bluuebunny/crossref_metadata_2025_split huggingface dataset:
A spatial-temporal gated attention module for molecular property prediction based on molecular geometry
Authors: Li Chunyan , Wang Jianmin , Niu Zhangming , Yao Junfeng , Zeng Xiangxiang 
Published: February 2021

Abstract

Motivation
Geometry-based properties and characteristics of drug molecules play an important role in drug development for virtual screening in computational chemistry. The 3D characteristics of molecules largely determine the properties of the drug and the binding characteristics of the target. However, most of the previous studies focused on 1D or 2D molecular descriptors while ignoring the 3D topological structure, thereby degrading the performance of molecule-related prediction. Because it is very time-consuming to use dynamics to simulate molecular 3D conformer, we aim to use machine learning to represent 3D molecules by using the generated 3D molecular coordinates from the 2D structure.

Results
We proposed Drug3D-Net, a novel deep neural network architecture based on the spatial geometric structure of molecules for predicting molecular properties. It is grid-based 3D convolutional neural network with spatial-temporal gated attention module, which can extract the geometric features for molecular prediction tasks in the process of convolution. The effectiveness of Drug3D-Net is verified on the public molecular datasets. Compared with other deep learning methods, Drug3D-Net shows superior performance in predicting molecular properties and biochemical activities.

Availability and implementation
https://github.com/anny0316/Drug3D-Net

Supplementary Data
Supplementary data are available online at https://academic.oup.com/bib.
E-MAGMA: an eQTL-informed method to identify risk genes using genome-wide association study summary statistics
Authors: Gerring Zachary F , Mina-Vargas Angela , Gamazon Eric R , Derks Eske M 
Published: February 2021

Abstract

Motivation
Genome-wide association studies have successfully identified multiple independent genetic loci that harbour variants associated with human traits and diseases, but the exact causal genes are largely unknown. Common genetic risk variants are enriched in non-protein-coding regions of the genome and often affect gene expression (expression quantitative trait loci, eQTL) in a tissue-specific manner. To address this challenge, we developed a methodological framework, E-MAGMA, which converts genome-wide association summary statistics into gene-level statistics by assigning risk variants to their putative genes based on tissue-specific eQTL information.

Results
We compared E-MAGMA to three eQTL informed gene-based approaches using simulated phenotype data. Phenotypes were simulated based on eQTL reference data using GCTA for all genes with at least one eQTL at chromosome 1. We performed 10 simulations per gene. The eQTL-h2 (i.e. the proportion of variation explained by the eQTLs) was set at 1%, 2% and 5%. We found E-MAGMA outperforms other gene-based approaches across a range of simulated parameters (e.g. the number of identified causal genes). When applied to genome-wide association summary statistics for five neuropsychiatric disorders, E-MAGMA identified more putative candidate causal genes compared to other eQTL-based approaches. By integrating tissue-specific eQTL information, these results show E-MAGMA will help to identify novel candidate causal genes from genome-wide association summary statistics and thereby improve the understanding of the biological basis of complex disorders.

Availability and implementation
A tutorial and input files are made available in a github repository: https://github.com/eskederks/eMAGMA-tutorial.

Supplementary information
Supplementary data are available at Bioinformatics online.
Abolishment of high-risk left lateral accessory pathway by myocardial infarction: a blessing in disguise? A case report
Authors: O’Brien Jim , Kozhuharov Nikola , Chin Shui Hao , Hall Mark 
Published: February 2021

Abstract

Background
Antegradely conducting left lateral accessory pathways are a risk for supraventricular tachycardias and pre-excited atrial fibrillation. Rarely, an anomalous coronary sinus can cause difficulty in locating the pathway. The left circumflex coronary artery and obtuse marginal branches supply the posterolateral left ventricle. We describe a case report of a high-risk accessory pathway associated with an anomalous coronary sinus which, between successive electrophysiology studies, was obliterated by a felicitous acute coronary syndrome in the left circumflex territory.

