bluuebunny/crossref_metadata_2025_split huggingface dataset:
Algunos aportes teóricos y metodológicos de Amado Luiz Cervo al estudio de las relaciones internacionales de Brasil y América Latina
Authors: Bernal-Meza Raúl 
Published: January 2021

El artículo presenta la obra del profesor Amado Luiz Cervo, citando sus trabajos sobre metodología de investigación, historia de las relaciones internacionales de Brasil y América y Latina y sus aportes teórico-metodológicos para el estudio de las relaciones internacionales y la política exterior. Se pone atención preferencial y específica en los aportes del profesor al desarrollo de un pensamiento teórico y analítico original, que sea propio de América Latina, a través de la elaboración de paradigmas, conceptos y categorías. El trabajo del profesor Cervo sobre la formulación de un pensamiento regional y brasileño para estudiar la inserción internacional, junto a otros profesores latinoamericanos, ha contrapuesto la visión dominante del pensamiento anglosajón con la elaboración la región para comprender la especificidad de las relaciones internacionales de nuestra región a partir de las condiciones que derivan de las características histórico-estructurales de la inserción internacional de América Latina. Después de presentar su metodología de trabajo, el texto analiza algunos de los aportes conceptuales más importantes, entre ellos la formulación de paradigmas y conceptos, poniendo de relevancia su aplicación e influencia sobre otras comunidades de pensamiento en Sudamérica.
MEF2 (Myocyte Enhancer Factor 2) Is Essential for Endothelial Homeostasis and the Atheroprotective Gene Expression Program
Authors: Lu Yao Wei , Martino Nina , Gerlach Brennan D. , Lamar John M. , Vincent Peter A. , Adam Alejandro P. , Schwarz John J. 
Published: January 2021

Objective:
Atherosclerosis predominantly forms in regions of oscillatory shear stress while regions of laminar shear stress are protected. This protection is partly through the endothelium in laminar flow regions expressing an anti-inflammatory and antithrombotic gene expression program. Several molecular pathways transmitting these distinct flow patterns to the endothelium have been defined. Our objective is to define the role of the MEF2 (myocyte enhancer factor 2) family of transcription factors in promoting an atheroprotective endothelium.

Approach and Results:

Here, we show through endothelial-specific deletion of the 3 MEF2 factors in the endothelium, Mef2a, -c, and -d, that MEF2 is a critical regulator of vascular homeostasis. MEF2 deficiency results in systemic inflammation, hemorrhage, thrombocytopenia, leukocytosis, and rapid lethality. Transcriptome analysis reveals that MEF2 is required for normal regulation of 3 pathways implicated in determining the flow responsiveness of the endothelium. Specifically, MEF2 is required for expression of Klf2 and Klf4, 2 partially redundant factors essential for promoting an anti-inflammatory and antithrombotic endothelium. This critical requirement results in phenotypic similarities between endothelial-specific deletions of
Mef2a/c/d
and
Klf2/4
. In addition, MEF2 regulates the expression of Notch family genes, Notch1, Dll1, and Jag1, which also promote an atheroprotective endothelium. In contrast to these atheroprotective pathways, MEF2 deficiency upregulates an atherosclerosis promoting pathway through increasing the amount of TAZ (transcriptional coactivator with PDZ-binding motif).

Conclusions:
Our results implicate MEF2 as a critical upstream regulator of several transcription factors responsible for gene expression programs that affect development of atherosclerosis and promote an anti-inflammatory and antithrombotic endothelium.

Graphic Abstract:
A graphic abstract is available for this article.
ODC (Ornithine Decarboxylase)-Dependent Putrescine Synthesis Maintains MerTK (MER Tyrosine-Protein Kinase) Expression to Drive Resolution
Authors: Yurdagul Arif , Kong Na , Gerlach Brennan D. , Wang Xiaobo , Ampomah Patrick , Kuriakose George , Tao Wei , Shi Jinjun , Tabas Ira 
Published: January 2021

Objective:
ODC (ornithine decarboxylase)-dependent putrescine synthesis promotes the successive clearance of apoptotic cells (ACs) by macrophages, contributing to inflammation resolution. However, it remains unknown whether ODC is required for other arms of the resolution program.

