bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparação sobre a eficácia e sensibilidade dos diferentes tipos de clareamento dental: uma revisão de literatura
Authors: Manna Maria Paula Novaes Camargo , Moreira Rafaela Henriques , Medeiros Yuri de Lima , Santos Isabella Silva , Lana Augusto de Sousa , Faria Luan Viana , Moreira Lúcia Andrea Contin , Oliveira Milene de , Pazinatto Rafael Barroso
Published: July 2021

Nos dias atuais, a estética do sorriso vem crescendo no mercado, visto que muitos consideram como parte do padrão de beleza desejável, o sorriso alinhado e os dentes brancos. Assim sendo, o clareamento dental constitui um dos procedimentos mais procurados e realizados pelos cirurgiões-dentistas, no quesito estética. Dessa forma, o cirurgião-dentista deve ter uma base sólida de conhecimento a respeito, para que faça uma avaliação clínica e o correto diagnóstico da estrutura dental, indicando a melhor técnica em cada caso. Para tanto, foi realizada uma revisão de literatura sobre os tipos de clareamento dental, comparando-os quanto à eficácia, em relação à alteração de cor, e quanto à sensibilidade, com buscas nas bases de dados, Pubmed, Scielo e Scopus, através dos descritores: Tooth bleaching; Carbamide peroxide; Hydrogen Peroxide; Dentin Sensitivity. Foram considerados elegíveis estudos em inglês, português ou espanhol, publicados entre 01/2006 a 05/2021. Assim, notou-se que as técnicas de clareamento são capazes de atingir os mesmos resultados quanto à mudança de cor, mas com variação no tempo e indicação. Quanto à sensibilidade, há uma tendência dessa ser maior, quando usado gel de maior concentração. Porém, já existem atualmente, géis clareadores contendo substâncias dessensibilizantes, e/ou protocolos que podem ser utilizados, para que se tenha uma redução da mesma. Além disso, quando realizada a técnica de clareamento caseiro, sugere-se dar preferência ao gel de Peróxido de Carbamida na menor concentração, uma vez que esse apresenta menor risco de desenvolvimento de sensibilidade dentária e é eficaz, se comparado às maiores concentrações.
The concept of probation and the implementation of probation control over persons with a suspended sentence in the Republic of Kazakhstan
Authors: Adilbekova Anastasiya
Published: July 2021

The article is devoted to the issues related to the formation of the state probation service in the Republic of Kazakhstan and the legislative regulation of its activities. Possible prospects for the development of this service are outlined, taking into account foreign experience, and some aspects of improving the system of execution of non-custodial sentences are also studied. Probation is presented as criminal supervision (criminal guardianship). Based on the conducted research, the author comes to the conclusion that probation should be understood as a set of measures aimed at social rehabilitation and adaptation, protection of the legal rights and interests of persons who have been prosecuted and found themselves in the current difficult life situation, as well as control and supervision of their behavior. The essence of probation is that, along with serious restrictions on the daily living conditions of the offender, in case of violation of the order and conditions of serving a sentence without deprivation of liberty, probation period of a suspended sentence, they can be replaced by real imprisonment.
Problems of penalty execution in the form of deprivation of the right to free movement in Mongolia
Authors: Batbold Galbadrakh , Sanzhaasuren Zul-Ochir
Published: July 2021

Mongolia's criminal policy after the legal reform is focused on the use of non-custodial criminal penalties. For this reason, there is a problem of understanding the social and legal content of these types of punishment. The analysis of the current criminal legislation and the practice of sentencing allowed the authors to draw certain conclusions about the problems of application and execution of punishment in the form of restrictions on the right to free movement.
Analysis of progressivity, normality and responsibility principles in the progressive system of serving criminal sentences in the form of imprisonment
Authors: Krudu Aleksandr
Published: July 2021

Ensuring the proper functioning of the progressive system of serving a criminal sentence in the form of deprivation of liberty is an urgent problem for the Republic of Moldova. The international recommendations in this area, as well as the practice of other states that apply the progressive system, in order to identify the most optimal solutions for its implementation are analyzed in the article. Special literature is studied, in which important studies is conducted on the role of sentences execution principles in achieving their goals. Recommendations for changing the existing regulatory framework are formulated. According to the results of the study, the author comes to the conclusion that although most of the principles reflected in the Penal Code of the Republic of Moldova are characteristic of a progressive system of serving sentences, their list is incomplete. International practice recognizes the important role of the principles of normality, responsibility and progressivity in a progressive system of serving a sentence of imprisonment. Therefore, in order to intensify the national correctional process and achieve more effective results in the execution of criminal penalties, it is necessary to expand the list of principles enshrined in the Penal Code of the Republic of Moldova and to create correctional mechanisms that correspond to their proper application.
Fibrous Scaffolds From Elastin-Based Materials
Authors: Rodriguez-Cabello Jose Carlos , Gonzalez De Torre Israel , González-Pérez Miguel , González-Pérez Fernando , Montequi Irene
Published: July 2021