Case summary
A 49-year-old male with palpitations and manifest pre-excitation was referred for electrophysiology study. Initial study revealed a high-risk left lateral accessory pathway with antegrade effective refractory period of 240 ms and rapidly conducting pre-excited atrial fibrillation. The coronary sinus could not be cannulated to localize the pathway. Coronary angiography and cardiac computed tomography showed an anomalous coronary sinus emptying into the right atrial free wall and patent coronaries. While awaiting repeat electrophysiology study, the patient suffered an acute coronary syndrome with immediate loss of previously visible pre-excitation on electrocardiogram, and underwent stenting of an occluded marginal branch of the circumflex. Repeat electrophysiology study demonstrated a now low-risk accessory pathway (effective refractory period 390 ms). Since infarction, the patient’s palpitations have fully settled with all subsequent electrocardiograms devoid of manifest pre-excitation.

Discussion
Left lateral accessory pathways, which can associate with an anomalous coronary sinus, derive from tissue similar to normal ventricular myocardium and are vulnerable to ischaemic insults in the area subtended by the circumflex artery.
Association of the combined effects of air pollution and changes in physical activity with cardiovascular disease in young adults
Authors: Kim Seong Rae , Choi Seulggie , Kim Kyuwoong , Chang Jooyoung , Kim Sung Min , Cho Yoosun , Oh Yun Hwan , Lee Gyeongsil , Son Joung Sik , Kim Kyae Hyung , Park Sang Min 
Published: February 2021

AbstractAimsLittle is known about the trade-off between the health benefits of physical activity (PA) and the potential harmful effects of increased exposure to air pollution during outdoor PA. We examined the association of the combined effects of air pollution and changes in PA with cardiovascular disease (CVD) in young adults.Methods and resultsThis nationwide cohort study included 1 469 972 young adults aged 20–39 years. Air pollution exposure was estimated by the annual average cumulative level of particulate matter (PM). PA was calculated as minutes of metabolic equivalent tasks per week (MET-min/week) based on two consecutive health examinations from 2009 to 2012. Compared with the participants exposed to low-to-moderate levels of PM2.5 or PM10 who continuously engaged in ≥1000 MET-min/week of PA, those who decreased their PA from ≥1000 MET-min/week to 1–499 MET-min/week [PM10 adjusted hazard ratio (aHR) 1.22; 95% confidence interval (CI) 1.00–1.48] and to 0 MET-min/week (physically inactive; PM10 aHR 1.38; 95% CI 1.07–1.78) had an increased risk of CVD (P for trend &lt;0.01). Among participants exposed to high levels of PM2.5 or PM10, the risk of CVD was elevated with an increase in PA above 1000 MET-min/week.ConclusionReducing PA may lead to subsequent elevation of CVD risk in young adults exposed to low-to-moderate levels of PM2.5 or PM10, whereas a large increase in PA in a high-pollution environment may adversely affect cardiovascular health.
A proteomic atlas of the neointima identifies novel druggable targets for preventive therapy
Authors: Wierer Michael , Werner Julia , Wobst Jana , Kastrati Adnan , Cepele Ganildo , Aherrahrou Redouane , Sager Hendrik B , Erdmann Jeanette , Dichgans Martin , Flockerzi Veit , Civelek Mete , Dietrich Alexander , Mann Matthias , Schunkert Heribert , Kessler Thorsten 
Published: February 2021

Abstract

Aims
In-stent restenosis is a complication after coronary stenting associated with morbidity and mortality. Here, we sought to investigate the molecular processes underlying neointima formation and to identify new treatment and prevention targets.

Methods and results
Neointima formation was induced by wire injury in mouse femoral arteries. High-accuracy proteomic measurement of single femoral arteries to a depth of about 5000 proteins revealed massive proteome remodelling, with more than half of all proteins exhibiting expression differences between injured and non-injured vessels. We observed major changes in the composition of the extracellular matrix and cell migration processes. Among the latter, we identified the classical transient receptor potential channel 6 (TRPC6) to drive neointima formation. While Trpc6 −/− mice presented reduced neointima formation compared to wild-type mice (1.44 ± 0.39 vs. 2.16 ± 0.48, P = 0.01), activating or repressing TRPC6 in human vascular smooth muscle cells resulted in increased [vehicle 156.9 ± 15.8 vs. 1-oleoyl-2-acetyl-sn-glycerol 179.1 ± 8.07 (103 pixels), P = 0.01] or decreased migratory capacity [vehicle 130.0 ± 26.1 vs. SAR7334 111.4 ± 38.0 (103 pixels), P = 0.04], respectively. In a cohort of individuals with angiographic follow-up (n = 3068, males: 69.9%, age: 59 ± 11 years, follow-up 217.1 ± 156.4 days), homozygous carriers of a common genetic variant associated with elevated TRPC6 expression were at increased risk of restenosis after coronary stenting (adjusted odds ratio 1.49, 95% confidence interval 1.08–2.05; P = 0.01).

