, which disengage the plasma membrane from cytoskeleton and then impair cell movement. Our findings also conceptualize that interactions between membrane domains, in this case converge of lipid rafts and TEMs by CD82, can change cell movement. Moreover, CD82 coalescences with both lipid rafts and TEMs are essential for its inhibition of tumour cell movement and for its enhancement of EV release. Finally, our study underpins that tetraspanins as a superfamily of functionally versatile molecules are cholesterol‐binding proteins.Abbreviations:Ab: antibody; CBM: cholesterol‐binding motif; CCM: cholesterol consensus motif; CRAC/CARC: cholesterol recognition or interaction amino‐acid consensus; CTxB: cholera toxin B subunit; ECM: extracellular matrix; ERM: ezrin, radixin and moesin; EV: extracellular vesicles; FBS: foetal bovine serum; mAb: monoclonal antibody; MST: microscale thermophoresis; pAb: polyclonal antibody; and TEM: tetraspanin‐enriched microdomain
Standardised quantitative radioiodine SPECT/CT Imaging for multicentre dosimetry trials in molecular radiotherapy
Authors: Gregory Rebecca A , Murray Iain , Gear Jonathan , Leek Francesca , Chittenden Sarah , Fenwick Andrew , Wevrett Jill , Scuffham James , Tipping Jill , Murby Brian , Jeans Steve , Stuffins Martha , Michopoulou Sofia , Guy Matthew , Morgan Darren , Hallam Aida , Hall David , Polydor Heather , Brown Colin , Gillen Gerry , Dickinson Nathan , Brown Sarah , Wadsley Jonathan , Flux Glenn 
Published: November 2019

Abstract
The SEL-I-METRY trial (EudraCT No 2015-002269-47) is the first multicentre trial to investigate the role of 123I and 131I SPECT/CT-based tumour dosimetry to predict response to radioiodine therapy. Standardised dosimetry methodology is essential to provide a robust evidence-base for absorbed dose–response thresholds for molecular radiotherapy (MRT). In this paper a practical standardised protocol is used to establish the first network of centres with consistent methods of radioiodine activity quantification.
Nine SPECT/CT systems at eight centres were set-up for quantitative radioiodine imaging. The dead-time of the systems was characterised for up to 2.8 GBq 131I. Volume dependent calibration factors were measured on centrally reconstructed images of 123I and 131I in six (0.8–196 ml) cylinders. Validation of image quantification using these calibration factors was performed on three systems, by imaging a 3D-printed phantom mimicking a patient’s activity distribution. The percentage differences between the activities measured in the SPECT/CT image and those measured by the radionuclide calibrator were calculated. Additionally uncertainties on the SPECT/CT-based activities were calculated to indicate the limit on the quantitative accuracy of this method.
For systems set-up to image high 131I count rates, the count rate versus activity did not peak below 2.8 GBq and fit a non-paralysable model. The dead-times and volume-dependent calibration factors were comparable between systems of the same model and crystal thickness. Therefore a global calibration curve could be fitted to each. The errors on the validation phantom activities’ were comparable to the measurement uncertainties derived from uncertainty analysis, at 10% and 16% on average for 123I and 131I respectively in a 5 cm sphere.
In conclusion, the dead-time and calibration factors varied between centres, with different models of system. However, global calibration factors may be applied to the same system model with the same crystal thickness, to simplify set-up of future multi-centre MRT studies.
Effects of noble metal doping on hydrogen sensing performances of monolayer MoS2
Authors: Zhang Zheng , Chen Kai , Zhao Qiang , Huang Mei , Ouyang Xiaoping 
Published: November 2019

