bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced biventricular contractility during exercise in adults with small, unrepaired ventricular septal defects: an echocardiographic study
Authors: Maagaard Marie , Heiberg Johan , Redington Andrew N , Hjortdal Vibeke E 
Published: October 2019

Abstract

OBJECTIVES
Small ventricular septal defects are often considered to be without long-term haemodynamic consequences and so the majority remains unrepaired. However, we recently showed reduced functional capacity and altered right ventricular morphology in adults with small, unrepaired ventricular septal defects. The underlying mechanisms behind these findings remain unclear, and so, biventricular contractility during exercise was evaluated.

METHODS
Adults with small, unrepaired ventricular septal defects and healthy controls were examined with echocardiography during supine bicycle exercise with increasing workload. Tissue velocity Doppler was used for evaluating isovolumetric acceleration and systolic velocities during exercise.

RESULTS
In total, 34 patients with ventricular septal defects, a median shunt- ratio of 1.2 (26 ± 6 years), and 28 healthy peers (27 ± 5 years) were included. Right ventricular isovolumetric acceleration was lower in patients as compared with controls at rest (97 ± 40 vs 158 ± 43 cm/s2, P = 0.01) and at peak heart rate (222 ± 115 vs 410 ± 120 cm/s2, P < 0.01). Peak systolic velocities were similar at rest, but differed with exercise (13 ± 3 vs 16 ± 3 cm/s, P = 0.02). Left ventricular isovolumetric acceleration was lower in patients as compared with controls throughout the test (P < 0.01). Septal isovolumetric acceleration was similar at rest, but reduced during increasing exercise as compared with controls (220 ± 108 vs 303 ± 119 cm/s2, P = 0.03). Left ventricular isovolumetric acceleration was negatively correlated with the shunt- ratio, and right ventricular and septal peak systolic velocities were positively correlated with lower functional capacity.

CONCLUSIONS
Altered biventricular contractility is present during exercise in adults with small, unrepaired ventricular septal defects. These results add to the growing number of studies showing that long-term outcome in unrepaired ventricular septal defects may not be benign.
‘Much land and water have I and my sweet companion run over…’: newly discovered letters from Muzio Clementi to Gottfried Christoph Härtel
Authors: Sala Luca Lévi 
Published: October 2019

Abstract
Three newly discovered letters from Muzio Clementi to Gottfried Christoph Härtel make a valuable addition to the known corpus of his correspondence with the Leipzig publisher. Held at the Staatsbibliothek zu Berlin (Mus. Slg. Härtel 28–30), these three letters originate in the early years of the second lengthy international trip that Clementi undertook, encompassing the end of 1804 and the first months of 1805, a period when he moved through Germany and settled for a while in Berlin before leaving for his honeymoon in Italy, prior to returning to Berlin. Since the bulk of the extant correspondence between Clementi and Härtel dates from between 1815 and 1822, these letters offer new knowledge about aspects of Clementi’s friendship and business relationship with the German publisher, and about some details of Clementi’s own private life.
Have Changes in Gender Segregation and Occupational Closure Contributed to Increasing Wage Inequality in Germany, 1992–2012?
Authors: Witte Nils 
Published: October 2019

AbstractWage inequality continued to increase through the 1990s and 2000s in post-industrial economies. This article contributes to the debate on occupations and inequality by assessing the role of occupational segregation and occupational closure for understanding the increase in inequality. Using employee data for West Germany in 1992 and 2012 and based on decompositions of unconditional quantile regressions the article investigates the contribution of changes in both occupational characteristics to changes in the wage structure. Our findings suggest that both the employment increase in more closed occupations and increased rewards in these occupations have contributed to wage increases across the distribution, especially in the lower half of the wage distribution. Our results further suggest disproportional wage increases in female-dominated occupations at the bottom of the distribution and disproportional wage decreases in male-dominated occupations at the top. If these occupational characteristics had remained at 1992 levels, then 90/10 wage inequality would have been 25 per cent higher in 2012. Thus, changes in occupational characteristics have contributed to wage compression in the observation period.
The association between patterns of atrial fibrillation, anticoagulation, and cardiovascular events
Authors: Atar Dan , Berge Eivind , Le Heuzey Jean-Yves , Virdone Saverio , Camm A John , Steffel Jan , Gibbs Harry , Goldhaber Samuel Z , Goto Shinya , Kayani Gloria , Misselwitz Frank , Stepinska Janina , Turpie Alexander G G , Bassand Jean-Pierre , Kakkar Ajay K ,   for the GARFIELD-AF Investigators
Published: October 2019

Abstract

Aims
Guidelines do not recommend to take pattern of atrial fibrillation (AF) into account for the indication of anticoagulation (AC). We assessed AF pattern and the risk of cardiovascular events during 2-years of follow-up.

