bluuebunny/crossref_metadata_2025 huggingface dataset:
Metformin: From Immediate Release to Extended Release Formula, Effectiveness, And Safety in Patients With Chronic Kidney Disease
Authors: Derosa Giuseppe , Rivera Rodolfo , D'Angelo Angela , Maffioli Pamela
Published: December 2021

Type 2 diabetes mellitus is currently the main cause of chronic kidney disease, leading to end-stage renal disease in most countries around the world. Metformin is the most commonly prescribed oral antihyperglycaemic in the world and after approval by the U.S. Food and Drug Administration (FDA) in 1994, it is currently recommended as the first-line pharmacological agent for newly diagnosed Type 2 diabetes mellitus by many professional diabetes associations. In this review, the authors analysed efficacy and safety of metformin in patients with chronic kidney disease.
Screening for Heart Failure in Diabetes: A Way to Reduce Its Prevalence? A Proof of Concept of a Risk Assessment Tool
Authors: Martin Pablo Millares , Reyes Rosa Bobet
Published: December 2021

Background: Heart failure (HF) is underdiagnosed among patients with diabetes. Awareness is required to improve its management and to reduce its impact.

Objectives: To suggest a risk assessment tool that could facilitate the early diagnosis of HF and even reduce its incidence by facilitating individualised management plans.

Methods: Assess current medical literature, searching for parameters that indicate a higher risk of HF among the diabetic population.

Results: Twenty-four parameters were found that could be the potential basis for a risk stratification tool.

Conclusion: The concept of a risk stratification tool is presented. Work on validating will be required. It has the potential to affect the future management of patients with diabetes and to reduce the incidence and prevalence of HF in this population.
Long-Term Performance of Jointed Plain Concrete Pavement with Rapid Strength Concrete On California Highways
Authors: Darter Michael
Published: December 2021

Rapid Strength Concrete (RSC) slabs on six California jointed plain concrete pavement (JPCP) highway projects were surveyed. These projects had been previously surveyed in 2008 at 3-years of age and by 2018 had reached a service life of 13-years. Of the initial 5430 slabs examined in 2008, a total of 1493 RSC slabs, located on 12 traffic lanes, were observed and distress types recorded again in 2018. These slabs included both CTS and 4x4 RSC located in both inner and outer lanes. Only a small percentage (1.4%) of the 5,430 RSC slabs exhibited any distress in 2008 after 3-years' service and the increases were small over the next 10 years of service with the exception of transverse fatigue cracks. The transverse (top down fatigue) type of cracking had the highest percentage and largest increase of any distress type. The heavy truck outside lanes exhibited 21% transversely cracked RSC slabs and the inner passing lanes 3%. The outer truck lanes carried over 3 times more trucks than inner lanes. The RSC slabs were mostly 200-223 mm thick and thus susceptible to fatigue damage. The overall performance of the RSC slabs (both CTS and 4x4 RSC materials) were similar and considered to be outstanding over 13 years with a large majority expected to survive many more years.
Analysis and Evaluation of the Development of Various k-Values for Use in Design
Authors: Rodden Robert , Ferrebee Eric
Published: December 2021

Inconsistency exists between common conversions from soil index properties (e.g., CBR) to a design k-value and a widespread nomograph that has become the definitive industry reference on the topic in the United States. Propagation of these inconsistencies into guidance from groups like the American Concrete Pavement Association (ACPA) and American Concrete Institute (ACI) Committees 330 and 360 has contributed to confusion in the industry. Advancements between the pavement and slab-on-ground communities have occurred in parallel but are inconsistent with each other, thus adding more confusion. ACPA developed a conversion set to better align the industry on a static k-value for design. While the ACPA model is included in StreetPave, PavementDesigner.org, and the ACPA App Library, outdated conversion equations are frequently used due to familiarity and lack of understanding of the underlying principles. This paper presents a summary of the industry's prior practices and recommendations, a detailing of the approach proposed by ACPA, and guidance on which k-value is recommended for design of concrete pavements and slabs-on-ground.
Como lidar com os fascismos hoje?
Authors: Schurster Karl , Gherman Michel
Published: December 2021

Recebido: 03/07/2020

Aprovado: 20/07/2020

 

Este artigo tem como objetivo analisar as práticas discursivas e o agir político dos variados tipos de fascismo hoje. Partindo da crise das instituições democráticas e do avanço de políticas da chamada direita radical, procuramos compreender quais as características desse “novo” fascismo e como ele se desenvolve, utilizando para isso o campo teórico clássico e contemporâneo e a metodologia comparativa. Além de um breve histórico sobre o conceito de fascismo no Brasil, enveredamos para a elaboração de um mínimo comum entre esses novos fascismos, comparando-os com o dos anos 20 e 30 do século passado. Sendo assim, problematizar categorias como conspiração, negacionismo, negação da alteridade, guerra permanente e disseminação do ódio são fundamentais para entendimento desse “novo” fenômeno político e histórico.

Palavras-chaves: Fascismos. Direita Radical. Nazismo.
Fontes Históricas:
Authors: D’Assunção Barros José
Published: December 2021

Recebido: 14/09/2020

Aprovado: 16/11/2020

Este artigo busca discutir o que é uma fonte histórica, conceituando-a de maneira mais geral e relacionando-a mais especificamente com a necessidade de que, em uma pesquisa histórica, problema historiográfico e fonte histórica estejam intimamente relacionados. Na segunda parte do artigo, discutimos a variedade de diferentes tipos de fontes históricas, mostrando que, desde o século XIX e até hoje, os historiadores vêm expandindo consideravelmente a variedade de fontes históricas com as quais podemos lidar na pesquisa histórica. O artigo é conduzido para a elaboração de uma taxonomia relacionada aos diferentes tipos de fontes históricas.