Approach and Results:
RNA sequencing of ODC-deficient macrophages exposed to ACs showed increases in mRNAs associated with heightened inflammation and decreases in mRNAs related to resolution and repair compared with WT (wild type) macrophages. In zymosan peritonitis, myeloid ODC deletion led to delayed clearance of neutrophils and a decrease in the proresolving cytokine, IL (interleukin)-10. Nanoparticle-mediated silencing of macrophage ODC in a model of atherosclerosis regression lowered IL-10 expression, decreased efferocytosis, enhanced necrotic core area, and reduced fibrous cap thickness. Mechanistically, ODC deletion lowered basal expression of MerTK (MER tyrosine-protein kinase)—an AC receptor—via a histone methylation–dependent transcriptional mechanism. Owing to lower basal MerTK, subsequent exposure to ACs resulted in lower MerTK-Erk (extracellular signal-regulated kinase) 1/2–dependent IL-10 production. Putrescine treatment of ODC-deficient macrophages restored the expression of both MerTK and AC-induced IL-10.

Conclusions:
These findings demonstrate that ODC-dependent putrescine synthesis in macrophages maintains a basal level of MerTK expression needed to optimally resolve inflammation upon subsequent AC exposure.

Graphic Abstract:
A graphic abstract is available for this article.
Early NT-ProBNP (N-Terminal Probrain Natriuretic Peptide) Elevation Predicts Malignant Edema and Death After Reperfusion Therapy in Acute Ischemic Stroke Patients
Authors: Zhang Xuting , Yan Shenqiang , Zhong Wansi , Yu Yannan , Lou Min 
Published: January 2021

Background and Purpose:
We aimed to investigate the relationship between early NT-proBNP (N-terminal probrain natriuretic peptide) and all-cause death in patients receiving reperfusion therapy, including intravenous thrombolysis and endovascular thrombectomy (EVT).

Methods:
This study included 1039 acute ischemic stroke patients with early NT-proBNP data at 2 hours after the beginning of alteplase infusion for those with intravenous thrombolysis only or immediately at the end of EVT for those with EVT. We performed natural log transformation for NT-proBNP (Ln(NT-proBNP)). Malignant brain edema was ascertained by using the SITS-MOST (Safe Implementation of Thrombolysis in Stroke-Monitoring Study) criteria.

Results:

Median serum NT-proBNP level was 349 pg/mL (interquartile range, 89–1250 pg/mL). One hundred twenty-one (11.6%) patients died. Malignant edema was observed in 78 (7.5%) patients. Ln(NT-proBNP) was independently associated with 3-month mortality in patients with intravenous thrombolysis only (odds ratio, 1.465 [95% CI, 1.169–1.836];
P
=0.001) and in those receiving EVT (odds ratio, 1.563 [95% CI, 1.139–2.145];
P
=0.006). The elevation of Ln(NT-proBNP) was also independently associated with malignant edema in patients with intravenous thrombolysis only (odds ratio, 1.334 [95% CI, 1.020–1.745];
P
=0.036), and in those with EVT (odds ratio, 1.455 [95% CI, 1.057–2.003];
P
=0.022).

Conclusions:
An early increase in NT-proBNP levels was related to malignant edema and stroke mortality after reperfusion therapy.
Dynamics of Simulated High-Shear, Low-CAPE Supercells
Authors: Wade Andrew R. , Parker Matthew D. 
Published: January 2021

AbstractHigh-shear, low-CAPE environments prevalent in the southeastern United States account for a large fraction of tornadoes and pose challenges for operational meteorologists. Yet, existing knowledge of supercell dynamics, particularly in the context of cloud-resolving modeling, is dominated by moderate- to high-CAPE environments typical of the Great Plains. This study applies high-resolution modeling to clarify the behavior of supercells in the more poorly understood low-CAPE environments, and compares them to a benchmark simulation in a higher-CAPE environment. Simulated low-CAPE supercells’ main updrafts do not approach the theoretical equilibrium level; their largest vertical velocities result not from buoyancy, but from dynamic accelerations associated with low-level mesocyclones and vortices. Surprisingly, low-CAPE tornado-like vortex parcels also sometimes stop ascending near the vortex top instead of carrying large vorticity upward into the midlevel updraft, contributing to vortex shallowness. Each of these low-CAPE behaviors is attributed to dynamic perturbation pressure gradient accelerations that are maximized in low levels, which predominate when the buoyancy is small.
Extreme Temperatures in the Antarctic
Authors: Turner John , Lu Hua , King John , Marshall Gareth J. , Phillips Tony , Bannister Dan , Colwell Steve 
Published: January 2021

