bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors of Coronary Artery Abnormalities and Resistance to Intravenous Immunoglobulin Plus Corticosteroid Therapy in Severe Kawasaki Disease
Authors: Miyata Koichi , Miura Masaru , Kaneko Tetsuji , Morikawa Yoshihiko , Sakakibara Hiroshi , Matsushima Takahiro , Misawa Masahiro , Takahashi Tsutomu , Nakazawa Maki , Tsuchihashi Takatoshi , Yamashita Yukio , Obonai Toshimasa , Chiga Michiko , Hori Naoaki , Komiyama Osamu , Yamagishi Hiroyuki 
Published: February 2021

Background:
Coronary artery abnormalities (CAAs) still occur in patients with Kawasaki disease receiving intensified treatment with corticosteroids. We aimed to determine the risk factors of CAA development and resistance to intensified treatment in Post RAISE (Prospective Observational Study on Stratified Treatment With Immunoglobulin Plus Steroid Efficacy for Kawasaki Disease)—the largest prospective cohort of Kawasaki disease patients to date.

Methods:
In Post RAISE, 2648 consecutive patients with Kawasaki disease were enrolled. The present study analyzed 724 patients predicted to be intravenous immunoglobulin (IVIG) nonresponders (Kobayashi score ≥5) who received intensified treatment consisting of IVIG plus prednisolone. The association between the baseline characteristics and CAA at 1 month after disease onset was examined. The association between the baseline characteristics and treatment resistance was also investigated.

Results:

Maximum
Z
score at baseline ≥2.5 (odds ratio, 3.4 [95% CI, 1.5–7.8]), age at fever onset <1 year (odds ratio, 3.4 [95% CI, 1.6–7.4]), and nonresponsiveness to IVIG plus prednisolone treatment (odds ratio, 6.8 [95% CI, 3.3–14.0]) were independent predictors of CAA development. Nonresponsiveness to IVIG plus prednisolone was significantly associated with 8 baseline variables. Baseline total bilirubin (odds ratio, 1.4 [95% CI, 1.2–1.7]) was the only significant independent predictor other than the variables included in the Kobayashi score, enabling treatment resistance to be identified at diagnosis. The area under the ROC curve was 0.74 (95% CI, 0.69–0.79). At a cutoff point of 1.0, the sensitivity and specificity for predicting treatment resistance were 71% and 65%, respectively.

Conclusions:

In Post RAISE, younger age at fever onset, a larger maximum
Z
score at baseline, and nonresponsiveness to IVIG plus prednisolone were risk factors significantly associated with CAA development. Nonresponders were able to be identified at diagnosis based on the total bilirubin value. To prevent CAA, more intensified or adjunctive therapies using other agents, such as pulsed methylprednisolone, ciclosporin, infliximab, and Anakinra, should be considered for patients with these risk factors.

Registration:

URL:
https://www.umin.ac.jp/ctr/
; Unique identifier: UMIN000007133.
MicroRNA Biophysically Modulates Cardiac Action Potential by Direct Binding to Ion Channel
Authors: Yang Dandan , Wan Xiaoping , Dennis Adrienne T. , Bektik Emre , Wang Zhihua , Costa Mauricio G.S. , Fagnen Charline , Vénien-Bryan Catherine , Xu Xianyao , Gratz Daniel H. , Hund Thomas J. , Mohler Peter J. , Laurita Kenneth R. , Deschênes Isabelle , Fu Ji-Dong 
Published: February 2021

Background:
MicroRNAs (miRs) play critical roles in regulation of numerous biological events, including cardiac electrophysiology and arrhythmia, through a canonical RNA interference mechanism. It remains unknown whether endogenous miRs modulate physiologic homeostasis of the heart through noncanonical mechanisms.

Methods:
We focused on the predominant miR of the heart (miR1) and investigated whether miR1 could physically bind with ion channels in cardiomyocytes by electrophoretic mobility shift assay, in situ proximity ligation assay, RNA pull down, and RNA immunoprecipitation assays. The functional modulations of cellular electrophysiology were evaluated by inside-out and whole-cell patch clamp. Mutagenesis of miR1 and the ion channel was used to understand the underlying mechanism. The effect on the heart ex vivo was demonstrated through investigating arrhythmia-associated human single nucleotide polymorphisms with miR1-deficient mice.

