bluuebunny/crossref_metadata_2025_split huggingface dataset:
A sequential interferon gamma directed chemotactic cellular immune response determines survival and cardiac function post-myocardial infarction
Authors: Finger Stefanie , Knorr Maike , Molitor Michael , Schüler Rebecca , Garlapati Venkata , Waisman Ari , Brandt Moritz , Münzel Thomas , Bopp Tobias , Kossmann Sabine , Karbach Susanne , Wenzel Philip 
Published: April 2019

Abstract

Aims
Myelomonocytic cells are critical in injury and healing post-myocardial infarction (MI). Mechanisms of regulation, however, are incompletely understood. The aim of the study was to elucidate the role of interferon gamma (IFN-γ) in the orchestrated inflammatory response in a murine model of MI.

Methods and results
MI was induced in 8- to 12-week-old male mice (C57BL/6 background) by permanent ligation of the left anterior descending (LAD) coronary artery. Lysozyme M (LysM)+ cell-depleted LysMiDTR transgenic mice displayed a reduced influx of CD45.2+/CD3−/CD11b+/Gr-1high neutrophils into infarcted myocardium 1 day post-MI compared with infarcted controls, paralleled by decreased cardiac mRNA levels of IFN-γ and tumour necrosis factor alpha (TNF-α). Mortality after MI was significantly increased in LysM+ cell-depleted mice within 28 days post-MI. To more specifically address the role of neutrophils, we depleted C57BL/6 mice with a monoclonal anti-Gr-1 antibody and found increased mortality, deteriorated cardiac function as well as decreased cardiac IFN-γ mRNA expression early after MI. Ccl2, Cxcl1, Cx3cl1, and Il12b mRNA were reduced 3 days after MI, as was the amount of CD11b+/Ly-6G−/Ly-6Chigh inflammatory monocytes. LAD-ligated Cramp−/− mice lacking cathelicidin important in neutrophil-dependent monocyte chemotaxis as well as IFNγ−/− and TNFα−/− mice phenocopied Gr-1+ cell-depleted mice, supporting a regulatory role of IFN-γ impacting on both the sequence of inflammatory cell invasion and cardiac outcome early after MI. The use of conditional IFN-γ receptor deficient mice indicated a direct effect of IFN-γ on LysM+ cells in cardiac injury post-MI. Using IFN-γ reporter mice and flow cytometry, we identified cardiac lymphoid cells (CD4+ and CD8+ T cells and natural killer cells) as primary source of this cytokine in the cardiac inflammatory response post-MI.

Conclusion
IFN-γ directs a sequential chemotactic cellular immune response and determines survival and cardiac function post-MI.
Magnetic resonance hyperpolarization imaging detects early myocardial dysfunction in a porcine model of right ventricular heart failure
Authors: Agger Peter , Hyldebrandt Janus Adler , Hansen Esben Søvsø Szocska , Omann Camilla , Bøgh Nikolaj , Waziri Farhad , Nielsen Per Mose , Laustsen Christoffer 
Published: April 2019

AbstractAimsEarly detection of heart failure is important for timely treatment. During the development of heart failure, adaptive intracellular metabolic processes that evolve prior to macro-anatomic remodelling, could provide an early signal of impending failure. We hypothesized that metabolic imaging with hyperpolarized magnetic resonance would detect the early development of heart failure before conventional echocardiography could reveal cardiac dysfunction.Methods and resultsFive 8.5 kg piglets were subjected to pulmonary banding and subsequently examined by [1-13C]pyruvate hyperpolarization, conventional magnetic resonance imaging, echocardiography, and blood testing, every 4 weeks for 16 weeks. They were compared with a weight matched, healthy control group. Conductance catheter examination at the end of the study showed impaired right ventricular systolic function along with compromised left ventricular diastolic function. After 16 weeks, we saw a significant decrease in the conversion ratio of pyruvate/bicarbonate in the left ventricle from 0.13 (0.04) in controls to 0.07 (0.02) in animals with pulmonary banding, along with a significant increase in the lactate/bicarbonate ratio to 3.47 (1.57) compared with 1.34 (0.81) in controls. N-terminal pro-hormone of brain natriuretic peptide was increased by more than 300%, while cardiac index was reduced to 2.8 (0.95) L/min/m2 compared with 3.9 (0.95) in controls. Echocardiography revealed no changes.ConclusionHyperpolarization detected a shift towards anaerobic metabolism in early stages of right ventricular dysfunction, as evident by an increased lactate/bicarbonate ratio. Dysfunction was confirmed with conductance catheter assessment, but could not be detected by echocardiography. Hyperpolarization has a promising future in clinical assessment of heart failure in both acquired and congenital heart disease.
Evaluation of a simple technique aiming at optimizing point-by-point isolation of the left pulmonary veins: a randomized study
Authors: Kyriakopoulou Maria , Strisciuglio Teresa , El Haddad Milad , De Pooter Jan , Almorad Alexandre , Van Beeumen Katarina , Unger Philippe , Vandekerckhove Yves , Tavernier René , Duytschaever Mattias , Knecht Sébastien 
Published: April 2019