Palavras-Chave: Fonte Histórica; Problema historiográfico; Historiografia; Metodologia; Documento histórico.
Postar, curtir e aprender?:
Authors: S. C. Maynard Andreza
Published: December 2021

Recebido: 20/11/2020

Aprovado: 09/12/2020

Nos últimos anos os celulares, a internet e as redes sociais tem se colocado como fortes elementos concorrenciais de atenção na sala de aula. E ainda que algumas instituições coloquem como norma a proibição dos equipamentos, os alunos continuam conectados ao mundo virtual. Numa tentativa de atrair a atenção dos alunos para as aulas de história, estimar e dar visibilidade à produção das atividades realizadas por eles, foi realizada uma experiência com o uso do aplicativo Instagram no ano letivo de 2019, com alunos de 9º ano e 3º ano, do Colégio de Aplicação da Universidade Federal de Sergipe. Esse texto apresenta uma reflexão crítica acerca dessa experiência. A prática consistiu em orientar uma sequência de postagens de imagens com conteúdo histórico, acompanhadas por uma legenda, explicando-as. As postagens foram realizadas no perfil historia_codap, podendo ser acessadas por alunos, comunidade escolar e público mais amplo. A ideia do uso do Instagram e a provocação para que os alunos participassem da aula, tentava retirá-los da posição de passivos, colocando-os inclusive como criadores de um conteúdo digital que envolvia a história.

Palavras-chave: Ensino de História, Instagram, educação básica, História Digital, Brasil.
Demonstrações pró-impeachment no Brasil:
Authors: Dantas de Figueiredo Carolina
Published: December 2021

Recebido: 10/08/2019

Aprovado: 17/04/2020

Ao ir às ruas em diversos protestos desde 2013, o povo brasileiro respondeu ao chamado de diferentes movimentos sociais baseados na internet. Contudo, houve negação, por parte dos indivíduos, assim como dos movimentos em si, de que havia lideranças por trás da organização desses protestos, mais especificamente dos protestos pró-impeachment, criando o que chamamos de mito da ausência de liderança. Uma pesquisa bibliográfica foi feita, em paralelo com a coleta e tabulação de textos noticiosos sobre as manifestações pró-impeachment publicados na mídia corporativa brasileira. O cruzamento da pesquisa bibliográfica com a tabulação indicou a existência efetiva de algumas lideranças por detrás das manifestações pró-impeachment que ocorreram no Brasil em 2016. Como conclusão, indicamos que a insistência no mito da ausência de liderança pode ser uma ameaça às democracias contemporâneas, já que impede que os movimentos sociais baseados na internet sejam olhados de forma política complexa.

Palavras-chave: Actante. Movimentos Sociais. Liderança.
A História do Tempo Presente:
Authors: Elíbio Júnior Antônio Manoel
Published: December 2021

Recebido: 16/07/2020

Aprovado: 14/10/2020

A História do Tempo Presente, ao menos desde a criação do Institut d'Histoire du Temps Présent, surgiu como um campo de conhecimento entre os anos de 1978 e 1980, na França, quando o CNRS - Centre National de la Recherche Scientifique começou a patrocinar, sob a liderança de Henry Rousso, os estudos cujos os temas, para o historiador, ainda estavam em curso. Uma história que se propusesse a pensar o “seu próprio tempo”, o passado-presente. Nesse aspecto, evocava duas questões centrais: um marco cronológico que delimitasse o campo de estudo da História do Tempo Presente e um corpus documental com o qual iria trabalhar os historiadores. Esse artigo pretende problematizar o surgimento deste campo de pesquisa, tomando como premissa a História do Tempo Presente como aquela cujas questões afligem o homem real, em uma história que transcorre na vida real.

 Palavras-chaves: periodização; tempo presente; memória; testemunho.
Judeus contra Bolsonaro:
Authors: Ehrlich Michel
Published: December 2021

Recebido: 07/07/2020

Aprovado: 04/01/2021

O presente artigo analisa um conjunto de três abaixo-assinados online produzidos entre 2017 e 2018 por grupos judaicos contrários a então candidatura de Jair Bolsonaro à presidência da república e sua aproximação com a comunidade judaica brasileira. Sobretudo a partir de sua palestra no clube Hebraica-RJ em abril de 2017, a imagem da comunidade judaica brasileira foi muitas vezes atrelada à figura do ex-militar. Diante disso, grupos de judeus se mobilizaram em diversas ações, entre as quais a divulgação de abaixo-assinados. Além de se juntar à oposição a Bolsonaro e suas declarações preconceituosas e anti-democráticas, a análise desses textos permitiu observar a intenção de disputar os espaços das coletividade judaicas, de afirmar uma judaicidade democrática e de se contrapor à imagem monolítica da comunidade judaica como supostamente bolsonarista.