Results:

We found that endogenous miR1 could physically bind with cardiac membrane proteins, including an inward-rectifier potassium channel Kir2.1. The miR1–Kir2.1 physical interaction was observed in mouse, guinea pig, canine, and human cardiomyocytes. miR1 quickly and significantly suppressed I
K1
at sub–pmol/L concentration, which is close to endogenous miR expression level. Acute presence of miR1 depolarized resting membrane potential and prolonged final repolarization of the action potential in cardiomyocytes. We identified 3 miR1-binding residues on the C-terminus of Kir2.1. Mechanistically, miR1 binds to the pore-facing G-loop of Kir2.1 through the core sequence AAGAAG, which is outside its RNA interference seed region. This biophysical modulation is involved in the dysregulation of gain-of-function Kir2.1–M301K mutation in short QT or atrial fibrillation. We found that an arrhythmia-associated human single nucleotide polymorphism of miR1 (hSNP14A/G) specifically disrupts the biophysical modulation while retaining the RNA interference function. It is remarkable that miR1 but not hSNP14A/G relieved the hyperpolarized resting membrane potential in miR1-deficient cardiomyocytes, improved the conduction velocity, and eliminated the high inducibility of arrhythmia in miR1-deficient hearts ex vivo.

Conclusions:
Our study reveals a novel evolutionarily conserved biophysical action of endogenous miRs in modulating cardiac electrophysiology. Our discovery of miRs’ biophysical modulation provides a more comprehensive understanding of ion channel dysregulation and may provide new insights into the pathogenesis of cardiac arrhythmias.
Endothelial Conditional Knockdown of NMMHC IIA (Nonmuscle Myosin Heavy Chain IIA) Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury
Authors: Gong Shuaishuai , Cao Guosheng , Li Fang , Chen Zhuo , Pan Xuewei , Ma Huifen , Zhang Yuanyuan , Yu Boyang , Kou Junping 
Published: February 2021

Background and Purpose:
In ischemic stroke, breakdown of the blood-brain barrier (BBB) aggravates brain damage. Endothelial detachment contributes to BBB disruption and neurovascular dysfunction, but its regulation in stroke has yet to be clarified. We investigated the function of NMMHC IIA (nonmuscle myosin heavy chain IIA) in the endothelium on BBB breakdown and its potential mechanisms.

Methods:

Endothelial conditional knockdown NMMHC IIA (

Myh9
ECKD

) was constructed in vivo and in vitro, and its role was explored in middle cerebral artery occlusion/reperfusion–injured mice and oxygen-glucose deprivation/reoxygenation–injured brain microvascular endothelial cells. The degree of brain injury was analyzed using staining (2,3,5-triphenyltetrazolium chloride, hematoxylin, and eosin) and electron microscopy. BBB breakdown was investigated with leakage of Evans Blue dye and expression of TJs (tight junctions) and MMP (matrix metallopeptidase)-2/9. Transcriptomics for enrichment analysis was adopted to explore the potential downstream signaling pathways of NMMHC IIA involved in middle cerebral artery occlusion/reperfusion–induced BBB dysfunction.

Results:

NMMHC IIA expression was upregulated in endothelial cells after cerebral ischemia/reperfusion injury.

Myh9
ECKD

mice exhibited improvement in endothelial barrier hyperpermeability and TJs integrity stimulated by cerebral ischemia/reperfusion. Blebbistatin (NMMHC II inhibitor) treatment exerted the same effect. Transcriptomics showed that NMMHC IIA was involved in regulating various BBB-related genomic changes in the middle cerebral artery occlusion/reperfusion model, and NMMHC IIA was confirmed to significantly modulate Hippo and peroxisome proliferator-activated receptor gamma/nuclear factor-kappa B signaling pathways, which are closely related to BBB damage.

Conclusions:
Our findings provide some new insights into how NMMHC IIA contributes to maintaining the integrity of the cerebral endothelial barrier. NMMHC IIA could be a potential therapeutic target for ischemic stroke.
Subclinical Atrial Fibrillation Burden and Adverse Clinical Outcomes in Patients With Permanent Pacemakers
Authors: Park Young Jun , Kim June Soo , Park Kyoung-Min , On Young Keun , Park Seung-Jung 
Published: February 2021

Background and Purpose:
Unlike clinical atrial fibrillation (AF), the significance of subclinical AF (SCAF) burden in patients with permanent pacemakers has not been fully evaluated.

Methods:
We investigated whether the SCAF burden was associated with increased risks of composite adverse outcomes, including progression to clinical AF, ischemic stroke, myocardial infarction, heart failure-related hospitalization, or cardiac death, in patients without previous AF. To quantify the 6-month SCAF burden, the total cumulative time spent in SCAF during every 6-month follow-up was summed.