AbstractAimsWe sought to evaluate the efficacy and the safety of a simple technique for stabilizing the ablation catheter during anterior pulmonary vein (PV) encirclement in patients ablated for paroxysmal atrial fibrillation. This consisted of bending the ablation catheter in the left atrium, creating a loop that was cautiously advanced together with the long sheath at the ostium and then within the left superior PV. The curve was then progressively released to reach a stable contact with the anterior part of the left PVs.Methods and resultsEighty consecutive patients (age 64 ± 11 years, left atrial diameter 43 ± 8 mm) undergoing ‘CLOSE’-guided PV isolation were prospectively randomized into two groups depending on whether the loop technique was used or not. When using the loop technique, the encirclement of the left PVs was shorter [20 min (interquartile range, IQR 17–24) vs. 26 min (IQR 18–33), P < 0.01] with a high rate of first pass isolation [(100%) vs. (97%), P = 0.9] and adenosine proof isolation [(93%) vs. (95%), P = 0.67]. Most specifically, at the anterior part of the left PVs, there were less dislocations [0 (IQR 0–0) vs. 1 (IQR 0–4), P < 0.001], radiofrequency duration was shorter (272 ± 85 s vs. 378 ± 122 s, P < 0.001), force-time integral was higher [524 gs (IQR 427–687) vs. 398 gs (IQR 354–451), P < 0.001], average contact force was higher [20 g (IQR 13–27) vs. 11g (IQR 9–16), P < 0.001], and impedance drop was higher [12 Ω (IQR 9–19) vs. 10 Ω (IQR 7–14), P < 0.001].ConclusionThis study describes a simple technique to facilitate catheter stability at the anterior part of the left PVs, resulting in more efficient left PV encirclement without compromising safety.
Incidence of appropriate implantable cardioverter-defibrillator therapy and mortality after implantable cardioverter-defibrillator generator replacement: results from a real-world nationwide cohort
Authors: Ruwald Martin H , Ruwald Anne-Christine , Johansen Jens Brock , Gislason Gunnar , Nielsen Jens Cosedis , Philbert Berit , Riahi Sam , Vinther Michael , Lindhardt Tommi B 
Published: April 2019

Abstract

Aims
The safety of omitting implantable cardioverter-defibrillator (ICD) generator replacement in patients with no prior appropriate therapy, comorbid conditions, and advanced age is unclear. The aim was to investigate incidence of appropriate ICD therapy after generator replacement.

Methods and results
We identified patients implanted with a primary prevention ICD (n = 4630) from 2007 to 2016, who subsequently underwent an elective ICD generator replacement (n = 670) from the Danish Pacemaker and ICD Register. The data were linked to other databases and evaluated the outcomes of appropriate therapy and death. Predictors of ICD therapy were identified using multivariate Cox regression analyses. A total of 670 patients underwent elective ICD generator replacement. Of these, 197 (29.4%) patients had experienced appropriate therapy in their 1st generator period. During follow-up of 2.0 ± 1.6 years, 95 (14.2%) patients experienced appropriate therapy. Predictors of appropriate therapy in 2nd generator period was low initial left ventricular ejection fraction (≤25%) [hazard ratio (HR) 1.87, confidence interval (CI) 1.13–1.95] and appropriate therapy in 1st generator period (HR 3.95, CI 2.57–6.06). For patients with appropriate therapy in 1st generator period, 4-year incidence of appropriate therapy was 50.6% vs. 16.4% in those without (P < 0.001). Among patients >80 years with no prior appropriate therapy 8.8% of patients experienced appropriate therapy after replacement. Comorbidity burden and advanced age were associated with reduced device utilization after replacement and a high competing risk of death without preceding appropriate therapy.