Abstract
To develop a new kind of hydrogen sensor based on monolayer MoS2, we investigated effects of noble metal doping on hydrogen sensing performances of the monolayer MoS2 by using the first principles calculation method. The Cu, Pd, and Pt doping decrease the adsorption energy of a hydrogen molecule on the monolayer MoS2, while Ag and Au doping have little effect on the adsorption energy. The adsorption energy change indicates that the Cu, Pd, and Pt doping strengthen the interaction between the hydrogen molecule and the monolayer MoS2. The density of states shows that the hybridization of H s, noble metals d, S p, and Mo d orbitals contributes to the adsorption of the hydrogen molecule on the noble metal doped monolayer MoS2. The changes in bader charge and charge density difference indicate that noble metal doping increases the charge transfer between the hydrogen molecule and the monolayer MoS2. All of the results demonstrate that noble metal doping can improve the hydrogen sensing performances of the monolayer MoS2, especially the Pd and Pt doping.
Local Perturbations of Cortical Excitability Propagate Differentially Through Large-Scale Functional Networks
Authors: Rosenthal Zachary P , Raut Ryan V , Yan Ping , Koko Deima , Kraft Andrew W , Czerniewski Leah , Acland Benjamin , Mitra Anish , Snyder Lawrence H , Bauer Adam Q , Snyder Abraham Z , Culver Joseph P , Raichle Marcus E , Lee Jin-Moo 
Published: November 2019

Abstract
Electrophysiological recordings have established that GABAergic interneurons regulate excitability, plasticity, and computational function within local neural circuits. Importantly, GABAergic inhibition is focally disrupted around sites of brain injury. However, it remains unclear whether focal imbalances in inhibition/excitation lead to widespread changes in brain activity. Here, we test the hypothesis that focal perturbations in excitability disrupt large-scale brain network dynamics. We used viral chemogenetics in mice to reversibly manipulate parvalbumin interneuron (PV-IN) activity levels in whisker barrel somatosensory cortex. We then assessed how this imbalance affects cortical network activity in awake mice using wide-field optical neuroimaging of pyramidal neuron GCaMP dynamics as well as local field potential recordings. We report 1) that local changes in excitability can cause remote, network-wide effects, 2) that these effects propagate differentially through intra- and interhemispheric connections, and 3) that chemogenetic constructs can induce plasticity in cortical excitability and functional connectivity. These findings may help to explain how focal activity changes following injury lead to widespread network dysfunction.
Long-term Mortality and Epilepsy in Patients After Brain Abscess: A Nationwide Population-Based Matched Cohort Study
Authors: Bodilsen Jacob , Dalager-Pedersen Michael , van de Beek Diederik , Brouwer Matthijs C , Nielsen Henrik 
Published: November 2019

Abstract

Background
We aimed to determine the long-term risks of mortality and new-onset epilepsy after brain abscess.

Methods
Using nationwide population-based medical registries, we examined all patients with first-time brain abscess in Denmark, 1982–2016. Comparison cohorts individually matched on age, sex, and residence were identified, as were siblings of all study participants. Next, we computed cumulative incidences and hazard rate ratios (HRRs) with 95% confidence intervals of mortality and new-onset epilepsy among study populations.

Results
We identified 1384 brain abscess patients (37% females) with a median follow-up time of 5.9 years (interquartile range [IQR] 1.1–14.2). The 1-year, 2–5 year, and 6–30 year mortality of patients after brain abscess was 21%, 16%, and 27% as compared to 1%, 6%, and 20% for population controls. Cox regression analyses adjusted for Charlson comorbidity index score showed 1-year, 2–5 year, and 6–30 year HRRs of 17.5 (13.9–22.0), 2.61 (2.16–3.16), and 1.94 (1.62–2.31). The mortality in brain abscess patients was significantly increased regardless of sex or age group except among subjects 80 years or older, and in both previously healthy individuals and immunocompromised persons.
Among the 30-day survivors of brain abscess (median follow-up 7.6 years [IQR 2.2–15.5]), new-onset epilepsy occurred in 32% compared to 2% in matched population controls. Cause-specific Cox regression analysis adjusted for stroke, head trauma, alcohol abuse, and cancer showed 1-year, 2–5 year, and 6–30 year HRRs for new-onset epilepsy of 155 (78.8–304), 37.7 (23.0–59.9), and 8.93 (5.62–14.2).

