bluuebunny/crossref_metadata_2025 huggingface dataset:
Saúde Mental e Diabetes Mellitus: alterações psicoemocionais durante o período de distanciamento social na pandemia da COVID-19
Authors: Monção Anne Caroline de Moraes , Pedroza Giulia Gabriella de Oliveira , Souza Victor Hugo Maria Paura , Valladares Heitor Oliveira , Mello Sávio Dias de Paula , Silva Júlio Cesar Santos , Ferreira Marcela dos Santos
Published: December 2020

Objetivo: caracterizar o estado de saúde mental, dos portadores de diabetes mellitus, e identificar fatores determinantes para o seu desequilíbrio, durante o período da pandemia de COVID-19. Metodologia: estudo transversal, quantitativo de caráter exploratório, desenvolvido entre agosto e setembro de 2020. Os 126 indivíduos abordados no estudo foram submetidos a questionário respondido virtualmente, baseado no Self-Report Questionnaire (SRQ-20), que contemplou questões acerca da situação sociodemográfica e estado psicoemocional durante o período de distanciamento social adotado na pandemia do COVID-19. Os dados foram analisados por estatística descritiva e inferencial. Resultados: ocorreram mudanças em aspectos psicoemocionais em consequência ao desafio da vida cotidiana e mudança de rotina durante a pandemia. Todas estas evidências resultaram em estresse mental associado a presença de dores de cabeça frequentes. Foi constatado que 50% dos idosos desenvolveu o sentimento de inutilidade, considerando a dependência familiar para o cumprimento de atividades rotineiras básicas. Houve impacto da diminuição de renda no estado psicoemocional, mantendo relação com dificuldade de dormir. Em contrapartida, as respostas positivas em relação a adaptação ao distanciamento social, é visto nos portadores de DM que mantiveram atividades laborais em casa. Conclusão: as alterações psicoemocionais possuem o potencial de agravar patologias ou propriamente serem fatores de risco para a condições crônicas, como a DM. O estudo demonstra a importância da criação e proteção de medidas de diminuição dos efeitos do distanciamento social na vida das pessoas do grupo de risco.
Reflexão sobre o coaching educacional como um processo prático em sala de aula
Authors: Bernárdez Gómez Abraham , García Carmen María Caballero , Santa-María Yonatan Díaz
Published: December 2020

Nas últimas décadas, o coaching educacional tem sido proposto como uma ferramenta de uso para auxiliar o professor em seu trabalho e, desta forma, os alunos alcançam o sucesso esperado em seu processo de aprendizagem. Para isso, há inúmeros teóricos que avançaram na pesquisa desse construto e acredita-se que é necessário fazer uma sistematização humilde do que significa implementar esse processo em sala de aula. Para realizar o objetivo proposto: explorar e oferecer pesquisas relacionadas à aplicação do coaching educacional em sala de aula; desenvolve-se uma revisão da literatura que, após a realização de uma análise de conteúdo, tem extraído diferentes considerações e o processo a ser realizado para estabelecer um processo de ensino-aprendizagem no qual o coaching educacional é medido.
The prisoners work in the prisons on the Belarusian lands at the end of the 19th – early 20th centuries
Authors: Chaikin Sergey N.
Published: December 2020

The history of the development of the prisoners work on the Belarusian lands after the prison reform of 1879 is the object of examination. In the historiography of pre-revolutionary, Soviet and modern periods this problem has never been studied by neither Russian nor Belarusian scientists. The examination of the prisoners work development in the local prisons as well as the determination of its common patterns for the Belarusian lands and the Russian Empire in general, and of the regional characteristics of this process are the purpose of the research. The main ways of action of the General Directorate of the Corps of Prison on the labour productivity of the prisoners on Belarusian lands (organisation of its local structural subdivision (province prison inspections) which managed the prisoners work, the organisation of the melioration and logging, the development of work in the prisons workshops) are being examined by the author on the base of the study of the archive data. The core activity of the fulfilment in the local prisons at the end of the 19th – early 20th centuries and the negative phenomena which interrupt it (in general the overcrowding of the places of determination that influenced the closure of the workshops) are being determined. The results of the prisoners work development by the turn of the second decade of the 20th century which are the growing numbers of the working prisoners and the increase of their salary activity from the beginning of the 20th century are being appreciated. The undertaken research will make it possible to determine the historical continuity of the series of measures to develop the prisoners work in the places of detention at the end of the 19th – early 20th centuries with the activity of the manufacturing establishments of the penitentiary system of the Republic of Belarus at the present time.
On outlier detection with the Chebyshev type inequalities
Authors: Chepulis Michael A. , Shevlyakov Georgy L.
Published: December 2020

This work considers algorithms of outlier detection based on the Chebyshev inequality. It compares these algorithms with such classical methods as Tukey’s boxplot, the N-sigma rule and its robust modifications based on MAD and FQ scale estimates. To adjust the parameters of the algorithms, a selection procedure is proposed based on the complete knowledge of the data distribution model. Areas of suboptimal parameters are also determined in case of incomplete knowledge of the distribution model. It is concluded that the direct use of the Chebyshev inequality implies the classical N-sigma rule. With the non-classical Chebyshev inequality, a robust outlier detection method is obtained, which slightly outperforms other considered algorithms.
IMPLEMENTATION OF ELECTRONIC MONITORING OF SENTENCED PERSONS IN THE SLOVAK REPUBLIC
Authors:   Matej Bel University, Banská Bystrica, Slovak Republic, KLÁTIK JAROSLAV , KLIMEK LIBOR
Published: December 2020

