bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the bathymetric evolution of the Northern North Sea: from Jurassic synrift archipelago through Cretaceous–Tertiary post-rift subsidence
Authors: Roberts Alan M. , Kusznir Nick J. , Yielding Graham , Beeley Hugh 
Published: January 2019

The post-rift history of the North Viking Graben has been backstripped in 3D, producing a sequence of palaeobathymetric maps that culminates at the Late Jurassic synrift stage. The backstripping takes into account the three main processes which drive post-rift basin development: thermal subsidence, flexural-isostatic loading and sediment compaction. Before backstripping was performed, the Norwegian Trench, a bathymetric feature within the present-day seabed, was smoothed in order to remove associated decompaction artefacts within the backstripping results.
Palaeobathymetric restorations at the top and base of the Paleocene take into account regional transient dynamic uplift, probably related to the Iceland Plume. 350 m of uplift is incorporated at the Base Tertiary (65 Ma) and 300 m at the Top Balder Formation (54 Ma), followed by rapid collapse of this same uplift.
At the top of the Lower Cretaceous (98.9 Ma), very localized fault-block topography, inherited from the Jurassic rift, is predicted to have remained emergent within the basin. At the Base Cretaceous (140 Ma), the fault-block topography is much more prominent and numerous isolated footwall islands are shown to have been present. At the Late Jurassic synrift stage (155 Ma), these islands are linked to form emergent island chains along the footwalls of all of the major faults. This is the Jurassic archipelago, the islands of which were the products of synrift footwall uplift. The predicted magnitude and distribution of footwall emergence calibrates well against available well data and published stratigraphic information, providing important constraints on the reliability of the results.
PIMap
Authors: Liu Gai , Zhang Zhiru 
Published: January 2019

Modern FPGA synthesis tools typically apply a predetermined sequence of logic optimizations on the input logic network before carrying out technology mapping. While the “known recipes” of logic transformations often lead to improved mapping results, there remains a nontrivial gap between the quality metrics driving the pre-mapping logic optimizations and those targeted by the actual technology mapping. Needless to mention, such miscorrelations would eventually result in suboptimal quality of results.
In this article, we propose PIMap, which couples logic transformations and technology mapping under an iterative improvement framework for LUT-based FPGAs. In each iteration, PIMap randomly proposes a transformation on the given logic network from an ensemble of candidate optimizations; it then invokes technology mapping and makes use of the mapping result to determine the likelihood of accepting the proposed transformation. By adjusting the optimization objective and incorporating required time constraints during the iterative process, PIMap can flexibly optimize for different objectives including area minimization, delay optimization, and delay-constrained area reduction. To mitigate the runtime overhead, we further introduce parallelization techniques to decompose a large design into multiple smaller sub-netlists that can be optimized simultaneously. Experimental results show that PIMap achieves promising quality improvement over a set of commonly used benchmarks, including improving the majority of the best-known area and delay records for the EPFL benchmark suite.
Prognostic Significance of PR Interval Prolongation in Adult Patients With Total Correction of Tetralogy of Fallot
Authors: Kimura Yoshitaka , Fukuda Koji , Nakano Makoto , Hasebe Yuhi , Fukasawa Kyoshiro , Chiba Takahiko , Miki Keita , Tatebe Shunsuke , Miyata Satoshi , Ota Hideki , Kimura Masato , Adachi Osamu , Saiki Yoshikatsu , Shimokawa Hiroaki 
Published: January 2019

Background:
Several studies have demonstrated the importance of mechanoelectrical interaction in patients with surgically corrected tetralogy of Fallot. However, the significance of atrioventricular conduction disturbance, that is PR interval prolongation, on adverse cardiac events in those patients remains to be elucidated.

Methods:
We examined electrocardiograms at baseline and their temporal change in a total of 176 patients with repaired tetralogy of Fallot (49% men; median age, 17.4 years). Then, we evaluated their correlation with right ventricular volume and function measured by cardiac magnetic resonance and the significance as a risk factor of adverse cardiac events: lethal ventricular arrhythmias, atrial arrhythmias, heart failure hospitalization, complete atrioventricular block (AVB), and all-cause death.

