bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of multiparity on left ventricular diastolic dysfunction in women: cross-sectional study of the KoRean wOmen’S chest pain rEgistry (KoROSE)
Authors: Kim Hyun-Jin , Kim Myung-A , Kim Hack-Lyoung , Shim Wan Joo , Park Seong Mi , Kim Mina , Yoon Hyun Ju , Shin Mi Seung , Hong Kyung-Soon , Shin Gil Ja , Kim Yong-Hyun , Na Jin Oh , Jeong Jin-Ok 
Published: December 2018

ObjectivesTo investigate the association between left ventricular (LV) diastolic dysfunction and multiparity in patients with suspected coronary artery disease (CAD).DesignCross-sectional study.SettingLinked secondary and tertiary care records from 29 cardiac centres which participated in KoRean wOmen’S chest pain rEgistry.Participants960 women with suspected CAD who underwent invasive coronary angiography from February 2011 to May 2017. The patients were classified by parity number, as follows: low-parity, 0 to <3; multiparity, ≥3 pregnancies.Main outcome measurePrevalence of LV diastolic dysfunction.ResultsThere were 302 and 658 low-parity and multiparity patients, respectively. The prevalence of LV diastolic dysfunction was significantly higher in the multiparity than in the low-parity group. The multiparity group had significantly lower E and e´ septal velocities and E/A ratio, and had a significantly higher E/e´ ratio and right ventricular systolic pressure, which are parameters of LV diastolic dysfunction, than the low-parity group. The prevalence of CAD was significantly higher in the multiparity than in the low-parity group. Receiver operating characteristic curve analysis identified a parity of 2.5 as the cut-off for predicting LV diastolic dysfunction (area under the curve, 0.66; sensitivity, 74.1%; specificity, 52.0%; 95% CI 0.607 to 0.706; p<0.001). After adjustment for confounding factors, multivariate regression analysis showed that multiparity had a 1.80-fold increased risk for LV diastolic dysfunction (OR 1.80, 95% CI 1.053 to 3.081, p=0.032).ConclusionsThe prevalence of LV diastolic dysfunction was higher in multiparity than in low-parity women with suspected CAD. Multiparity was an independent risk factor for LV diastolic dysfunction. LV diastolic dysfunction should be evaluated in multiparous women for the risk of subsequent cardiovascular disease and facilitate the initiation of appropriate treatment.
Collaborative sensorimotor intelligence: the scrum as a model
Authors: Wang Danping , Mahe Gaël , Fang Junying , Piscione Julien , Couvet Serge , Retiere Didier , Laporte Sébastien , Vidal Pierre-Paul 
Published: December 2018

AimUsing M-Rex, a rugby scrum simulator, we developed tools to describe scrummaging forces and to prevent accident.MethodsWe tested three groups of frontliners at national level. The simulator was passive or responded to the player(s) to simulate the reaction of opposite players. Sensors in the beam measured the force exerted by each of the players. Their movements were recorded with a Codamotion system.ResultsThe force signals exhibited two phases: a transient phase, similar to a damped sinusoid with a dominant frequency around 5 Hz when the players scrummaged alone and with a wider range when playing together; then, a sustained phase could be decomposed in two components: a DC component remained stable whether frontliners played alone or together. In contrast, its variability decreased when the frontliners played together compared with when they played alone. As for the oscillations, the frontliners exhibited a large variability in their ability to synchronise their efforts during the sustained phase. The synchronisation between the hooker and the props was quite efficient, while it was always missing between two props. Finally, we were able to study postural readjustments and their synchronisation among players during the sustained phase.ConclusionThis study shows that by using adequate methods, it is possible to assess the frontline collective intelligence. These findings may pave the way for innovative methods of training to improve players’ collective behaviour.
Bone health in elite Norwegian endurance cyclists and runners: a cross-sectional study
Authors: Klomsten Andersen Oddbjørn , Clarsen Benjamin , Garthe Ina , Mørland Morten , Stensrud Trine 
Published: December 2018