Conclusion
A significant residual risk of appropriate therapy in the 2nd generator was present even among patients with advanced age and with a full prior generator period without any appropriate ICD events.
Patterns of alcohol consumption and alcohol-related harm among European university students
Authors: Cooke Richard , Beccaria Franca , Demant Jakob , Fernandes-Jesus Maria , Fleig Lena , Negreiros Jorge , Scholz Urte , de Visser Richard 
Published: April 2019

Abstract

Background
To compare patterns of alcohol consumption and alcohol-related harm from a survey of university students sampled from universities in Denmark, England, Germany, Italy, Portugal and Switzerland.

Methods
A total of 2191 university students (70% female, 90% white ethnic group, age range 18–25) completed the survey. Participants completed measures of demographic variables (age, age of onset, ethnic group and sex) and the Alcohol Use Disorders Identification Test (AUDIT), which was the primary outcome.

Results
Sixty-three percent of the sample scored negative for harmful drinking on the AUDIT (&lt;8), with 30% categorized as hazardous drinkers, 4% harmful drinkers and 3% with probable dependence. Analysis of variance, including demographic factors as covariates, identified a main effect of country on AUDIT scores F(5, 2086) = 70.97, P &lt; 0.001, partial eta square = 0.15. AUDIT scores were highest in England (M = 9.99; SD = 6.17) and Denmark (M = 9.52; SD = 4.86) and lowest in Portugal (M = 4.90; ° = 4.60). Post hoc tests indicated large effect size differences between scores in Denmark and England and scores in all other countries (0.79 &lt; d &lt; 0.94; all P’s &lt; 0.001).

Conclusions
European university students in our sample mainly reported low risk patterns of alcohol consumption and alcohol-related harm. However, students from Northern European countries had significantly higher AUDIT scores compared with students from Central and Southern European countries. Research is needed to replicate the present study using nationally representative samples to estimate the prevalence of alcohol use disorders among university students in different European countries.
Discovered by genomics: putative reductive dehalogenases with N-terminus transmembrane helixes
Authors: Atashgahi Siavash 
Published: April 2019

ABSTRACTAttempts for bioremediation of toxic organohalogens resulted in the identification of organohalide-respiring bacteria harbouring reductive dehalogenases (RDases) enzymes. RDases consist of the catalytic subunit (RdhA, encoded by rdhA) that does not have membrane-integral domains, and a small putative membrane anchor (RdhB, encoded by rdhB) that (presumably) locates the A subunit to the outside of the cytoplasmic membrane. Recent genomic studies identified a putative rdh gene in an uncultured deltaproteobacterial genome that was not accompanied by an rdhB gene, but contained transmembrane helixes in N-terminus. Therefore, rather than having a separate membrane anchor protein, this putative RDase is likely a hybrid of RdhA and RdhB, and directly connected to the membrane with transmembrane helixes. However, functionality of the hybrid putative RDase remains unknown. Further analysis showed that the hybrid putative rdh genes are present in the genomes of pure cultures and uncultured members of Bacteriodetes and Deltaproteobacteria, but also in the genomes of the candidate divisions. The encoded hybrid putative RDases have cytoplasmic or exoplasmic C-terminus localization, and cluster phylogenetically separately from the existing RDase groups. With increasing availability of (meta)genomes, more diverse and likely novel rdh genes are expected, but questions regarding their functionality and ecological roles remain open.
A de novo substitution in BCL11B leads to loss of interaction with transcriptional complexes and craniosynostosis
Authors: Goos Jacqueline A C , Vogel Walter K , Mlcochova Hana , Millard Christopher J , Esfandiari Elahe , Selman Wisam H , Calpena Eduardo , Koelling Nils , Carpenter Evan L , Swagemakers Sigrid M A , van der Spek Peter J , Filtz Theresa M , Schwabe John W R , Iwaniec Urszula T , Mathijssen Irene M J , Leid Mark , Twigg Stephen R F 
Published: April 2019

