bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implications of Higgs’ universality for physics beyond the Standard Model
Authors: Goldman T. , Stephenson G. J. 
Published: June 2017

We emulate Cabibbo by assuming a kind of universality for fermion mass terms in the Standard Model. We show that this is consistent with all current data and with the concept that deviations from what we term Higgs’ universality are due to corrections from currently unknown physics of nonetheless conventional form. The application to quarks is straightforward, while the application to leptons makes use of the recognition that Dark Matter can provide the “sterile” neutrinos needed for the seesaw mechanism. Requiring agreement with neutrino oscillation results leads to the prediction that the mass eigenstates of the sterile neutrinos are separated by quadratically larger ratios than for the charged fermions. Using consistency with the global fit to LSND-like, short-baseline oscillations to determine the scale of the lowest mass sterile neutrino strongly suggests that the recently observed astrophysical 3.55 keV [Formula: see text]-ray line is also consistent with the mass expected for the second most massive sterile neutrino in our analysis.
Dietary nitrate restores compensatory vasodilation and exercise capacity in response to a compromise in oxygen delivery in the noncompensator phenotype
Authors: Bentley Robert F. , Walsh Jeremy J. , Drouin Patrick J. , Velickovic Aleksandra , Kitner Sarah J. , Fenuta Alyssa M. , Tschakovsky Michael E. 
Published: June 2017

Recently, dietary nitrate supplementation has been shown to improve exercise capacity in healthy individuals through a potential nitrate-nitrite-nitric oxide pathway. Nitric oxide has been shown to play an important role in compensatory vasodilation during exercise under hypoperfusion. Previously, we established that certain individuals lack a vasodilation response when perfusion pressure reductions compromise exercising muscle blood flow. Whether this lack of compensatory vasodilation in healthy, young individuals can be restored with dietary nitrate supplementation is unknown. Six healthy (21 ± 2 yr), recreationally active men completed a rhythmic forearm exercise. During steady-state exercise, the exercising arm was rapidly transitioned from an uncompromised (below heart) to a compromised (above heart) position, resulting in a reduction in local pressure of −31 ± 1 mmHg. Exercise was completed following 5 days of nitrate-rich (70 ml, 0.4 g nitrate) and nitrate-depleted (70 ml, ~0 g nitrate) beetroot juice consumption. Forearm blood flow (in milliliters per minute; brachial artery Doppler and echo ultrasound), mean arterial blood pressure (in millimeters of mercury; finger photoplethysmography), exercising forearm venous effluent (ante-cubital vein catheter), and plasma nitrite concentrations (chemiluminescence) revealed two distinct vasodilatory responses: nitrate supplementation increased (plasma nitrite) compared with placebo (245 ± 60 vs. 39 ± 9 nmol/l; P < 0.001), and compensatory vasodilation was present following nitrate supplementation (568 ± 117 vs. 714 ± 139 ml ⋅ min−1⋅ 100 mmHg−1; P = 0.005) but not in placebo (687 ± 166 vs. 697 ± 171 min−1⋅ 100 mmHg−1; P = 0.42). As such, peak exercise capacity was reduced to a lesser degree (−4 ± 39 vs. −39 ± 27 N; P = 0.01). In conclusion, dietary nitrate supplementation during a perfusion pressure challenge is an effective means of restoring exercise capacity and enabling compensatory vasodilation.NEW & NOTEWORTHY Previously, we identified young, healthy persons who suffer compromised exercise tolerance when exercising muscle perfusion pressure is reduced as a result of a lack of compensatory vasodilation. The ability of nitrate supplementation to restore compensatory vasodilation in such noncompensators is unknown. We demonstrated that beetroot juice supplementation led to compensatory vasodilation and restored perfusion and exercise capacity. Elevated plasma nitrite is an effective intervention for correcting the absence of compensatory vasodilation in the noncompensator phenotype.
ERRα Maintains Mitochondrial Oxidative Metabolism and Constitutes an Actionable Target in PGC1α-Elevated Melanomas
Authors: Luo Chi , Balsa Eduardo , Thomas Ajith , Hatting Maximilian , Jedrychowski Mark , Gygi Steven P. , Widlund Hans R. , Puigserver Pere 
Published: June 2017