BackgroundAthletes who compete in non-weight-bearing activities such as swimming and cycling are at risk of developing low bone mineral density (BMD). Athletes in long-distance running are at risk of low BMD.Objective (1) To evaluate the bone health in Norwegian male and female national elite road cyclists and middle-distance and long-distance runners, and to identify cases of low BMD. (2) To identify possible risk factors associated with low BMD.MethodsTwenty-one runners (11 females and 10 males) and 19 road cyclists (7 females and 12 males) were enrolled in this cross-sectional study. Dual-energy X-ray absorptiometry measurement of BMD in total body, femoral neck and lumbar spine was measured. Participants completed a questionnaire regarding training, injuries, calcium intake and health variables.ResultsThe cyclists had lower BMD for all measured sites compared with the runners (p≤0.05). Ten of 19 cyclists were classified as having low BMD according to American College of Sports Medicine criteria (Z-score ≤−1), despite reporting to train heavy resistance training on the lower extremities. Low BMD was site specific having occurred in the lumbar spine and the femoral neck and was not confined to females. Type of sport was the only factor significantly associated with low BMD.ConclusionNational elite Norwegian road cyclists had lower BMD compared with runners, and a large proportion was classified as having low BMD, despite having performed heavy resistance training. Interventions to increase BMD in this population should be considered.
Longitudinal evaluation of SMN levels as biomarker for spinal muscular atrophy: results of a phase IIb double-blind study of salbutamol
Authors: Tiziano Francesco Danilo , Lomastro Rosa , Abiusi Emanuela , Pasanisi Maria Barbara , Di Pietro Lorena , Fiori Stefania , Baranello Giovanni , Angelini Corrado , Sorarù Gianni , Gaiani Alessandra , Mongini Tiziana , Vercelli Liliana , Mercuri Eugenio , Vasco Gessica , Pane Marika , Vita Giuseppe , Vita Gianluca , Messina Sonia , Petillo Roberta , Passamano Luigia , Politano Luisa , Campanella Angela , Mantegazza Renato , Morandi Lucia 
Published: December 2018

BackgroundSpinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, due to the loss of function of the survival motor neuron (SMN1) gene. The first treatment for the condition, recently approved, is based on the reduction of exon 7 skipping in mRNAs produced by a highly homologous gene (SMN2). The primary objective of the present study was to evaluate the applicability of the dosage of SMN gene produts in blood, as biomarker for SMA, and the safety of oral salbutamol, a beta2-adrenergic agonist modulating SMN2 levels.MethodsWe have performed a 1-year multicentre, double-blind, placebo-controlled study with salbutamol in 45 adult patients with SMA. Patients assumed 4 mg of salbutamol or placebo/three times a day. Molecular tests were SMN2 copy number, SMN transcript and protein levels. We have also explored the clinical effect, by the outcome measures available at the time of study design.ResultsThirty-six patients completed the study. Salbutamol was safe and well tolerated. We observed a significant and progressive increase in SMN2 full-length levels in peripheral blood of the salbutamol-treated patients (p<0.00001). The exploratory analysis of motor function showed an improvement in most patients.ConclusionsOur data demonstrate safety and molecular efficacy of salbutamol. We provide the first longitudinal evaluation of SMN levels (both transcripts and protein) in placebo and in response to a compound modulating the gene expression: SMN transcript dosage in peripheral blood is reliable and may be used as pharmacodynamic marker in clinical trials with systemic compounds modifying SMN2levels.Trial registration numberEudraCT no. 2007-001088-32.
Interpersonal violence in peacetime Malawi
Authors: Maine Rebecca G , Williams Brittney , Kincaid Jennifer A , Mulima Gift , Varela Carlos , Gallaher Jared R , Reid Trista D , Charles Anthony G 
Published: December 2018