Palavras-chave: Bolsonaro, judeus, abaixo-assinados.
A Segunda Guerra Mundial nos Livros Didáticos de História:
Authors: Pérola Dantas Barros Maria Luiza
Published: December 2021

Recebido: 07/12/2020

Aprovado: 08/02/2021

No presente artigo se propõe investigar a maneira como a temática da Segunda Guerra Mundial (1939-1945) se encontra trabalhada nos livros didáticos de História aprovados pelo Programa Nacional do Livro Didático (PNLD) 2018, e destinados aos alunos e professores do ensino médio das escolas públicas brasileiras. A partir de um estudo comparado dos capítulos dessas obras que tratam diretamente o conflito, busca-se compreender quais fatos foram elencados, bem como quais abordagens foram feitas, por parte dos autores de cada coleção à temática em questão.

Palavras-chave: Segunda Guerra Mundial, Livro Didático, PNLD 2018.
IoT-based Framework for Coordinating Smart Home
Authors: Ahmadi Julaihi Azlina
Published: December 2021

IOT RFID Door Open Notification for Homestay is a system that focuses on the use of RFID as a door lock and keeps track the database of Homestay’s guest check-in and check-out time data. By implementing this project, the homestay owner can view and update the check-in and check-out time of their guest whenever required. MySQL will be used in this project for database support and logging the Homestay Web-based System. In this paper, a new framework with Radio Frequency Identification technology (RFID) applied to homestay door lock is exposed. In order to validate the designed framework, an experiment to configure the speed capture by the RFID reader was carried out.
Weighting the Position & Skillset of Players in League of Legends Using Analytic Hierarchy Process
Authors: Jeremiah Anyi Wan Jr  , Ahmad Alif bin Kamal  , Shapi-ee bin Abd Rahman
Published: December 2021

Today, esports such as League of Legends are a popular form of competition using video games. Many researchers have conducted studies in the esports field such as player psychology, training, and physical exercise; however, those that apply quantitative techniques are still scarce. In this paper, Analytic Hierarchy Process is proposed for weighting position and skillsets of players in League of Legends. It is hypothesized by the developer that pairwise comparison can be used to derive priority scale through the judgment of experts. A questionnaire is designed to obtain pairwise comparison from players which are then used to develop the priority scale. The empirical results obtained show the weightage of position and skillset of each player. This weightage shows the priorities of certain position compared to other positions, and the priorities of skillsets needed to perform well in each position, based on their judgment. The results can be used to determine the most suitable players for each position with the right skillset quantitatively and systematically.
An AODV Based Multifactor Authentication Scheme for Wireless Sensor Network
Authors: Yong Jane , Chai Zi Jian , Chin Kah Hao , Chee Christopher Chin Fung , Soh Daniel , Kwong Jing Yong , Ooi Wei Yin
Published: December 2021

Wireless Sensor Network (WSN) is a type of wireless network that is fast getting a lot of attention in scientific and industrial applications, and it is a network of decentralized autonomous standalone sensor devices. However, WSN is easily prone to malicious attacks as anyone can access the server through the node without a proper security authentication. In this paper, we proposed a secure AODV based multi-factor authentication scheme for WSN to mitigate physical attack, offline guessing attack and replay attack. Our proposed scheme is preferred to keep the scheme lightweight while providing enough security that requires smart card, user identity, password, and OTP. Our proposed scheme has relatively lower computational cost with a total of 10Th than the other compared schemes except for Adil et al.’s scheme. However, we have around 8288 bits of authentication overhead due to the nature of packet and the addition of factors. Hence, our scheme is outperformed from computational cost perspective, but the scheme is slightly higher on authentication overhead perspective. In the future, multiple device authentication, implementation of biometric feature can be added to improve the scheme.
Bitcoin and Stone Money: Anglophone Use of Yapese Economic Cultures 1910-2020
Authors: Walton Jo
Published: December 2021

Recently parallels have been drawn between Bitcoin and Yapese stone money. The analogy between Bitcoin and Yapese stone money is based on proposed commonalities that are inaccurate, ill-defined, and/or trivial. However, this does not signal a need to refine the comparison, but rather a need to reconsider the rationale for attempting it in the first place. Recent attempts to redescribe Yapese stone money using the vocabulary and concepts from the field of cryptocurrency participate in a longer textual history, whereby Anglophone writers have misrepresented Yap for pedagogic or polemic convenience. This history features frequent colonialist troping of Yap and the erasure of histories of colonial violence and power. This paper uses desk research to provide an overview of this textual history. It celebrates broad scholarly exploration of more-than-capitalist practices, but recommends greater caution in the study and pedagogic representation of Yapese economies.
Mobilizing Endogenous Repair Through Understanding Immune Reaction With Biomaterials
Authors: Karkanitsa Maria , Fathi Parinaz , Ngo Tran , Sadtler Kaitlyn
Published: December 2021

With few exceptions, humans are incapable of fully recovering from severe physical trauma. Due to these limitations, the field of regenerative medicine seeks to find clinically viable ways to repair permanently damaged tissue. There are two main approaches to regenerative medicine: promoting endogenous repair of the wound, or transplanting a material to replace the injured tissue. In recent years, these two methods have fused with the development of biomaterials that act as a scaffold and mobilize the body’s natural healing capabilities. This process involves not only promoting stem cell behavior, but by also inducing activity of the immune system. Through understanding the immune interactions with biomaterials, we can understand how the immune system participates in regeneration and wound healing. In this review, we will focus on biomaterials that promote endogenous tissue repair, with discussion on their interactions with the immune system.
Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering
Authors: Shafiee Sepehr , Shariatzadeh Siavash , Zafari Ali , Majd Alireza , Niknejad Hassan
Published: December 2021