Abstract
The uncontrolled growth of tumors provides metabolic dependencies that can be harnessed for therapeutic benefit. Although tumor cells exhibit these increased metabolic demands due to their rapid proliferation, these metabolic processes are general to all cells, and furthermore, targeted therapeutic intervention can provoke compensatory adaptation that alters tumors' characteristics. As an example, a subset of melanomas depends on the transcriptional coactivator PGC1α function to sustain their mitochondrial energy-dependent survival. However, selective outgrowth of resistant PGC1α-independent tumor cells becomes endowed with an augmented metastatic phenotype. To find PGC1α-dependent components that would not affect metastasis in melanomas, an unbiased proteomic analyses was performed and uncovered the orphan nuclear receptor ERRα, which supports PGC1α's control of mitochondrial energetic metabolism, but does not affect the antioxidant nor antimetastatic regulatory roles. Specifically, genetic or pharmacologic inhibition of ERRα reduces the inherent bioenergetic capacity and decreases melanoma cell growth, but without altering the invasive characteristics. Thus, within this particularly aggressive subset of melanomas, which is characterized by heighted expression of PGC1α, ERRα specifically mediates prosurvival functions and represents a tangible therapeutic target.
Implications: ERRα, a druggable protein, mediates the bioenergetic effects in melanomas defined by high PGC1α expression, suggesting a rational means for therapeutic targeting of this particularly aggressive melanoma subtype. Mol Cancer Res; 15(10); 1366–75. ©2017 AACR.
Platelet receptors as therapeutic targets: Past, present and future
Authors: Jamasbi Janina , Ayabe Keng , Goto Shinya , Nieswandt Bernhard , Peter Karlheinz , Siess Wolfgang 
Published: June 2017

SummaryAnti-platelet drugs reduce arterial thrombosis after plaque rupture and erosion, prevent stent thrombosis and are used to prevent and treat myocardial infarction and ischaemic stroke. Some of them may also be helpful in treating less frequent diseases such as thrombotic thrombocytopenic purpura. The present concise review aims to cover current and future developments of anti-platelet drugs interfering with the interaction of von Willebrand factor (VWF) with glycoprotein (GP) Ibα, and directed against GPVI, GPIIb/IIIa (integrin αIIbβ3), the thrombin receptor PAR-1, and the ADP receptor P2Y12. The high expectations of having novel antiplatelet drugs which selectively inhibit arterial thrombosis without interfering with normal haemostasis could possibly be met in the near future.
Human Blood Monocyte Subsets
Authors: Thomas Graham D. , Hamers Anouk A.J. , Nakao Catherine , Marcovecchio Paola , Taylor Angela M. , McSkimming Chantel , Nguyen Anh Tram , McNamara Coleen A. , Hedrick Catherine C. 
Published: June 2017

Objective—

Human monocyte subsets are defined as classical (CD14
++
CD16
−
), intermediate (CD14
++
CD16
+
), and nonclassical (CD14
+
CD16
+
). Alterations in monocyte subset frequencies are associated with clinical outcomes, including cardiovascular disease, in which circulating intermediate monocytes independently predict cardiovascular events. However, delineating mechanisms of monocyte function is hampered by inconsistent results among studies.

Approach and Results—
We use cytometry by time-of-flight mass cytometry to profile human monocytes using a panel of 36 cell surface markers. Using the dimensionality reduction approach visual interactive stochastic neighbor embedding (viSNE), we define monocytes by incorporating all cell surface markers simultaneously. Using viSNE, we find that although classical monocytes are defined with high purity using CD14 and CD16, intermediate and nonclassical monocytes defined using CD14 and CD16 alone are frequently contaminated, with average intermediate and nonclassical monocyte purity of ≈86.0% and 87.2%, respectively. To improve the monocyte purity, we devised a new gating scheme that takes advantage of the shared coexpression of cell surface markers on each subset. In addition to CD14 and CD16, CCR2, CD36, HLA-DR, and CD11c are the most informative markers that discriminate among the 3 monocyte populations. Using these additional markers as filters, our revised gating scheme increases the purity of both intermediate and nonclassical monocyte subsets to 98.8% and 99.1%, respectively. We demonstrate the use of this new gating scheme using conventional flow cytometry of peripheral blood mononuclear cells from subjects with cardiovascular disease.

Conclusions—
Using cytometry by time-of-flight mass cytometry, we have identified a small panel of surface markers that can significantly improve monocyte subset identification and purity in flow cytometry. Such a revised gating scheme will be useful for clinical studies of monocyte function in human cardiovascular disease.
NLRP3 Inflammasome Inhibition by MCC950 Reduces Atherosclerotic Lesion Development in Apolipoprotein E–Deficient Mice—Brief Report
Authors: van der Heijden Thomas , Kritikou Eva , Venema Wouter , van Duijn Janine , van Santbrink Peter J. , Slütter Bram , Foks Amanda C. , Bot Ilze , Kuiper Johan 
Published: June 2017

Objective—

Inflammasomes are multiprotein complexes, and their activation has been associated with cardiovascular disease. Inflammasome activation leads to secretion of caspase-1 by innate immune cells, resulting in the activation of interleukin-1β. Recently, a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, was described. In this study, we investigated the effect of MCC950 on atherosclerotic lesion development in apoE
−/−
mice.