Results:

First-degree AVB was noted in 25 patients (14%). During a median follow-up of 10.0 (5.0–14.2) years, there was a progressive prolongation of PR interval (2.00±3.99 ms/y). Importantly, there were significant correlations between PR interval prolongation and right ventricular enlargement or right ventricular dysfunction. In contrast, in patients who underwent pulmonary valve replacement (n=23), significant shortening of PR interval by pulmonary valve replacement was noted (204±32 versus 176±34 ms;
P
=0.007). Cox regression analysis showed that first-degree AVB was an independent risk factor for lethal ventricular arrhythmias (hazard ratio, 5.479; 95% CI, 1.181–25.42;
P
=0.030) and complete AVB (hazard ratio, 27.67; 95% CI, 4.152–184.3;
P
<0.001) and had a tendency for heart failure hospitalization (hazard ratio, 3.301; 95% CI, 0.864–11.80;
P
=0.069). In addition, PR interval prolongation >2 ms/y was also a significant risk factor for lethal ventricular arrhythmias, regardless of the presence or absence of first-degree AVB at enrollment (hazard ratio, 24.18; 95% CI, 2.080–281.1;
P
=0.011).

Conclusions:
These results indicate that progressive atrioventricular conduction disturbance is correlated with right ventricular enlargement and could be a useful predictor for increased risk of lethal ventricular arrhythmias in patients with repaired tetralogy of Fallot.
Tissue-Specific Differential Expression of Novel Genes and Long Intergenic Noncoding RNAs in Humans With Extreme Response to Evoked Endotoxemia
Authors: Ferguson Jane F. , Xue Chenyi , Gao Yuanfeng , Tian Tian , Shi Jianting , Zhang Xuan , Wang Ying , Li Yuhuang D. , Wei Zhi , Li Mingyao , Zhang Hanrui , Reilly Muredach P. 
Published: January 2019

Background:
Cytokine responses to activation of innate immunity differ between individuals, yet the genomic and tissue-specific transcriptomic determinants of inflammatory responsiveness are not well understood. We hypothesized that tissue-specific mRNA and long intergenic noncoding RNA (lincRNA) induction differs between individuals with divergent evoked inflammatory responses.

Methods:
In the GENE Study (Genetics of Evoked Response to Niacin and Endotoxemia), we performed an inpatient endotoxin challenge (1 ng/kg lipopolysaccharide [LPS]) in healthy humans. We selected individuals in the top (high responders) and bottom (low responders) extremes of inflammatory responses and applied RNA sequencing to CD14 monocytes (N=15) and adipose tissue (N=25) before and after LPS administration.

Results:

Although only a small number of genes were differentially expressed at baseline, there were clear differences in the magnitude of the transcriptional response post-LPS between high and low responders, with a far greater number of genes differentially expressed by endotoxemia in high responders. Furthermore, tissue responses differed during inflammation, and we found a number of tissue-specific differentially expressed lincRNAs post-LPS, which we validated. Relative to nondifferentially expressed lincRNAs, differentially expressed lincRNAs were equally likely to be nonconserved as conserved between human and mouse, indicating that conservation is not a predictor of lincRNAs associated with human inflammatory pathophysiology. Differentially expressed genes also were enriched for signals with inflammatory and cardiometabolic disease in published genome-wide association studies.
CTB-41I6.2
(
AC002091.1
), a nonconserved human-specific lincRNA, is one of the top lincRNAs regulated by endotoxemia in monocytes, but not in adipose tissue. Knockdown experiments in THP-1 monocytes suggest that this lincRNA enhances LPS-induced interleukin 6 (
IL6
) expression in monocytes, and we now refer to this as monocyte LPS-induced lincRNA regulator of IL6 (
MOLRIL6
).