Current cutting-edge strategies in biomaterials science are focused on mimicking the design of natural systems which, over millions of years, have evolved to exhibit extraordinary properties. Based on this premise, one of the most challenging tasks is to imitate the natural extracellular matrix (ECM), due to its ubiquitous character and its crucial role in tissue integrity. The anisotropic fibrillar architecture of the ECM has been reported to have a significant influence on cell behaviour and function. A new paradigm that pivots around the idea of incorporating biomechanical and biomolecular cues into the design of biomaterials and systems for biomedical applications has emerged in recent years. Indeed, current trends in materials science address the development of innovative biomaterials that include the dynamics, biochemistry and structural features of the native ECM. In this context, one of the most actively studied biomaterials for tissue engineering and regenerative medicine applications are nanofiber-based scaffolds. Herein we provide a broad overview of the current status, challenges, manufacturing methods and applications of nanofibers based on elastin-based materials. Starting from an introduction to elastin as an inspiring fibrous protein, as well as to the natural and synthetic elastin-based biomaterials employed to meet the challenge of developing ECM-mimicking nanofibrous-based scaffolds, this review will follow with a description of the leading strategies currently employed in nanofibrous systems production, which in the case of elastin-based materials are mainly focused on supramolecular self-assembly mechanisms and the use of advanced manufacturing technologies. Thus, we will explore the tendency of elastin-based materials to form intrinsic fibers, and the self-assembly mechanisms involved. We will describe the function and self-assembly mechanisms of silk-like motifs, antimicrobial peptides and leucine zippers when incorporated into the backbone of the elastin-based biomaterial. Advanced polymer-processing technologies, such as electrospinning and additive manufacturing, as well as their specific features, will be presented and reviewed for the specific case of elastin-based nanofiber manufacture. Finally, we will present our perspectives and outlook on the current challenges facing the development of nanofibrous ECM-mimicking scaffolds based on elastin and elastin-like biomaterials, as well as future trends in nanofabrication and applications.
Prognostic Value of a Novel Signature With Nine Hepatitis C Virus-Induced Genes in Hepatic Cancer by Mining GEO and TCGA Databases
Authors: Wei Jianming , Wang Bo , Gao Xibo , Sun Daqing
Published: July 2021

Background

Hepatitis C virus-induced genes (HCVIGs) play a critical role in regulating tumor development in hepatic cancer. The role of HCVIGs in hepatic cancer remains unknown. This study aimed to construct a prognostic signature and assess the value of the risk model for predicting the prognosis of hepatic cancer.

Methods

Differentially expressed HCVIGs were identified in hepatic cancer data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases using the library (“limma”) package of R software. The protein–protein interaction (PPI) network was constructed using the Cytoscape software. Functional enrichment analysis was performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Univariate and multivariate Cox proportional hazard regression analyses were applied to screen for prognostic HCVIGs. The signature of HCVIGs was constructed. Gene Set Enrichment Analysis (GSEA) compared the low-risk and high-risk groups. Finally, the International Cancer Genome Consortium (ICGC) database was used to validate this prognostic signature. Polymerase chain reaction (PCR) was performed to validate the expression of nine HCVIGs in the hepatic cancer cell lines.

Results

A total of 143 differentially expressed HCVIGs were identified in TCGA hepatic cancer dataset. Functional enrichment analysis showed that DNA replication was associated with the development of hepatic cancer. The risk score signature was constructed based on the expression of ZIC2, SLC7A11, PSRC1, TMEM106C, TRAIP, DTYMK, FAM72D, TRIP13, and CENPM. In this study, the risk score was an independent prognostic factor in the multivariate Cox regression analysis [hazard ratio (HR) = 1.433, 95% CI = 1.280–1.605, P < 0.001]. The overall survival curve revealed that the high-risk group had a poor prognosis. The Kaplan–Meier Plotter online database showed that the survival time of hepatic cancer patients with overexpression of HCVIGs in this signature was significantly shorter. The prognostic signature-associated GO and KEGG pathways were significantly enriched in the risk group. This prognostic signature was validated using external data from the ICGC databases. The expression of nine prognostic genes was validated in HepG2 and LO-2.

Conclusion

This study evaluates a potential prognostic signature and provides a way to explore the mechanism of HCVIGs in hepatic cancer.
Children With Autism Spectrum Disorder Can Attribute False Beliefs in a Spontaneous-Response Preferential-Looking Task
Authors: Glenwright Melanie , Scott Rose M. , Bilevicius Elena , Pronovost Megan , Hanlon-Dearman Ana
Published: July 2021

An established body of literature indicates that children with autism spectrum disorder (ASD) have difficulty understanding figurative language due to a deficit in theory of mind, or the ability to consider the beliefs of other people. Children with ASD tend to similarly fail traditional theory of mind tasks, which assess their ability to represent false beliefs. Our claim is, however, that these tasks involve cognitive processing demands that might mask false belief understanding because they require elicited responses. We examined whether children with ASD demonstrate false-belief understanding when tested with a spontaneous-response false belief task that measures children’s eye gaze durations. The two child participant groups were composed of 20 males with ASD (aged 3–9 years) and 20 typically developing males (aged 2–5 years) who were individually matched according to verbal mental age. Children with ASD and typically developing children listened to a change-of-location story accompanied by a book with matching and non-matching pictures. The final page showed the character searching for her object in a location that was either consistent or inconsistent with her belief. Both groups of children looked reliably longer at the belief-consistent picture, regardless of whether the character’s belief was true or false, though children with ASD were slower to do so. We suggest that a spontaneous-response assessment technique can potentially reveal figurative language comprehension in children with ASD in future research.
Uncovering Potential lncRNAs and mRNAs in the Progression From Acute Myocardial Infarction to Myocardial Fibrosis to Heart Failure
Authors: Wang Shuo , Wang Enmao , Chen Qincong , Yang Yan , Xu Lei , Zhang Xiaolei , Wu Rubing , Hu Xitian , Wu Zhihong
Published: July 2021

Background: Morbidity and mortality of heart failure (HF) post-myocardial infarction (MI) remain elevated. The aim of this study was to find potential long non-coding RNAs (lncRNAs) and mRNAs in the progression from acute myocardial infarction (AMI) to myocardial fibrosis (MF) to HF.