Approach and Results—

First, we determined the efficacy of MCC950 in vitro. Bone marrow–derived macrophages and dendritic cells were stimulated with lipopolysaccharide and cholesterol crystals resulting in high levels of interleukin-1β release, which was inhibited by MCC950. In vivo MCC950 treatment reduced lipopolysaccharide–induced interleukin-1β secretion, without affecting the tumor necrosis factor-α response. Subsequently, atherosclerotic plaques were induced in Western-type diet fed apoE
−/−
mice by semiconstrictive perivascular collar placement at the carotid arteries, after which the mice received MCC950 (10 mg/kg) or vehicle control 3× per week intraperitoneally for 4 weeks. After euthanize, atherosclerotic plaque size and volume were quantified in hematoxylin-eosin–stained 10-µm cryosections throughout the artery. MCC950 treatment significantly reduced the development of atherosclerotic lesions as determined by maximal stenosis, average plaque size, and plaque volume. Although the amount of collagen and the necrotic core size were not affected, the number of macrophages in the plaque was significantly reduced on treatment. In addition, VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) mRNA expression was significantly reduced in the carotids of MCC950-treated mice.

Conclusions—
These findings show that specific inhibition of the NLRP3 inflammasome using MCC950 can be a promising therapeutic approach to inhibit atherosclerotic lesion development.
Prevalence of Fabry Disease and Outcomes in Young Canadian Patients With Cryptogenic Ischemic Cerebrovascular Events
Authors: Lanthier Sylvain , Saposnik Gustavo , Lebovic Gerald , Pope Karen , Selchen Daniel , Moore David F. , Selchen Dan , Boulanger Jean-Martin , Buck Brian , Butcher Ken , del Campo Martin , Gosselin Sylvie , Hachinski Vladimir , Hill Michael D. , Mackey Ariane , Mehdiratta Manu , Spence J. David , Stotts Grant , Swartz Rick , West Michael L. , Yegappan Chidam 
Published: June 2017

Background and Purpose—
Previous studies reported Fabry disease in 0% to 4% of young patients with cryptogenic ischemic stroke (IS). We sought to determine the prevalence of Fabry and outcomes among young Canadians with cryptogenic IS or transient ischemic attack (TIA).

Methods—

We prospectively enrolled individuals aged 18 to 55 with IS or speech or motor TIA, and no cause identified despite predetermined investigation.
α-galactosidase-A
gene was sequenced for Fabry diagnosis. National Institutes of Health Stroke Scale score was measured at presentation to quantify stroke severity. Modified Rankin Scale determined functional outcomes ≤7 days after presentation and 6 months later.

Results—

We enrolled 365 patients with IS and 32 with TIA.
α-galactosidase-A
sequencing identified a single carrier of a genetic variant of unknown significance (p.R118C) and no well-recognized pathogenic variants. Mean National Institutes of Health Stroke Scale score was 3.1. Proportion of patients with modified Rankin Scale of 0 to 2 was 70.7% at ≤7 days and 87.4% at 6 months. National Institutes of Health Stroke Scale score at presentation and diabetes mellitus predicted 6-month modified Rankin Scale. Thirteen patients experienced 5 recurrent IS and 9 TIA during follow-up. No patient died. Most patients (98.7%) returned home. Among previous workers, 43% had residual working limitations.

Conclusions—
In this Canadian cohort of patients with cryptogenic IS or TIA, the prevalence of Fabry was 0.3% if p.R118C variant is considered as pathogenic. This suggests that more cost-effective methods should be applied for diagnosis of Fabry rather than systematic genetic screening in this population. Overall, cryptogenic IS in young adults is associated with favorable outcomes.
Impact of Thrombus Length on Outcomes After Intra-Arterial Aspiration Thrombectomy in the THERAPY Trial
Authors: Yoo Albert J. , Khatri Pooja , Mocco J , Zaidat Osama O. , Gupta Rishi , Frei Donald , Lopes Demetrius , Shownkeen Harish , Berkhemer Olvert A. , Meyer Denise , Hak Susana S. , Kuo Sophia S. , Buell Hope , Bose Arani , Sit Siu Po , von Kummer Rüdiger 
Published: June 2017

Background and Purpose—
Increasing thrombus length (TL) impedes recanalization after intravenous (IV) thrombolysis. We sought to determine whether the clinical benefit of aspiration thrombectomy relative to IV r-tPA (recombinant tissue-type plasminogen activator) may be greater at longer TL.