Methods and results
We categorized AF as paroxysmal, persistent, or permanent in 29 181 patients enrolled (2010–15) in the Global Anticoagulant Registry In the FIELD of AF (GARFIELD-AF). We used multivariable Cox regression to assess the risks of stroke/systemic embolism (SE) and death across patterns of AF, and whether this changed with AC on outcomes. Atrial fibrillation pattern was paroxysmal in 14 344 (49.2%), persistent in 8064 (27.6%), and permanent 6773 (23.2%) patients. Median CHA2DS2-VASc, GARFIELD-AF, and HAS-BLED scores assessing the risk of stroke/SE and/or bleeding were similar across AF patterns, but the risk of death, as assessed by the GARFIELD-AF risk calculator, was higher in non-paroxysmal than in paroxysmal AF patterns. During 2-year follow-up, after adjustment, non-paroxysmal AF patterns were associated with significantly higher rates of all-cause death, stroke/SE, and new/worsening congestive heart failure (CHF) than paroxysmal AF in non-anticoagulated patients only. In anticoagulated patients, a significantly higher risk of death but not of stroke/SE and new/worsening CHF persisted in non-paroxysmal compared with paroxysmal AF patterns.

Conclusion
In non-anticoagulated patients, non-paroxysmal AF patterns were associated with higher risks of stroke/SE, new/worsening HF and death than paroxysmal AF. In anticoagulated patients, the risk of stroke/SE and new/worsening HF was similar across all AF patterns. Thus AF pattern is no longer prognostic for stroke/SE when patients are treated with anticoagulants.

Clinical Trial Registration
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.
Attenuation in the mantle wedge beneath super-volcanoes of the Taupo Volcanic Zone, New Zealand
Authors: Eberhart-Phillips Donna , Bannister Stephen , Reyners Martin 
Published: October 2019

SUMMARYThe Taupo Volcanic Zone has a 120-km-long section of rhyolitic volcanism, within which is a 60-km-long area of supervolcanoes. The underlying subducted slab has along-strike heterogeneity due to the Hikurangi Plateau's prior subduction history. We studied 3-D Qs (1/attenuation) using t* spectral decay from local earthquakes to 370-km depth. Selection emphasized those events with data quality to sample the low Qs mantle wedge, and Qs inversion used varied linking of nodes to obtain resolution in regions of sparse stations, and 3-D initial model. The imaged mantle wedge has a 250-km-long 150-km-wide zone of low Qs (<300) at 65–85 km depth which includes two areas of very low Qs (<120). The most pronounced low Qs feature underlies the Mangakino and Whakamaru super-eruptive calderas, with inferred melt ascending under the central rift structure. The slab is characterized by high Qs (1200–2000), with a relatively small area of reduction in Qs (<800) underlying Taupo at 65-km depth, and adjacent to the mantle wedge low Qs. This suggests abundant dehydration fluids coming off the slab at specific locations and migrating near-vertically upward to the volcanic zone. The seismicity in the subducted slab has a patch of dense seismicity underlying the rhyolitic volcanic zone, consistent with locally abundant fractures and fluid flux. The relationship between the along-arc and downdip slab heterogeneity and dehydration implies that patterns of volcanism may be strongly influenced by large initial outer rise hydration which occurred while the edge of the Hikurangi Plateau hindered subduction. A second very low Qs feature is 50-km west above the 140-km-depth slab. The distinction suggests involvement of a second dehydration peak at that depth, consistent with some numerical models.
Preferred conformations of lipooligosaccharides and oligosaccharides of Moraxella catarrhalis
Authors: Gao Ya , Lee Jumin , Widmalm Göran , Im Wonpil 
Published: October 2019