Currently, the fabrication of a functional vascular network to maintain the viability of engineered tissues is a major bottleneck in the way of developing a more advanced engineered construct. Inspired by vasculogenesis during the embryonic period, thein vitroprevascularization strategies have focused on optimizing communications and interactions of cells, biomaterial and culture conditions to develop a capillary-like network to tackle the aforementioned issue. Many of these studies employ a combination of endothelial lineage cells and supporting cells such as mesenchymal stem cells, fibroblasts, and perivascular cells to create a lumenized endothelial network. These supporting cells are necessary for the stabilization of the newly developed endothelial network. Moreover, to optimize endothelial network development without impairing biomechanical properties of scaffolds or differentiation of target tissue cells, several other factors, including target tissue, endothelial cell origins, the choice of supporting cell, culture condition, incorporated pro-angiogenic factors, and choice of biomaterial must be taken into account. The prevascularization method can also influence the endothelial lineage cell/supporting cell co-culture system to vascularize the bioengineered constructs. This review aims to investigate the recent advances on standard cells used in in vitro prevascularization methods, their co-culture systems, and conditions in which they form an organized and functional vascular network.
Use of Electrospun Phenylalanine/Poly-ε-Caprolactone Chiral Hybrid Scaffolds to Promote Endothelial Remodeling
Authors: Sun Benlin , Hou Lei , Sun Binbin , Han Yu , Zou Yunqing , Huang Juexin , Zhang Yanan , Feng Chuanliang , Dou Xiaoqiu , Xu Feng
Published: December 2021

The fabrication of tissue-engineered vascular grafts to replace damaged vessels is a promising therapy for cardiovascular diseases. Endothelial remodeling in the lumen of TEVGs is critical for successful revascularization. However, the construction of well-functioning TEVGs remains a fundamental challenge. Herein, chiral hybrid scaffolds were prepared by electrospinning using D/L-phenylalanine based gelators [D(L)PHEG] and poly-ε-caprolactone (PCL). The chirality of scaffolds significantly affected the endothelial remodeling progress of TEVGs. Compared with L-phenylalanine based gelators/poly-ε-caprolactone (L/PCL) and PCL, D-phenylalanine based gelators/poly-ε-caprolactone (D/PCL) scaffolds enhanced cell adhesion, and proliferation and upregulated the expression of fibronectin-1, and vinculin. These results suggests that chiral hybrid scaffolds can promote endothelial remodeling of TEVGs by upregulating adhesion-associated protein levels. This study offers an innovative strategy for endothelial remodeling of TEVGs by fabricating chiral hybrid scaffolds, and provides new insight for the treatment of cardiovascular diseases.
Association Study of Genetic Variants in Calcium Signaling-Related Genes With Cardiovascular Diseases
Authors: Li Sen , Jia Zhaoqi , Zhang Zhang , Li Yuxin , Yan Meihui , Yu Tingting
Published: December 2021

Background: Calcium ions (Ca2+) play an essential role in excitation–contraction coupling in the heart. The association between cardiovascular diseases (CVDs) and genetic polymorphisms in key regulators of Ca2+ homeostasis is well established but still inadequately understood.

Methods: The associations of 11,274 genetic variants located in nine calcium signaling-related genes with 118 diseases of the circulatory system were explored using a large sample from the United Kingdom Biobank (N = 308,366). The clinical outcomes in electronic health records were mapped to the phecode system. Survival analyses were employed to study the role of variants in CVDs incidence and mortality. Phenome-wide association studies (PheWAS) were performed to investigate the effect of variants on cardiovascular risk factors.

Results: The reported association between rs1801253 in β1-adrenergic receptor (ADRB1) and hypertension was successfully replicated, and we additionally found the blood pressure-lowering G allele of this variant was associated with a delayed onset of hypertension and a decreased level of apolipoprotein A. The association of rs4484922 in calsequestrin 2 (CASQ2) with atrial fibrillation/flutter was identified, and this variant also displayed nominal evidence of association with QRS duration and carotid intima-medial thickness. Moreover, our results indicated suggestive associations of rs79613429 in ryanodine receptor 2 (RYR2) with precordial pain.

Conclusion: Multiple novel associations established in our study highlight genetic testing as a useful method for CVDs diagnosis and prevention.
Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis
Authors: Mukherjee Moumita , Goswami Srikanta
Published: December 2021

RNA-binding proteins (RBPs) play a significant role in multiple cellular processes with their deregulations strongly associated with cancer. However, there are not adequate evidences regarding global alteration and functions of RBPs in pancreatic cancer, interrogated in a systematic manner. In this study, we have prepared an exhaustive list of RBPs from multiple sources, downloaded gene expression microarray data from a total of 241 pancreatic tumors and 124 normal pancreatic tissues, performed a meta-analysis, and obtained differentially expressed RBPs (DE-RBPs) using the Limma package of R Bioconductor. The results were validated in microarray datasets and the Cancer Genome Atlas (TCGA) RNA sequencing dataset for pancreatic adenocarcinoma (PAAD). Pathway enrichment analysis was performed using DE-RBPs, and we also constructed the protein–protein interaction (PPI) network to detect key modules and hub-RBPs. Coding and noncoding targets for top altered and hub RBPs were identified, and altered pathways modulated by these targets were also investigated. Our meta-analysis identified 45 upregulated and 15 downregulated RBPs as differentially expressed in pancreatic cancer, and pathway enrichment analysis demonstrated their important contribution in tumor development. As a result of PPI network analysis, 26 hub RBPs were detected and coding and noncoding targets for all these RBPs were categorized. Functional exploration characterized the pathways related to epithelial-to-mesenchymal transition (EMT), cell migration, and metastasis to emerge as major pathways interfered by the targets of these RBPs. Our study identified a unique meta-signature of 26 hub-RBPs to primarily modulate pancreatic tumor cell migration and metastasis in pancreatic cancer. IGF2BP3, ISG20, NIP7, PRDX1, RCC2, RUVBL1, SNRPD1, PAIP2B, and SIDT2 were found to play the most prominent role in the regulation of EMT in the process. The findings not only contribute to understand the biology of RBPs in pancreatic cancer but also to evaluate their candidature as possible therapeutic targets.
Cell Cycle Dysregulation and Renal Fibrosis
Authors: Wu Yun-Shan , Liang Shan , Li Dong-Yi , Wen Jun-Hao , Tang Ji-Xin , Liu Hua-Feng
Published: December 2021