BackgroundThe contribution of interpersonal violence (IPV) to trauma burden varies greatly by region. The high rates of IPV in sub-Saharan Africa are thought to relate in part to the high rates of collective violence. Malawi, a country with no history of internal collective violence, provides an excellent setting to evaluate whether collective violence drives the high rates of IPV in this region.MethodsThis is a retrospective review of a prospective trauma registry from 2009 through 2016 at Kamuzu Central Hospital in Lilongwe, Malawi. Adult (>16 years) victims of IPV were compared with non-intentional trauma victims. Log binomial regression determined factors associated with increased risk of mortality for victims of IPV.ResultsOf 72 488 trauma patients, 25 008 (34.5%) suffered IPV. Victims of IPV were more often male (80.2% vs. 74.8%; p<0.001), younger (median age: 28 years (IQR: 23–34) vs. 30 years (IQR: 24–39); p<0.001), and were more often admitted at night (47.4% vs. 31.9%; p<0.001). Of the IPV victims, 16.5% admitted alcohol use, compared with only 4.4% in other trauma victims (p<0.001). In regression modeling, compared with extremity injuries, head injuries (3.14, 2.24–4.39; p<0.001) and torso injuries (4.32, 2.98–6.27; p<0.001) had increased risk of mortality. Compared with other or unknown mechanisms, penetrating injuries also had increased risk of mortality (1.46, 95% CI 1.17 to 1.81, p=0.001). Alcohol use was associated with a lower risk of mortality (0.54, 95% CI 0.39 to 0.75; p<0.001).DiscussionEven in a sub-Saharan country that never experienced internal collective violence, IPV injury rates are high. Public health efforts to measure and address alcohol use, and studies to determine the role of “mob justice,” poverty, and intimate partner violence in IPV, in Malawi are needed.Level of evidenceLevel III.
TAp73 Modifies Metabolism and Positively Regulates Growth of Cancer Stem–Like Cells in a Redox-Sensitive Manner
Authors: Sharif Tanveer , Dai Cathleen , Martell Emma , Ghassemi-Rad Mohammad Saleh , Hanes Mark Robert , Murphy Patrick J. , Kennedy Barry E. , Venugopal Chitra , Subapanditha Minomi , Giacomantonio Carman A. , Marcato Paola , Singh Sheila K. , Gujar Shashi 
Published: December 2018

Abstract

Purpose:
Stem-like cancer cells, with characteristic self-renewal abilities, remain highly refractory to various clinical interventions. As such, stemness-inhibiting entities, such as tumor suppressor p53, are therapeutically pursued for their anticancer activities. Interestingly, similar implications for tumor suppressor TAp73 in regulating stemness features within stem-like cancer cells remain unknown.
Experimental Design: This study utilizes various in vitro molecular biology techniques, including immunoblotting, qRT-PCR, and mass spectrometry–based proteomics, and metabolomics approaches to study the role of TAp73 in human and murine embryonal carcinoma stem-like cells (ECSLC) as well as human breast cancer stem-like cells (BCSLC). These findings were confirmed using patient-derived brain tumor–initiating cells (BTIC) and in vivo xenograft models.

Results:
TAp73 inhibition decreases the expression of stem cell transcription factors Oct4, Nanog, and Sox-2, as well as tumorsphere formation capacity in ECSLCs. In vivo, TAp73-deficient ECSLCs and BCSLCs demonstrate decreased tumorigenic potential when xenografted in mice. Mechanistically, TAp73 modifies the proline regulatory axis through regulation of enzymes GLS, OAT, and PYCR1 involved in the interconversion of proline–glutamine–ornithine. Further, TAp73 deficiency exacerbates glutamine dependency, enhances accumulation of reactive oxygen species through reduced superoxide dismutase 1 (SOD1) expression, and promotes differentiation by arresting cell cycle and elevating autophagy. Most importantly, the knockdown of TAp73 in CD133HI BTICs, separated from three different glioblastoma patients, strongly decreases the expression of prosurvival factors Sox-2, BMI-1, and SOD1, and profoundly decreases their self-renewal capacity as evidenced through their reduced tumorsphere formation ability.

Conclusions:
Collectively, we reveal a clinically relevant aspect of cancer cell growth and stemness regulation through TAp73-mediated redox-sensitive metabolic reprogramming.
Of Microbes and Microsatellites
Authors: Atreya Chloe E. , Venook Alan P. 
Published: December 2018

Abstract
A ubiquitous oral cavity microbe, Fusobacterium nucleatum, is increasingly being implicated in colorectal cancer pathogenesis. An article in this issue elucidates the differential association of F. nucleatum with tumor-infiltrating lymphocytes depending on microsatellite instability status. Cancer Immunol Res; 6(11); 1290–1. ©2018 AACR.
See article by Hamada et al., p. 1327.
Evaluation of Macitentan in Patients With Eisenmenger Syndrome
Authors: Gatzoulis Michael A. , Landzberg Michael , Beghetti Maurice , Berger Rolf M. , Efficace Michela , Gesang Sophie , He Jian’guo , Papadakis Kelly , Pulido Tomás , Galiè Nazzareno ,   On behalf of the MAESTRO Study Investigators
Published: December 2018

Background:
Eisenmenger syndrome describes congenital heart disease-associated severe pulmonary hypertension accompanied by right-to-left shunting. The multicenter, double-blind, randomized, placebo-controlled, 16-week, phase III MAESTRO study (Macitentan in Eisenmenger Syndrome to Restore Exercise Capacity) evaluated the efficacy and safety of the endothelin receptor antagonist macitentan in patients with Eisenmenger syndrome.