Conclusions
Brain abscess is associated with an increased long-term risk of mortality and new-onset epilepsy for several years after infection.
Prevalence of clinical, pathological and molecular features of glomerular basement membrane nephropathy caused byCOL4A3orCOL4A4mutations: a systematic review
Authors: Matthaiou Andreas , Poulli Tsielestina , Deltas Constantinos 
Published: November 2019

AbstractBackgroundPatients heterozygous for COL4A3 or COL4A4 mutations show a wide spectrum of disease, extending from familial isolated microscopic haematuria, as a result of thin basement membranes (TBMs), to autosomal dominant Alport syndrome (ADAS) and end-stage renal disease (ESRD). Many patients are mentioned in the literature under the descriptive diagnosis of TBM nephropathy (TBMN), in which case it actually describes a histological finding that represents the carriers of autosomal recessive Alport syndrome (ARAS), a severe glomerulopathy, as most patients reach ESRD at a mean age of 25 years.MethodsWe performed a systematic literature review for patients with heterozygous COL4A3/A4 mutations with the aim of recording the spectrum and frequency of pathological features. We searched three databases (PubMed, Embase and Scopus) using the keywords ‘Autosomal Dominant Alport Syndrome’ OR ‘Thin Basement Membrane Disease’ OR ‘Thin Basement Membrane Nephropathy’. We identified 48 publications reporting on 777 patients from 258 families.ResultsIn total, 29% of the patients developed chronic kidney disease (CKD) and 15.1% reached ESRD at a mean age of 52.8 years. Extrarenal features and typical Alport syndrome (AS) findings had a low prevalence in patients as follows: hearing loss, 16%; ocular lesions, 3%; basement membrane thickening, 18.4%; and podocyte foot process effacement, 6.9%. Data for 76 patients from 54 families emphasize extensive inter- and intrafamilial heterogeneity, with age at onset of ESRD ranging between 21 and 84 years (mean 52.8).ConclusionsThe analysis enabled a comparison of the clinical course of patients with typical ARAS or X-linked AS with those with heterozygous COL4A mutations diagnosed with TBMN or ADAS. Despite the consequence of a potential ascertainment bias, an important outcome is that TBM poses a global high risk of developing severe CKD, over a long follow-up, with a variable spectrum of other findings. The results are useful to practicing nephrologists for better evaluation of patients.
Post-Post-Truth: An Adaptationist Theory of Journalistic Verism
Authors: Godler Yigal 
Published: November 2019

AbstractIn the age of post-truth, media studies find themselves trapped between the desire to restore journalism’s authority as a veristic (truth-seeking) institution and the lack of a coherent, applicable and consensual theory of truth. In order to develop such a theory of truth, this study bases itself on a detailed picture of how a sample of mainstream Israeli journalists covered 20 cases of factual controversies, drawing on journalists’ own accounts of their work, an independent analysis of documents they relied on, as well as their published output. Findings show that during actual situations of coverage journalists’ operative conceptions of truth match, at a minimum, the theories of coherence, correspondence and pragmatism. I argue that a novel adaptationist theory of truth may not only provide an adequate description of journalists’ actual pursuit of truth, but also contribute to their reflexivity vis-à-vis the inevitable context-dependence of their own veristic criteria.
Mothers’ and fathers’ cognitive and affective responses to epigenetics concepts
Authors: Hollister Brittany M , Yaremych Haley E , Goldring Megan R , Persky Susan 
Published: November 2019

Abstract
Advances in our understanding of epigenetics present new opportunities to improve children’s health through the counseling of parents about epigenetics concepts. However, it is important to first evaluate how parents respond to this type of information and determine the consequences of educating parents about epigenetics. We have taken an initial step toward this goal by assessing parental responses to an epigenetics learning module. Parents (n = 190, 126 mothers) responded to pre- and post-module survey questions. Prior to the module, parents reported that mothers’ lifestyles prior to conception were more important for children’s health than fathers’ lifestyles prior to conception (t = 4.49, df = 316.5, P < 0.0001). However, after the module, there was no difference between ratings of the importance of mothers’ and fathers’ preconception lifestyles (t = 1.18, df = 319.8, P = NS). Furthermore, after viewing the module, parents increased their ratings of the importance of both mothers’ (t = −5.65, df = 294.8, P < 0.0001) and father’s (t = −9.01, df = 287.2, P < 0.0001) preconception lifestyles for child health. After viewing the module, most parents reported feelings of guilt and negativity regarding epigenetics (78 and 55%, respectively). When compared with lean parents, parents with overweight more often reported feelings of guilt (χ2 =10.27, P = 0.001). This work represents an important first step in evaluating parental responses to epigenetics concepts.
The impact of an automated antibiotic stewardship intervention for the management of Staphylococcus aureus bacteraemia utilizing the electronic health record
Authors: Brotherton Amy L , Rab Saira , Kandiah Sheetal , Kriengkauykiat Jane , Wong Jordan R 
Published: November 2019