Precise regulation of cell cycle is essential for tissue homeostasis and development, while cell cycle dysregulation is associated with many human diseases including renal fibrosis, a common process of various chronic kidney diseases progressing to end-stage renal disease. Under normal physiological conditions, most of the renal cells are post-mitotic quiescent cells arrested in the G0 phase of cell cycle and renal cells turnover is very low. Injuries induced by toxins, hypoxia, and metabolic disorders can stimulate renal cells to enter the cell cycle, which is essential for kidney regeneration and renal function restoration. However, more severe or repeated injuries will lead to maladaptive repair, manifesting as cell cycle arrest or overproliferation of renal cells, both of which are closely related to renal fibrosis. Thus, cell cycle dysregulation of renal cells is a potential therapeutic target for the treatment of renal fibrosis. In this review, we focus on cell cycle regulation of renal cells in healthy and diseased kidney, discussing the role of cell cycle dysregulation of renal cells in renal fibrosis. Better understanding of the function of cell cycle dysregulation in renal fibrosis is essential for the development of therapeutics to halt renal fibrosis progression or promote regression.
Recombinant Human Bone Morphogenic Protein-2 Immobilized Fabrication of Magnesium Functionalized Injectable Hydrogels for Controlled-Delivery and Osteogenic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells in Femoral Head Necrosis Repair
Authors: Lu Xueliang , Guo Hongyu , Li Jiaju , Sun Tianyu , Xiong Mingyue
Published: December 2021

Femoral head necrosis (FHN) is a clinically progressive disease that leads to overwhelming complications without an effective therapeutic approach. In recent decades, transplantation of mesenchymal stem cells (MSCs) has played a promising role in the treatment of FHN in the initial stage; however, the success rate is still low because of unsuitable cell carriers and abridged osteogenic differentiation of the transplanted MSCs. Biopolymeric-derived hydrogels have been extensively applied as effective cell carriers and drug vesicles; they provide the most promising contributions in the fields of tissue engineering and regenerative medicine. However, the clinical potential of hydrogels may be limited because of inappropriate gelation, swelling, mechanical characteristics, toxicity in the cross-linking process, and self-healing ability. Naturally, gelated commercial hydrogels are not suitable for cell injection and infiltration because of their static network structure. In this study, we designed a novel thermogelling injectable hydrogel using natural silk fibroin-blended chitosan (CS) incorporated with magnesium (Mg) substitutes to improve physical cross-linking, stability, and cell osteogenic compatibility. The presented observations demonstrate that the developed injectable hydrogels can facilitate the controlled delivery of immobilized recombinant human bone morphogenic protein-2 (rhBMP-2) and rat bone marrow-derived MSCs (rBMSCs) with greater cell encapsulation efficiency, compatibility, and osteogenic differentiation. In addition, outcomes of in vivo animal studies established promising osteoinductive, bone mineral density, and bone formation rate after implantation of the injectable hydrogel scaffolds. Therefore, the developed hydrogels have great potential for clinical applications of FHN therapy.
ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression
Authors: Dwucet Annika , Pruss Maximilian , Cao Qiyu , Tanriover Mine , Prabhu Varun V. , Allen Joshua E. , Peraud Aurelia , Westhoff Mike-Andrew , Siegelin Markus D. , Wirtz Christian Rainer , Karpel-Massler Georg
Published: December 2021

The purpose of this study was to examine whether the imipridone ONC201/TIC10 affects the metabolic and proliferative activity of medulloblastoma cells in vitro. Preclinical drug testing including extracellular flux analyses (agilent seahorse), MTT assays and Western blot analyses were performed in high and low c-myc-expressing medulloblastoma cells. Our data show that treatment with the imipridone ONC201/TIC10 leads to a significant inihibitory effect on the cellular viability of different medulloblastoma cells independent of c-myc expression. This effect is enhanced by glucose starvation. While ONC201/TIC10 decreases the oxidative consumption rates in D458 (c-myc high) and DAOY (c-myc low) cells extracellular acidification rates experienced an increase in D458 and a decrease in DAOY cells. Combined treatment with ONC201/TIC10 and the glycolysis inhibitor 2-Deoxyglucose led to a synergistic inhibitory effect on the cellular viability of medulloblastoma cells including spheroid models. In conclusion, our data suggest that ONC201/TIC10 has a profound anti-proliferative activity against medulloblastoma cells independent of c-myc expression. Metabolic targeting of medulloblastoma cells by ONC201/TIC10 can be significantly enhanced by an additional treatment with the glycolysis inhibitor 2-Deoxyglucose. Further investigations are warranted.
Molecular Characterization and Clinical Relevance of ANXA1 in Gliomas via 1,018 Chinese Cohort Patients
Authors: Qian Zenghui , Fan Wenhua , Meng Fanlin , Sun Zhiyan , Li Guanzhang , Zhai You , Chang Yuanhao , Yang Changlin , Zeng Fan , Chai Ruichao , Wu Fan , Zhao Zheng
Published: December 2021