Abstract
Craniosynostosis, the premature ossification of cranial sutures, is a developmental disorder of the skull vault, occurring in approximately 1 in 2250 births. The causes are heterogeneous, with a monogenic basis identified in ~25% of patients. Using whole-genome sequencing, we identified a novel, de novo variant in BCL11B, c.7C>A, encoding an R3S substitution (p.R3S), in a male patient with coronal suture synostosis. BCL11B is a transcription factor that interacts directly with the nucleosome remodelling and deacetylation complex (NuRD) and polycomb-related complex 2 (PRC2) through the invariant proteins RBBP4 and RBBP7. The p.R3S substitution occurs within a conserved amino-terminal motif (RRKQxxP) of BCL11B and reduces interaction with both transcriptional complexes. Equilibrium binding studies and molecular dynamics simulations show that the p.R3S substitution disrupts ionic coordination between BCL11B and the RBBP4–MTA1 complex, a subassembly of the NuRD complex, and increases the conformational flexibility of Arg-4, Lys-5 and Gln-6 of BCL11B. These alterations collectively reduce the affinity of BCL11B p.R3S for the RBBP4–MTA1 complex by nearly an order of magnitude. We generated a mouse model of the BCL11B p.R3S substitution using a CRISPR-Cas9-based approach, and we report herein that these mice exhibit craniosynostosis of the coronal suture, as well as other cranial sutures. This finding provides strong evidence that the BCL11B p.R3S substitution is causally associated with craniosynostosis and confirms an important role for BCL11B in the maintenance of cranial suture patency.
Sexually Antagonistic Mitonuclear Coevolution in Duplicate Oxidative Phosphorylation Genes
Authors: Havird Justin C , McConie Hunter J 
Published: April 2019

Abstract
Mitochondrial function is critical in eukaryotes. To maintain an adequate supply of energy, precise interactions must be maintained between nuclear- and mitochondrial-encoded gene products. Such interactions are paramount in chimeric enzymes such as the oxidative phosphorylation (OXPHOS) complexes. Mutualistic coevolution between the two genomes has therefore been suggested to be a critical, ubiquitous feature of eukaryotes that acts to maintain cellular function. However, mitochondrial genomes can also act selfishly and increase their own transmission at the expense of organismal function. For example, male-harming mutations are predisposed to accumulate in mitochondrial genomes due to their maternal inheritance (“mother’s curse”). Here, we investigate sexually antagonistic mitonuclear coevolution in nuclear-encoded OXPHOS paralogs from mammals and Drosophila. These duplicate genes are highly divergent but must interact with the same set of mitochondrial-encoded genes. Many such paralogs show testis-specific expression, prompting previous hypotheses suggesting they may have evolved under selection to counteract male-harming mitochondrial mutations. We found increased rates of evolution in OXPHOS paralogs with testis-specific expression in mammals and Drosophila, supporting this hypothesis. However, further analyses suggested such patterns may be due to relaxed, not positive selection, especially in Drosophila. Structural data also suggest that mitonuclear interactions do not play a major role in the evolution of many OXPHOS paralogs in a consistent way. In conclusion, no single OXPHOS paralog met all our criteria for being under selection to counteract male-harming mitochondrial mutations. We discuss alternative explanations for the drastic patterns of evolution in these genes, including mutualistic mitonuclear coevolution, adaptive subfunctionalization after gene duplication, and relaxed selection on OXPHOS in male tissues.
Developing spatio-temporal models using multiple data types for evaluating population trends and habitat usage
Authors: Grüss Arnaud , Thorson James T 
Published: April 2019

AbstractSpatio-temporal models have become key tools for evaluating population trends and habitat usage. We developed a spatio-temporal modelling framework employing a combination of encounter/non-encounter, count, and biomass data collected by different monitoring programs (“combined data”). The three data types are predicted using a computationally efficient approximation to a compound Poisson-gamma process. We fitted spatio-temporal models to combined data for Gulf of Mexico (GOM) red snapper (Lutjanus campechanus) for 2006–2014. These spatio-temporal models provided insights into GOM red snapper spatial distribution patterns, which we corroborated by comparing to past predictions generated using only encounter/non-encounter data. However, relying on biomass and count data in addition to encounter/non-encounter data also allowed us to reconstruct biomass trends for GOM red snapper and to examine patterns of distribution shifts and range expansion/contraction for this population for the first time. Moreover, combining multiple data types improved the precision of reconstructed population trends and some variables quantifying habitat usage. Finally, scenarios and simulation experiments conditioned upon red snapper data showed that the improvement in fitting to combined data is greater when biomass data for the study population are lacking for an entire subregion and, to a lesser extent, for an entire time period (e.g. in early years).
Excluding Women
Authors: Dauvergne Catherine , Lindy Hannah 
Published: April 2019

Abstract
This article reviews 16 years of Canadian case law applying the Refugee Convention’s exclusion provisions to women. Despite a quarter of a century of strong scholarly and policy-making work asserting the need for attention to gender in refugee law, this dataset shows that, in questions of exclusion, gendered analysis is almost entirely absent. By contrast, in seeking explanations for the factual basis of exclusion in these cases, gender is almost always an explanatory factor. This stark observation leads us to conclude that significant additional work – both scholarly and policy-focused – is required. The article also considers whether a more robust application of existing Supreme Court jurisprudence can address the problems we have identified and reaches a mixed conclusion. Overall, the article points out an important gap in current understandings of gender in refugee law, and maps a way forward for future work in the area.
Stabilization of high order cut finite element methods on surfaces
Authors: Larson Mats G , Zahedi Sara 
Published: April 2019