The work deals with implementation of electronic monitoring of sentenced persons in the Slovak Republic. It is divided into eight sections. The first section introduces restorative justice as a prerequisite of electronic monitoring in criminal proceedings. While the second section points out at the absence of legal regulation of electronic monitoring of sentenced persons at European level, the third section points out at recommendations of the Council of Europe addressed to European States. The fourth section analyses relevant alternative punishments in Slovak criminal justice. The fifth section introduces early beginnings of implementation of concerned system - the pilot project “Electronic Personnel Monitoring System” of the Ministry of Justice of the Slovak Republic. While the sixth section is focused on Slovak national law regulating electronic monitoring of sentenced persons - the Act No. 78/2015 Coll. on Control of the Enforcement of Certain Decisions by Technical Instruments, the seventh section is focused on further amendments of Slovak national law - namely the Act No. 321/2018 Coll. and the Act No. 214/2019 Coll. The last eight section introduces costs of system implementation and its operation.
TRANSFORMATION OF TRADITIONAL MECHANISMS FOR PROTECTING THE COMPETITIVE ENVIRONMENT UNDER THE INFLUENCE OF NETWORK ECONOMY: THE PLACE OF BLOCKCHAIN IN THE REGULATORY SYSTEM AND NEW COMPETITIVE TOOLS (AGGREGATORS AND PRICE ALGORITHMS)
Authors:   Peoples Friendship University of Russia (RUDN University), Moscow, Russian Federation, BELIKOVA KSENIA
Published: December 2020

This article is aimed at understanding the current state and necessity of transformation of traditional mechanisms for protecting the competitive environment under the influence of networking and the place of blockchain in the regulatory system in the context of applying new competitive tools (aggregators price algorithms) based on the experience of foreign countries, including the perspective and approaches of newest law enforcement (judicial) practice, taking into account the fact that its knowledge allowed and allows to successfully solve current problems of legal regulation in our country. The starting point of the research is network communication as a non-market type of communication. Based on analytical reflections on the information gathered from sources and literature from the list of references the author analyzes legal framework of competition protection developed in the new technological reality, takes into account the approaches of foreign countries and the Russian Federation that determine the acceptability of the application of blockchain in the field of legal protection of competition. The relevance, theoretical and practical significance of this research is due to the emergence of new tools (aggregators and price algorithms) of competitive market struggle in the light of application of a blockchain technology that might influence the competition. The author's results are presented, among others, in the idea of the possibility of “transfer” of anti-competitive actions (price manipulation and collusion, unequal sale / distribution of information / advertising, etc. conditions) to the niche occupied by price algorithms and aggregators of information, and the need to establish a new legal framework of these new market factors.
ACTIVITIES OF NON-STATE PENSION FUNDS IN THE FIELD OF EARLY NON-STATE PENSION PROVISION
Authors:   Presidential Administration, Moscow, Russian Federation, YUDINA EKATERINA
Published: December 2020

The system of early retirement pensions was inherited from the USSR and every third Russian pensioner receives a preferential pension. It is assigned to metallurgists, oil workers, coal miners, ballerinas, trolleybus drivers, teachers - the lists of early retired pensioners are huge. The conduction of pension reform involved seeking resources within the system itself. To solve the problem of financing preferential pensions, a system of early non-state pension provision was created, implemented through non-state pension funds. However, the existing legislative regulation does not stimulate employers of hazardous and dangerous industries to create corporate pension programs due to the fact that they will not exempt employers from paying additional insurance premiums in favor of employees on preferential lists. As a result, there are no employers in the country who will not only pay wages on time, transfer insurance premiums in a timely manner, but for this category in an increased amount, but will also form additional contributions for the same employees under the early non-state pension system. The non-state pension paid in the frame of this system does not replace the early insurance old-age pension, that is, it does not entail a decrease in federal budget costs. The purpose of this study is to consider the main legal acts and the process of development of legislation on early non-state pension provision. The result of the study is practical proposals for improving the legal framework of the early retirement pension system.
CASE-LAW OF THE COURT OF JUSTICE OF THE EUROPEAN UNION ON MARKET ABUSE AT EUROPEAN LEVEL
Authors:   Matej Bel University, Banská Bystrica, Slovak Republic, KLIMEK LIBOR
Published: December 2020

A set of legislative instruments regulating market abuse have been adopted by the European Union. The principal contemporary legislative instrument in this field, addressed to its Member States, is the Regulation No 596/2014 of the European Parliament and of the Council on market abuse. Legislation has been supplemented by the case-law of the Court of Justice of the European Union (formerly known as the Court of Justice of the European Communities). It is a key element for the development of legal practice in all Member States of the European Union. The assessment of case-law on market abuse is therefore needed. The paper analyses relevant cases. In each case at the outset a reference for a preliminary ruling is mentioned. Further, dispute in the main proceedings and the question(s) referred for a preliminary ruling are analysed. The most important parts of analyses are considerations by the Court of Justice and its rulings
A Self-Enforced Optimal Framework for Inter-Platoon Transfer in Connected Vehicles.
Authors: Puthusseri Sahal Ali Ahmed
Published: December 2020