Methods: Firstly, blood samples from AMI, MF, and HF patients were used for RNA sequencing. Secondly, differentially expressed lncRNAs and mRNAs were obtained in MF vs. AMI and HF vs. MF, followed by functional analysis of shared differentially expressed mRNAs between two groups. Thirdly, interaction networks of lncRNA-nearby targeted mRNA and lncRNA-co-expressed mRNA were constructed in MF vs. AMI and HF vs. MF. Finally, expression validation and diagnostic capability analysis of selected lncRNAs and mRNAs were performed.

Results: Several lncRNA-co-expressed/nearby targeted mRNA pairs including AC005392.3/AC007278.2-IL18R1, AL356356.1/AL137145.2-PFKFB3, and MKNK1-AS1/LINC01127-IL1R2 were identified. Several signaling pathways including TNF and cytokine–cytokine receptor interaction, fructose and mannose metabolism and HIF-1, hematopoietic cell lineage and fluid shear stress, and atherosclerosis and estrogen were selected. IL1R2, IRAK3, LRG1, and PLAC4 had a potential diagnostic value for both AMI and HF.

Conclusion: Identified AC005392.3/AC007278.2-IL18R1, AL356356.1/AL137145.2-PFKFB3, and MKNK1-AS1/LINC01127-IL1R2 lncRNA-co-expressed/nearby targeted mRNA pairs may play crucial roles in the development of AMI, MF, and HF.
Traditional Chinese Medication Qiliqiangxin Attenuates Diabetic Cardiomyopathy via Activating PPARγ
Authors: Wu Xiaodong , Zhang Ting , Lyu Ping , Chen Mengli , Ni Gehui , Cheng Huiling , Xu Guie , Li Xinli , Wang Lijun , Shang Hongcai
Published: July 2021

Background: Diabetic cardiomyopathy is the primary complication associated with diabetes mellitus and also is a major cause of death and disability. Limited pharmacological therapies are available for diabetic cardiomyopathy. Qiliqiangxin (QLQX), a Chinese medication, has been proven to be beneficial for heart failure patients. However, the role and the underlying protective mechanisms of QLQX in diabetic cardiomyopathy remain largely unexplored.

Methods: Primary neonatal rat cardiomyocytes (NRCMs) were treated with glucose (HG, 40 mM) to establish the hyperglycemia-induced apoptosis model in vitro. Streptozotocin (STZ, 50 mg/kg/day for 5 consecutive days) was intraperitoneally injected into mice to establish the diabetic cardiomyopathy model in vivo. Various analyses including qRT-PCR, western blot, immunofluorescence [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining] histology (hematoxylin–eosin and Masson's trichrome staining), and cardiac function (echocardiography) were performed in these mice. QLQX (0.5 μg/ml in vitro and 0.5 g/kg/day in vivo) was used in this study.

Results: QLQX attenuated hyperglycemia-induced cardiomyocyte apoptosis via activating peroxisome proliferation-activated receptor γ (PPARγ). In vivo, QLQX treatment protected mice against STZ-induced cardiac dysfunction and pathological remodeling.

Conclusions: QLQX attenuates diabetic cardiomyopathy via activating PPARγ.
Evaluation of Abdominal Computed Tomography Scans for Differentiating the Discrepancies in Abdominal Adipose Tissue Between Two Major Subtypes of Primary Aldosteronism
Authors: Chen Kuan-Ming , Lee Bo-Ching , Chen Po-Ting , Liu Kao-Lang , Lin Kuan-Heng , Chang Chin-Chen , Wu Tung-Hsin , Hong Jia-Sheng , Lin Yen-Hung
Published: July 2021

The aim of this study was to analyze the differences in the distribution of abdominal adipose tissue between the two subtypes of primary aldosteronism (PA) using abdominal computed tomography. We retrospectively analyzed patients diagnosed as having essential hypertension (EH) or PA from the prospectively collected Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Patients with PA were divided into the subgroups of idiopathic hyperaldosteronism (IHA) and unilateral aldosterone-producing adenoma (APA). Patients’ basic clinicodemographic data were collected, and a self-developed CT-based software program was used to quantify the abdominal adiposity indexes, including visceral adipose tissue (VAT) area, VAT ratio, waist circumference (WC), subcutaneous adipose tissue (SAT) area, and SAT ratio. We included 190 patients with EH and 436 patients with PA (238 with IHA and 198 with APA). The APA group had significantly lower abdominal adiposity indexes than the other groups. We also found negative correlations of aldosterone-to-renin ratio (ARR) with VAT area, VAT ratio, WC, and body mass index (BMI) in the APA group. After propensity score matching (which left 184 patients each in the IHA and APA groups), patients in the APA group still had significantly lower WC, SAT area, SAT ratio, and VAT ratio than those in the IHA group. Furthermore, logistic regression analysis indicated that lower probability of abdominal obesity was significantly related to patients with APA. Our data revealed that the distribution of abdominal adipose tissue was similar in patients with IHA and those with EH, but the abdominal adiposity indexes were significantly lower in patients with APA than in those with IHA and EH.
Human Beta Cell Regenerative Drug Therapy for Diabetes: Past Achievements and Future Challenges
Authors: Wang Peng , Karakose Esra , Choleva Lauryn , Kumar Kunal , DeVita Robert J. , Garcia-Ocaña Adolfo , Stewart Andrew F.
Published: July 2021