AbstractWe present the first Antarctic-wide analysis of extreme near-surface air temperatures based on data collected up to the end of 2019 as part of the synoptic meteorological observing programs. We consider temperatures at 17 stations on the Antarctic continent and nearby sub-Antarctic islands. We examine the frequency distributions of temperatures and the highest and lowest individual temperatures observed. The variability and trends in the number of extreme temperatures were examined via the mean daily temperatures computed from the 0000, 0600, 1200, and 1800 UTC observations, with the thresholds for extreme warm and cold days taken as the 5th and 95th percentiles. The five stations examined from the Antarctic Peninsula region all experienced a statistically significant increase (p < 0.01) in the number of extreme high temperatures in the late-twentieth-century part of their records, although the number of extremes decreased in subsequent years. For the period after 1979 we investigate the synoptic background to the extreme events using ECMWF interim reanalysis (ERA-Interim) fields. The majority of record high temperatures were recorded after the passage of air masses over high orography, with the air being warmed by the foehn effect. At some stations in coastal East Antarctica the highest temperatures were recorded after air with a high potential temperature descended from the Antarctic plateau, resulting in an air mass 5°–7°C warmer than the maritime air. Record low temperatures at the Antarctic Peninsula stations were observed during winters with positive sea ice anomalies over the Bellingshausen and Weddell Seas.
Genomic imbalances in the placenta are associated with poor fetal growth
Authors: Del Gobbo Giulia F. , Yin Yue , Choufani Sanaa , Butcher Emma A. , Wei John , Rajcan-Separovic Evica , Bos Hayley , von Dadelszen Peter , Weksberg Rosanna , Robinson Wendy P. , Yuen Ryan K. C. 
Published: January 2021

Abstract
Background
Fetal growth restriction (FGR) is associated with increased risks for complications before, during, and after birth, in addition to risk of disease through to adulthood. Although placental insufficiency, failure to supply the fetus with adequate nutrients, underlies most cases of FGR, its causes are diverse and not fully understood. One of the few diagnosable causes of placental insufficiency in ongoing pregnancies is the presence of large chromosomal imbalances such as trisomy confined to the placenta; however, the impact of smaller copy number variants (CNVs) has not yet been adequately addressed. In this study, we confirm the importance of placental aneuploidy, and assess the potential contribution of CNVs to fetal growth.

Methods
We used molecular-cytogenetic approaches to identify aneuploidy in placentas from 101 infants born small-for-gestational age (SGA), typically used as a surrogate for FGR, and from 173 non-SGA controls from uncomplicated pregnancies. We confirmed aneuploidies and assessed mosaicism by microsatellite genotyping. We then profiled CNVs using high-resolution microarrays in a subset of 53 SGA and 61 control euploid placentas, and compared the load, impact, gene enrichment and clinical relevance of CNVs between groups. Candidate CNVs were confirmed using quantitative PCR.

Results
Aneuploidy was over tenfold more frequent in SGA-associated placentas compared to controls (11.9% vs. 1.1%; p = 0.0002, OR = 11.4, 95% CI 2.5–107.4), was confined to the placenta, and typically involved autosomes, whereas only sex chromosome abnormalities were observed in controls. We found no significant difference in CNV load or number of placental-expressed or imprinted genes in CNVs between SGA and controls, however, a rare and likely clinically-relevant germline CNV was identified in 5.7% of SGA cases. These CNVs involved candidate genes INHBB, HSD11B2, CTCF, and CSMD3.

Conclusions
We conclude that placental genomic imbalances at the cytogenetic and submicroscopic level may underlie up to ~ 18% of SGA cases in our population. This work contributes to the understanding of the underlying causes of placental insufficiency and FGR, which is important for counselling and prediction of long term outcomes for affected cases.
Immunogenicity of biologic therapies for migraine: a review of current evidence
Authors: Cohen Joshua M. , Ning Xiaoping , Kessler Yoel , Rasamoelisolo Michele , Campos Verena Ramirez , Seminerio Michael J. , Krasenbaum Lynda J. , Shen Honglue , Stratton Jennifer 
Published: January 2021

AbstractBackgroundMonoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have been shown to be effective in migraine prevention. Eptinezumab, erenumab, fremanezumab, and galcanezumb have shown efficacy in clinical trials along with favorable safety and tolerability profiles. Although erenumab is a human mAb and the others have been humanized to varying degrees, they all have the capacity to provoke immune reactions. The present review article aims to discuss the current relationship between mAbs targeting the CGRP pathway (CGRP mAbs) and immunogenicity and their potential clinical implications.FindingsThe incidence of patients developing anti-drug antibodies (ADAs), their titer, and clinical significance are highly variable and depend on a variety of different drug and patient factors. Neutralizing ADAs (NAbs) bind to and inhibit or reduce the pharmacologic activity of the biologic drug molecule, whereas non-neutralizing antibodies (Non-NAbs) bind to the biologic drug molecule without affecting pharmacologic activity in an in vitro test, although pharmacokinetics and drug clearance may be affected. A direct comparison of immunogenicity data across clinical trials with different biologics is not possible due to a lack of standardized assays. Several phase 2, phase 3, and long-term studies evaluating CGRP mAbs for migraine prevention have reported immunogenicity data (5 studies each for eptinezumab, erenumab, fremanezumab, and galcanezumab). Across these studies, prevalence of ADAs varied, ranging from < 1% to ~ 18%. Neutralizing ADAs were slightly less common, with a prevalence ranging from 0 to 12%. Adverse events related to ADA formation were rare.ConclusionsAs more CGRP mAb studies are conducted and more long-term follow-up data become available, evidence is increasing that immunogenicity rates of biologic therapies for migraine are low, and adverse events related to ADAs are rare. Taken together, these results add to the growing body of evidence for the safety and tolerability of this class of migraine medications.
Emergency medicine in Japan: past, present, and future
Authors: Shimizu Kentaro , Hibino Seikei , Biros Michelle H. , Irisawa Taro , Shimazu Takeshi 
Published: January 2021

AbstractQuite a few changes and challenges have arisen in society in general as technology has advanced and the aging population has increased. These can lead to the recognition of the shortcomings of a society’s traditional systems and the various changes that are needed, especially in providing emergency medical care. A super-aged society has been developing in Japan, and the emergency care system needs to change according to these new demographics and society’s needs. The focus has been shifting from critical care and trauma to medical and surgical conditions involving the elderly. Challenges in triage, ambulance diversion, and staffing are discussed in this review. Possible solutions currently underway, such as a public helpline, smartphone app system, coordination by designated hospitals, and universal coverage/government support, are discussed as future directions. Emergency medicine in Japan needs to develop in a more flexible way to meet the upcoming robust challenges of the changing demographics.
Adaptation Mechanism of Roots to Low and High Nitrogen Revealed by Proteomic Analysis
Authors: Xin Wei , Zhang Lina , Gao Jiping , Zhang Wenzhong , Yi Jun , Zhen Xiaoxi , Bi Congyuan , He Dawei , Liu Shiming , Zhao Xinyu 
Published: January 2021

Abstract
Background
Nitrogen-based nutrients are the main factors affecting rice growth and development. Root systems play an important role in helping plants to obtain nutrients from the soil. Root morphology and physiology are often closely related to above-ground plant organs performance. Therefore, it is important to understand the regulatory effects of nitrogen (N) on rice root growth to improve nitrogen use efficiency.

Results
In this study, changes in the rice root traits under low N (13.33 ppm), normal N (40 ppm) and high N (120 ppm) conditions were performed through root morphology analysis. These results show that, compared with normal N conditions, root growth is promoted under low N conditions, and inhibited under high N conditions. To understand the molecular mechanism underlying the rice root response to low and high N conditions, comparative proteomics analysis was performed using a tandem mass tag (TMT)-based approach, and differentially abundant proteins (DAPs) were further characterized. Compared with normal N conditions, a total of 291 and 211 DAPs were identified under low and high N conditions, respectively. The abundance of proteins involved in cell differentiation, cell wall modification, phenylpropanoid biosynthesis, and protein synthesis was differentially altered, which was an important reason for changes in root morphology. Furthermore, although both low and high N can cause nitrogen stress, rice roots revealed obvious differences in adaptation to low and high N.