Abstract
We develop and analyse a stabilization term for cut finite element approximations of an elliptic second-order partial differential equation on a surface embedded in ${\mathbb{R}}^d$. The new stabilization term combines properly scaled normal derivatives at the surface together with control of the jump in the normal derivatives across faces, and provides control of the variation of the finite element solution on the active three-dimensional elements that intersect the surface. We show that the condition number of the stiffness matrix is $O(h^{-2})$, where $h$ is the mesh parameter. The stabilization term works for linear as well as for higher-order elements and the derivation of its stabilizing properties is quite straightforward, which we illustrate by discussing the extension of the analysis to general $n$-dimensional smooth manifolds embedded in ${\mathbb{R}}^d$, with codimension $d-n$. We also state the properties of a general stabilization term that are sufficient to prove optimal scaling of the condition number and optimal error estimates in energy- and $L^2$-norm. We finally present numerical studies confirming our theoretical results.
Effect of TIPE1 on Immune Function of Dendritic Cells and Its Signaling Pathway in Septic Mice
Authors: Luan Ying-yi , Zhang Lei , Zhu Fu-jun , Dong Ning , Lu Jiang-yang , Yao Yong-ming 
Published: April 2019

AbstractDendritic cell (DC) dysfunction plays a pivotal role in sepsis-induced immunosuppression. Tumor necrosis factor α (TNF-α)–induced protein 8 like-1 (TIPE1), a new member of the tumor necrosis factor α–induced protein 8 family, may be related to cell death. The aim of the present study was to elucidate the effect of TIPE1 on the immune function of DCs and its regulatory mechanism via PD-L1/PD-1 signaling in mice. Sepsis was induced in adult C57BL/6 male mice via cecal ligation and puncture. In vitro, we found that expression of CD80, CD86, and major histocompatibility complex class II in DCs and levels of cytokines, including tumor necrosis factor α and interleukin 12p40, were elevated; similarly, T-cell proliferation and differentiation were promoted when the gene expressing TIPE1 was silenced. Next, we examined the in vivo role of TIPE1 in a cecal ligation and puncture animal model system. Flow cytometry of the immune functional status in DCs revealed negative regulation of TIPE1 on DC maturation, as well as activation. Moreover, changes in PD-L1/PD-1 levels confirmed the negative effect of TIPE1 in DCs. Collectively, we report that TIPE1 might exert negative regulation in sepsis, at least in part by inhibiting DC maturation and subsequent T-cell–mediated immunity via PD-L1/PD-1 signaling.
Species Diversity and Seasonal Distribution of Hard Ticks (Acari: Ixodidae) Infesting Mammalian Hosts in Various Districts of Riyadh Province, Saudi Arabia
Authors: Alanazi Abdullah D , Al-Mohammed Hamdan I , Alyousif Mohamed S , Said Ashraf E , Salim Bashir , Abdel-Shafy Sobhy , Shaapan Raafat M 
Published: April 2019

Abstract
Hard ticks are among the most important blood sucking arthropods that transmit pathogens to humans and animals. This study was designed to determine prevalence, mapping, geographical distribution, and seasonal activity of hard tick species infesting the most common domestic and wild mammals in various districts of Riyadh Province, Saudi Arabia, during the period January to December 2017. In total, 10,832 adult hard ticks were collected from the bodies of 8,435 animals belonging to 18 different mammalian species. The ticks were preserved in 70% alcohol and microscopy was used to identify species. Two genera, Hyalomma and Rhipicephalus, were identified, comprising 10 species of hard ticks, with Hyalomma comprising 68.3% and Rhipicephalus comprising 31.7% of species. The most common species on domestic mammalian hosts was Hyalomma dromedarii (Koch 1844) (39.9%) followed by Rhipicephalus turanicus (Pomerantsev, Matikashvili & Lotosky 1936) (34.9%), whereas on wild mammalian hosts Rhipicephalus sanguineus (Latreille 1806) was by far the most prevalent species (83.0%). However, ticks were most abundant during May through July (36.0%) in the studied areas, and tick intensity and abundance differed among seasons. Our results provide information for human and animal health service managers, as well as governmental authorities, to gain a better understanding of hard ticks infesting mammalian hosts in Riyadh Province, Saudi Arabia, which can help improve prevention and control of tick-borne diseases, especially during outbreaks.