A quantitative deficiency of normally functioning insulin-producing pancreatic beta cells is a major contributor to all common forms of diabetes. This is the underlying premise for attempts to replace beta cells in people with diabetes by pancreas transplantation, pancreatic islet transplantation, and transplantation of beta cells or pancreatic islets derived from human stem cells. While progress is rapid and impressive in the beta cell replacement field, these approaches are expensive, and for transplant approaches, limited by donor organ availability. For these reasons, beta cell replacement will not likely become available to the hundreds of millions of people around the world with diabetes. Since the large majority of people with diabetes have some residual beta cells in their pancreata, an alternate approach to reversing diabetes would be developing pharmacologic approaches to induce these residual beta cells to regenerate and expand in a way that also permits normal function. Unfortunately, despite the broad availability of multiple classes of diabetes drugs in the current diabetes armamentarium, none has the ability to induce regeneration or expansion of human beta cells. Development of such drugs would be transformative for diabetes care around the world. This picture has begun to change. Over the past half-decade, a novel class of beta cell regenerative small molecules has emerged: the DYRK1A inhibitors. Their emergence has tremendous potential, but many areas of uncertainty and challenge remain. In this review, we summarize the accomplishments in the world of beta cell regenerative drug development and summarize areas in which most experts would agree. We also outline and summarize areas of disagreement or lack of unanimity, of controversy in the field, of obstacles to beta cell regeneration, and of challenges that will need to be overcome in order to establish human beta cell regenerative drug therapeutics as a clinically viable class of diabetes drugs.
JunD Regulates Pancreatic β-Cells Function by Altering Lipid Accumulation
Authors: Wang Kexin , Cui Yixin , Lin Peng , Yao Zhina , Sun Yu
Published: July 2021

The impairment of pancreatic β-cells function is partly caused by lipotoxicity, which aggravates the development of type 2 diabetes mellitus. Activator Protein 1 member JunD modulates apoptosis and oxidative stress. Recently, it has been found that JunD regulates lipid metabolism in hepatocytes and cardiomyocytes. Here, we studied the role of JunD in pancreatic β-cells. The lipotoxic effects of palmitic acid on INS-1 cells were measured, and JunD small-interfering RNA was used to assess the effect of JunD in regulating lipid metabolism and insulin secretion. The results showed that palmitic acid stimulation induced the overexpression of JunD, impaired glucose-stimulated insulin secretion, and increased intracellular lipid accumulation of β-cells. Moreover, the gene expression involved in lipid metabolism (Scd1, Fabp4, Fas, Cd36, Lpl, and Plin5) was upregulated, while gene expression involved in the pancreatic β-cells function (such as Pdx1, Nkx6.1, Glut2, and Irs-2) was decreased. Gene silencing of JunD reversed the lipotoxic effects induced by PA on β-cells. These results suggested that JunD regulated the function of pancreatic β-cells by altering lipid accumulation.
The Effect of Forest Management on the Avifauna of a Brazilian Dry Forest
Authors: Ribeiro Jonathan Ramos , Las-Casas Flor Maria Guedes , Lima Hevana Santana de , Silva Weber Andrade de Girão e , Naka Luciano Nicolás
Published: July 2021

The conversion of tropical habitats has dramatic implications on biodiversity and represents one of the greatest conservation challenges of our time. Seasonally Dry Tropical Forests (SDTF), which are disjointly distributed throughout the Neotropics, are especially susceptible to human activities. The Caatinga Dry Forest, located in the semi-arid interior of northeastern Brazil, represents not only the largest and most biologically diverse nucleus of SDTF, but also the world’s most densely populated semi-arid region, with ever-growing pressure on its natural resources. To prevent illegal logging, conservation agencies looked at forest management, where an area is divided in smaller stands which are gradually logged and allowed to regrow for a period of time, when a new cutting cycle should reinitiate. The impacts of these management schemes on biodiversity, however, remain largely untested. We conducted standardized avian surveys to evaluate the effects of forest management on the avian community at a 1,670 ha privately owned property located on the Chapada do Araripe, northeastern Brazil. This area was divided in 22 forest stands, half of which had already been logged at the time of our sampling, creating a gradient of logged and natural forests and an 11-yr chrono-sequence of forest regeneration. Our results show that logged areas present fewer individuals, fewer species, and different avian assemblages than unlogged forests. Such differences are mostly driven by forest-dependent species, which were overwhelmingly affected by forest management. Our results show that although logged forests tend to recover its height after a decade, they do not recover the originally forest cover, measured by the Normalized Difference Vegetation Index. Likewise, decade-long recovering stands continue to show lower species richness, lower bird abundance, and different avian composition than unlogged forests. We identified a set of bird species that are more affected by forest management (ecological losers) and a group of birds that apparently benefit from the referred changes in land use (ecological winners). We conclude that completely managing an entire area may cause the extirpation of several forest-dependent species. We therefore suggest keeping logged and unlogged plots intermingled, to avoid local extinctions and the complete modification of the original avifauna.
Potential for Antigen-Specific Tolerizing Immunotherapy in Systematic Lupus Erythematosus
Authors: Robinson Sean , Thomas Ranjeny
Published: July 2021

