bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tubulosine selectively inhibits JAK3 signalling by binding to the ATP‐binding site of the kinase of JAK3
Authors: Kim Byung‐Hak , Yi Eun Hee , Jee Jun‐Goo , Jeong Ae Jin , Sandoval Claudio , Park In‐Chul , Baeg Gyeong Hun , Ye Sang‐Kyu 
Published: June 2020

AbstractGain‐ or loss‐of‐function mutations in Janus kinase 3 (JAK3) contribute to the pathogenesis of various haematopoietic malignancies and immune disorders, suggesting that aberrant JAK3 signalling is an attractive therapeutic target to treat these disorders. In this study, we performed structure‐based computational database screening using the 3D structure of the JAK3 kinase domain and the National Cancer Institute diversity set and identified tubulosine as a novel JAK3 inhibitor. Tubulosine directly blocked the catalytic activity of JAK3 by selective interacting with the JAK3 kinase domain. Consistently, tubulosine potently inhibited persistently activated and interleukin‐2‐dependent JAK3, and JAK3‐mediated downstream targets. Importantly, it did not affect the activity of other JAK family members, particularly prolactin‐induced JAK2/signal transducer and activator of transcription 5 and interferon alpha‐induced JAK1‐TYK2/STAT1. Tubulosine specifically decreased survival and proliferation of cancer cells, in which persistently active JAK3 is expressed, by inducing apoptotic and necrotic/autophagic cell death without affecting other oncogenic signalling. Collectively, tubulosine is a potential small‐molecule compound that selectively inhibits JAK3 activity, suggesting that it may serve as a promising therapeutic candidate for treating disorders caused by aberrant activation of JAK3 signalling.
Perceived dietary salt intake and the risk of primary liver cancer: a population‐based prospective study
Authors: Sun M. , Cui H. , Liang M. , Wang W. , Wang Y. , Liu X. , Liu S. , Cao L. 
Published: June 2020

AbstractBackgroundAlthough a high‐salt diet is associated with high risk of chronic diseases such as hypertension, stroke and cardiovascular disease, little is known about the relationship between a high‐salt diet and the risk of primary liver cancer (PLC). Consequently, we prospectively assessed the association of high perceived salt intake with the risk of PLC in the Kailuan Study.MethodsIn total, 97 006 participants who were healthy adults or free living adults at the baseline (2006) were included in the present study. The data of perceived salt intake were collected via questionnaire and classified into three categories: <6 g day−1 for low salt intake, 6–10 g day−1 for intermediate salt intake, >10 g day−1 for high‐salt intake. PLC including hepatocellular carcinoma and intrahepatic cholangiocarcinoma (excluding liver metastasis), and was confirmed by review of medical records. We used a Cox proportional hazards model to analyse the association between high perceived salt diet and the risk of PLC after adjusting for possible confounders, including age, gender, body mass index, high sensitivity‐C‐reactive protein, low‐density lipoprotein‐cholesterol, total cholesterol, triglycerides, alanine aminotransferase, HbsAg positive, cirrhosis, fatty liver, hypertension, diabetes, drinking status, smoking status and physical exercise.ResultsDuring the follow‐up period of 1 113 816 person‐years, 397 PLC events were diagnosed. After adjusting for most potential confounders, subjects in intermediate salt intake and high salt intake had a multivariable hazard ratio and 95% confidence interval of 1.49 (0.97–2.29) and 1.98 (1.22–3.22) (P for trend = 0.0042), respectively, compared to low salt intake.ConclusionsA higher perceived salt intake was associated with a higher risk of PLC.
Association between viral hepatitis infection and Parkinson's disease: A population‐based prospective study
Authors: Choi Hwa‐Young , Mai Thi Ha , Kim Kyung‐Ah , Cho Hyunsoon , Ki Moran 
Published: June 2020