Platooning has been identified as a promising strategy towards energy, time management and throughput. In such, a Platoon Leader (PL) provides the Platoon Members (PMs) with autonomous driving service to specific locations. This paper investigates and presents an approach for formulating an architecture to coordinate platoon manipulations while at transit rather than at signalized intersections. The data broadcast by the Vehicles are used to evaluate scores such that a PM can choose a PL and the Platoon analogous to it. Based on this, a multiple-stage platoon formation framework is put forward, which considers the aforementioned nature along with the assessment of an optimal velocity and position for the Incoming Member. It utilizes Vehicle-to-Vehicle communication and a negotiation algorithm based on Dynamic Games of Complete Information towards optimal and fair platoon formation. Simulation results demonstrate that the algorithm significantly reduces the energy consumption along with substantial time gains.
Causes of Multi Years Contract Project Delay
Authors: Sajiah Faslan Syam
Published: December 2020

Delay in construction projects is considered one of the most common problems, causing a multitude of negative effects on the project and its participating parties. Delays can cause losses to the economy, cost overruns, disputes, arbitration, abandonment, and poor quality of finished project. This paper aims to identify the main causes of delay in multi years infrastructure projects in Indonesia. Based on secondary data from documents for Proposals and Completion of Extension of Multi-Year Contract Approval in the FY 2018 and 2019 which are processed at the Ministry of Finance, 19 factors that caused the delay were identified. The importance indexes measured and ranked the level of importance of the delay factors. The main five causes of time delays included land acquisition problem, design change, failed tender, inadequate site investigation, and shortage of construction materials. Majority of the cause is attributed to Ministry/Institution as project owner. The results can help project owners, contractors, and consultants in understanding the reasons for the delay, so that each party, especially the Ministry/Agency as the project owner, can eliminate or minimize these causes.
Establishing a Urine-Based Biomarker Assay for Prostate Cancer Risk Stratification
Authors: Guo Jinan , Liu Dale , Zhang Xuhui , Johnson Heather , Feng Xiaoyan , Zhang Heqiu , Wu Alan H. B. , Chen Lingwu , Fang Jiequn , Xiao Zhangang , Xiao Kefeng , Persson Jenny L. , Zou Chang
Published: December 2020

One of the major features of prostate cancer (PCa) is its heterogeneity, which often leads to uncertainty in cancer diagnostics and unnecessary biopsies as well as overtreatment of the disease. Novel non-invasive tests using multiple biomarkers that can identify clinically high-risk cancer patients for immediate treatment and monitor patients with low-risk cancer for active surveillance are urgently needed to improve treatment decision and cancer management. In this study, we identified 14 promising biomarkers associated with PCa and tested the performance of these biomarkers on tissue specimens and pre-biopsy urinary sediments. These biomarkers showed differential gene expression in higher- and lower-risk PCa. The 14-Gene Panel urine test (PMP22, GOLM1, LMTK2, EZH2, GSTP1, PCA3, VEGFA, CST3, PTEN, PIP5K1A, CDK1, TMPRSS2, ANXA3, and CCND1) was assessed in two independent prospective and retrospective urine study cohorts and showed high diagnostic accuracy to identify higher-risk PCa patients with the need for treatment and lower-risk patients for surveillance. The AUC was 0.897 (95% CI 0.939–0.855) in the prospective cohort (n = 202), and AUC was 0.899 (95% CI 0.964–0.834) in the retrospective cohort (n = 97). In contrast, serum PSA and Gleason score had much lower accuracy in the same 202 patient cohorts [AUC was 0.821 (95% CI 0.879–0.763) for PSA and 0.860 (95% CI 0.910–0.810) for Gleason score]. In addition, the 14-Gene Panel was more accurate at risk stratification in a subgroup of patients with Gleason scores 6 and 7 in the prospective cohort (n = 132) with AUC of 0.923 (95% CI 0.968–0.878) than PSA [AUC of 0.773 (95% CI 0.852–0.794)] and Gleason score [AUC of 0.776 (95% CI 0.854–0.698)]. Furthermore, the 14-Gene Panel was found to be able to accurately distinguish PCa from benign prostate with AUC of 0.854 (95% CI 0.892–0.816) in a prospective urine study cohort (n = 393), while PSA had lower accuracy with AUC of 0.652 (95% CI 0.706–0.598). Taken together, the 14-Gene Panel urine test represents a promising non-invasive tool for detection of higher-risk PCa to aid treatment decision and lower-risk PCa for active surveillance.
Accumulated Effect of Intra-Seasonal Oscillation Convections over the Tropical Western North Pacific on the Meridional Location of Western Pacific Subtropical High
Authors: Huang Zongci , Zhang Wenjun , Geng Xin , Hsu Pang-Chi
Published: December 2020

An extreme northward displacement of the western Pacific subtropical high (WPSH) was detected during the boreal mid-late summer (July-August) of 2018, bringing record-breaking heat waves over northern East Asia. Negative sea surface temperature (SST) anomalies in the northern India Ocean (NIO) are usually accompanied with a northward shift of the WPSH. However, no prominent NIO SST anomalies were observed during the 2018 boreal summer. It is found that this extreme northward-shifted WPSH event is largely attributed to the accumulated effect of intra-seasonal oscillation (ISO) convection anomalies over the tropical western North Pacific (WNP). The accumulated effect on the WPSH meridional location is further supported by their significant correlation based on the data since 1979. While the relationship between the NIO SST anomalies and WPSH meridional location has substantially weakened since the late 1990s, the accumulated effect of the tropical WNP ISO convections keeps playing a crucial role in modulating the WPSH meridional displacement. The active WNP ISO activities can stimulates a poleward propagating Rossby wave train, which favors a northward shift of the WPSH. Our results suggest that the accumulated effect of the tropical WNP ISO convections should be considered when predicting the WPSH during the boreal mid-late summer season.
Impact of Coseismic Frictional Melting on Particle Size, Shape Distribution and Chemistry of Experimentally-Generated Pseudotachylite
Authors: Montheil Leny , Toy Virginia G. , Scott James M. , Mitchell Thomas M. , Dobson David P.
Published: December 2020

