Analysis of Tat protein characteristics in human immunodeficiency virus type 1 sub-subtype A6 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1)

Introduction. Tat protein is a major factor of HIV (human immunodeficiency virus) transcription regulation and has other activities. Tat is characterized by high variability, with some amino acid substitutions, including subtypespecific ones, being able to influence on its functionality. HIV type 1 (HIV-1) sub-subtype A6 is the most widespread in Russia. Previous studies of the polymorphisms in structural regions of the A6 variant have shown numerous characteristic features; however, Tat polymorphism in A6 has not been studied.Goals and tasks. The main goal of the work was to analyze the characteristics of Tat protein in HIV-1 A6 variant, that is, to identify substitutions characteristic for A6 and A1 variants, as well as to compare the frequency of mutations in functionally significant domains in sub-subtype A6 and subtype B.Material and methods. The nucleotide sequences of HIV-1 sub-subtypes A6, A1, A2, A3, A4, subtype B and the reference nucleotide sequence were obtained from the Los Alamos international database.Results and discussion. Q54H and Q60H were identified as characteristic substitutions. Essential differences in natural polymorphisms between sub-subtypes A6 and A1 have been demonstrated. In the CPP-region, there were detected mutations (R53K, Q54H, Q54P, R57G) which were more common in sub-subtype A6 than in subtype B.Conclusion. Tat protein of sub-subtype A6 have some characteristics that make it possible to reliably distinguish it from other HIV-1 variants. Mutations identified in the CPP region could potentially alter the activity of Tat. The data obtained could form the basis for the drugs and vaccines development.

IDbSV: An Open-Access Repository for Monitoring SARS-CoV-2 Variations and Evolution

Ending COVID-19 pandemic requires a collaborative understanding of SARS-CoV-2 and COVID-19 mechanisms. Yet, the evolving nature of coronaviruses results in a continuous emergence of new variants of the virus. Central to this is the need for a continuous monitoring system able to detect potentially harmful variants of the virus in real-time. In this manuscript, we present the International Database of SARS-CoV-2 Variations (IDbSV), the result of ongoing efforts in curating, analyzing, and sharing comprehensive interpretation of SARS-CoV-2's genetic variations and variants. Through user-friendly interactive data visualizations, we aim to provide a novel surveillance tool to the scientific and public health communities. The database is regularly updated with new records through a 4-step workflow (1—Quality control of curated sequences, 2—Call of variations, 3—Functional annotation, and 4—Metadata association). To the best of our knowledge, IDbSV provides access to the largest repository of SARS-CoV-2 variations and the largest analysis of SARS-CoV-2 genomes with over 60 thousand annotated variations curated from the 1,808,613 genomes alongside their functional annotations, first known appearance, and associated genetic lineages, enabling a robust interpretation tool for SARS-CoV-2 variations to help understanding SARS-CoV-2 dynamics across the world.

Fraud - A multidisciplinary element. Famous case studies in such different fields

Research Question: RQ1: What is fraud? RQ2: Where do we find fraud? It is fraud a multidisciplinary element? Why? Motivation: Most of the literature states that fraud is a topic of great interest, but no one has tried to prove why, but also to show how much interest in publishing about the subject of fraud has increased. Idea: Our study looked at an international database (Web of Science) to demonstrate the growing interest in studying fraud in various fields. But we also did a case study presenting a complex case of fraud, discovered by DGAF in Romania. Data: The data were collected from Web of Science database and an analysis was made based on the 17,825 results found when searching for the word "fraud", and then we also did a case study presenting a complex case of fraud, discovered by DGAF in Romania, collecting data by direct observation of one of the authors. Tools: To test study’s hypotheses, we analyzed the Web of Science database. Findings: The results answer in the affirmative to the research question. Also, the implications of the results are that all actors can outline an overview of the phenomenon, but especially reveals the gaps in the discovery of the phenomenon. Contribution: Most of the literature states that fraud is a topic of great interest, but no one has tried to prove why, but also to show how much interest in publishing about the subject of fraud has increased.

Optimization of Gobak Sodor Based Neuroscience Learning Game as Character Education in Intellectual Disabilities

The purpose of writing this article is to find out the optimization of traditional gobak sodor neuroscience learning-based game activities as character education in intellectual disability with grade medium (ATG). Referring to the problems, most schools do not have policies and administrations regarding character education, most schools that have an environment that supports the implementation of character education, most teachers do not have good knowledge and attitude in character education, most teachers do not have good competence, most schools have used the curriculum and most teachers have not used assessments that are suitable for children. Character education and most of the community has not supported the course of character education. The purpose of writing this article is to find out the optimization of traditional "gobak sodor" neuroscience learning-based game activities as character education in children ATG. The method used in writing this article is the study of non-systematic literature from national & international database. Based on the concept of a previous relevant frame of mind, schema, and research, it can be concluded that there will be optimization of traditional "gobak sodor" game activities based on neuroscience learning as character education in children. Optimization of adaptive physical education learning can occur through synergistic contributions through neuroscience learning in traditional games and character education of lightly impaired children. The results of adaptation of these mechanisms are able to reduce the barriers of cognitive domains, practice domains, and social domains of lightly impaired children. Keywords: character, neuroscience learning, traditional games, ATG