Conclusions
Our study provides a proteomic atlas of the healthy and injured arterial wall that can be used to define novel factors for therapeutic targeting. We present TRPC6 as an actionable target to prevent neointima formation secondary to vascular injury and stent implantation.
Serial assessment of biomarkers and the risk of stroke or systemic embolism and bleeding in patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial
Authors: Oyama Kazuma , Giugliano Robert P , Berg David D , Ruff Christian T , Jarolim Petr , Tang Minao , Murphy Sabina A , Lanz Hans J , Grosso Michael A , Antman Elliott M , Braunwald Eugene , Morrow David A 
Published: February 2021

Abstract

Aims
We investigated whether patients with atrial fibrillation (AF) demonstrate detectable changes in biomarkers including high-sensitivity troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) over 12 months and whether such changes from baseline to 12 months are associated with the subsequent risk of stroke or systemic embolic events (S/SEE) and bleeding.

Methods and results
ENGAGE AF-TIMI 48 was a randomized trial of the oral factor Xa inhibitor edoxaban in patients with AF and a CHADS2 score of ≥2. We performed a nested prospective biomarker study in 6308 patients, analysing hsTnT, NT-proBNP, and GDF-15 at baseline and 12 months. hsTnT was dynamic in 46.9% (≥2 ng/L change), NT-proBNP in 51.9% (≥200 pg/mL change), GDF-15 in 45.6% (≥300 pg/mL change) during 12 months. In a Cox regression model, upward changes in log2-transformed hsTnT and NT-proBNP were associated with increased risk of S/SEE [adjusted hazard ratio (adj-HR) 1.74; 95% confidence interval (CI) 1.36–2.23 and adj-HR 1.27; 95% CI 1.07–1.50, respectively] and log2-transformed GDF-15 with bleeding (adj-HR 1.40; 95% CI 1.02–1.92). Reassessment of ABC-stroke (age, prior stroke/transient ischaemic attack, hsTnT, and NT-proBNP) and ABC-bleeding (age, prior bleeding, haemoglobin, hsTnT, and GDF-15) risk scores at 12 months accurately reclassified a significant proportion of patients compared with their baseline risk [net reclassification improvement (NRI) 0.50; 95% CI 0.36–0.65; NRI 0.42; 95% CI 0.33–0.51, respectively].

Conclusion
Serial assessment of hsTnT, NT-proBNP, and GDF-15 revealed that a substantial proportion of patients with AF had dynamic values. Greater increases in these biomarkers measured over 1 year are associated with important clinical outcomes in anticoagulated patients with AF.
The European TeleCheck-AF project on remote app-based management of atrial fibrillation during the COVID-19 pandemic: centre and patient experiences
Authors: Gawałko Monika , Duncker David , Manninger Martin , van der Velden Rachel M.J. , Hermans Astrid N.L. , Verhaert Dominique V.M. , Pison Laurent , Pisters Ron , Hemels Martin , Sultan Arian , Steven Daniel , Gupta Dhiraj , Heidbuchel Hein , Sohaib Afzal , Wijtvliet Petra , Tieleman Robert , Gruwez Henri , Chun Julian , Schmidt Boris , Keaney John J. , Müller Patrick , Lodziński Piotr , Svennberg Emma , Hoekstra Olga , Jansen Ward P.J. , Desteghe Lien , de Potter Tom , Tomlinson David R. , Neubeck Lis , Crijns Harry J.G.M. , Pluymaekers Nikki A.H.A. , Hendriks Jeroen M. , Linz Dominik ,   the TeleCheck-AF investigators
Published: February 2021

Abstract

Aims
TeleCheck-AF is a multicentre international project initiated to maintain care delivery for patients with atrial fibrillation (AF) during COVID-19 through teleconsultations supported by an on-demand photoplethysmography-based heart rate and rhythm monitoring app (FibriCheck®). We describe the characteristics, inclusion rates, and experiences from participating centres according the TeleCheck-AF infrastructure as well as characteristics and experiences from recruited patients.