Results:

During the median 5.2-year follow-up, 496 consecutive permanent pacemaker patients were classified into the no SCAF (no SCAF episode in any device analysis; n=152), low-burden SCAF (6-month SCAF <24 hours in at least one device analysis; n=287), or high-burden SCAF (6-month SCAF ≥24 hours in at least 1 device analysis; n=57) groups. The risk of composite adverse outcomes was greatest in the high-burden SCAF group (
P
<0.001) and was primarily driven by progression to clinical AF (
P
<0.001) and ischemic stroke (
P
<0.001). The presence of high-burden SCAF, which always preceded ischemic stroke events, was independently associated with composite adverse outcomes (odds ratio=20.1 [95% CI, 7.60−52.7],
P
<0.001) and progression to clinical AF (odds ratio, 36.2 [95% CI, 15.9−87.8],
P
<0.001).

Conclusions:
In permanent pacemaker patients without preexisting AF, the presence of high-burden SCAF was closely associated with increased risks of composite adverse outcomes, particularly progression to clinical AF and ischemic stroke. Therefore, prospective studies deserve to be performed on the optimal anticoagulation therapy for permanent pacemaker patients with both high-burden SCAF and high stroke risk.
The Quest for the “Charity Dish”: Interpretation in the Hebrew Arthurian Translation Melekh Artus (1279, Northern Italy)
Authors: Gruenbaum Caroline 
Published: February 2021

Abstract
This article analyzes Melekh Artus (King Arthur), a unique Hebrew translation of sections from the old French prose Merlin and mort Artu in the Lancelot-Grail cycle. Written in a single fragment from 1279 in northern Italy, this translation proves close Jewish engagement with old French texts. Through satirical biblical references and subtle critique of his material, the author reframes the Arthurian narrative to promote universal morals. Rather than Judaize the Arthurian canon and its Christian characters, he validates them as viable models for his Jewish audience.
Les Intellectuels Camerounais Sous le Regime Ahidjo (1958-1982)
Authors: Emagna Maximin 
Published: February 2021

The Intellectuals in Cameroon Under the Rule of Ahidjo (1958-1982)
A study concerning the intellectuals of the Third World in general, and African intellectuals in particular, should not exclude the political context in which intellectuals live and work. Indeed, democracy cannot truly emerge and remain durable without the existence of freedom of thought and criticism.
In Cameroon, intellectuals and their ideas have always been considered seditious and subversive. For this reason, they have often been persecuted. Some have chosen freely or by the force of circumstances to become bureaucrats within the administrative and political structures of the country to ensure their survival (political and social immortality) as also that of their family. Others, by principle, have combined their intellectual and cyclical factors which push intellectuals either to become civil servants or to choose exile. It also contradicts the idea of intellectual deficiency in Africa. Indeed, some categories of intellectuals such as writers, via their writings, ask questions and provide a critical review of the economic, political and social reality of the country. They even propose alternative ideas and proposals to such questions as management, government and governance in the coutry. Dictatorships may destroy individuals, but never ideas or the spirit of liberty.
Het Spaar- En Kredietprogramma Van Vredeseilanden / Rafia in Noord-Togo: Een Kritische Evaluatie
Authors: Van Damme Patrick , Hatse Inge 
Published: February 2021

The Savings and Credit Program of Vredeseilanden (Islands of Peace) / Rafia in Northern-Togo: A Critical Evaluation
Northern Togo has never been over-assisted as some of the other dry and poor areas of West Africa have been. It has never been a priority of national or international development organisations. As a consequence, the area has intermittent food security problems. Islands of Peace (Vredeseilanden), a Flemish NGO for development cooperation, however, has initiated a (successful) savings and credit scheme based on local surpluses which now allows local populations to invest and consolidate their (food security) situation.
Absence of strict monogamy in the Eurasian jackdaw, Coloeus monedula
Authors: Turjeman Sondra , Chen Ron , Nathan Ran 
Published: February 2021

Abstract
The Eurasian Jackdaw is thought to be archetypically monogamous, but recent tagging research uncovered extra-pair copulations in the species. Here we examined extra-pair paternity (genetic monogamy) in Eurasian jackdaws breeding in the Judean Hills, Israel, at the global edge of the species range, using a set of highly polymorphic molecular microsatellites. We found roughly a sixth of nests sampled showed deviations from monogamy, more than previously found in DNA fingerprinting studies of jackdaws, suggesting a mixed mating strategy in this population. These findings support the trend of extra-pair paternity in avian species, even when social monogamy remains the rule, and highlight the importance of continued study of species throughout their geographical range.
Impact of Evaporation and Precipitation on Estuarine Mixing
Authors: Lorenz Marvin , Klingbeil Knut , Burchard Hans 
Published: February 2021