AbstractThe association between hepatitis virus infection and Parkinson's disease remains controversial. To determine whether hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are associated with an increased risk of Parkinson's disease in Korean aged ≥40 years, we completed a population‐based prospective study including patients without infections and those with HBV, HCV and HBV/HCV infections from 2005 to 2015. We used the International Classification of Diseases 10th Revision to identify Parkinson's disease (G20) and chronic hepatitis C virus (B18.2) and chronic hepatitis B virus infections (B18.0 or B18.1). To identify Parkinson's disease risk, competing risk analysis adjusted for age, sex, comorbidities and death was performed. Overall, 1 010 317 patients (358 052, noninfection; 488 990, hepatitis B; 144 459 hepatitis C; and 18 680 hepatitis B/C) were included. The incidence density of Parkinson's disease per 10 000 person‐years was highest in the hepatitis C group (8.0), followed by the hepatitis B/C (6.8) and hepatitis B (5.0) groups. Hypertension, ischaemic heart disease, epilepsy, stroke and depressive disorder increased the hazard of Parkinson's disease in all groups. The adjusted hazard ratios were 1.25 (95% confidence interval: 1.17‐1.35), 1.39 (95% confidence interval: 1.27‐1.52) and 1.46 (95% confidence interval: 1.14‐1.85) in the HBV, HCV, and HBV/HCV groups, respectively. Our findings suggest that adult patient of 40 years and older with HBV and HCV infections should be monitored for signs of Parkinson's disease so that early intervention and accurate treatment can be provided for minimizing the development and consequences of Parkinson's disease.
Who cares about the stream of consciousness? On Dorothy Richardson's Pilgrimage
Authors: Guy Adam 
Published: June 2020

AbstractThis article brings the concept of care into the discussion of the literary representation of the stream of consciousness in Dorothy Richardson's thirteen‐volume novel sequence Pilgrimage. I begin by looking at recent theorizations of care by Joan C. Tronto and Berenice Fisher, by Maria Puig de la Bellacasa, and by Sandra Laugier. I show confluences between this work and May Sinclair's famous essay on Richardson—in which the term “stream of consciousness” was first applied to a literary text. I then explore three interrelated forms of care that are central to Richardson's work. Subsequently, I isolate a particular strand in Pilgrimage in which Richardson's protagonist, Miriam Henderson, consistently conceives of her own consciousness in terms of care. I reflect in conclusion on the broader ramifications that care might have for considerations of the stream of consciousness in relation to the modernist novel.
Andrew Shanks, German Idealism, and the Speculative Redemption of Theodicy
Authors: O’Regan Cyril 
Published: June 2020

AbstractIn this review essay I discuss and critically evaluate the neo‐Hegelian theologian Andrew Shanks’ Theodicy Beyond the Death of ‘God’ with regard to its central argument of the theological adequacy of the composite theodicy funded by Hegel, Jacob Boehme (1575‐1624) and F. W. J. Schelling and also its highly individual theological style. While I commend Shanks’ impulses to enlarge the Hegelian discourse by speculative discourses that are more mythopoetic, especially given Shanks’ long‐standing interest in the critical and constructive power of poetry, I consider it to be an open question not only as to whether Shanks has sustained his case for the theological adequacy of the composite theodicy, but whether this composite speculative matrix has the capacity to enlist the prophetic discourses of both the Bible and modern poetry that Shanks thinks it has. In addition, while Shanks’ theological style is a unique blend of disciplined analysis with a more hortatory rhetoric, as rendered in this his latest book, the generally polemical tone and the tendency to dismissive judgments not only regarding particular philosophers and theologians, but also particular forms of historical Christianity such as Roman Catholicism, compromise – if not entirely invalidate – its repeated message of inclusion.
Root‐knot nematode genetic diversity associated with host compatibility to sweetpotato cultivars
Authors: Asamizu Erika , Shirasawa Kenta , Hirakawa Hideki , Iwahori Hideaki 
Published: June 2020