Systemic lupus erythematosus (SLE) is a chronic complex systemic autoimmune disease characterized by multiple autoantibodies and clinical manifestations, with the potential to affect nearly every organ. SLE treatments, including corticosteroids and immunosuppressive drugs, have greatly increased survival rates, but there is no curative therapy and SLE management is limited by drug complications and toxicities. There is an obvious clinical need for safe, effective SLE treatments. A promising treatment avenue is to restore immunological tolerance to reduce inflammatory clinical manifestations of SLE. Indeed, recent clinical trials of low-dose IL-2 supplementation in SLE patients showed thatin vivoexpansion of regulatory T cells (Treg cells) is associated with dramatic but transient improvement in SLE disease markers and clinical manifestations. However, the Treg cells that expanded were short-lived and unstable. Alternatively, antigen-specific tolerance (ASIT) approaches that establish long-lived immunological tolerance could be deployed in the context of SLE. In this review, we discuss the potential benefits and challenges of nanoparticle ASIT approaches to induce prolonged immunological tolerance in SLE.
Inhibition of Extracellular Cathepsin D Reduces Hepatic Lipid Accumulation and Leads to Mild Changes in Inflammationin NASH Mice
Authors: Yadati Tulasi , Houben Tom , Bitorina Albert , Oligschlaeger Yvonne , Gijbels Marion J. , Mohren Ronny , Lütjohann Dieter , Khurana Princy , Goyal Sandeep , Kulkarni Aditya , Theys Jan , Cillero-Pastor Berta , Shiri-Sverdlov Ronit
Published: July 2021

Background & Aims

The lysosomal enzyme, cathepsin D (CTSD) has been implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH), a disease characterised by hepatic steatosis and inflammation. We have previously demonstrated that specific inhibition of the extracellular CTSD leads to improved metabolic features in Sprague-Dawley rats with steatosis. However, the individual roles of extracellular and intracellular CTSD in NASH are not yet known. In the current study, we evaluated the underlying mechanisms of extracellular and intracellular CTSD fractions in NASH-related metabolic inflammation using specific small-molecule inhibitors.

Methods

Low-density lipoprotein receptor knock out (Ldlr-/-) mice were fed a high-fat, high cholesterol (HFC) diet for ten weeks to induce NASH. Further, to investigate the effects of CTSD inhibition, mice were injected either with an intracellular (GA-12) or extracellular (CTD-002) CTSD inhibitor or vehicle control at doses of 50 mg/kg body weight subcutaneously once in two days for ten weeks.

Results

Ldlr-/- mice treated with extracellular CTSD inhibitor showed reduced hepatic lipid accumulation and an associated increase in faecal bile acid levels as compared to intracellular CTSD inhibitor-treated mice. Furthermore, in contrast to intracellular CTSD inhibition, extracellular CTSD inhibition switched the systemic immune status of the mice to an anti-inflammatory profile. In line, label-free mass spectrometry-based proteomics revealed that extra- and intracellular CTSD fractions modulate proteins belonging to distinct metabolic pathways.

Conclusion

We have provided clinically translatable evidence that extracellular CTSD inhibition shows some beneficial metabolic and systemic inflammatory effects which are distinct from intracellular CTSD inhibition. Considering that intracellular CTSD inhibition is involved in essential physiological processes, specific inhibitors capable of blocking extracellular CTSD activity, can be promising and safe NASH drugs.
A Comparative Transcriptome Between Anti-drug Sensitive and Resistant Candida auris in China
Authors: Zhou Wenkai , Li Xiuzhen , Lin Yiqing , Yan Wei , Jiang Shuling , Huang Xiaotian , Yang Xinglong , Qiao Dan , Li Na
Published: July 2021

Candida auris emerged as a pathogenic species of fungus that causes severe and invasive outbreaks worldwide. The fungus exhibits high intrinsic resistance rates to various first-line antifungals, and the underlying molecular mechanism responsible for its multidrug resistance is still unclear. In this study, a transcriptomic analysis was performed between two C. auris isolates that exhibited different anti-drug patterns by RNA-sequencing, namely, CX1 (anti-drug sensitive) and CX2 (resistant). Transcriptomic analysis results revealed 541 upregulated and 453 downregulated genes in the resistant C. auris strain compared with the susceptible strain. In addition, our findings highlight the presence of potential differentially expressed genes (DEGs), which may play a role in drug resistance, including genes involved in ergosterol and efflux pump biosynthesis such as SNQ2, CDR4, ARB1, MDR1, MRR1, and ERG genes. We also found that Hsp related genes were upregulated for expression in the anti-drug-resistant strain. Biofilm formation and growth conditions were also compared between the two isolates. Our study provides novel clues for future studies in terms of understanding multidrug resistance mechanisms of C. auris strains.
A Potential circRNA-miRNA-mRNA Regulatory Network in Asthmatic Airway Epithelial Cells Identified by Integrated Analysis of Microarray Datasets
Authors: Chen Dian , Wu Wenliang , Yi Lingling , Feng Yuchen , Chang Chenli , Chen Shengchong , Gao Jiali , Chen Gongqi , Zhen Guohua
Published: July 2021

Background: Asthma is one of the most prevalent chronic respiratory diseases worldwide. Bronchial epithelial cells play a critical role in the pathogenesis of asthma. Circular RNAs (circRNAs) act as microRNA (miRNA) sponges to regulate downstream gene expression. However, the role of epithelial circRNAs in asthma remains to be investigated. This study aims to explore the potential circRNA-miRNA-messenger RNA (mRNA) regulatory network in asthma by integrated analysis of publicly available microarray datasets.