In natural friction melts, or pseudotachylites, clast textures and glass compositions can influence the frictional behavior of faults hosting pseudotachylites, and are, in turn, sensitive to the processes involved in pseudotachylite formation. Quantification of these parameters in situations where the host rock composition and formation conditions are well-constrained, such as analogue experiments, may yield calibrations that can be employed in analysis of natural pseudotachylites. In this paper, we experimentally-generated pseudotachylites in granitoid rocks (tonalite and Westerly granite) at Pconf= 40 MPa and slip rates of ∼0.1 m s−1, comparable to the conditions under which natural pseudotachylite is known to form in Earth’s upper crust. We find variations in both clast textures and glass compositions that reflect formation processes, and probably influence the frictional behavior of similar natural faults hosting pseudotachylite. Quantification of particle size and shape distribution with a semi-automatic image analysis method, combined with analysis of glass and host-rock composition of these experimentally generated pseudotachylites, reveals that the textures of pseudotachylite material evolved by combinations of 1) comminution, 2) heterogeneous frictional flash melting, and 3) homogeneous (diffusive) clast melting and/or marginal decrepitation. Fractal dimensions of pseudotachylite-hosted clasts (D ∼ 3) that are greater than those of marginal fragmented host rock particles (gouge, D ∼ 2.4), reflect an increase of the intensity of comminution by slip localisation during a pre-melting phase. Chemical analyses demonstrate that these pseudotachylite glasses were generated by frictional flash melting, where host rock phases melt individually. Biotite is the least resistant to melting, feldspar intermediate, and quartz is the most resistant. The peudotachylite glass generated in these experiments has an alkaline composition, is depleted in SiO2compared to the bulk host-rock, and shows heterogeneous compositions in a single sample related to proximity to host-rock minerals. The percentage contributions of host rock phases to the melt, calculated by a mixing model, shows that glass compositions are dominated by plagioclase and biotite. Within the melt, margins of clasts were dissolved uniformly by diffusion and/or affected by marginal decrepitation, resulting in convex and round shapes with convexities averaging ∼0.8 and circularities averaging ∼0.65.
Gender Participation and Preference: A Multiple-Case Study on Teaching Circus at PE in Brazilians Schools
Authors: Bortoleto Marco Antonio Coelho , Ontañón Barragán Teresa , Cardani Leonora Tanasovici , Funk Alisan , Melo Caroline Capellato , Santos Rodrigues Gilson
Published: December 2020

Introduction: After more than a decade monitoring physical education instruction in Brazilian elementary schools we noticed an exponential increase in circus activities in both curricular physical education (PE) and in after-school programs. The purpose of this study was to analyze the children's participation and gender preferences in circus activities, with regard to recent studies reporting substantial gender inequalities in Brazilian PE.

Method: A qualitative study, based on multiple-cases design, was conducted in two public and six private Brazilian elementary schools. Data collection consisted of 17 semi-structured interviews with PE teachers and school administrators and in situ observations totalizing more than 130 h. The data were analyzed using Content Analysis (thematic categories).

Results: Boys and girls showed high participation levels in both curricular and extracurricular PE circus activities. In grades 1–5, participant activity preference was not linked to gender in either curricular or extracurricular situations and overall physical engagement was high. Gender preferences between activities were identified in grades 6–12: girls for aerial activities (trapeze, silks) and boys for juggling activities. Teacher preferences played an important role in the process of linking activities to specific genders both through modeled behavior and gendered encouragement of participants.

Conclusion: Circus instruction engages children of all genders and is thereby an effective activity to counter low participation in PE for boys and, especially, girls. Although circus activities are not inherently gendered, gender preferences are cultivated by teachers through gendered behavior modeling (their activity preferences) and encouragement strategies (guiding students to activities based on gender), which is often observed in traditional PE school activities and sports.
Factors and Recommendations to Support Students’ Enjoyment of Online Learning With Fun: A Mixed Method Study During COVID-19
Authors: Okada Alexandra , Sheehy Kieron
Published: December 2020

Understanding components that influence students’ enjoyment of distance higher education is increasingly important to enhance academic performance and retention. Although there is a growing body of research about students’ engagement with online learning, a research gap exists concerning whether fun affect students’ enjoyment. A contributing factor to this situation is that the meaning of fun in learning is unclear, and its possible role is controversial. This research is original in examining students’ views about fun and online learning, and influential components and connections. This study investigated the beliefs and attitudes of a sample of 551 distance education students including pre-services and in-service teachers, consultants and education professionals using a mixed-method approach. Quantitative and Qualitative data were generated through a self-reflective instrument during the COVID-19 pandemic. The findings revealed that 88.77% of participants valued fun in online learning; linked to well-being, motivation and performance. However, 16.66% mentioned that fun within online learning could take the focus off their studies and result in distraction or loss of time. Principal component analysis revealed three groups of students who found (1) fun relevant in socio-constructivist learning (2) no fun in traditional transmissive learning and (3) disturbing fun in constructivist learning. This study also provides key recommendations extracted from participants’ views supported by consensual review for course teams, teaching staff and students to enhance online learning experiences with enjoyment and fun.
Identification and Validation of Potential Pathogenic Genes and Prognostic Markers in ESCC by Integrated Bioinformatics Analysis
Authors: Tang Lu , Chen Yuqiao , Peng Xiong , Zhou Yuan , Jiang Hong , Wang Guo , Zhuang Wei
Published: December 2020