AbstractPlant parasitic root‐knot nematodes (RKN) such as Meloidogyne incognita cause significant crop losses worldwide. Although RKN are polyphagous, with wide host ranges, races with differing host compatibilities have evolved. Associations between genotype and infection phenotype in M. incognita have not yet been discovered. In this study, 48 M. incognita isolates were collected from geographically diverse fields in Japan and their genomes sequenced. The isolates exhibited various infection compatibilities to five sweetpotato (SP) cultivars and were assigned to SP races. Genome‐wide association analysis identified 743 SNPs affecting gene coding sequences, a large number of which (575) were located on a single 1 Mb region. To examine how this polymorphic region evolved, nucleotide diversity (Pi) was scanned at the whole genome scale. The SNP‐rich 1 Mb region exhibited high Pi values and was clearly associated with the SP races. SP1 and 2 races showed high Pi values in this region whereas the Pi values of SP3, 4, and 6 were low. Principal component analysis of isolates from this study and globally collected isolates showed selective divergence in this 1 Mb region. Our results suggest for the first time that the host could be a key determining factor stimulating the genomic divergence of M. incognita.
Why Do Citizens Vote Against Their Basic Political Values?
Authors: Lauener Lukas 
Published: June 2020

AbstractThe literature on correct and consistent voting has focused on issue‐opinions and argument‐positions when examining whether vote decisions correspond to individual political preferences. However, the question whether vote decisions align with basic political values has largely been neglected so far. This paper introduces a novel measure named value consistent voting. It finds that, in Switzerland, around 25% jettison their basic political values when deciding on proposals. Using multilevel regression analysis of survey data, this paper investigates the determinants of value consistent voting. Three theoretical approaches are tested; the sophistication, identification and ambivalence hypotheses. The results show that political sophistication and identification foster value consistent voting. Moreover, there is an interaction between education and adhering to the preferred party’s vote recommendation. This finding supports the thesis that highly educated citizens use heuristics most efficiently. However, the more ambivalent people are, the more often they vote against their basic political values.
In Vivo Characterization of the Swine Airway Morphometry and Motion Based on Computed Tomographic Imaging During Respiration
Authors: Castro Meryll Grace B. , Varble Nicole A. , Yung Rex C. , Wood Bradford J. , Karanian John W. , Pritchard William F. 
Published: June 2020

Abstract
Swine are a commonly used model in translational pulmonary research. However, in vivo airway morphometry during respiration has not been studied in extensive detail using modern imaging tools. Chest computed tomographic was performed in swine (n = 3) at multiple stages of respiration. Morphometric parameters of each airway segment at end-expiration and end-inspiration were compared as well as among matched anatomical regions (proximal and distal; ventral, lateral, and dorsal). Analysis included segment diameter, length, ellipticity, and the bifurcation angle between daughter branches. Deformation of the airway during respiration was qualitatively visualized using a point-to-point deformation map. Comparison of airway generation showed airway diameter and length were larger at end-inspiration in the fourth and seventh generations compared to end-expiration. Bifurcation angle was larger at end-inspiration compared to end-expiration. Analysis by anatomical region showed that length and bifurcation angle were larger at inspiration in the distal airway regions only. Regardless of respiratory phase, the lateral regions had larger diameters and lengths compared to the ventral and dorsal regions at similar generations and proximal regions had larger bifurcation angles. The findings that morphological changes were more prevalent in distal airways during respiration was confirmed by analysis of a deformation map. Compared to human airway models, the relative diameter may be smaller and length may be greater in swine in similar airway generations. This morphometric description of the swine airways during respiration may guide conduct of preclinical translational studies, revealing advantages and limitations of swine models for specific evaluations. Such morphometric parameters may directly determine the suitability of the swine model for the study of lung interventions, in terms of recapitulation of human morphometry dynamics.
Brane gravity in 4D from Chern–Simons gravity theory
Authors: Díaz R. , Gómez F. , Pinilla M. , Salgado P. 
Published: June 2020

AbstractWe evaluate a 5-dimensional Randall Sundrum type metric in the Lagrangian of the Einstein–Chern–Simons gravity, and then we derive an action and its corresponding field equations, for a 4-dimensional brane embedded in the 5-dimensional space-time of the theory, which in the limit $$l\rightarrow 0$$l→0 leads to the 4-dimensional general relativity with cosmological constant. An interpretation of the $$h^{a}$$ha matter field present in the Einstein–Chern–Simons gravity action is given. As an application, we find some Friedmann–Lemaitre–Robertson–Walker cosmological solutions that exhibit accelerated behavior.
Insult detection using a partitional CNN-LSTM model
Authors: Ben Ismail Mohamed Maher 
Published: June 2020