Methods—
THERAPY was a randomized trial of aspiration thrombectomy plus IV r-tPA versus IV r-tPA alone in large-vessel stroke patients with prospective TL measurement ≥8 mm. In this post hoc study, we evaluated the association of TL with trial end points and potential endovascular treatment effect, using univariate, multivariable, and multiplicative interaction analyses.

Results—

TL data were available for all 108 patients (28% internal carotid artery, 62% M1, and 10% M2). Median TL was 14.0 mm (interquartile range, 9.7–19.5 mm). Longer TL was associated with worse outcome (90-day modified Rankin Scale score: odds ratio, 1.24 per 5-mm TL increment; 95% confidence interval, 1.04–1.52;
P
=0.02), even after adjusting for key outcome predictors (adjusted
P
=0.004). Longer TL was also associated with more serious adverse events (adjusted
P
=0.01), more symptomatic hemorrhages (adjusted
P
=0.03), and increased mortality (adjusted
P
=0.01). No significant relationship was observed between TL and angiographic reperfusion (modified thrombolysis in cerebral ischemia 2b-3), but greater TL was associated with longer endovascular procedural times (ρ=0.36;
P
=0.045). Increasing TL was associated with greater aspiration thrombectomy treatment effect (interaction term
P
=0.03). This might be related to a potentially stronger adverse effect of increasing TL on 90-day modified Rankin Scale for patients treated with IV r-tPA (ρ=0.39;
P
=0.01) compared with intra-arterial therapy (ρ=0.20;
P
=0.165).

Conclusions—
Ischemic stroke patients with longer symptomatic thrombi have worse 90-day clinical outcomes but may have a greater relative benefit of aspiration thrombectomy over IV r-tPA alone.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01429350.
Statin Adherence Is Associated With Reduced Recurrent Stroke Risk in Patients With or Without Atrial Fibrillation
Authors: Flint Alexander C. , Conell Carol , Ren Xiushui , Kamel Hooman , Chan Sheila L. , Rao Vivek A. , Johnston S. Claiborne 
Published: June 2017

Background and Purpose—
Outpatient statin use reduces the risk of recurrent ischemic stroke among patients with stroke of atherothrombotic cause. It is not known whether statins have similar effects in ischemic stroke caused by atrial fibrillation (AFib).

Methods—
We studied outpatient statin adherence, measured by percentage of days covered, and the risk of recurrent ischemic stroke in patients with or without AFib in a 21-hospital integrated healthcare delivery system.

Results—
Among 6116 patients with ischemic stroke discharged on a statin over a 5-year period, 1446 (23.6%) had a diagnosis of AFib at discharge. The mean statin adherence rate (percentage of days covered) was 85, and higher levels of percentage of days covered correlated with greater degrees of low-density lipoprotein suppression. In multivariable survival models of recurrent ischemic stroke over 3 years, after controlling for age, sex, race/ethnicity, medical comorbidities, and hospital center, higher statin adherence predicted reduced stroke risk both in patients without AFib (hazard ratio, 0.78; 95% confidence interval, 0.63–0.97) and in patients with AFib (hazard ratio, 0.59; 95% confidence interval, 0.43–0.81). This association was robust to adjustment for the time in the therapeutic range for international normalized ratio among AFib subjects taking warfarin (hazard ratio, 0.61; 95% confidence interval, 0.41–0.89).

Conclusions—
The relationship between statin adherence and reduced recurrent stroke risk is as strong among patients with AFib as it is among patients without AFib, suggesting that AFib status should not be a reason to exclude patients from secondary stroke prevention with a statin.
Task-context-dependent Linear Representation of Multiple Visual Objects in Human Parietal Cortex
Authors: Jeong Su Keun , Xu Yaoda 
Published: June 2017