Methods:
Patients with Eisenmenger syndrome aged ≥12 years and in World Health Organization functional class II–III were randomized 1:1 to placebo or macitentan 10 mg once daily for 16 weeks. Patients with complex cardiac defects, Down syndrome and background PAH therapy were eligible. The primary end point was change from baseline to week 16 in 6-minute walk distance. Secondary end points included change from baseline to week 16 in World Health Organization functional class. Exploratory end points included NT-proBNP (N-terminal pro-B-type natriuretic peptide) at end of treatment expressed as a percentage of baseline. In a hemodynamic substudy, exploratory end points included pulmonary vascular resistance index (PVRi) at week 16 as a percentage of baseline.

Results:

Two hundred twenty six patients (macitentan n=114; placebo n=112) were randomized. At baseline, 60% of patients were in World Health Organization functional class II and 27% were receiving phosphodiesterase type-5 inhibitors. At week 16, the mean change from baseline in 6-minute walk distance was 18.3 m and 19.7 m in the macitentan and placebo groups (least-squares mean difference, -4.7 m; 95% confidence limit (CL), -22.8, 13.5;
P
=0.612). World Health Organization functional class improved from baseline to week 16 in 8.8% and 14.3% of patients in the macitentan and placebo groups (odds ratio, 0.53; 95% CL, 0.23, 1.24). NT-proBNP levels decreased with macitentan versus placebo (ratio of geometric means, 0.80; 95% CL, 0.68, 0.94). In the hemodynamic substudy (n=39 patients), macitentan decreased PVRi compared with placebo (ratio of geometric means, 0.87; 95% CL, 0.73, 1.03). The most common adverse events with macitentan versus placebo were headache (11.4 versus 4.5%) and upper respiratory tract infection (9.6 versus 6.3%); a hemoglobin decrease from baseline of ≥2 g/dL occurred in 36.0% versus 8.9% of patients. Five patients (3 macitentan; 2 placebo) prematurely discontinued treatment and 1 patient died (macitentan group).

Conclusions:
Macitentan did not show superiority over placebo on the primary end point of change from baseline to week 16 in exercise capacity in patients with Eisenmenger syndrome.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01743001.
Glycolytic Switch Is Required for Transdifferentiation to Endothelial Lineage
Authors: Lai Li , Reineke Erin , Hamilton Dale J. , Cooke John P. 
Published: December 2018

Background:
We have previously shown that activation of cell-autonomous innate immune signaling facilitates the transdifferentiation of fibroblasts into induced endothelial cells, and is required to generate induced endothelial cells with high fidelity for endothelial lineage. Recent studies indicate that a glycolytic switch plays a role in induced pluripotent stem cell generation from somatic cells.

Methods:
Seahorse and metabolomics flux assays were used to measure the metabolic changes during transdifferentiation in vitro, and Matrigel plug assay was used to assess the effects of glycolysis modulators on transdifferentiation in vivo.

Results:
The metabolic switch begins rapidly after activation of innate immunity, before the expression of markers of endothelial lineage. Inhibiting glycolysis impaired, whereas facilitating glycolysis enhanced, the generation of induced endothelial cells. The toll-like receptor 3 agonist poly I:C increased expression of the mitochondrial citrate transporter Slc25A1, and the nuclear ATP-citrate lyase, in association with intracellular accumulation of citrate, the precursor for acetyl coenzyme A. These metabolic changes were coordinated with increased histone acetylation during transdifferentiation.

Conclusion:
Innate immune signaling promotes a glycolytic switch that is required for transdifferentiation, both processes being attenuated by ATP-citrate lyase knockdown. These data shed light on a novel link between metabolism and epigenetic modulation in transdifferentiation.
Randomized All-Comers Evaluation of a Permanent Polymer Zotarolimus-Eluting Stent Versus a Polymer-Free Amphilimus-Eluting Stent
Authors: Rozemeijer Rik , Stein Mera , Voskuil Michiel , van den Bor Rutger , Frambach Peter , Pereira Bruno , Koudstaal Stefan , Leenders Geert E. , Timmers Leo , Rittersma Saskia Z. , Kraaijeveld Adriaan O. , Agostoni Pierfrancesco , Roes Kit C. , Doevendans Pieter A. , Stella Pieter R. ,   For the ReCre8 Study Investigators
Published: December 2018

Background:
Polymer-free amphilimus-eluting stents (PF-AES) represent a novel elution technology in the current era of drug-eluting stents. The clinical safety and efficacy of PF-AES as compared with latest-generation permanent-polymer zotarolimus-eluting stents (PP-ZES) have not yet been investigated in a large randomized trial.