Methods: Five mRNA microarray datasets derived from bronchial brushing samples from asthma patients and control subjects were downloaded from the Gene Expression Omnibus (GEO) database. The robust rank aggregation (RRA) method was used to identify robust differentially expressed genes (DEGs) in bronchial epithelial cells between asthma patients and controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to annotate the functions of the DEGs. Protein-protein interaction (PPI) analysis was performed to identify hub genes. Three miRNA databases (Targetscan, miRDB, and miRWalk) were used to predict the miRNAs which potentially target the hub genes. A miRNA microarray dataset derived from bronchial brushings was used to validate the miRNA-mRNA relationships. Finally, a circRNA-miRNA-mRNA network was constructed via the ENCORI database.

Results: A total of 127 robust DEGs in bronchial epithelial cells between steroid-naïve asthma patients (n = 272) and healthy controls (n = 165) were identified from five mRNA microarray datasets. Enrichment analyses showed that DEGs were mainly enriched in several biological processes related to asthma, including humoral immune response, salivary secretion, and IL-17 signaling pathway. Nineteen hub genes were identified and were used to construct a potential epithelial circRNA-miRNA-mRNA network. The top 10 competing endogenous RNAs were hsa_circ_0001585, hsa_circ_0078031, hsa_circ_0000552, hsa-miR-30a-3p, hsa-miR-30d-3p, KIT, CD69, ADRA2A, BPIFA1, and GGH.

Conclusion: Our study reveals a potential role for epithelial circRNA-miRNA-mRNA network in the pathogenesis of asthma.
Initial Experience With the Trevo NXT Stent Retriever
Authors: Etter Manina M. , Möhlenbruch Markus , Weyland Charlotte S. , Pérez-García Carlos , Moreu Manuel , Capasso Francesco , Limbucci Nicola , Nikoubashman Omid , Wiesmann Martin , Blackham Kristine , Tsogkas Ioannis , Sporns Peter , Ospel Johanna Maria , Brehm Alex , Psychogios Marios-Nikos
Published: July 2021

Background: The application of a new coating to the delivery wire of the Trevo retriever has the potential to improve its handling. We therefore report our initial experience with this new stent retriever for mechanical thrombectomy of large and medium vessel occlusions.

Methods: We pooled data of four high-volume European stroke centers over the time period from October 2020 to February 2021. Patients were included in our study if the Trevo NXT stent retriever was used as a first-line device. Primary endpoints were first-pass near-complete or complete reperfusion, defined as mTICI score of ≥2c. Secondary endpoints were final reperfusion, National Institutes of Health Stroke Scale (NIHSS) at 24 h and discharge, device malfunctions, complications during the procedure, and subjective ratings of the interventionalists regarding device functionality.

Results: Eighty patients (39 women, mean age 74 ± 14 years) were eligible for our study. Median NIHSS at admission was 15 (IQR, 8–19), and median Alberta Stroke Program Early CT Score at baseline was 9 (IQR, 8–10). In 74 (93%) patients a primary combined approach was used as first-line technique. First-pass near-complete reperfusion was achieved in 43 (54%) and first-pass complete reperfusion in 34 (43%) patients. Final near-complete reperfusion was achieved in 66 (83%) patients after a median of 1.5 (1–3) passes, while final successful reperfusion was observed in 96% of our cases. We observed no device malfunctions. Median NIHSS at discharge was 2 (IQR, 0–5), and 3 patients (4%) suffered a symptomatic intracranial hemorrhage.

Conclusions: Based on our initial data, we conclude that the Trevo NXT is an effective and safe tool for mechanical thrombectomy especially when used for combined approaches.
Endovascular Treatment of Posterior Circulation Saccular Aneurysms With the p64 Flow Modulation Device: Mid-and Long-Term Results in 54 Aneurysms From a Single Center
Authors: Hellstern Victoria , Aguilar-Pérez Marta , Henkes Elina , Serna-Candel Carmen , Wendl Christina , Bäzner Hansjörg , Ganslandt Oliver , Henkes Hans
Published: July 2021

Objective: Flow diverter (FD) stents have become one of the most common tools for treating intracranial aneurysms; however, their role in treating posterior circulation aneurysms is still discussed with controversy. In this study, we evaluated the safety and effectiveness of p64 FD for the treatment of saccular, unruptured aneurysms in the posterior circulation over a long-term follow-up period in a single center.

Methods: From our prospectively maintained database, we retrospectively identified patients who underwent treatment of an intracranial saccular aneurysm arising from the posterior circulation with ≥1 p64 FD implanted or attempted between October 2012 and December 2019. Aneurysms could have been treated with prior or concomitant saccular treatment (e.g., coiling, intra-aneurysmal flow diversion). Aneurysms with parent vessel implants other than p64, fusiform aneurysms, and dissections were excluded. Peri- and postprocedural complications, clinical outcome, and clinical and angiographic follow-up results were evaluated.

Results: In total, 54 patients (45 female, 9 male; mean age 55.1 years) with 54 intracranial aneurysms met the inclusion criteria. In 51 cases (94.4%), one p64 was implanted; in 2 cases (3.7 %), two p64s were implanted; in one case, deployment of the p64 was not feasible. Procedural complications occurred in 3.7% and postprocedural complications in 9.3 %, respectively. Hemorrhagic complications occurred in 2/54 patients (3.7%), thereof one fatal parenchymal hemorrhage. Ischemic complications were observed in 5/54 patients (9.3%). Early, mid-term, and long-term angiographic follow-up examinations showed complete or near-complete aneurysm occlusion, defined according to the O'Kelly –Marotta (OKM) scale as OKM C + D in 56, 75.6, and 82.9 %, respectively. Asymptomatic side vessel occlusions occurred in 3.8%, each during the first follow-up.