AbstractRecent studies could link the quantities of estuarine exchange flows to the volume-integrated mixing inside an estuary, where mixing is defined as the destruction of salinity variance. The existing mixing relations quantify mixing inside an estuary by the net boundary fluxes of volume, salinity, and salinity variance, which are quantified as Knudsen or total exchange flow bulk values. So far, river runoff is the only freshwater flux included, and the freshwater exchange due to precipitation and evaporation is neglected. Yet, the latter is the driving force of inverse estuaries, which could not be described by the existing relations. To close this gap, this study considers evaporation and precipitation to complete the existing mixing relations by including cross-surface salinity variance transport. This allows decomposing the mixing into a riverine and a surface transport contribution. The improved relations are tested against idealized two-dimensional numerical simulations of different combinations of freshwater forcing. The mixing diagnosed from the model results agrees exactly with the derived mixing relation. An annual hindcast simulation of the Persian Gulf is then used to test the mixing relations, both exact and approximated, e.g., long-term averaged, for a realistic inverse estuary. The results show that the annual mean mixing contributions of river discharge and evaporation are almost equal, although the freshwater transport due to evaporation is about one order of magnitude larger than the river runoff.
Identifying Priorities for Harmonizing Guidelines for the Long-Term Surveillance of Childhood Cancer Survivors in the Chinese Children Cancer Group (CCCG)
Authors: Cheung Yin Ting , Zhang Hui , Cai Jiaoyang , Au-Doung Lung Wai Phillip , Yang Lok Sum , Yan Cuixia , Zhou Fen , Chen Xiaojuan , Guan Xianmin , Pui Ching-Hon , Hudson Melissa M. , Li Chi-kong 
Published: February 2021

PURPOSE Survivors of childhood cancer often experience treatment-related chronic health conditions. Given its vast population, China shares a large proportion of the global childhood cancer burden. Yet, screening and treatment of late effects in survivors of childhood cancer remain underaddressed in most regions of China. This study aimed to identify high-priority late effects for harmonizing screening guidelines within the Chinese Children's Cancer Group (CCCG), as well as barriers and enablers of the implementation of surveillance recommendations in local practice. METHODS To establish clinical consensus, 12 expert panelists who represent major institutions within the CCCG completed a Delphi survey and participated in a focus group discussion. The survey solicited ratings of the prevalence, severity, and priority for screening of 45 late effects. Major themes identified from the focus group were analyzed using thematic analysis. RESULTS The Delphi survey identified eight high-priority late effects for harmonization within CCCG: osteonecrosis, osteoporosis, left ventricular dysfunction, secondary brain tumors, treatment-related myeloid leukemia, gonadal dysfunction, growth hormone deficiency, and neurocognitive deficits. The common barriers to implementing survivorship programs include lack of support and resources for clinicians to provide follow-up care. Patients were also concerned about privacy issues and lacked awareness of late effects. Many institutions also lacked rehabilitation expertise and referral pathways. CONCLUSION By identifying obstacles related to the professional setting, patient behavior, and organization of care, our study identified resources and a framework for establishing collaborative strategies to facilitate follow-up care of childhood cancer survivors in China.
Lumbar Scoliosis in Postmenopausal Women Increases with Age but is not Associated with Osteoporosis
Authors: Rubin Janet , Cleveland Rebecca J , Padovano Alexander , Hu David , Styner Maya , Sanders James 
Published: February 2021

Abstract

Context
The contribution of lumbar scoliosis to osteoporosis is unknown.

Objective
This work aimed to determine the prevalence and relationship of lumbar scoliosis to osteoporosis in aging women.

Methods
A cross-sectional analysis used dual-energy x-ray absorptiometry (DXA) scans of randomly selected groups of postmenopausal women (64-68, 74-78, and 84-88 years; N = 300 each) in a university teaching hospital from 2014 to 2019. Lumbar Cobb angle was tested for an association to femoral neck (FN), total hip (TH), and spine T score, age, weight, and ethnicity. Logistic regression tested an association between scoliosis (Cobb angle &gt; 10°) and osteoporosis (T score ≤ –2.5). Available sequential DXA scans (N = 51) were analyzed for changes in Cobb angle using a linear mixed model of these longitudinal data.