Conclusions:
We highlight mRNAs and lincRNAs that represent novel candidates for modulation of innate immune and metabolic responses in humans.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00953667.
Biomarker Glycoprotein Acetyls Is Associated With the Risk of a Wide Spectrum of Incident Diseases and Stratifies Mortality Risk in Angiography Patients
Authors: Kettunen Johannes , Ritchie Scott C. , Anufrieva Olga , Lyytikäinen Leo-Pekka , Hernesniemi Jussi , Karhunen Pekka J. , Kuukasjärvi Pekka , Laurikka Jari , Kähönen Mika , Lehtimäki Terho , Havulinna Aki S. , Salomaa Veikko , Männistö Satu , Ala-Korpela Mika , Perola Markus , Inouye Michael , Würtz Peter 
Published: January 2019

Background:
Integration of systems-level biomolecular information with electronic health records has led to recent interest in the glycoprotein acetyls (GlycA) biomarker—a serum- or plasma-derived nuclear magnetic resonance spectroscopy signal that represents the abundance of circulating glycated proteins. GlycA predicts risk of diverse outcomes, including cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality; however, the underlying detailed associations of GlycA’s morbidity and mortality risk are currently unknown.

Methods:
We used 2 population-based cohorts totaling 11 861 adults from the Finnish general population to test for an association with 468 common incident hospitalization and mortality outcomes during an 8-year follow-up. Further, we utilized 900 angiography patients to test for GlycA association with mortality risk and potential utility for mortality risk discrimination during 12-year follow-up.

Results:
New associations with GlycA and incident alcoholic liver disease, chronic renal failure, glomerular diseases, chronic obstructive pulmonary disease, inflammatory polyarthropathies, and hypertension were uncovered, and known incident disease associations were replicated. GlycA associations for incident disease outcomes were in general not attenuated when adjusting for hsCRP (high-sensitivity C-reactive protein). Among 900 patients referred to angiography, GlycA had hazard ratios of 4.87 (95% CI, 2.45–9.65) and 5.00 (95% CI, 2.38–10.48) for 12-year risk of mortality in the fourth and fifth quintiles by GlycA levels, demonstrating its prognostic potential for identification of high-risk individuals. When modeled together, both hsCRP and GlycA were attenuated but remained significant.

Conclusions:
GlycA was predictive of myriad incident diseases across many major internal organs and stratified mortality risk in angiography patients. Both GlycA and hsCRP had shared and independent contributions to mortality risk, suggesting chronic inflammation as an etiological factor. GlycA may be useful in improving risk prediction in specific disease settings.
Impact of Preexisting Left Bundle Branch Block in Transcatheter Aortic Valve Replacement Recipients
Authors: Fischer Quentin , Himbert Dominique , Webb John G. , Eltchaninoff Helene , Muñoz-García Antonio J. , Tamburino Corrado , Nombela-Franco Luis , Nietlispach Fabian , Moris Cesar , Ruel Marc , Dager Antonio E. , Serra Vicenç , Cheema Asim N. , Amat-Santos Ignacio J. , de Brito Fabio Sandoli , Ribeiro Henrique , Abizaid Alexandre , Sarmento-Leite Rogério , Dumont Eric , Barbanti Marco , Durand Eric , Alonso Briales Juan H. , Bouleti Claire , Immè Sebastiano , Maisano Francesco , del Valle Raquel , Miguel Benitez Luis , García del Blanco Bruno , Côté Mélanie , Philippon François , Urena Marina , Rodés-Cabau Josep 
Published: January 2019

Background:
The impact of preexisting left bundle branch block (LBBB) in transcatheter aortic valve replacement (TAVR) recipients is unknown. The aim of this study was to determine the impact of preexisting LBBB on clinical outcomes after TAVR.

Methods and Results:

