Portuguese Twitter Dataset on COVID-19

Over the last two years, the COVID-19 pandemic has affected hundreds of millions of people around the world. As in many crises, people turn to social media platforms, like Twitter, to communicate and share information. Twitter datasets have been used over the years in many research studies to extract valuable information. Therefore, several large COVID-19 Twitter datasets have been released over the last two years. However, none of these datasets contains only Portuguese Tweets, despite the Portuguese Language being reported as one of the top five languages used on Twitter. In this paper, we present the first large-scale Portuguese COVID-19 Twitter dataset. The dataset contains over 19 million Tweets spanning 2020 and 2021, allowing the entire pandemic to be analyzed. We also conducted a sentiment analysis on the dataset and correlated the various spikes in Tweet count and sentiment scores to various news articles and government announcements in Portugal and Brazil. The dataset is available at: https://github.com/bioinformatics-ua/Portuguese-Covid19-Dataset © 2022 IEEE.

ENDOTHELIAL INFLAMMATION AND DYSFUNCTION INDUCED BY SARS-COV-2 SPIKE PROTEIN 1 INVOLVE ADAM17 AND INTERFERON ACTIVATION PATHWAYS

Objective: COVID19 is associated with vascular inflammation. IFN-alpha (IFNa) and IFN-lambda3 (IFNl3) are potent cytokines produced in viral infections. Their effects involve interferon-stimulated genes (ISGs) and may influence expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. We hypothesized that S1P-induced immune/inflammatory responses in endothelial cells (EC) are mediated via IFN-activated pathways Design and methods: Human ECs were stimulated with S1P (1 mg/mL), IFNa (100ng/mL) or IFNl3 (100IU/mL). Because ACE2, ADAM17 and TMPRSS2 are important for SARS-CoV-2 infection, we used inhibitors of ADAM17 (marimastat, 3.8 nM), ACE2 (MLN4760, 440pM), and TMPRSS2 (camostat, 50 mM). Gene and protein expression was investigated by real-time PCR and immunoblotting, respectively. Vascular function was assessed in mesenteric arteries from wild-type (WT) normotensive and hypertensive (LinA3) mice and in ISG15-deficient (ISG15KO) mice. Results: S1P increased expression of IFNa (3-fold), IFNl3 (4-fold) and ISGs (2-fold) in EC (p < 0.05). EC responses to IFNa (ISG15: 16-fold) were greater than to IFNl3 (ISG15: 1.7-fold) (p < 0.05). S1P increased gene expression of IL-6 (1.3-fold), TNFa (6.2-fold) and IL-1b (3.3-fold), effects that were amplified by IFNs. Only the ADAM17 inhibitor marimastat inhibited S1P effects. IFNa and IFNl3 increase protein expression of ADAM17 (27%) and TMPRSS2 (38%). No changes were observed on ACE2 expression. This was associated with increased phosphorylation of Stat1 (134%), Stat2 (102%), ERK1/2 (42%). EC production of IL-6 was increased by IFNa (1,230pg/mL) and IFNl3 (1,124pg/mL) vs control (591pg/mL). Nitric oxide generation and eNOS phosphorylation (Ser1177) were reduced by IFNa (40%) and IFNl3 (40%). Vascular functional responses demonstrated that endothelium-dependent vasorelaxation (% Emax) in vessels from WT-mice stimulated with IFNa (67%) and IFNl3 (71%) were reduced vs control (82%) (p < 0.05). Responses were not altered in vessels from ISG15KO mice. Increased contraction was observed only in vessels from hypertensive mice treated with IFNa (9.1 ± 0.5mN vs control: 7.3 ± 0.3mN) (p < 0.05). Conclusions: In ECs, S1P, IFNa and IFNl3 increased ISG15 and IL-6 by mechanisms dependent on ADAM17. IFNs amplifies endothelial cell inflammatory responses and induced vascular dysfunction through ISG15-dependent mechanisms, with augmented effects in hypertension. Our findings demonstrate that S1P induces immune/inflammatory responses that may be important in endotheliitis associated with COVID-19. This may be especially important in the presence of cardiovascular risk factors, including hypertension.