Conclusions
These results provide insights into global changes in the response of rice roots to nitrogen availability and may facilitate the development of rice cultivars with high nitrogen use efficiency through root-based genetic improvements.
G-Tric: generating three-way synthetic datasets with triclustering solutions
Authors: Lobo João , Henriques Rui , Madeira Sara C. 
Published: January 2021

Abstract
Background
Three-way data started to gain popularity due to their increasing capacity to describe inherently multivariate and temporal events, such as biological responses, social interactions along time, urban dynamics, or complex geophysical phenomena. Triclustering, subspace clustering of three-way data, enables the discovery of patterns corresponding to data subspaces (triclusters) with values correlated across the three dimensions (observations $$\times$$
×
features $$\times$$
×
contexts). With increasing number of algorithms being proposed, effectively comparing them with state-of-the-art algorithms is paramount. These comparisons are usually performed using real data, without a known ground-truth, thus limiting the assessments. In this context, we propose a synthetic data generator, G-Tric, allowing the creation of synthetic datasets with configurable properties and the possibility to plant triclusters. The generator is prepared to create datasets resembling real 3-way data from biomedical and social data domains, with the additional advantage of further providing the ground truth (triclustering solution) as output.

Results
G-Tric can replicate real-world datasets and create new ones that match researchers needs across several properties, including data type (numeric or symbolic), dimensions, and background distribution. Users can tune the patterns and structure that characterize the planted triclusters (subspaces) and how they interact (overlapping). Data quality can also be controlled, by defining the amount of missing, noise or errors. Furthermore, a benchmark of datasets resembling real data is made available, together with the corresponding triclustering solutions (planted triclusters) and generating parameters.

Conclusions
Triclustering evaluation using G-Tric provides the possibility to combine both intrinsic and extrinsic metrics to compare solutions that produce more reliable analyses. A set of predefined datasets, mimicking widely used three-way data and exploring crucial properties was generated and made available, highlighting G-Tric’s potential to advance triclustering state-of-the-art by easing the process of evaluating the quality of new triclustering approaches.
PyConvU-Net: a lightweight and multiscale network for biomedical image segmentation
Authors: Li Changyong , Fan Yongxian , Cai Xiaodong 
Published: January 2021

AbstractBackgroundWith the development of deep learning (DL), more and more methods based on deep learning are proposed and achieve state-of-the-art performance in biomedical image segmentation. However, these methods are usually complex and require the support of powerful computing resources. According to the actual situation, it is impractical that we use huge computing resources in clinical situations. Thus, it is significant to develop accurate DL based biomedical image segmentation methods which depend on resources-constraint computing.ResultsA lightweight and multiscale network called PyConvU-Net is proposed to potentially work with low-resources computing. Through strictly controlled experiments, PyConvU-Net predictions have a good performance on three biomedical image segmentation tasks with the fewest parameters.ConclusionsOur experimental results preliminarily demonstrate the potential of proposed PyConvU-Net in biomedical image segmentation with resources-constraint computing.
First insights into the molecular basis association between promoter polymorphisms of the IL1B gene and Helicobacter pylori infection in the Sudanese population: computational approach
Authors: Idris Abeer Babiker , Idris Einas Babiker , Ataelmanan Amany Eltayib , Mohamed Ali Elbagir Ali , Osman Arbab Bashir M. , Ibrahim El-Amin Mohamed , Hassan Mohamed A. 
Published: January 2021

Abstract
Background
Helicobacter pylori (H. pylori) infects nearly half of the world’s population with a variation in incidence among different geographic regions. Genetic variants in the promoter regions of the IL1B gene can affect cytokine expression and creates a condition of hypoacidity which favors the survival and colonization of H. pylori. Therefore, the aim of this study was to characterize the polymorphic sites in the 5′- region [−687_ + 297] of IL1B in H. pylori infection using in silico tools.

Results
A total of five nucleotide variations were detected in the 5′-regulatory region [−687_ + 297] of IL1B which led to the addition or alteration of transcription factor binding sites (TFBSs) or composite regulatory elements (CEs). Genotyping of IL1B − 31 C > T revealed a significant association between -31 T and susceptibility to H. pylori infection in the studied population (P = 0.0363). Comparative analysis showed conservation rates of IL1B upstream [−368_ + 10] region above 70% in chimpanzee, rhesus monkey, a domesticated dog, cow and rat.

Conclusions
In H. pylori-infected patients, three detected SNPs (− 338, − 155 and − 31) located in the IL1B promoter were predicted to alter TFBSs and CE, which might affect the gene expression. These in silico predictions provide insight for further experimental in vitro and in vivo studies of the regulation of IL1B expression and its relationship to H. pylori infection. However, the recognition of regulatory motifs by computer algorithms is fundamental for understanding gene expression patterns.