Abstract
Moraxella catarrhalis (M. catarrhalis) is a pathogenic gram-negative bacterium that causes otitis media and sinusitis in children. Three major serotypes A, B and C are identified to account for approximately 95% of the clinical isolates. Understanding the conformational properties of different serotypes of M. catarrhalis provides insights into antigenic determinants. In this work, all-atom molecular dynamics simulations were conducted for M. catarrhalis lipooligosaccharide (LOS) bilayer systems and oligosaccharides (OS) in water solution to investigate the conformational similarities and differences of three serotypes. For up to 10 neutral monosaccharides in the core part, the conformational ensembles described by the pair-wise root mean square deviation distributions are similar among the three serotypes of either the LOS or OS. At the central β-($1\to4$)-linkage, anti-$\psi$ conformation in conjunction with the gauche-gauche (g−) conformation of the central trisubstituted glucosyl residue is observed as the dominant conformation to sustain the structural characteristics of M. catarrhalis three types, which is further supported by calculated transglycosidic ${}^3{J}_{C,H}\Big({\psi}_H\Big)$ of serotype A in comparison to experimental data. Interestingly, the conformational variability of three serotypes is more restricted for the OS in water solution than that in the LOS bilayer systems. The LOS–LOS interactions in the bilayer systems are responsible for the increased conformational diversity despite of tight packing. Solvent-accessible surface area analysis suggests that a trisaccharide attached to the β-($1\to 6$)-linked sugar in all three serotypes of LOS could be the common epitope and have the possibility to interact with antibodies.
Online STI information seeking behaviour and condom use intentions among young Facebook users in Malaysia
Authors: Mohamad Shakir Sharina Mahavera , Wong Li Ping , Lim Abdullah Khatijah , Adam Phillipe 
Published: October 2019

Abstract
The Internet has opened pathways for youth to find sexual health information which was not easily available to them in the past. Studies have shown that seeking sexual health information online may potentially influence an individuals’ decision-making to change their sexual health behaviours. However, there is a gap in research on the associations of seeking online sexually transmitted infection (STI) information with STI prevention among young people, particularly in Malaysia. This study investigated the associations of seeking STI information online with the intentions of condom use among young adult online users in Malaysia. A cross-sectional online survey was conducted among Malaysian youth aged 18–25 years old who were recruited through Facebook. In total, 1530 respondents completed the survey, identifying 874 respondents who had sought STI information online. The majority of respondents had intentions to use condoms as protection against STI. Respondents who sought online STI information were significantly more likely to have the intention to use condoms compared to respondents who did not seek online STI information (OR = 1.33, 95% CI = 1.01–1.76, p = 0.040). Online STI information has the potential to increase access to STI information among young online users in Malaysia amid the stigma surrounding sex-related issues. Providing accurate STI information online from reliable sources may equip young people who have Internet access with awareness of sexual health protective behaviours such as condom use. It is recommended to facilitate Internet access to reach sectors of the population that currently do not have access, as the Internet is useful in STI prevention.
Point of Care Exome Sequencing Reveals Allelic and Phenotypic Heterogeneity Underlying Mendelian disease in Qatar
Authors: Fakhro Khalid A , Robay Amal , Rodrigues-Flores Juan L , Mezey Jason G , Al-Shakaki Alya A , Chidiac Omar , Stadler Dora , Malek Joel A , Imam Abu Bakr , Sheikh Arwa , Azzam Asmaa , Janahi Ibrahim , Khanjar Izzat , Osman Kamal , Ziki Maen Abu , Mahmah Mohamed Adnan , Selim Mohamed , Numeiri Nuha , Ali Rehab , Lakhani Shenela , Butt Fizza , Omran Tawfeg Ben , Crystal Ronald G 
Published: October 2019