Recently, deep learning has been coupled with notice- able advances in Natural Language Processing related research. In this work, we propose a general framework to detect verbal offense in social networks comments. We introduce a partitional CNN-LSTM architecture in order to automatically recognize ver- bal offense patterns in social network comments. Specifically, we use a partitional CNN along with a LSTM model to map the social network comments into two predefined classes. In particular, rather than considering a whole document/comments as input as performed using typical CNN, we partition the comments into parts in order to capture and weight the locally relevant information in each partition. The resulting local information is then sequentially exploited across partitions using LSTM for verbal offense detection. The combination of the partitional CNN and LSTM yields the integration of the local within comments information and the long distance correlation across comments. The proposed approach was assessed using real dataset, and the obtained results proved that our solution outperforms existing relevant solutions.
American Heart Association COVID-19 CVD Registry Powered by Get With The Guidelines
Authors: Alger Heather M. , Rutan Christine , Williams Joseph H. , Walchok Jason G. , Bolles Michele , Hall Jennifer L. , Bradley Steven M. , Elkind Mitchell S. V. , Rodriguez Fatima , Wang Tracy Y. , Morrow David A. , Das Sandeep R. , de Lemos James A. 
Published: June 2020

Background:
In response to the public health emergency created by the coronavirus disease 2019 (COVID-19) pandemic, American Heart Association volunteers and staff aimed to rapidly develop and launch a resource for the medical and research community to expedite scientific advancement through shared learning, quality improvement, and research. In <4 weeks after it was first announced on April 3, 2020, AHA’s COVID-19 CVD Registry powered by Get With The Guidelines received its first clinical records.

Methods and Results:
Participating hospitals are enrolling consecutive hospitalized patients with active COVID-19 disease, regardless of CVD status. This hospital quality improvement program will allow participating hospitals and health systems to evaluate patient-level data including mortality rates, intensive care unit bed days, and ventilator days from individual review of electronic medical records of sequential adult patients with active COVID-19 infection. Participating sites can leverage these data for onsite, rapid quality improvement, and benchmarking versus other institutions. After 9 weeks, >130 sites have enrolled in the program and >4000 records have been abstracted in the national dataset. Additionally, the aggregate dataset will be a valuable data resource for the medical research community.

Conclusions:
The AHA COVID-19 CVD Registry will support greater understanding of the impact of COVID-19 on cardiovascular disease and will inform best practices for evaluation and management of patients with COVID-19.
Somatic Gain of KRAS Function in the Endothelium Is Sufficient to Cause Vascular Malformations That Require MEK but Not PI3K Signaling
Authors: Fish Jason E. , Flores Suarez Carlos Perfecto , Boudreau Emilie , Herman Alexander M. , Gutierrez Manuel Cantu , Gustafson Dakota , DiStefano Peter V. , Cui Meng , Chen Zhiqi , De Ruiz Karen Berman , Schexnayder Taylor S. , Ward Christopher S. , Radovanovic Ivan , Wythe Joshua D. 
Published: June 2020

Rationale:

We previously identified somatic activating mutations in the
KRAS
(
Kirsten rat sarcoma viral oncogene homologue
) gene in the endothelium of the majority of human sporadic brain arteriovenous malformations; a disorder characterized by direct connections between arteries and veins. However, whether this genetic abnormality alone is sufficient for lesion formation, as well as how active KRAS signaling contributes to arteriovenous malformations, remains unknown.

Objective:
To establish the first in vivo models of somatic KRAS gain of function in the endothelium in both mice and zebrafish to directly observe the phenotypic consequences of constitutive KRAS activity at a cellular level in vivo, and to test potential therapeutic interventions for arteriovenous malformations.