Annexin A1 (ANXA1) is a calcium-dependent phospholipid-binding protein and has been implicated in multiple functions essential in cancer, including cell proliferation, apoptosis, chemosensitivity, metastasis, and invasion. However, the biological role and clinical behavior of ANXA1 in glioma remain unclear. In this study, RNA-seq (n = 1018 cases) and whole-exome sequencing (WES) (n = 286 cases) data on a Chinese cohort, RNA-seq data with different histological regions of glioblastoma blocks (n = 270 cases), and scRNA-seq data (n = 7630 cells) were used. We used the R software to perform statistical calculations and graph rendering. We found that ANXA1 is closely related to the malignant progression in gliomas. Meanwhile, ANXA1 is significantly associated with clinical behavior. Furthermore, the mutational profile revealed that glioma subtypes classified by ANXA1 expression showed distinct genetic features. Functional analyses suggest that ANXA1 correlates with the immune-related function and cancer hallmark. At a single-cell level, we found that ANXA1 is highly expressed in M2 macrophages and tumor cells of the mesenchymal subtype. Importantly, our result suggested that ANXA1 expression is significant with the patient’s survival outcome. Our study revealed that ANXA1 was closely related to immune response. ANXA1 plays a key factor in M2 macrophages and MES tumor cells. Patients with lower ANXA1 expression levels tended to experience improved survival. ANXA1 may become a valuable factor for the diagnosis and treatment of gliomas in clinical practice.
Genomic Variation Prediction: A Summary From Different Views
Authors: Lin Xiuchun
Published: December 2021

Structural variations in the genome are closely related to human health and the occurrence and development of various diseases. To understand the mechanisms of diseases, find pathogenic targets, and carry out personalized precision medicine, it is critical to detect such variations. The rapid development of high-throughput sequencing technologies has accelerated the accumulation of large amounts of genomic mutation data, including synonymous mutations. Identifying pathogenic synonymous mutations that play important roles in the occurrence and development of diseases from all the available mutation data is of great importance. In this paper, machine learning theories and methods are reviewed, efficient and accurate pathogenic synonymous mutation prediction methods are developed, and a standardized three-level variant analysis framework is constructed. In addition, multiple variation tolerance prediction models are studied and integrated, and new ideas for structural variation detection based on deep information mining are explored.
High Loading Capacity and Wear Resistance of Graphene Oxide/Organic Molecule Assembled Multilayer Film
Authors: Chen Li , Wu Gang , Huang Yin , Bai Changning , Yu Yuanlie , Zhang Junyan
Published: December 2021

Taking advantage of the strong charge interactions between negatively charged graphene oxide (GO) sheets and positively charged poly(diallyldimethylammonium chloride) (PDDA), self-assembled multilayer films of (GO/PDDA)n were created on hydroxylated silicon substrates by alternating electrostatic adsorption of GO and PDDA. The formation and structure of the films were analyzed by means of water contact angle measurement, thickness measurement, atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). Meanwhile, tribological behaviors in micro- and macro- scale were investigated by AFM and a ball-on-plate tribometer, respectively. The results showed that (GO/PDDA)n multilayer films exhibited excellent friction-reducing and anti-wear abilities in both micro- and macro-scale, which was ascribed to the special structure in (GO/PDDA)n multilayer films, namely, a well-stacked GO–GO layered structure and an elastic 3D crystal stack in whole. Such a film structure is suitable for design molecular lubricants for MEMS and other microdevices.
Quercetin Rejuvenates Sensitization of Colistin-Resistant Escherichia coli and Klebsiella Pneumoniae Clinical Isolates to Colistin
Authors: Lin Yishuai , Zhang Ying , Liu Shixing , Ye Dandan , Chen Liqiong , Huang Na , Zeng Weiliang , Liao Wenli , Zhan Yizhou , Zhou Tieli , Cao Jianming
Published: December 2021

Colistin is being considered as “the last ditch” treatment in many infections caused by Gram-negative stains. However, colistin is becoming increasingly invalid in treating patients who are infected with colistin-resistant Escherichia coli (E. coli) and Klebsiella Pneumoniae (K. pneumoniae). To cope with the continuous emergence of colistin resistance, the development of new drugs and therapies is highly imminent. Herein, in this work, we surprisingly found that the combination of quercetin with colistin could efficiently and synergistically eradicate the colistin-resistant E. coli and K. pneumoniae, as confirmed by the synergy checkboard and time-kill assay. Mechanismly, the treatment of quercetin combined with colistin could significantly downregulate the expression of mcr-1 and mgrB that are responsible for colistin-resistance, synergistically enhancing the bacterial cell membrane damage efficacy of colistin. The colistin/quercetin combination was notably efficient in eradicating the colistin-resistant E. coli and K. pneumoniae both in vitro and in vivo. Therefore, our results may provide an efficient alternative pathway against colistin-resistant E. coli and K. pneumoniae infections.
A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among Clinical Leishmania donovani Isolates of the Indian Subcontinent Exhibiting Resistance to Multiple Drugs
Authors: Ghosh Souradeepa , Biswas Souvik , Mukherjee Sandip , Pal Arijit , Saxena Aaditya , Sundar Shyam , Dujardin Jean-Claude , Das Soumen , Roy Syamal , Mukhopadhyay Rupkatha , Mukherjee Budhaditya
Published: December 2021