Abstract
The effectiveness of next generation sequencing at solving genetic disease has motivated the rapid adoption of this technology into clinical practice around the world. In this study, we use whole exome sequencing (WES) to assess 48 patients with Mendelian disease from 30 serial families as part of the “Qatar Mendelian Disease pilot program” – a coordinated multi-center effort to build capacity and clinical expertise in genetic medicine in Qatar. By enrolling whole families (parents plus available siblings), we demonstrate significantly improved discriminatory power for candidate variant identification over trios for both de novo and recessive inheritance patterns. For the same index cases, we further demonstrate that even in the absence of families, variant prioritization is improved up to 8-fold when a modest set of population-matched controls is used vs large public databases, stressing the poor representation of Middle Eastern alleles in presently available databases. Our in-house pipeline identified candidate disease variants in 27 of 30 families (90%), 23 of which (85%) harbor novel pathogenic variants in known disease genes, pointing to significant allelic heterogeneity and founder mutations underlying Mendelian disease in the Middle East. For 6 of these families, the clinical presentation was only partially explained by the candidate gene, suggesting phenotypic expansion of known syndromes. Our pilot study demonstrates the utility of WES for Middle Eastern populations, the dramatic improvement in variant prioritization conferred by enrolling population-matched controls and/or enrolling additional unaffected siblings at the point-of-care, and 25 novel disease-causing alleles, relevant to newborn and premarital screening panels in regional populations.
Imprinting effects of UBE3A loss on synaptic gene networks and Wnt signaling pathways
Authors: Lopez S Jesse , Laufer Benjamin I , Beitnere Ulrika , Berg Elizabeth L , Silverman Jill L , O’Geen Henriette , Segal David J , LaSalle Janine M 
Published: October 2019

Abstract
Ubiquitin E3 ligase 3A (UBE3A) encodes an E3 ubiquitin ligase whose loss from the maternal allele causes the neurodevelopmental disorder Angelman syndrome (AS). Previous studies of UBE3A function have not examined full Ube3a deletion in mouse, the complexity of imprinted gene networks in brain nor the molecular basis of systems-level cognitive dysfunctions in AS. We therefore utilized a systems biology approach to elucidate how UBE3A loss impacts the early postnatal brain in a novel CRISPR/Cas9-engineered rat Angelman model of a complete Ube3a deletion. Strand-specific transcriptome analysis of offspring from maternally or paternally inherited Ube3a deletions revealed the expected parental expression patterns of Ube3a sense and antisense transcripts by postnatal day 2 (P2) in hypothalamus and day 9 (P9) in cortex, compared to wild-type littermates. The dependency of genome-wide effects on parent-of-origin, Ube3a genotype and time (P2 and P9) was investigated through transcriptome (RNA sequencing of cortex and hypothalamus) and methylome (whole-genome bisulfite sequencing of hypothalamus). Weighted gene co-expression and co-methylation network analyses identified co-regulated networks in maternally inherited Ube3a deletion offspring enriched in postnatal developmental processes including Wnt signaling, synaptic regulation, neuronal and glial functions, epigenetic regulation, ubiquitin, circadian entrainment and splicing. Furthermore, we showed that loss of the paternal Ube3a antisense transcript resulted in both unique and overlapping dysregulated gene pathways with maternal loss, predominantly at the level of differential methylation. Together, these results provide a holistic examination of the molecular impacts of UBE3A loss in brain, supporting the existence of interactive epigenetic networks between maternal and paternal transcripts at the Ube3a locus.
Smcr8 deficiency disrupts axonal transport-dependent lysosomal function and promotes axonal swellings and gain of toxicity in C9ALS/FTD mouse models
Authors: Liang Chen , Shao Qiang , Zhang Wei , Yang Mei , Chang Qing , Chen Rong , Chen Jian-Fu 
Published: October 2019