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies of the digestive tract, but its underlying molecular mechanisms are not known. We aim to identify the genes involved in ESCC carcinogenesis and discover potential prognostic markers using integrated bioinformatics analysis. Three pairs of ESCC tissues and paired normal tissues were sequenced by high-throughput RNA sequencing (RNA-seq). Integrated bioinformatics analysis was used to identify differentially expressed coding genes (DECGs) and differentially expressed long non-coding RNA (lncRNA) genes (DELGs). A protein–protein interaction (PPI) network of DECGs was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) website and visualized with Cytoscape. Survival analysis was conducted by log-rank tests to identify “hub” genes with potential prognostic value, and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was conducted to assess expression of these genes in ESCC tissues. TranswellTM assays were employed to examine the migration ability of cells after knockdown of LINC01614 expression, followed by investigation of epithelial–mesenchymal transition (EMT) by western blotting (WB). A total of 106 upregulated genes and 42 downregulated genes were screened out from the ESCC data sets. Survival analysis showed two hub protein-coding genes with higher expression in module 1 of the PPI network (SPP1 and BGN) and another three upregulated lncRNAs (LINC01614, LINC01415, NKILA) that were associated with a poor prognosis. High expression of SPP1, BGN, LINC01614, and LINC01415 in tumor samples was validated further by RT-qPCR. In vitro experiments show that knockdown of LINC01614 expression could significantly inhibit the migration of ESCC cells by regulating EMT, which was confirmed by WB. These results indicate that BGN, SPP1, LINC01614, and LINC01415 might be critical genes in ESCC and potential prognostic biomarkers.
Combining Bioinformatics Techniques to Study the Key Immune-Related Genes in Abdominal Aortic Aneurysm
Authors: Nie Han , Qiu Jiacong , Wen Si , Zhou Weimin
Published: December 2020

Approximately 13,000 people die of an abdominal aortic aneurysm (AAA) every year. This study aimed to identify the immune response-related genes that play important roles in AAA using bioinformatics approaches. We downloaded the GSE57691 and GSE98278 datasets related to AAA from the Gene Expression Omnibus database, which included 80 AAA and 10 normal vascular samples. CIBERSORT was used to analyze the samples and detect the infiltration of 22 types of immune cells and their differences and correlations. The principal component analysis showed significant differences in the infiltration of immune cells between normal vascular and AAA samples. High proportions of CD4+ T cells, activated mast cells, resting natural killer cells, and 12 other types of immune cells were found in normal vascular tissues, whereas high proportions of macrophages, CD8+ T cells, resting mast cells, and six other types of immune cells were found in AAA tissues. In the selected samples, we identified 39 upregulated (involved in growth factor activity, hormone receptor binding, and cytokine receptor activity) and 133 downregulated genes (involved in T cell activation, cell chemotaxis, and regulation of immune response mediators). The key differentially expressed immune response-related genes were screened using the STRING database and Cytoscape software. Two downregulated genes, PI3 and MAP2K1, and three upregulated genes, SSTR1, GPER1, and CCR10, were identified by constructing a protein–protein interaction network. Functional enrichment of the differentially expressed genes was analyzed, and the expression of the five key genes in AAA samples was verified using quantitative polymerase chain reaction, which revealed that MAP2K1 was downregulated in AAA, whereas SSTR1, GEPR1, and CCR10 were upregulated; there was no significant difference in PI3 expression. Our study shows that normal vascular and AAA samples can be distinguished via the infiltration of immune cells. Five genes, PI3, MAP2K1, SSTR1, GPER1, and CCR10, may play important roles in the development, diagnosis, and treatment of AAA.
Expression and Prognostic Characteristics of m6 A RNA Methylation Regulators in Breast Cancer
Authors: Zhang Bo , Gu Yanlin , Jiang Guoqin
Published: December 2020

Purpose

N6-methyladenosine (m6A) is the most prevalent modification in mRNA methylation which has a wide effect on biological functions. This study aims to figure out the efficacy of m6A RNA methylation regulator-based biomarkers with prognostic significance in breast cancer.

Patients and Methods

The 23 RNA methylation regulators were firstly analyzed through ONCOMINE, then relative RNA-seq transcriptome and clinical data of 1,096 breast cancer samples and 112 normal tissue samples were acquired from The Cancer Gene Atlas (TCGA) database. The expressive distinction was also showed by the Gene Expression Omnibus (GEO) database. The gene expression data of m6A RNA regulators in human tissues were acquired from the Genotype-Tissue Expression (GTEx) database. The R v3.5.1 and other online tools such as STRING, bc-GeneExminer v4.5, Kaplan-Meier Plotter were applied for bioinformatics analysis.