The extent of susceptibility towards miltefosine (Mil), amphotericin B (AmpB), and paromomycin (Paro) was measured among 19 clinical isolates of Leishmania donovani (LD). Thirteen of these clinical isolates were reported to exhibit low susceptibility towards sodium stibogluconate (SSG-R), while six of them were highly susceptible (SSG-S). The degree of clearance of amastigotes (EC50) for these predefined SSG-R- and SSG-S-infected macrophages was determined against Mil, AmpB, and Paro. Two out of the 13 SSG-R isolates (BHU575 and BHU814) showed low susceptibility towards all three drugs studied, while the rest of the 11 SSG-R isolates showed varying degrees of susceptibility either towards none or only towards individual drugs. Interestingly, all the SSG-S isolates showed high susceptibility towards Mil/AmpB/Paro. The total intracellular non-protein thiol content of the LD promastigotes, which have been previously reported to be positively co-related with EC50 towards SSG, was found to be independent from the degree of susceptibility towards Mil/AmpB/Paro. Impedance spectra analysis, which quantifies membrane resistance, revealed lower impedimetric values for all those isolates exhibiting low efficacy to Mil (Mil-R). Our analysis points out that while non-protein thiol content can be an attribute of SSG-R, lower impedimetric values can be linked with lower Mil susceptibility, although neither of these parameters seems to get influenced by the degree of susceptibility towards AmpB/Paro. Finally, a correlation analysis with established biological methods suggests that impedance spectral analysis can be used for the accurate determination of lower Mil susceptibility among LD isolates, which is further validated in the LD-infected in vivo hamster model.
“Kung Flu”—The Dynamics of Fear, Popular Culture, and Authenticity in the Anatomy of Populist Communication
Authors: Kurilla Robin
Published: December 2021

The article presents results of a study on the dynamics between Donald Trump’s use of terms that relate COVID-19 to China and news media publications concerning this use. Qualitative content analysis with elements of discourse analysis was conducted to 1) describe the case as a type of populist discourse on COVID-19, and 2) illustrate the following hypotheses with the help of empirical material: 1) News media and the dynamics of political communication based on the difference of friend and enemy help legitimizing populist claims and directing public attention toward them while feeding into a narrative of a diffuse category of threats that creates objects ofangstand thereby enhances social cohesion. 2) With resources derived from popular culture, populists exploit the culture of political correctness, which is facilitated through the ascription of authenticity. The hypotheses emerged in the course of organizing and preliminarily examining the data collected for an ongoing broader study on populist communication and its repercussions in different public spheres in view of the following assumptions: 1) Political communication is guided by the distinction of friend and enemy. 2) In populist communication, this distinction appears as the difference of ‘the people’ and allegedly corrupt elites, including news media. 3)Angstenhances social cohesion among the audiences of populist speakers directly or mediated by fear. 4) Populist communication is more likely to produce a type of fear that populists benefit from when it depicts the elite as a diffuse category composed of various interlinked enemies. Trump’s contextualized use of the following terms in the time period between March 13 and September 15, 2020, was examined: China flu, China plague, China virus, Chinese plague, Chinese flu, Chinese virus, Wuhan virus, and Kung flu. 38 speeches from Trump’s election campaign or rallies, 28 talks at presidential events or meetings, 47 interviews, 37 press conferences, 35 tweets and seven re-tweets as well as selected news media responses were subjected to analysis. The case has been successfully described as a type of populist discourse on COVID-19 and both hypotheses have been illustrated with empirical material.
Broad Learning Aided Model Predictive Control With Application to Continuous Stirred Tank Heater
Authors: Tao Mo , Gao Tianyi , Li Xianling , Li Kuan
Published: December 2021

This paper presents a data-driven predictive controller based on the broad learning algorithm without any prior knowledge of the system model. The predictive controller is realized by regressing the predictive model using online process data and the incremental broad learning algorithm. The proposed model predictive control (MPC) approach requires less online computational load compared to other neural network based MPC approaches. More importantly, the precision of the predictive model is enhanced with reduced computational load by operating an appropriate approximation of the predictive model. The approximation is proved to have no influence on the convergence of the predictive control algorithm. Compared with the partial form dynamic linearization aided model free control (PFDL-MFC), the control performance of the proposed predictive controller is illustrated through the continuous stirred tank heater (CSTH) benchmark.
Altered Expression of Transfer-RNA-Derived Small RNAs in Human With Rheumatic Heart Disease
Authors: Yang Zhao-yu , Li Peng-fei , Li Zhi-qing , Tang Tao , Liu Wei , Wang Yang
Published: December 2021