Conclusions: The implantation of a p64 FD is a safe and effective device for endovascular treatment of posterior circulation saccular aneurysms with a high success rate and low morbi-mortality.
Brain Functional Changes in Stroke Following Rehabilitation Using Brain-Computer Interface-Assisted Motor Imagery With and Without tDCS: A Pilot Study
Authors: Hu Mengjiao , Cheng Hsiao-Ju , Ji Fang , Chong Joanna Su Xian , Lu Zhongkang , Huang Weimin , Ang Kai Keng , Phua Kok Soon , Chuang Kai-Hsiang , Jiang Xudong , Chew Effie , Guan Cuntai , Zhou Juan Helen
Published: July 2021

Brain-computer interface-assisted motor imagery (MI-BCI) or transcranial direct current stimulation (tDCS) has been proven effective in post-stroke motor function enhancement, yet whether the combination of MI-BCI and tDCS may further benefit the rehabilitation of motor functions remains unknown. This study investigated brain functional activity and connectivity changes after a 2 week MI-BCI and tDCS combined intervention in 19 chronic subcortical stroke patients. Patients were randomized into MI-BCI with tDCS group and MI-BCI only group who underwent 10 sessions of 20 min real or sham tDCS followed by 1 h MI-BCI training with robotic feedback. We derived amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) from resting-state functional magnetic resonance imaging (fMRI) data pre- and post-intervention. At baseline, stroke patients had lower ALFF in the ipsilesional somatomotor network (SMN), lower ReHo in the contralesional insula, and higher ALFF/Reho in the bilateral posterior default mode network (DMN) compared to age-matched healthy controls. After the intervention, the MI-BCI only group showed increased ALFF in contralesional SMN and decreased ALFF/Reho in the posterior DMN. In contrast, no post-intervention changes were detected in the MI-BCI + tDCS group. Furthermore, higher increases in ALFF/ReHo/FC measures were related to better motor function recovery (measured by the Fugl-Meyer Assessment scores) in the MI-BCI group while the opposite association was detected in the MI-BCI + tDCS group. Taken together, our findings suggest that brain functional re-normalization and network-specific compensation were found in the MI-BCI only group but not in the MI-BCI + tDCS group although both groups gained significant motor function improvement post-intervention with no group difference. MI-BCI and tDCS may exert differential or even opposing impact on brain functional reorganization during post-stroke motor rehabilitation; therefore, the integration of the two strategies requires further refinement to improve efficacy and effectiveness.
An Analytical Framework of Tonal and Rhythmic Hierarchy in Natural Music Using the Multivariate Temporal Response Function
Authors: Leahy Jasmine , Kim Seung-Goo , Wan Jie , Overath Tobias
Published: July 2021

Even without formal training, humans experience a wide range of emotions in response to changes in musical features, such as tonality and rhythm, during music listening. While many studies have investigated how isolated elements of tonal and rhythmic properties are processed in the human brain, it remains unclear whether these findings with such controlled stimuli are generalizable to complex stimuli in the real world. In the current study, we present an analytical framework of a linearized encoding analysis based on a set of music information retrieval features to investigate the rapid cortical encoding of tonal and rhythmic hierarchies in natural music. We applied this framework to a public domain EEG dataset (OpenMIIR) to deconvolve overlapping EEG responses to various musical features in continuous music. In particular, the proposed framework investigated the EEG encoding of the following features: tonal stability, key clarity, beat, and meter. This analysis revealed a differential spatiotemporal neural encoding of beat and meter, but not of tonal stability and key clarity. The results demonstrate that this framework can uncover associations of ongoing brain activity with relevant musical features, which could be further extended to other relevant measures such as time-resolved emotional responses in future studies.
A Personalized Therapeutics Approach Using an In Silico Drosophila Patient Model Reveals Optimal Chemo- and Targeted Therapy Combinations for Colorectal Cancer
Authors: Gondal Mahnoor Naseer , Butt Rida Nasir , Shah Osama Shiraz , Sultan Muhammad Umer , Mustafa Ghulam , Nasir Zainab , Hussain Risham , Khawar Huma , Qazi Romena , Tariq Muhammad , Faisal Amir , Chaudhary Safee Ullah
Published: July 2021

In silico models of biomolecular regulation in cancer, annotated with patient-specific gene expression data, can aid in the development of novel personalized cancer therapeutic strategies. Drosophila melanogaster is a well-established animal model that is increasingly being employed to evaluate such preclinical personalized cancer therapies. Here, we report five Boolean network models of biomolecular regulation in cells lining the Drosophila midgut epithelium and annotate them with colorectal cancer patient-specific mutation data to develop an in silico Drosophila Patient Model (DPM). We employed cell-type-specific RNA-seq gene expression data from the FlyGut-seq database to annotate and then validate these networks. Next, we developed three literature-based colorectal cancer case studies to evaluate cell fate outcomes from the model. Results obtained from analyses of the proposed DPM help: (i) elucidate cell fate evolution in colorectal tumorigenesis, (ii) validate cytotoxicity of nine FDA-approved CRC drugs, and (iii) devise optimal personalized treatment combinations. The personalized network models helped identify synergistic combinations of paclitaxel-regorafenib, paclitaxel-bortezomib, docetaxel-bortezomib, and paclitaxel-imatinib for treating different colorectal cancer patients. Follow-on therapeutic screening of six colorectal cancer patients from cBioPortal using this drug combination demonstrated a 100% increase in apoptosis and a 100% decrease in proliferation. In conclusion, this work outlines a novel roadmap for decoding colorectal tumorigenesis along with the development of personalized combinatorial therapeutics for preclinical translational studies.
Identification of Key Circulating Exosomal microRNAs in Gastric Cancer
Authors: Qian Xiaoqing , Xie Feng , Wei Huabing , Cui Daxiang
Published: July 2021