Abstract
A host of recent studies have reported robust representations of visual object information in the human parietal cortex, similar to those found in ventral visual cortex. In ventral visual cortex, both monkey neurophysiology and human fMRI studies showed that the neural representation of a pair of unrelated objects can be approximated by the averaged neural representation of the constituent objects shown in isolation. In this study, we examined whether such a linear relationship between objects exists for object representations in the human parietal cortex. Using fMRI and multivoxel pattern analysis, we examined object representations in human inferior and superior intraparietal sulcus, two parietal regions previously implicated in visual object selection and encoding, respectively. We also examined responses from the lateral occipital region, a ventral object processing area. We obtained fMRI response patterns to object pairs and their constituent objects shown in isolation while participants viewed these objects and performed a 1-back repetition detection task. By measuring fMRI response pattern correlations, we found that all three brain regions contained representations for both single object and object pairs. In the lateral occipital region, the representation for a pair of objects could be reliably approximated by the average representation of its constituent objects shown in isolation, replicating previous findings in ventral visual cortex. Such a simple linear relationship, however, was not observed in either parietal region examined. Nevertheless, when we equated the amount of task information present by examining responses from two pairs of objects, we found that representations for the average of two object pairs were indistinguishable in both parietal regions from the average of another two object pairs containing the same four component objects but with a different pairing of the objects (i.e., the average of AB and CD vs. that of AD and CB). Thus, when task information was held consistent, the same linear relationship may govern how multiple independent objects are represented in the human parietal cortex as it does in ventral visual cortex. These findings show that object and task representations coexist in the human parietal cortex and characterize one significant difference of how visual information may be represented in ventral visual and parietal regions.
Meloidogyne brasiliensis Charchar & Eisenback, 2002 is a junior synonym of M. ethiopica Whitehead, 1968
Authors: Monteiro Jessica M.S. , Cares Juvenil E. , Correa Valdir R. , Pinheiro Jadir B. , Mattos Vanessa S. , Silva Joelma G.P. , Gomes Ana C.M.M. , Santos Marcilene F.A. , Castagnone-Sereno Philippe , Carneiro Regina M.D.G. 
Published: June 2017

The type population ofMeloidogyne brasiliensisis synonymised underM. ethiopicabased on morphological and morphometric similarities, as well as through biochemical, molecular and phylogenetic studies.Meloidogyne ethiopicawas first described in 1968 in Tanzania using specimens from a single egg mass culture on tomato and re-described in 2004 using an isolate from Brazil.Meloidogyne brasiliensiswas described in 2002 in Brazil based on specimens collected from tomato (type population) and pea. Morphological and morphometric studies of their descriptions showed important similarities in major characters as well as some general variability in others. Characterisation of esterase isozyme phenotypes of three populations ofM. ethiopicafrom Brazil, Chile and Kenya, and twoM. brasiliensispopulations, resulted in only one esterase pattern (E3), a phenotype already known forM. ethiopica. In PCR assays, the species-specific 350 bp SCAR marker developed forM. ethiopicawas amplified from theM. brasiliensispopulations tested. In phylogenetic analyses based either on sequences of the ITS1-5.8S-ITS2 and D2-D3 (28S) rRNA regions or on RAPD and AFLP data, the populations of both species clustered together with a strong bootstrap support. Altogether, these results provide congruent evidence thatM. brasiliensisis not a valid species but rather a junior synonym ofM. ethiopica.
Can MRI detect pulmonary hypertension in a population pre-selected by echocardiography?
Authors: Venner Clement , Odille Freddy , Voilliot Damien , Chaouat Ari , Chabot François , Felblinger Jacques , Bonnemains Laurent 
Published: June 2017

Background The place of magnetic resonance imaging (MRI) in the assessment of pulmonary hypertension (PH) remains controversial. Several studies proposed to use MRI to assess pulmonary pressure but the level of proof is low. Purpose To evaluate the diagnostic power of cardiac MRI within a non-selected population of patients suspected of PH after an echocardiography. Material and Methods Fifty-six consecutive patients, suspected of PH after an echocardiography, were assessed with right heart catheterization and cardiac MRI (including a high temporal resolution pulmonary flow curve). We extracted from the MRI data the main parameters proposed by all precedent studies available in the literature. We looked for multivariate linear relations between those parameters and the mean pulmonary arterial pressure (mPAP), and eventually assessed with a logit regression the ability of those parameters to diagnose PH in our population. Results The multivariate model retained only two parameters: the right ventricle ejection fraction and the pulmonary trunk minimum area. The prediction of mPAP (r2 = 0.5) yielded limits of agreement of 15 mmHg. However, the prediction of PH within the population was feasible and the method yielded a specificity of 80% for a sensitivity of 100%. Conclusion The performance of MRI to assess mPAP is too low to be used as a replacement for right heart catheterization but MRI could be used as second line examination after echocardiography to avoid right heart catheterization for normal patients.