This multicenter study evaluated 3404 TAVR candidates according to the presence or absence of LBBB on baseline ECG. TAVR complications and causes of death were defined according to Valve Academic Research Consortium-2 definitions. Follow-up outpatient visits or telephone interviews were conducted at 30 days, 12 months, and yearly thereafter. Echocardiography examinations were performed at baseline, at hospital discharge, and at 1-year follow-up. Preexisting LBBB was present in 398 patients (11.7%) and was associated with an increased risk of permanent pacemaker implantation (PPI; 21.1% versus 14.8%; adjusted odds ratio, 1.51; 95% CI, 1.12–2.04) but not death (7.3% versus 5.5%; adjusted odds ratio, 1.33; 95% CI, 0.84–2.12) at 30 days. At a mean follow-up of 22±21 months, there were no differences between patients with and without preexisting LBBB in overall mortality (adjusted hazard ratio, 0.94; 95% CI, 0.75–1.18) and cardiovascular mortality (adjusted hazard ratio, 0.90; 95% CI, 0.68–1.21). In a subanalysis of 2421 patients without PPI at 30 days and with complete follow-up about the PPI, preexisting LBBB was not associated with an increased risk of PPI or sudden cardiac death. Patients with preexisting LBBB had a lower left ventricular ejection fraction (LVEF) at baseline and at 1-year follow-up (
P
<0.001 for both), but those with low LVEF exhibited a similar increase in LVEF over time after TAVR compared with patients with no preexisting LBBB (
P
=0.327).

Conclusions:
Preexisting LBBB significantly increased the risk of early (but not late) PPI after TAVR, without any significant effect on overall mortality or cardiovascular mortality. Preexisting LBBB was associated with lower LVEF pre-TAVR but did not prevent an increase in LVEF post-TAVR similar to patients without LBBB.
Serial Fractional Flow Reserve Measurements Post Coronary Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Karamasis Grigoris V. , Kalogeropoulos Andreas S. , Mohdnazri Shah R. , Al-Janabi Firas , Jones Richard , Jagathesan Rohan , Aggarwal Rajesh K. , Clesham Gerald J. , Tang Kare H. , Kelly Paul A. , Davies John R. , Werner Gerald S. , Keeble Thomas R. 
Published: January 2019

Background
The aim of this study was to evaluate the functional result of chronic total occlusion percutaneous coronary intervention (PCI) measured by fractional flow reserve (FFR) immediately post the index procedure and at short-term follow-up.

Methods and Results

This was a prospective single-center observational study. Consecutive patients with right coronary artery chronic total occlusion scheduled for elective PCI were included. FFR measurements were performed immediately after successful PCI and at 4 months follow-up. Twenty-six patients completed baseline and follow-up measurements. Mean age was 61.2±9.7 years, 88.5% of the patients were male, and 19.2% were diabetic. The mean FFR immediately after successful chronic total occlusion PCI was 0.82±0.10 and significantly increased to 0.89±0.07 at 4 months (
P
<0.001). The FFR increased in 77% of the patients with a mean absolute increase of 0.07±0.08. The incidence of FFR ≤0.80 immediately after PCI was significantly higher amongst patients with subintimal versus intraplaque recanalization (23% versus 12%;
P
=0.03). At 4 months, FFR ≤0.80 was found only in 2 patients with subintimal recanalization. At follow-up, 42.7% of the patients continued to have an FFR <0.90.

Conclusions
Post chronic total occlusion PCI, FFR increased significantly at short-term follow-up compared with measurements post index procedure. Because FFR remained <0.90 in many cases, further efforts should be made to optimize procedural results.
Fish Oil and Perioperative Bleeding
Authors: Akintoye Emmanuel , Sethi Prince , Harris William S. , Thompson Paul A. , Marchioli Roberto , Tavazzi Luigi , Latini Roberto , Pretorius Mias , Brown Nancy J. , Libby Peter , Mozaffarian Dariush 
Published: January 2019

Background
Fish oil is among the most common natural supplements for treatment of hypertriglyceridemia or prevention of cardiovascular disease. However, concerns about theoretical bleeding risk have led to recommendations that patients should stop taking fish oil before surgery or delay in elective procedures for patients taking fish oil by some health care professionals.