Methods:
In this physician-initiated, prospective, multicenter, randomized, noninferiority trial, an all-comers population requiring percutaneous coronary intervention was enrolled across 3 European sites. Randomization (1:1 ratio) to PP-ZES or PF-AES was performed after stratification for troponin status and diabetes mellitus. In both treatment arms, troponin-positive patients were planned for 12-month dual antiplatelet therapy, whereas troponin-negative patients were planned for 1-month dual antiplatelet therapy. Outcome assessors were blinded to the allocated treatment. The device-oriented primary end point of target-lesion failure was defined as cardiac death, target-vessel myocardial infarction, or target-lesion revascularization at 12-months as analyzed by modified intention-to-treat (80% power, and a 3.5% noninferiority margin).

Results:

In total, 1502 patients were randomized and 1491 treated with the assigned stent and available for follow-up. The primary end point occurred in 42 (5.6%) of the 744 patients receiving PP-ZES versus 46 (6.2%) of the 747 patients receiving PF-AES. PF-AES were clinically noninferior to PP-ZES (risk difference, 0.5%; upper limit 1-sided 95% confidence interval, 2.6%;
P
noninferiority
=0.0086). Cardiac death occurred in 10 (1.3%) versus 10 patients (1.3%;
P
value for difference, 1.00), target-vessel myocardial infarction occurred in 18 (2.4%) versus 17 patients (2.3%;
P
value for difference, 0.87), and target-lesion revascularization occurred in 22 (2.9%) versus 20 patients (2.6%;
P
value for difference, 0.75) for PF-AES as compared with PP-ZES. Overall, definite or probable stent thrombosis occurred in 1.0%.

Conclusions:
PF-AES were noninferior to PP-ZES regarding target-lesion failure at 12 months. Findings regarding the secondary end point and prespecified subgroups were generally consistent with that of the primary end point.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02328898.
Sex Differences in Severity of Stroke in the INSTRUCT Study: a Meta‐Analysis of Individual Participant Data
Authors: Phan Hoang T. , Reeves Mathew J. , Blizzard Christopher L. , Thrift Amanda G. , Cadilhac Dominique A. , Sturm Jonathan , Otahal Petr , Rothwell Peter , Bejot Yannick , Cabral Norberto L. , Appelros Peter , Kõrv Janika , Vibo Riina , Minelli Cesar , Gall Seana L. 
Published: December 2018

Background
Women have worse outcomes after stroke than men, and this may be partly explained by stroke severity. We examined factors contributing to sex differences in severity of acute stroke assessed by the National Institutes of Health Stroke Scale.

Methods and Results

We pooled individual participant data with National Institutes of Health Stroke Scale assessment (N=6343) from 8 population‐based stroke incidence studies (1996–2014), forming part of INSTRUCT (International Stroke Outcomes Study). Information on sociodemographics, stroke‐related clinical factors, comorbidities, and pre‐stroke function were obtained. Within each study, relative risk regression using log‐binominal modeling was used to estimate the female:male relative risk (
RR
) of more severe stroke (National Institutes of Health Stroke Scale>7) stratified by stroke type (ischemic stroke and intracerebral hemorrhage). Study‐specific unadjusted and adjusted
RR
s, controlling for confounding variables, were pooled using random‐effects meta‐analysis. National Institutes of Health Stroke Scale data were recorded in 5326 (96%) of 5570 cases with ischemic stroke and 773 (90%) of 855 participants with intracerebral hemorrhage. The pooled unadjusted female:male
RR
for severe ischemic stroke was 1.35 (95%
CI
1.24–1.46). The sex difference in severity was attenuated after adjustment for age, pre‐stroke dependency, and atrial fibrillation but remained statistically significant (pooled
RR
adjusted
1.20, 95%
CI
1.10–1.30). There was no sex difference in severity for intracerebral hemorrhage (
RR
crude
1.08, 95%
CI
0.97–1.21;
RR
adjusted
1.08, 95%
CI
0.96–1.20).

Conclusions
Although women presented with more severe ischemic stroke than men, much although not all of the difference was explained by pre‐stroke factors. Sex differences could potentially be ameliorated by strategies to improve pre‐stroke health in the elderly, the majority of whom are women. Further research on the potential biological origin of sex differences in stroke severity may also be warranted.