Results
Osteoporosis and Cobb angle both increased with age: from 22% and 4.4 (SD = 7.8) respectively in 64- to 68-year-olds to 32.9% and to 9.7 (SD = 9.2) in women age 84 to 88 years. The prevalence of clinically significant scoliosis rose from 11.5% in the youngest group, to 27.3% and 39.4% in the age 74 to 78 and 84 to 88 cohorts, respectively. Cobb angle increased 0.7° per year of follow-up. After adjusting for covariates, there was no significant association between T scores at any site (TH, FN, or spine) and Cobb angle.

Conclusion
Based on screening DXAs, the incidence and degree of lumbar scoliosis increases significantly in women between age 65 and 85 years. There was no association between the incidence of lumbar scoliosis and FN bone density.
Quality of Life of Primary Aldosteronism Patients by Mineralocorticoid Receptor Antagonists
Authors: Yoshida Yuichi , Yoshida Rika , Shibuta Kanako , Ozeki Yoshinori , Okamoto Mitsuhiro , Gotoh Koro , Masaki Takayuki , Shibata Hirotaka 
Published: February 2021

Abstract

Context
Although primary aldosteronism (PA) reduces quality of life (QOL), there have been no reports on whether treatment with a mineralocorticoid receptor antagonist (MRA) improves QOL in Japanese PA patients.

Objective
Using the 36-Item Short-Form Health Survey (SF-36), we compared the QOL of PA patients before and after treatment and evaluated whether the effectiveness of MRAs differs by sex and serum potassium level.

Methods
In 50 patients diagnosed with PA (with or without hypokalemia) and treated with an MRA, the SF-36 scores, blood pressure, and clinical features were assessed before, and 3 and 6 months after treatment. Separate analyses were also conducted for males and females.

Results
The normative mean SF-36 score of the healthy subjects was 50. The pretreatment Role-Physical (RP) (46.7 ± 1.8, P = .019), General Health (47.1 ± 1.3, P = .042), and Role-Emotional (47.2 ± 1.7, P = .045) SF-36 subscale scores of all PA patients were significantly lower than those of healthy subjects but were improved by MRA treatment. Females with PA had a lower RP score (45.1 ± 2.2, P = .008), which was not improved by MRA treatment (46.1 ± 2.4, P = .036). In addition, PA patients with hypokalemia had a lower Mental Health SF-36 subscale score (43.2 ± 4.4, P = .041), which was improved by treatment with an MRA.

Conclusion
MRAs improved the QOL of Japanese PA patients, but female PA patients may be more resistant to MRAs.
Understanding axial progenitor biology in vivo and in vitro
Authors: Wymeersch Filip J. , Wilson Valerie , Tsakiridis Anestis 
Published: February 2021

ABSTRACT
The generation of the components that make up the embryonic body axis, such as the spinal cord and vertebral column, takes place in an anterior-to-posterior (head-to-tail) direction. This process is driven by the coordinated production of various cell types from a pool of posteriorly-located axial progenitors. Here, we review the key features of this process and the biology of axial progenitors, including neuromesodermal progenitors, the common precursors of the spinal cord and trunk musculature. We discuss recent developments in the in vitro production of axial progenitors and their potential implications in disease modelling and regenerative medicine.
Mandibular cortical index in the screening of postmenopausal at low mineral density risk: a systematic review
Authors: Munhoz Luciana , Morita Lucas , Nagai Aline Yukari , Moreira Julia , Arita Emiko Saito 
Published: February 2021

Objectives:This systematic literature review addressed the use of mandibular cortical index (MCI), assessed by panoramic radiography, for the identification of postmenopausal women at risk of osteoporosis.Methods:Databases were searched for original research studies published from September 2010 to September 2020 using the following keywords: “postmenopausal osteoporosis” and synonyms combined with “panoramic radiography” and synonyms. Only English language manuscripts and studies pertaining to the MCI were selected.Results:A total of 24 studies were included. The publications were highly heterogeneous in terms of the subject of interest, i.e. the MCI, with some studies comparing the usefulness of the MCI using panoramic radiography and using cone beam computed tomography, and others comparing different radiomorphometric indexes developed for panoramic radiography.Conclusions:Based on the literature included in this systematic review, we conclude that the MCI is useful as an auxiliary tool for identifying postmenopausal females at risk of low bone mineral density (BMD), as it correlates with skeletal BMD measured by dual X-ray absorptiometry. Nevertheless, other radiomorphometric indexes obtained from panoramic radiographs, such as panoramic mandibular index, mental index, and mandibular cortical width, are also valuable as auxiliary tools in the identification of postmenopausal females at risk, as they also correlate with BMD. Thus, it is not possible to affirm which index is the most reliable for the identification of postmenopausal females considering the literature screened. PROSPERO registration systematic review CRD42020208152.