Abstract
G4C2 repeat expansions in an intron of C9ORF72 cause the most common familial amyotrophic lateral sclerosis and frontotemporal dementia (collectively, C9ALS/FTD). Mechanisms and mediators of C9ALS/FTD pathogenesis remain poorly understood. C9orf72 and Smcr8 form a protein complex. Here, we show that expression of Smcr8, like C9orf72, is reduced in C9ALS/FTD mouse models and patient tissues. Since Smcr8 is highly conserved between human and mouse, we evaluated the effects of Smcr8 downregulation in mice. Smcr8 knockout (KO) mice exhibited motor behavior deficits, which resemble those of C9ALS/FTD mouse models, and displayed axonal swellings in their spinal cords and neuromuscular junctions. These deficits are caused by impaired autophagy-lysosomal functions due to disrupted axonal transport in mutant motor neurons. Consistent with its interaction with C9orf72 and their downregulation in patient tissues, Smcr8 deficiency exacerbated autophagy-lysosomal impairment in C9orf72 KO mice. The disease relevance of Smcr8 downregulation was reflected by exacerbated axonal swellings and gain of toxicity pathology arising from Smcr8 haploinsufficiency in a mouse model of C9ALS/FTD. Thus, our in vivo studies suggested that Smcr8 deficiency impairs axonal transport dependent autophagy-lysosomal function and exacerbates axonal degeneration and gain of toxicity in C9ALS/FTD mouse models.
Functional characterization of a novel PBX1 de novo missense variant identified in a patient with syndromic congenital heart disease
Authors: Alankarage Dimuthu , Szot Justin O , Pachter Nick , Slavotinek Anne , Selleri Licia , Shieh Joseph T , Winlaw David , Giannoulatou Eleni , Chapman Gavin , Dunwoodie Sally L 
Published: October 2019

AbstractPre-B cell leukemia factor 1 (PBX1) is an essential developmental transcription factor, mutations in which have recently been associated with CAKUTHED syndrome, characterized by multiple congenital defects including congenital heart disease (CHD). During analysis of a whole-exome-sequenced cohort of heterogeneous CHD patients, we identified a de novo missense variant, PBX1:c.551G&gt;C p.R184P, in a patient with tetralogy of Fallot with absent pulmonary valve and extra-cardiac phenotypes. Functional analysis of this variant by creating a CRISPR-Cas9 gene-edited mouse model revealed multiple congenital anomalies. Congenital heart defects (persistent truncus arteriosus and ventricular septal defect), hypoplastic lungs, hypoplastic/ectopic kidneys, aplastic adrenal glands and spleen, as well as atretic trachea and palate defects were observed in the homozygous mutant embryos at multiple stages of development. We also observed developmental anomalies in a proportion of heterozygous embryos, suggestive of a dominant mode of inheritance. Analysis of gene expression and protein levels revealed that although Pbx1 transcripts are higher in homozygotes, amounts of PBX1 protein are significantly decreased. Here, we have presented the first functional model of a missense PBX1 variant and provided strong evidence that p.R184P is disease-causal. Our findings also expand the phenotypic spectrum associated with pathogenic PBX1 variants in both humans and mice.
Vacuum-assisted venous drainage in adult cardiac surgery: a propensity-matched study
Authors: Gao Sizhe , Li Yongnan , Diao Xiaolin , Yan Shujie , Liu Gang , Liu Mingyue , Zhang Qiaoni , Zhao Wei , Ji Bingyang 
Published: October 2019

AbstractOBJECTIVESConventional cardiopulmonary bypass with gravity drainage leads inevitably to haemodilution. Vacuum-assisted venous drainage (VAVD) utilizes negative pressure in the venous reservoir, allowing active drainage with a shortened venous line to reduce the priming volume. The goal of this study was to analyse the efficacy and safety of VAVD.METHODSData on 19 687 patients (18 681 with gravity drainage and 1006 with VAVD) who underwent cardiac operations between 1 January 2015 and 31 January 2018 were retrospectively collected from a single centre. Propensity matching identified 1002 matched patient pairs with VAVD and gravity drainage for comparison of blood product transfusion rate, major morbidities and in-hospital mortality rates.RESULTSThe blood transfusion rate of the VAVD group was lower than that of the gravity drainage group (28.1% vs 35% for red blood cells, 13% vs 18% for fresh frozen plasma and 0.1% vs 1.8% for platelets; P = 0.0009, 0.0020 and <0.0001, respectively). The mean difference (95% confidence interval) between the groups for red blood cells, fresh frozen plasma and platelets was −6.9% (−11.0% to −2.8%), −5.0% (−8.1% to −1.8%) and −1.7% (−2.5% to −0.9%), respectively. No difference was observed regarding the major morbidities of cerebrovascular accidents, acute kidney injury, hepatic failure and perioperative myocardial infarction and the in-hospital deaths between the 2 groups.CONCLUSIONSVAVD was associated with a reduction in blood product transfusions, and an increase in the risk of major morbidities and in-hospital deaths of the VAVD group was not observed.