Rheumatic heart disease (RHD) remains a severe public health problem in developing countries. Atrial fibrillation (AF) is a medical complication of RHD. Although the understanding of disease pathogenesis has advanced in recent years, the key questions need to be addressed. Transfer RNA–derived small RNAs (tsRNAs) are a novel type of short non-coding RNAs with potential regulatory functions in various physiological and pathological processes. The present study used tsRNAs sequencing to investigate the relationship between RHD and atrial fibrillation (AF). Three paired cardiac papillary muscles were taken from six rheumatic RHD patients with AF (3 cases) or without AF (3 cases) from January 2016 to January 2017 in Xiangya Hospital, Central South University. A total of 219 precisely matched tsRNAs were identified, and 77 tsRNAs (fold change > 2.0 and P < 0.05) were differently changed. Three tsRNAs (AS-tDR-001269, AS-tDR-001363, AS-tDR-006049) were randomly selected and confirmed by qRT-PCR. The results of qRT-PCR were consistent with tsRNAs sequencing, suggesting the tsRNAs sequencing was reliable. Subsequently, we predicted the target mRNAs of the three tsRNAs. Moreover, we verified the functions of tsRNAs targeting mRNAs in vitro. Finally, bioinformatics analysis indicated that the target genes were abundant in regulation of transcription, DNA binding, intracellular. Most of the genes were predicted to interplay with cytokine-cytokine receptor by KEGG analysis. Our findings uncover the pathological process of AF in RHD through tsRNAs sequencing. This research provides a new perspective for future research on elucidating the mechanism of AF in RHD and offers potential new candidates for the treatment and diagnosis.
Dosing Time Matters? Nighttime vs. Daytime Administration of Nifedipine Gastrointestinal Therapeutic System (GITS) or Amlodipine on Non-dipper Hypertension: A Randomized Controlled Trial of NARRAS
Authors: Liu Jing , Su Xiaofeng , Nie Ying , Zeng Zhihuan , Chen Hongyan
Published: December 2021

Background: Non-dipper hypertension is often characterized by a blunted decrease of nocturnal blood pressure (BP) and is associated with increased risk of target organ damage and cardiovascular (CV) events, while the optimal treatment strategy is yet to be established. This trial was designed to evaluate whether nocturnal BP reduction and arterial stiffness improvement differ from antihypertensive agents and time of administration.

Methods: Young and middle-aged adults (18–65 years) with non-dipper hypertension were randomly assigned to nifedipine GITS (gastrointestinal therapeutic system) 30 mg or amlodipine besylate 5 mg once daily for 8 weeks, either taken in the morning or at night. Dose was doubled at 4-week if BP is not at goal. Twenty-four hour ambulatory BP monitoring (ABPM) and arterial stiffness were evaluated before and after 8 weeks of pharmacotherapy. The primary efficacy measure was the average nighttime systolic BP reduction.

Results: A total of 98 non-dipper hypertensive patients (mean age 46.3 years) were randomized during Dec, 2016 and Dec, 2020, of whom 72 (73%) patients completed all ABPM and follow-up evaluations. Nighttime systolic BP significantly reduced at 8 weeks vs. baseline with nifedipine GITS or amlodipine, irrespective of dosing at nighttime (−9.9 vs −9.9 mmHg, P > 0.05) or daytime (−11.5 vs. −10.9 mmHg, P > 0.05). No difference was seen between these two agents, when combining the data of nighttime and daytime dosing together (−10.8 vs. −10.5 mmHg, respectively, P = 0.898). Daytime, 24-h systolic BP, diastolic BP at different time and pulse wave velocity reduced significantly and comparably, and recovery of dipping rhythm were similar among groups.

Conclusion: Nighttime dosing of long-acting antihypertensive preparations, nifedipine GITS or amlodipine demonstrated similar effects on nocturnal BP reduction, dipping rhythm restoration and arterial elasticity improvement in younger subjects with non-dipper hypertension. These effects were comparable with morning dosing.
Detailed Analyses of the Expression Patterns of Potential Severe Acute Respiratory Syndrome Coronavirus 2 Receptors in the Human Heart Using Single-Nucleus RNA Sequencing
Authors: Ren Jie , Zhang Yuze , Liu Shishi , Li Xiangjie , Sun Xiaogang
Published: December 2021

Cardiac injury is a common complication of coronavirus disease 2019 (COVID-19), but the exact mechanisms have not been completely elucidated. The virus receptors on subsets of cells are key determinants of susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Due to its high sequence similarity to SARS-CoV, SARS-CoV-2 also utilizes ACE2 as the cell entry receptor. A growing number of studies have indicated that other receptors apart from ACE2 are involved in SARS-CoV-2 infection. This study aimed to elucidate the expression characteristics of SARS-CoV-2 cellular receptors in the heart. We first investigated ACE2 expression in a comprehensive transcriptional landscape of the human heart comprising single-nucleus RNA-seq (snRNA-seq) data for >280,000 cells. Then, the expression distributions of novel SARS-CoV-2 receptors were analyzed at the single-cell level to clarify the cardiovascular complications in COVID-19. We observed a higher percentage of ACE2-positive cells in pericytes (8.3%), fibroblasts (5.1%), and adipocytes (4.4%) in the human heart, compared to other cell types. The frequency of ACE2-positive cells in each cell type from the ventricles was significantly higher than that in the atria, suggesting that the ventricular cells are more susceptible to SARS-CoV-2 infection. The distribution patterns of other receptors (BSG, HSPA5, KREMEN1, NRP1, ANPEP, AXL) were significantly different from those of ACE2, demonstrating higher expression levels in ventricular cardiomyocytes. Moreover, our results suggest that fibroblasts and adipocytes, aside from pericytes, may be vulnerable targets for SARS-CoV-2 infection in the human heart. Our study presents potential targets for future clinical studies and interventions for cardiac injury in patients with COVID-19.