Abstract

Background
Staphylococcus aureus bacteraemia (SAB) management bundles have been shown to improve performance measures and clinical outcomes. SAB bundles often require direct intervention by infectious diseases (ID) physicians or antibiotic stewardship programme (ASP) members or pharmacists. The purpose of this study was to evaluate an automated, real-time ASP intervention utilizing clinical decision support (CDS) in the electronic health record (EHR) for the management of SAB.

Methods
A retrospective, single-centre quasi-experimental study of hospitalized patients with known SAB was conducted. The intervention was the implementation of a hard-stop best practice advisory (BPA) alert that would prompt physicians to use an electronic order set, on identification of SAB, with management recommendations, including ID consultation. The primary outcome was overall adherence to six institutional ASP SAB bundle elements. Secondary outcomes included both clinical and process outcomes.

Results
A total of 227 patients were included, 111 in the pre-intervention and 116 in the post-intervention period. Completion of all six bundle elements improved by 27.2% in the post-intervention group (29.7% versus 56.9%, P &lt; 0.001). BPA activation and order-set utilization occurred in 95.7% and 57.8% in the post-intervention group, respectively. Composite outcome of 30 day mortality or 90 day readmission with SAB complication decreased in the post-intervention group by 9.6% (24.3% versus 14.7%, P = 0.092).

Conclusions
Optimization of CDS within the EHR, using real-time BPA alert and order set, demonstrated an immediate, sustainable intervention that improved adherence to institutional performance measures for SAB management without direct prospective audit with intervention and feedback.
Section 2 Mangled: FTC v Qualcomm on the Duty to Deal, Price Squeezes, and Exclusive Dealing
Authors: Edwards Lindsey M , Ginsburg Douglas H , Wright Joshua D 
Published: November 2019

Abstract
Judge Koh handed down a sweeping opinion in May 2019 condemning as antitrust violations many of Qualcomm’s licensing practices related to its patented chips and standard-essential technology used in mobile devices. The district court opinion significantly expands the scope of liability for refusals to deal and for non-predatory pricing, further eroding the longstanding symmetrical approach to antitrust enforcement regardless of the kind of property involved. We find three glaring errors in the district court opinion. First, the court expands the exception to the general rule permitting refusals to deal, as laid out in Aspen Skiing, well beyond the outer boundary of Section 2 by inappropriately inferring a prior course of dealing and erroneously finding a willingness to sacrifice profits. Secondly, the district court accepted a price squeeze theory—characterized by the FTC as a ‘tax’ on OEMs transacting with Qualcomm’s rivals—directly contrary to the Supreme Court’s holding in linkLine. Thirdly, the court erroneously concluded that Qualcomm’s exclusive dealing arrangements with Apple violate the Sherman Act, despite a glaring failure by the FTC to prove substantial foreclosure, contrary to modern antitrust precedent and economic theory. The district court’s inappropriate extension of antitrust liability in three separate areas of well-settled antitrust doctrine is remarkable and threatens to upend important precedent that has successfully guided business conduct for many years. Further, the remedy transforms the role of antitrust courts from adjudicators to central planners, a role for which the Trinko Court expressly stated they are ill suited. The decision invites plaintiffs to use the Sherman Act to reach conduct that has been generally shielded from antitrust liability. That invitation is ill advised and should be rejected by the Ninth Circuit, and if necessary, the Supreme Court.
Molecular bases of responses to abiotic stress in trees
Authors: Estravis-Barcala Maximiliano , Mattera María Gabriela , Soliani Carolina , Bellora Nicolás , Opgenoorth Lars , Heer Katrin , Arana María Verónica 
Published: November 2019