Methods and Results

We tested the effect of fish oil supplementation on perioperative bleeding in a multinational, placebo-controlled trial involving 1516 patients who were randomized to perioperative fish oil (eicosapentaenoic acid+docosahexaenoic acid; 8–10 g for 2–5 days preoperatively, and then 2 g/d postoperatively) or placebo. Primary outcome was major perioperative bleeding as defined by the Bleeding Academic Research Consortium. Secondary outcomes include perioperative bleeding per thrombolysis in myocardial infarction and International Society on Thrombosis and Hemostasis definitions, chest tube output, and total units of blood transfused. Participants’ mean (SD) age was 63 (13) years, and planned surgery included coronary artery bypass graft (52%) and valve surgery (50%). The primary outcome occurred in 92 patients (6.1%). Compared with placebo, risk of Bleeding Academic Research Consortium bleeding was not higher in the fish oil group: odds ratio, 0.81; 95% CI, 0.53–1.24; absolute risk difference, 1.1% lower (95% CI, −3.0% to 1.8%). Similar findings were seen for secondary bleeding definitions. The total units of blood transfused were significantly lower in the fish oil group compared with placebo (mean, 1.61 versus 1.92;
P
<0.001). Evaluating achieved plasma phospholipid omega-3 polyunsaturated fatty acids levels with supplementation (on the morning of surgery), higher levels were associated with lower risk of Bleeding Academic Research Consortium bleeding, with substantially lower risk in the third (odds ratio, 0.30 [95% CI, 0.11–0.78]) and fourth (0.36 [95% CI, 0.15–0.87]) quartiles, compared with the lowest quartile.

Conclusions
Fish oil supplementation did not increase perioperative bleeding and reduced the number of blood transfusions. Higher achieved n-3-PUFA levels were associated with lower risk of bleeding. These novel findings support the need for reconsideration of current recommendations to stop fish oil or delay procedures before cardiac surgery.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00970489.
Assessing the Causal Role of Body Mass Index on Cardiovascular Health in Young Adults
Authors: Wade Kaitlin H. , Chiesa Scott T. , Hughes Alun D. , Chaturvedi Nish , Charakida Marietta , Rapala Alicja , Muthurangu Vivek , Khan Tauseef , Finer Nicholas , Sattar Naveed , Howe Laura D. , Fraser Abigail , Lawlor Debbie A. , Davey Smith George , Deanfield John E. , Timpson Nicholas J. 
Published: January 2019

Background:
Body mass index (BMI) has been suggested to be causally related to cardiovascular health in mid-to-late life, but this has not been explored systematically at younger ages—nor with detailed cardiovascular phenotyping. Recall-by-Genotype (RbG) is an approach that enables the collection of precise phenotypic measures in smaller studies, while maintaining statistical power and ability for causal inference.

Methods:
In this study, we used a combination of conventional multivariable regression analysis, Mendelian randomization (MR), and subsample RbG methodologies to estimate the causal effect of BMI on gross-level and detailed cardiovascular health in healthy participants from the Avon Longitudinal Study of Parents and Children at age 17 years (N=1420–3108 for different outcomes) and an independent sample from the same cohort (for RbG) study at age 21 years (N=386–418).

Results:

In both MR and RbG analyses, results suggested that higher BMI causes higher blood pressure and left ventricular mass index in young adults (eg, difference in left ventricular mass index per 1 kg/m
2
using MR: 1.07 g/m
2.7
; 95% CI, 0.62–1.52;
P
=3.87×10
-06
and per 3.58 kg/m
2
using RbG: 1.65 g/m
2.7
; 95% CI, 0.83–2.47;
P
=0.0001). Additionally, RbG results suggested a causal role of higher BMI on higher stroke volume (difference per 3.58 kg/m
2
: 1.49 mL/m
2.04
; 95% CI, 0.62–2.35;
P
=0.001) and cardiac output (difference per 3.58 kg/m
2
: 0.11 L·min
-1
·m
-1.83
; 95% CI, 0.03–0.19;
P
=0.01) but no strong evidence for a causal role on systemic vascular resistance or total arterial compliance. Neither analysis supported a causal role of higher BMI on heart rate.

Conclusions:
Complementary MR and RbG causal methodologies, together with a range of sensitivity analyses, suggest that higher BMI is likely to cause worse cardiovascular health, specifically higher blood pressure and left ventricular mass index, even in youth. Higher BMI also resulted in increased cardiac output in the RbG study, which appeared to be solely driven by stroke volume, as neither MR nor RbG analyses suggested a causal effect of BMI on heart rate. These consistent results support efforts to reduce BMI from a young age to prevent later adverse cardiovascular health and illustrate the potential for phenotypic resolution with maintained analytic power using RbG.