Exosomal miRNAs (EmiRs) can be used for prediction of gastric cancer (GC) development. Supposedly, both plasma and urinary microRNAs can also be potential biomarkers for screening, but the diagnostic values of EmiRs in blood and urine are not fully studied. We here collected both types of samples from GC patients and healthy individuals and conducted miRNA sequencing to identify key members of EmiRs in GC. The exosomes samples derived from blood and urine were collected from 3 healthy individuals and 7 GC patients. Differentially expressed miRNAs (DEmiRNAs) were acquired, ontology enrichment analysis and Protein-protein Interaction (PPI) enrichment analysis were performed. There were 8 DEmiRNAs in the serum and 3 DEmiRNAs in the urine. For GC patients, there were three up-regulated DEmiRNAs (hsa-miR-130b-3p, hsa-miR-151a-3p and hsa-miR-15b-3p) in the serum exosomes, and one up-regulated DEmiRNA (hsa-miR-1246) in the urinary exosomes. Using miRNA target prediction databases, we found 418 common targets of hsa-miR-15b-3p, 35 common targets of hsa-miR-151a-3p, 117 common targets of hsa-miR-130b-3p, and 357 common targets of hsa-miR-1246. Some commonly enriched ontology terms were found, including GO BP terms like cell surface receptor signaling pathway involved in cell-cell signaling, positive regulation of catabolic process, morphogenesis of an epithelium, and GO CC terms perinuclear region of cytoplasm. The PPI network show some key nodes, including TAOK1, CMTM6, SCN3A, WASF3, IGF1, CNOT7, GABRG1, PRKD1. Together, this study provided an integrative analysis of expression profile of key circulating exosomal microRNAs. Four key exosomal miRNAs (hsa-miR-130b-3p, hsa-miR-151a-3p and hsa-miR-15b-3p) and the interaction network or enrichments based on their targets (TAOK1, CMTM6, SCN3A, WASF3, IGF1, CNOT7, GABRG1, PRKD1) may provide a reference of the molecular mechanisms in the GC development.
Aucuboside Inhibits the Generation of Th17 Cells in Mice Colitis
Authors: Mei Chenxue , Wang Xiao , Meng Fanxiang , Zhang Xiaoqing , Chen Ling , Yan Siqi , Xue Junxiu , Sun Xun , Wang Yuanyuan
Published: July 2021

Aucuboside is an iridoid glycoside extracted from traditional Chinese medicine such as Rehmannia glutinosa, possessing a wide range of biological activities, including antioxidant, anti-aging, anti-inflammatory, and anti-fibrotic effects. The effects of aucuboside on inflammatory bowel disease (IBD) have not been studied. Therefore, the effects of aucuboside on the generation of Foxp3+ regulatory T (Treg) cells and IL-17–producing T helper (Th17) cells in colitis were studied. A mouse colitis model was established by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to mimic human IBD. The generation of Treg and Th17 cells was evaluated by flow cytometry. Aucuboside significantly alleviated colitis symptoms, including weight loss, high disease activity index, and inflammatory responses. The generation of Th17 cells in colitis was significantly inhibited by aucuboside and accompanied by the suppression of IL-17 expression. In Raw264.7 cells, the LPS-induced increase in IL-17 expression was also suppressed by aucuboside, which was significantly blocked by the RORγt inhibitor sr2211. In addition, the decrease in the proportion of Treg cells was also partially reversed by aucuboside, which may reflect the aucuboside-induced inhibition of Th17 cells. This previously unrecognized immunoregulatory function of aucuboside may have clinical applications in IBD.
Targeting GluN2B/NO Pathway Ameliorates Social Isolation–Induced Exacerbated Attack Behavior in Mice
Authors: Fang Weiqing , Wang Xiaorong , Cai Miao , Liu Xinxin , Wang Xuemeng , Lu Wen
Published: July 2021

Exacerbated attack behavior has a profound socioeconomic impact and devastating social consequences; however, there is no satisfactory clinical management available for an escalated attack behavior. Social isolation (SI) is widespread during this pandemic and may exert detrimental effects on mental health, such as causing heightened attack behavior. To explore the therapeutic approaches that alleviate the SI-induced heightened attack behavior, we utilized pharmacological methods targeting the GluN2B/NO signaling pathway during the attack behavior. Ifenprodil and TAT-9C peptide targeting GluN2B showed that the inhibition of GluN2B mitigated the SI-induced escalated attack behavior and the SI-induced aberrant nitric oxide (NO) level in the brain. Additionally, the potentiation of the NO level by L-arginine reversed the effects of the inhibition of GluN2B. Moreover, we showed that high doses of L-NAME and 7-NI and subeffective doses of L-NAME in combination with ifenprodil or TAT-9C or subeffective doses of 7-NI plus ifenprodil or TAT-9C all decreased the SI-induced escalated attack behavior and reduced the NO level, further supporting the idea that GluN2B/NO signaling is a crucial modulator of the escalated attack behavior.