AbstractTrees are constantly exposed to climate fluctuations, which vary with both time and geographic location. Environmental changes that are outside of the physiological favorable range usually negatively affect plant performance and trigger responses to abiotic stress. Long-living trees in particular have evolved a wide spectrum of molecular mechanisms to coordinate growth and development under stressful conditions, thus minimizing fitness costs. The ongoing development of techniques directed at quantifying abiotic stress has significantly increased our knowledge of physiological responses in woody plants. However, it is only within recent years that advances in next-generation sequencing and biochemical approaches have enabled us to begin to understand the complexity of the molecular systems that underlie these responses. Here, we review recent progress in our understanding of the molecular bases of drought and temperature stresses in trees, with a focus on functional, transcriptomic, epigenetic, and population genomic studies. In addition, we highlight topics that will contribute to progress in our understanding of the plastic and adaptive responses of woody plants to drought and temperature in a context of global climate change.
High-energy gamma-ray sources in the VVV survey – I. The blazars
Authors: Pichel Ana , Donoso Laura G , Baravalle Laura D , Alonso M Victoria , Rovero Adrián C , Beamín Juan C , Minniti Dante , Cabral Juan B , Sánchez Bruno , Coldwell Georgina , Masetti Nicola 
Published: November 2019

ABSTRACT
There is a lack of blazar detections in the galactic plane area, even in the most recent blazar catalogues, mainly due to incompleteness resulting from interstellar dust and stellar contamination of our Galaxy. The VISTA Variables in the Vía Láctea survey (VVV) aims to map variable sources towards the galactic plane in the near-infrared (IR). There are three catalogued and one candidate blazars in the VVV area, which are also detected by Fermi-LAT in the gamma-ray band and by the Wide-field Infrared Survey Explorer (WISE) at mid-IR wavelengths. We study the physical properties of these blazars in order to use them as a reference that would allow us to find counterparts of other unidentified gamma-ray sources in the future. All four sources have VVV counterparts, and two of them, 5BZUJ1731−3003 and 5BZQJ1802−3940 are also associated with WISE sources. They present very different properties compared with stellar or extragalactic objects. Their VVV Ks light curves show significant variability, and are characterized using a machine learning analysis. In particular, the blazar 5BZQJ1802−3940, a flat spectrum radio quasar, exhibits the smallest uncertainties in the Fermi-LAT position and it is a bright WISE source. Its near-IR properties in the colour–magnitude and colour–colour diagrams are very different from the stars and extragalactic objects in the field. It has the highest amplitude in the Ks differential light curve and fractional variability amplitude. This pilot study will allow us to search for and identify other blazars hidden behind the Galactic plane using the VVV survey data base.
Formation of close binaries by disc fragmentation and migration, and its statistical modelling
Authors: Tokovinin Andrei , Moe Maxwell 
Published: November 2019

ABSTRACT
Joint statistics of periods and mass ratios of close binaries and its dependence on primary mass can be explained by assuming that seed binary companions are formed by disc fragmentation at random intervals during assemblage of stellar mass and migrate inwards as they accrete from the circumbinary disc. A toy model based on simple prescriptions for the companion growth and migration reproduces such aspects of close solar-mass binaries as the distribution of binary periods P, the brown dwarf desert at short P, the nearly uniform distribution of mass ratios, and a population of equal-mass binaries (twins) that decreases linearly in frequency with log P. For massive stars, the model predicts a large fraction of early mergers, a distribution of log P with a negative slope, and a mass-ratio distribution that is also uniform but with a substantially reduced twin fraction. By treating disc fragmentation as a stochastic process, we also reproduce the observed properties of compact triples. Success of our toy model suggests that most close binaries and compact triples indeed formed by disc fragmentation followed by accretion-driven inward migration.