Methods and results
Three surveys exploring centre characteristics (n = 25), centre experiences (n = 23), and patient experiences (n = 826) were completed. Self-reported patient characteristics were obtained from the app. Most centres were academic (64%) and specialized public cardiology/district hospitals (36%). Majority of the centres had AF outpatient clinics (64%) and only 36% had AF ablation clinics. The time required to start patient inclusion and total number of included patients in the project was comparable for centres experienced (56%) or inexperienced in mHealth use. Within 28 weeks, 1930 AF patients were recruited, mainly for remote AF control (31% of patients) and AF ablation follow-up (42%). Average inclusion rate was highest during the lockdown restrictions and reached a steady state at a lower level after easing the restrictions (188 vs. 52 weekly recruited patients). Majority (&gt;80%) of the centres reported no problems during the implementation of the TeleCheck-AF approach. Recruited patients [median age 64 (55–71), 62% male] agreed that the FibriCheck® app was easy to use (94%).

Conclusion
Despite different health care settings and mobile health experiences, the TeleCheck-AF approach could be set up within an extremely short time and easily used in different European centres during COVID-19.
Neoclassical Realist Theories, Intervening Variables, and Paradigmatic Boundaries
Authors: Götz Elias 
Published: February 2021

AbstractExtant neoclassical realist scholarship has identified a range of real-world factors (e.g., state capacity, interest group pressure, strategic culture, and leadership personality) that serve as intervening variables between systemic imperatives and states’ foreign policy behavior. Despite these elaborations, the intervening variable concept remains underdeveloped. In this article, I show that neoclassical realists have lumped together three different types of causal factors under the label intervening variable: (1) moderating factors, (2) complementary factors, and (3) primary causes. Making these distinctions explicit will enable scholars to increase the analytical precision of neoclassical realist approaches, choose appropriate research designs to test them, and define more clearly the paradigmatic boundaries of neoclassical realism vis-à-vis other perspectives.
The Domestic Sources of Détente: State–Society Relations and Foreign Policy Change during the Cold War
Authors: Chryssogelos Angelos , Martill Benjamin 
Published: February 2021

AbstractResearch on foreign policy change claims leaders seek to restructure their country's foreign relations when internal and external opportunity structures are permissive. However, a number of prominent efforts at achieving change have occurred during times of considerable domestic upheaval and rigid international constraints. To understand why, this article examines three well-known cases of Cold War foreign policy change, focusing on the external relations of Charles de Gaulle in France, John G. Diefenbaker in Canada, and Willy Brandt in West Germany. These cases suggest that domestic upheaval and foreign policy change were inextricably interwoven and that efforts to effect strategic change on a grand scale were motivated by a desire to respond to the demands of marginalized domestic constituencies without incurring the costs of domestic reform. Our analysis suggests key moments of international change are best understood as domestic incorporation strategies rather than instances of significant and principled foreign policy change.
Hydrogen Sulfide Upregulates Acid-sensing Ion Channels via the MAPK-Erk1/2 Signaling Pathway
Authors: Peng Zhong , Kellenberger Stephan 
Published: February 2021

Abstract
Hydrogen sulfide (H2S) emerged recently as a new gasotransmitter and was shown to exert cellular effects by interacting with proteins, among them many ion channels. Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive Na+ channels activated by extracellular protons. ASICs are involved in many physiological and pathological processes, such as fear conditioning, pain sensation, and seizures. We characterize here the regulation of ASICs by H2S. In transfected mammalian cells, the H2S donor NaHS increased the acid-induced ASIC1a peak currents in a time- and concentration-dependent manner. Similarly, NaHS potentiated also the acid-induced currents of ASIC1b, ASIC2a, and ASIC3. An upregulation induced by the H2S donors NaHS and GYY4137 was also observed with the endogenous ASIC currents of cultured hypothalamus neurons. In parallel with the effect on function, the total and plasma membrane expression of ASIC1a was increased by GYY4137, as determined in cultured cortical neurons. H2S also enhanced the phosphorylation of the extracellular signal-regulated kinase (pErk1/2), which belongs to the family of mitogen-activated protein kinases (MAPKs). Pharmacological blockade of the MAPK signaling pathway prevented the GYY4137-induced increase of ASIC function and expression, indicating that this pathway is required for ASIC regulation by H2S. Our study demonstrates that H2S regulates ASIC expression and function, and identifies the involved signaling mechanism. Since H2S shares several roles with ASICs, as for example facilitation of learning and memory, protection during seizure activity, and modulation of nociception, it may be possible that H2S exerts some of these effects via a regulation of ASIC function.
Application of the differential effective medium theory to determine fluid saturation and crack density from measured P- and S-wave velocities
Authors: Zillmer M , Kashtan B M , Doukoure F , Marthelot J-M 
Published: February 2021