Results

Results from ONCOMINE, TCGA, and GEO databases showed distinctive expression and clinical correlations of m6A RNA methylation regulators in breast cancer patients. The high expression of YTHDF3, ZC3H13, LRPPRC, and METTL16 indicated poor survival rate in patients with breast cancer, while high expression of RBM15B pointed to a better survival rate. Both univariate and multivariate Cox regression analyses revealed that age and risk scores were related to overall survival (OS). Univariate analysis also delineated that stage, tumor (T) status, lymph node (N) status, and metastasis (M) status were associated with OS. From another perspective, Kaplan-Meier Plotter platform showed that the relatively high expression of YTHDF3 and LRPPRC and the relatively low expression of RBM15B, ZC3H13, and METTL16 in breast cancer patients had worse Relapse-Free Survival (RFS). Breast Cancer Gene-Expression Miner v4.5 showed that LRPPRC level was negatively associated with ER and PR expression, while METTL16, RBM15B, ZC3H13 level was positively linked with ER and PR expression. In HER-2 (+) breast cancer patients, the expression of LRPPRC, METTL16, RBM15B, and ZC3H13 were all lower than the HER-2 (−) group.

Conclusion

The significant difference in expression levels and prognostic value of m6A RNA methylation regulators were analyzed and validated in this study. This signature revealed the potential therapeutic value of m6A RNA methylation regulators in breast cancer.
The Murine CD137/CD137 Ligand Signalosome: A Signal Platform Generating Signal Complexity
Authors: Choi Beom K. , Lee Hyeon-Woo
Published: December 2020

CD137, a member of the TNFR family, is a costimulatory receptor, and CD137L, a member of the TNF family, is its ligand. Studies using CD137- and CD137L-deficient mice and antibodies against CD137 and CD137L have revealed the diverse and paradoxical effects of these two proteins in various cancers, autoimmunity, infections, and inflammation. Both their cellular diversity and their spatiotemporal expression patterns indicate that they mediate complex immune responses. This intricacy is further enhanced by the bidirectional signal transduction events that occur when these two proteins interact in various types of immune cells. Here, we review the biology of murine CD137/CD137L, particularly, the complexity of their proximal signaling pathways, and speculate on their roles in immune responses.
Targeting IL-1β in the Treatment of Atherosclerosis
Authors: Mai Wuqian , Liao Yuhua
Published: December 2020

The role of inflammation in atherosclerosis has been recognized several decades ago and existing treatments provide benefits in part through non-specific anti-inflammatory actions. Compared with other cytokines, interleukin-1β (IL-1β) is associated with acute and chronic inflammation. Anti-inflammatory therapy with canakinumab targeting the IL-1β innate immunity pathway could significantly reduce the rate of recurrent cardiovascular events than placebo. The results of CANTOS suggested an important role of IL-1β in atherosclerosis. However, there are numerous mechanisms that are to be clarified. We herein discussed the important immunomodulatory effect IL-1β exerts on atherosclerosis and the potential mechanisms underlying it. We also reviewed bench-to-bedside clinical translation of IL-1β neutralizing strategies associated with the use of IL-1β blockade in patients with atherosclerosis.
Treatment of Rare Inflammatory Kidney Diseases: Drugs Targeting the Terminal Complement Pathway
Authors: Anliker-Ort Marion , Dingemanse Jasper , van den Anker John , Kaufmann Priska
Published: December 2020

The complement system comprises the frontline of the innate immune system. Triggered by pathogenic surface patterns in different pathways, the cascade concludes with the formation of a membrane attack complex (MAC; complement components C5b to C9) and C5a, a potent anaphylatoxin that elicits various inflammatory signals through binding to C5a receptor 1 (C5aR1). Despite its important role in pathogen elimination, priming and recruitment of myeloid cells from the immune system, as well as crosstalk with other physiological systems, inadvertent activation of the complement system can result in self-attack and overreaction in autoinflammatory diseases. Consequently, it constitutes an interesting target for specialized therapies. The paradigm of safe and efficacious terminal complement pathway inhibition has been demonstrated by the approval of eculizumab in paroxysmal nocturnal hematuria. In addition, complement contribution in rare kidney diseases, such as lupus nephritis, IgA nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, or antineutrophil cytoplasmic antibody-associated vasculitis has been demonstrated. This review summarizes the involvement of the terminal effector agents of the complement system in these diseases and provides an overview of inhibitors for complement components C5, C5a, C5aR1, and MAC that are currently in clinical development. Furthermore, a link between increased complement activity and lung damage in severe COVID-19 patients is discussed and the potential for use of complement inhibitors in COVID-19 is presented.
Acute and Chronic Sarcoid Arthropathies: Characteristics and Treatments From a Retrospective Nationwide French Study
Authors: Cacciatore Carlotta , Belnou Pierre , Thietart Sara , Desthieux Carole , Versini Mathilde , Abisror Noemie , Ottaviani Sébastien , Cormier Gregoire , Deroux Alban , Dellal Azeddine , Belhomme Nicolas , Kermanac'H Nathalie Saidenberg , Khafagy Philippe , Michaud Martin , Lanot Sylvain , Carrat Fabrice , Fain Olivier , Mékinian Arsène
Published: December 2020

Introduction: We aimed to analyze patients with acute and chronic joint involvements in sarcoidosis.

Methods: This is a retrospective multicenter analysis of patients with proven sarcoidosis, as defined by clinical, radiological, and histological criteria, with at least one clinical and/or ultrasonographic synovitis.