Lenalidomide-induced arthritis: A case report and review of literature and pharmacovigilance databases

Introduction Lenalidomide is an immunomodulatory agent with multiple mechanisms of action, and treatment with lenalidomide is associated with adverse events such as thrombosis and abdominal pain; nonetheless, other rarer adverse events do exist, with few knowledge from physicians and pharmacists. For such adverse events, pharmacovigilance databases are of great interest. Case report A 71-year-old patient with no rheumatologic history, in complete remission of a mantle-cell lymphoma following rituximab, doxorubicin, vincristine, cyclophosphamide, and prednisone induction, received a maintenance treatment with rituximab and lenalidomide. After each course of lenalidomide and with no other new medication, the patient presented with fever and high inflammatory markers level, and a scapular-belt arthritis. Management and outcome The patient was managed with non-steroidal anti-inflammatory drugs and colchicine, with symptomatology and inflammation improvement. After discontinuation of lenalidomide, he had no arthritis relapse; it was then concluded that the patient had a lenalidomide-induced arthritis. We interrogated the national and international (VigiBase®) pharmacovigilance databases and found that arthritis in the context of lenalidomide exposure is a rare finding, with only three reported cases in France; 0.13% of adverse events reported with lenalidomide in the international database VigiBase® were arthritis. Discussion Our case then reports an uncommon finding, of which both pharmacists and physicians should be aware due to the wide and increasing use of lenalidomide.

The International Database of Central Arterial Properties for Risk Stratification: Research Objectives and Baseline Characteristics of Participants

Objective To address to what extent central hemodynamic measurements, improve risk stratification, and determine outcome-based diagnostic thresholds, we constructed the International Database of Central Arterial Properties for Risk Stratification (IDCARS), allowing a participant-level meta-analysis. The purpose of this article was to describe the characteristics of IDCARS participants and to highlight research perspectives. Methods Longitudinal or cross-sectional cohort studies with central blood pressure measured with the SphygmoCor devices and software were included. Results The database included 10930 subjects (54.8% women; median age 46.0 years) from thirteen studies in Europe, Africa, Asia and South America. The prevalence of office hypertension was 4446 (40.1%), of which 2713 (61.0%) were treated, and of diabetes mellitus was 629 (5.8%). The peripheral and central systolic/diastolic blood pressure averaged 129.5/78.7 mm Hg and 118.2/79.7 mm Hg, respectively. Mean aortic pulse wave velocity was 7.3 meter per seconds. Among 6871 participants enrolled in 9 longitudinal studies, the median follow-up was 4.2 years (5th–95th percentile interval, 1.3–12.2 years). During 38957 person-years of follow-up, 339 participants experienced a composite cardiovascular event and 212 died, 67 of cardiovascular disease. Conclusions IDCARS will provide a unique opportunity to investigate hypotheses on central hemodynamic measurements that could not reliably be studied in individual studies. The results of these analyses might inform guidelines and be of help to clinicians involved in the management of patients with suspected or established hypertension.

The short-term mortality fluctuation data series, monitoring mortality shocks across time and space

The COVID-19 pandemic has revealed substantial coverage and quality gaps in existing international and national statistical monitoring systems. It is striking that obtaining timely, accurate, and comparable across countries data in order to adequately respond to unexpected epidemiological threats is very challenging. The most robust and reliable approach to quantify the mortality burden due to short-term risk factors is based on estimating weekly excess deaths. This approach is more reliable than monitoring deaths with COVID-19 diagnosis or calculating incidence or fatality rates affected by numerous problems such as testing coverage and comparability of diagnostic approaches. In response to the emerging data challenges, a new data resource on weekly mortality has been established. The Short-term Mortality Fluctuations (STMF, available at www.mortality.org) data series is the first international database providing open-access harmonized, uniform, and fully documented data on weekly all-cause mortality. The STMF online vizualisation tool provides an opportunity to perform a quick assessment of the excess weekly mortality in one or several countries by means of an interactive graphical interface.

Human mortality at extreme age

We use a combination of extreme value statistics, survival analysis and computer-intensive methods to analyse the mortality of Italian and French semi-supercentenarians. After accounting for the effects of the sampling frame, extreme-value modelling leads to the conclusion that constant force of mortality beyond 108 years describes the data well and there is no evidence of differences between countries and cohorts. These findings are consistent with use of a Gompertz model and with previous analysis of the International Database on Longevity and suggest that any physical upper bound for the human lifespan is so large that it is unlikely to be approached. Power calculations make it implausible that there is an upper bound below 130 years. There is no evidence of differences in survival between women and men after age 108 in the Italian data and the International Database on Longevity, but survival is lower for men in the French data.