SUMMARY
The differential effective medium (DEM) theory studied in this paper describes elastic moduli of a fractured medium with help of differential equations, where crack density is the independent variable and fluid saturation is a parameter. The effective medium is isotropic for randomly oriented flat ellipsoidal cracks and thus fully characterized by two elastic constants. In this article we derive an analytical solution of the equation for Poisson’s ratio and we transform the differential equation for Young’s modulus into a non-linear algebraic equation. Fluid saturation and crack density can then be determined from measured wave propagation velocities by a simple algorithm. We also derive approximate solutions for elastic moduli as a function of crack density and saturation, which allows to quantify the uncertainty of the result due to measurement errors. The DEM theory leads to higher crack densities than the self-consistent method and to lower crack densities than the non-interacting theory for measured elastic moduli, while all three methods give similar fluid saturation fractions. As an example of application of our theoretical results, we study weathered granite in the Strengbach water catchment in the Vosges mountains in France. We have performed full waveform sonic logging measurements in an 86-m-deep borehole located at an altitude of 1130 m above sea level, which is used for hydrogeophysical and geochemical studies of a granitic aquifer. The logging data allows us to investigate P and S waves in the depth range between 40 and 80 m. The P- and S-wave propagation velocities take average values of 5.0 and 2.7 km s–1, respectively, with the highest values of 5.8 and 3.2 km s–1 at 75–80 m depth. From these velocities we obtain a water saturation of 75 ± 25 per cent. The crack density describes the degree of weathering of the granite, which generally decreases with depth, but takes high values near layers of strongly weathered granite. Crack density is on average 0.5, with the highest value of 1.0 at 65 m and the lowest value of 0.2 at 75 m depth. The analysis of the full waveform logging data by the DEM method supports results from previous geochemical and hydrological studies in the Strengbach catchment which concluded that water is stored in deeper layers of the granitic aquifer.
A Comparative Study Between Two Combat Injury Severity Scores
Authors: García Cañas Rafael , Navarro Suay Ricardo , Rodríguez Moro Carlos , Crego Vita Diana M , Arias Díaz Javier , Areta Jiménez Fco. Javier 
Published: February 2021

ABSTRACT

Introduction
In recent years, specific trauma scoring systems have been developed for military casualties. The objective of this study was to examine the discrepancies in severity scores of combat casualties between the Abbreviated Injury Scale 2005-Military (mAIS) and the Military Combat Injury Scale (MCIS) and a review of the current literature on the application of trauma scoring systems in the military setting.

Methods
A cross-sectional, descriptive, and retrospective study was conducted between May 1, 2005, and December 31, 2014. The study population consisted of all combat casualties attended in the Spanish Role 2 deployed in Herat (Afghanistan). We used the New Injury Severity Score (NISS) as reference score. Severity of each injury was calculated according to mAIS and MCIS, respectively. The severity of each casualty was calculated according to the NISS based on the mAIS (Military New Injury Severity Score—mNISS) and MCIS (Military Combat Injury Scale-New Injury Severity Score—MCIS-NISS). Casualty severity were grouped by severity levels (mild—scores: 1-8, moderate—scores: 9-15, severe—scores: 16-24, and critical—scores: 25-75).

Results
Nine hundred and eleven casualties were analyzed. Most were male (96.37%) with a median age of 27 years. Afghan patients comprised 71.13%. Air medevac was the main casualty transportation method (80.13). Explosion (64.76%) and gunshot wound (34.68%) mechanisms predominated. Overall mortality was 3.51%. Median mNISS and MCIS-NISS were similar in nonsurvivors (36 [IQR, 25-49] vs. [IQR, 25-48], respectively) but different in survivors, 9 (IQR, 4-17) vs. 5 (IQR, 2-13), respectively (P &lt; .0001). The mNISS and MCIS-NISS were discordant in 34.35% (n = 313). Among cases with discordant severity scores, the median difference between mNISS and MCIS-NISS was 9 (IQR, 4-16); range, 1 to 57.

Conclusion
Our study findings suggest that discrepancies in injury severity levels may be observed in one in three of the casualties when using mNISS and MCIS-NISS.