Results: Thirty-nine patients with sarcoid arthropathy were included, and among them 19 had acute sarcoidosis (Lofgren's syndrome). Joint involvement and DAS44-CRP were not significantly different in acute and chronic sarcoid arthropathies. Acute forms were more frequent than chronic sarcoid arthropathy in Caucasians, without any difference of sex or age between these 2 forms. Joint involvement was frequently more symmetrical in acute than chronic forms (100 vs. 70%; p < 0.05), with a more frequent involvement in wrists and ankles in acute forms, whereas the tender and swollen joint counts and the DAS44-CRP were similar between the 2 groups. Skin lesions were significantly more frequent in patients with acute forms [17 (89%) vs. 5 (25%); p < 0.05] and were erythema nodosum in all patients with Löfgren's syndrome and sarcoid skin lesions in those with chronic sarcoidosis. Among 20 patients with chronic sarcoidosis, treatment was used in 17 (85%) cases, and consisted in NSAIDs alone (n = 5; 25%), steroids alone (n = 5; 25%), hydroxychloroquine (n = 2; 20%), methotrexate (n = 3; 15%), and TNF inhibitors (n = 2; 10%). A complete/partial joint response was noted in 14 (70%) cases with a DAS44-CRP reduction of 2.07 [1.85–2.44] (from 3.13 [2.76–3.42] to 1.06 [0.9–1.17]; p < 0.05).

Conclusion: Sarcoid arthropathies have different clinical phenotypes in acute and chronic forms and various treatment regimens such as hydroxychloroquine and methotrexate could be used in chronic forms.
Use of Venovenous Extracorporeal Membrane Oxygenation in Critically-Ill Patients With COVID-19
Authors: Jozwiak Mathieu , Chiche Jean-Daniel , Charpentier Julien , Ait Hamou Zakaria , Jaubert Paul , Benghanem Sarah , Dupland Pierre , Gavaud Ariane , Péne Frédéric , Cariou Alain , Mira Jean-Paul , Nguyen Lee S.
Published: December 2020

Acute respiratory distress syndrome (ARDS) related to Coronavirus disease (COVID-19) is associated with high mortality. It has been suggested that venovenous extracorporeal membrane oxygenation (ECMO) was suitable in this indication, albeit the effects of ECMO on the mechanical respiratory parameters have been scarcely described. In this case-series, we prospectively described the use of venovenous ECMO and its effects on mechanical respiratory parameters in eleven COVID-19 patients with severe ARDS. Implantation of ECMO occurred 6 [3–11] days after the onset of mechanical ventilation. At the time of ECMO implantation, all patients received neuromuscular blocking agents, three (27%) received inhaled nitric oxide and prone positioning was performed in all patients with 4 [3−5] sessions of PP per patient. Under ECMO, the tidal volume was significantly decreased from 6.1 [4.0–6.3] to 3.4 [2.5–3.6] mL/kg of predicted body weight and the positive end-expiratory pressure level was increased by 25 ± 27% whereas the driving pressure and the mechanical power decreased by 33 ± 25% and 71 ± 27%, respectively. The PaO2/FiO2 ratio significantly increased from 68 [58–89] to 168 [137–218] and the oxygenation index significantly decreased from 28 [26–35] to 13 [10–15]. The duration of ECMO was 12 [8–25] days. Nine (82%) patients experienced ECMO-related complications and the main complication was major bleeding requiring blood transfusions. Intensive care unit mortality rate was 55% but no patient died from ECMO-related complications. In COVID-19 patients with severe ARDS, venovenous ECMO allowed ultra-protective ventilation, improved oxygenation and should be considered in highly selected patients with the most severe ARDS.
Salt Stress Tolerance of Dark Septate Endophytes Is Independent of Melanin Accumulation
Authors: Gaber Dalia A. , Berthelot Charlotte , Camehl Iris , Kovács Gábor M. , Blaudez Damien , Franken Philipp
Published: December 2020

Dark septate endophytes (DSEs) represent a diverse group of root-endophytic fungi that have been isolated from plant roots in many different natural and anthropogenic ecosystems. Melanin is widespread in eukaryotic organisms and possesses various functions such as protecting human skin from UV radiation, affecting the virulence of pathogens, and playing a role in development and physiology of insects. Melanin is a distinctive feature of the cell walls of DSEs and has been thought to protect these fungi from abiotic stress. Melanin in DSEs is assumed to be synthesized via the 1,8-dihydroxynaphthalene (DHN) pathway. Its function in alleviation of salt stress is not yet known. The aims of this study were: (i) investigating the growth responses of three DSEs (Periconia macrospinosa, Cadophora sp., and Leptodontidium sp.) to salt stress, (ii) analyzing melanin production under salt stress and, (iii) testing the role of melanin in salt stress tolerance of DSEs. The study shows that the three DSE species can tolerate high salt concentrations. Melanin content increased in the hyphae of all DSEs at 100 mM salt, but decreased at 500 mM. This was not reflected in the RNA accumulation of the gene encoding scytalone dehydratase which is involved in melanin biosynthesis. The application of tricyclazole, a DHN-melanin biosynthesis inhibitor, did not affect either salt stress tolerance or the accumulation of sodium in the hyphae. In addition, melanin biosynthesis mutants of Leptodontidium sp. did not show decreased growth performance compared to the wild-type, especially not at high salt concentrations. This indicates that DSEs can live under salt stress and withstand these conditions regardless of melanin accumulation.
Targeting the Gut Microbiota in Chagas Disease: What Do We Know so Far?
Authors: Duarte-Silva Eduardo , Morais Livia H. , Clarke Gerard , Savino Wilson , Peixoto Christina
Published: December 2020