Methods and Results:

Using both postnatal and adult mice, as well as embryonic zebrafish, we demonstrate that endothelial-specific gain of function mutations in
Kras
(G12D or G12V) are sufficient to induce brain arteriovenous malformations. Active KRAS signaling leads to altered endothelial cell morphogenesis and increased cell size, ectopic sprouting, expanded vessel lumen diameter, and direct connections between arteries and veins. Furthermore, we show that these lesions are not associated with altered endothelial growth dynamics or a lack of proper arteriovenous identity but instead seem to feature exuberant angiogenic signaling. Finally, we demonstrate that KRAS-dependent arteriovenous malformations in zebrafish are refractory to inhibition of the downstream effector PI3K but instead require active MEK (mitogen-activated protein kinase kinase 1) signaling.

Conclusions:
We demonstrate that active KRAS expression in the endothelium is sufficient for brain arteriovenous malformations, even in the setting of uninjured adult vasculature. Furthermore, the finding that KRAS-dependent lesions are reversible in zebrafish suggests that MEK inhibition may represent a promising therapeutic treatment for arteriovenous malformation patients.

Graphical Abstract:
A graphical abstract is available for this article.
Pathological Role of Receptor for Advanced Glycation End Products in Calcified Aortic Valve Stenosis
Authors: Saku Kosuke , Tahara Nobuhiro , Takaseya Tohru , Otsuka Hiroyuki , Takagi Kazuyoshi , Shojima Takahiro , Shintani Yusuke , Zaima Yasuyuki , Kikusaki Satoshi , Fukuda Tomofumi , Oryoji Atsunobu , Nishino Yuri , Matsui Takanori , Kakuma Tatsuyuki , Akiba Jun , Fukumoto Yoshihiro , Yamagishi Sho‐ichi , Tanaka Hiroyuki 
Published: June 2020

Background

Aortic stenosis (
AS
) is highly prevalent in patients with atherosclerotic cardiovascular disease. Advanced glycation end products (
AGE
s) and the receptor for
AGE
s (
RAGE
) play a pivotal role for vascular calcification in atherosclerosis. We hypothesize that the AGEs–
RAGE
axis could also be involved in the pathophysiological mechanism of calcified
AS
.

Methods and Results

A total of 54 patients with calcified
AS
who underwent aortic valve replacement were prospectively enrolled from 2014 to 2016 (mean age 75.3±7.7 years). Aortic valve specimens were obtained from 47 patients and 16 deceased control subjects without aortic valve disease (mean age 63.2±14.5 years). The valvular expression of
RAGE
was evaluated by immunohistochemistry. Serum levels of
AGE
s and soluble
RAGE
were measured in 50 patients with calcified
AS
and 70 age‐matched and sex‐matched control subjects without heart disease. The valvular
RAGE
expression in patients with calcified
AS
was higher than controls (
P
=0.004) and was significantly associated with a decreased ankle‐brachial pressure index (
P
=0.007) and an increased intima‐media thickness (
P
=0.026).
RAGE
and α–smooth muscle actin were coexpressed and were partially costained with osteocalcin and alkaline phosphatase. The serum levels of
AGE
s and soluble RAGE were significantly higher in the patients with calcified
AS
than in the controls (
P
=0.013 and
P
<0.001, respectively). Soluble RAGE (inversely) and use of aspirin were independently correlated with changes in left ventricular systolic function after aortic valve replacement (
P
=0.012 and
P
=0.002, respectively).

Conclusions

Our present study suggests that
RAGE
may play a role in the pathogenesis of calcified
AS
, which is a prognostic marker in patients with
AS
after aortic valve replacement.
The Effects of Restricted Work Hours on Clinical Training
Authors: Karamanoukian Raffy L. , Ku Joseph K. , Delarosa Jacob , Karamanoukian Hratch L. , Evans Gregory R.D. 
Published: June 2020

Resident education has changed dramatically over the past 10 years. With the implementation of restricted work hours on clinical training, questions have arisen whether these restricted hours will affect clinical competency. This manuscript attempts to answer this question through a survey performed to assess the perception of residents about duty-hour restrictions and the potential effect on residents’ clinical exposure. In this study, a majority of the respondents did believe that work-week restrictions significantly affected patient care and clinical exposure. However, few respondents were willing to accept an additional year of training to compensate for the loss of this clinical exposure. Regardless, work-hour restrictions are here to stay and will probably be further limited in the future. Training programs will have to adjust to provide the necessary clinical exposure while complying with these new ACGME guidelines.