Chagas disease (CD) is a tropical and still neglected disease caused byTrypanosoma cruzithat affects >8 million of people worldwide. Although limited, emerging data suggest that gut microbiota dysfunction may be a new mechanism underlying CD pathogenesis.T. cruziinfection leads to changes in the gut microbiota composition of vector insects, mice, and humans. Alterations in insect and mice microbiota due toT. cruzihave been associated with a decreased immune response against the parasite, influencing the establishment and progression of infection. Further, changes in the gut microbiota are linked with inflammatory and neuropsychiatric disorders, comorbid conditions in CD. Therefore, this review article critically analyses the current data on CD and the gut microbiota of insects, mice, and humans and discusses its importance for CD pathogenesis. An enhanced understanding of host microbiota will be critical for the development of alternative therapeutic approaches to target CD, such as gut microbiota-directed interventions.
PET Imaging of Neutrophils Infiltration in Alzheimer's Disease Transgenic Mice
Authors: Kong Yanyan , Liu Kawai , Hua Tao , Zhang Chencheng , Sun Bomin , Guan Yihui
Published: December 2020

Neutrophils are important components in the innate immune system. Neutrophil hyperactivation is regarded as a characteristic of Alzheimer's disease (AD). But in vivo imaging tools observing neutrophil activity in AD dynamically is lacking. This study aimed to identify neutrophil infiltration in AD transgenic mice. We used the AD triple-mutant transgenic mouse model and identified the genotype with RT-PCR. Behavioral experiments including an open-field test, a Morris water maze, and a Y-maze test were performed to evaluate the status of this AD model. 18F-AV45, 18F-PM-PBB3, 68Ga-PEG-cFLFLFK, and 18F-DPA714 were synthesized according to previous reports. We employed microPET to detect tracer uptake in the AD model and the control mice at different stages. Western blotting was used to observe the expression of functional proteins. We proved the successful establishment of AD models by RT-PCR, behavioral tests, and 18F-AV45 and 18F-PM-PBB3 PET imaging. We found an increased neutrophil accumulation in the brains of the AD mice through 68Ga-PEG-cFLFLFK PET imaging and Western blot assay. Our studies also demonstrated an elevated level of CAP37, which is produced by neutrophils, in the AD brain, and treatment with CAP37 promoted the expression of Iba1, iNOS, and COX-2 in BV2 cultures. Furthermore, our 18F-DPA714 PET imaging studies verified the raised activation of microglia in the brain of transgenic AD mice. Collectively, our findings indicate the increased activity of neutrophils in the brain and heart of AD model mice, 68Ga-PEG-cFLFLFK PET imaging represents a sensitive method to observe the status of neutrophils in AD, and infiltrated neutrophils can induce the activation of microglia by releasing CAP37 and blocking the activity of neutrophils may be beneficial for the control of AD progression.
Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity
Authors: Zhu Mingqin , Ma Yuetao , Zekeridou Anastasia , Lennon Vanda A.
Published: December 2020

Paraneoplastic autoimmune neurological disorders reflect tumor-initiated immune responses against onconeural antigens. Symptoms and signs can affect the central and/or peripheral nervous systems, neuromuscular junction or muscle, and typically evolve subacutely before an underlying neoplasm is discovered. We describe four patients whose neurological symptoms were precipitated by potent innate immune system challenges: bladder instillation of BCG, tick bite and an “alternative cancer therapy” with bacterial extracts and TNF-α. We hypothesize that a tumor-initiated autoimmune response (evidenced by autoantibody profiles), pre-dating the immune system challenge, was unmasked or amplified in these patients by cytokines released systemically from innate immune cells activated by microbial pathogen-associated molecular patterns (PAMPs). The resultant upregulation of cognate onconeural peptides as MHC1 protein complexes on neural cell surfaces would render those cells susceptible to killing by CD8+ T cells, thus precipitating the patient's neurological symptoms.
Multidisciplinary Approach to the Diagnosis and In-Hospital Management of COVID-19 Infection: A Narrative Review
Authors: Lo Bianco Giuliano , Di Pietro Santi , Mazzuca Emilia , Imburgia Aurelio , Tarantino Luca , Accurso Giuseppe , Benenati Vincenzo , Vernuccio Federica , Bucolo Claudio , Salomone Salvatore , Riolo Marianna
Published: December 2020

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or COVID-19 disease) was declared a pandemic on 11th March 2020 by the World Health Organization. This unprecedented circumstance has challenged hospitals’ response capacity, requiring significant structural and organizational changes to cope with the surge in healthcare demand and to minimize in-hospital risk of transmission. As our knowledge advances, we now understand that COVID-19 is a multi-systemic disease rather than a mere respiratory tract infection, therefore requiring holistic care and expertise from various medical specialties. In fact, the clinical spectrum of presentation ranges from respiratory complaints to gastrointestinal, cardiac or neurological symptoms. In addition, COVID-19 pandemic has created a global burden of mental illness that affects the general population as well as healthcare practitioners. The aim of this manuscript is to provide a comprehensive and multidisciplinary insight into the complexity of this disease, reviewing current scientific evidence on COVID-19 management and treatment across several medical specialties involved in the in-hospital care of these patients.