ACE2 IS INVOLVED IN SARS-COV-2 INDUCED ENDOTHELIAL CELL INFLAMMATION INDEPENDENT OF VIRAL REPLICATION

Objective: COVID-19 association with cardiovascular disease is thought to be due to endothelial cell inflammation. ACE2 interactions with SARS-CoV-2 spike protein S1 subunit is important to viral infection. Here we questioned whether SARS-CoV-2 induces vascular inflammation via ACE2 and whether this is related to viral infection. Design and Methods: Human microvascular endothelial cells (EC) were exposed to recombinant S1p (rS1p) 0.66 ug/mL for 10 min, 5 h and 24 h. Gene expression was assessed by RT-PCR and levels of IL6 and MCP1, as well as ACE2 activity, were assessed by ELISA. Expression of ICAM1 and PAI1 was assessed by immunoblotting. ACE2 activity was blocked by MLN4760 (ACE2 inhibitor) and siRNA. Viral infection was assessed by exposing Vero E6 (kidney epithelial cells;pos ctl) and EC to 105 pfu of SARS-CoV-2 where virus titre was measured by plaque assay. Results: rS1p increased IL6 mRNA (14.2 ± 2.1 vs. C:0.61 ± 0.03 2-ddCT) and levels (1221.2 ± 18.3 vs. C:22.77 ± 3.2 pg/mL);MCP1 mRNA (5.55 ± 0.62 vs. C:0.65 ± 0.04 2-ddCT) and levels (1110 ± 13.33 vs. C:876.9 ± 33.4 pg/mL);ICAM1 (17.7 ± 3.1 vs. C:3.9 ± 0.4 AU) and PAI1 (5.6 ± 0.7 vs. C: 2.9 ± 0.2), p < 0.05. MLN4760, but not rS1p, decreased ACE2 activity (367.4 ± 18 vs. C: 1011 ± 268 RFU, p < 0.05) and blocked rS1p effects on ICAM1 and PAI1. ACE2 siRNA blocked rS1p-induced IL6 release, ICAM1, and PAI1 responses as well as rS1p-induced NFkB activation. EC were not susceptible to SARS-CoV-2 infection, while the virus replicated well in Vero E6. Conclusion: rS1p induces an inflammatory response through ACE2 in endothelial cells;an effect that was independent of viral infection.

Variables associated with bleeding and thrombotic outcomes among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomised clinical trial

Background: In the ACTION trial, therapeutic anticoagulation did not show benefit on mortality, days of hospitalization and oxygens therapy at 30 days among patients with COVID19. However, this strategy was associated with higher rate of bleeding and a potential reduction in the rate of clinical thrombotic events. The current analysis evaluated which variables were independently associated with both outcomes in order to help the identification of the risk for thrombotic and hemorrhagic events among patients with COVID19. Methods: A total of 615 patients hospitalized with COVID-19 and elevated D-dimer levels were randomly assigned to prophylactic anticoagulation (mainly in-hospital heparin) or a therapeutic strategy that used in-hospital rivaroxaban 20 mg daily for stable patients, or enoxaparin 1 mg/kg twice daily for unstable patients, followed by rivaroxaban through 30 days. One patient withdrew consent and was not included in the analysis. The current analysis tested baseline clinical characteristics and laboratorial exams one by one with independent logistic regressions for the composite of bleeding (major bleeding and clinically relevant nonmajor bleeding) and thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, and major adverse limb events). Significant variables (p<0.05) were selected to adjust several multiple logistic models. Final models were chosen based on Akaike information criterion and therapeutic anticoagulation was included in the final model based on the primary results of the trial. Results: The model for bleeding events showed an accuracy of area under the curve (AUC) of 0.635 (table 1) while the model for thrombotic events had an AUC of 0.725 (table 2). Level of respiratory support (especially invasive ventilation) was associated with both outcomes in the multivariable analysis (tables 1 and 2). Beyond respiratory support, level of creatinine and history of coronary disease were also independently associated to the risk of thrombotic events. When the utilization of therapeutic anticoagulation (mainly with rivaroxaban) was included in the multivariable analysis, this variable was strongly associated with higher risk of bleeding (model AUC of 0.718) but was not associated with lower rate of thrombotic events (Tables 1 and 2). Conclusion: Since the variables associated with higher risk of thrombotic events are similar to the variables associated to bleeding complications, the selection of patients with better balance of risk vs. benefit to use therapeutic anticoagulation in COVID-19 still a challenging decision. Coronary disease and creatine may help to identify patients at higher risk of thrombotic complications while the use of therapeutic dose of direct oral anticoagulant increased the risk of bleeding in almost 4 times among patients hospitalized due to COVID19. Funding Acknowledgement: Type of funding sources: Private company. Main funding source(s): Investigator initiated research with financial support of Bayer

Didactic bench to support automation learning - Industry 4.0 education

The teaching of automation is increasingly present in the industry, through increasingly aggregating and complete platforms. Automation teaching/learning faces several limitations. On the one hand, teaching automation using automata is done in laboratories whose didactic applications rarely replicate industrial applications. On the other hand, students' difficulties in accessing these spaces are often limited to the time allocated to each laboratory class, and it is often not possible to repeat assignments or work variants. It should be noted that the difficulty of accessibility for working students or students with COVID restrictions has a lot of impact. Thus, it would be important for a student to have access to an automation bench that replicates the needs of the industry and that includes remote access. The present work presents the development of a didactic workbench to support the teaching / learning of automation, with an industrial design and with the possibility of remote access. © 2022 IEEE.

IMMUNE DYSREGULATION INDUCED BY SPIKE PROTEIN 1 OF SARS-COV-2 INCREASES ENDOTHELIAL CELL DYSFUNCTION VIA TYPE I AND TYPE III INTERFERON ACTIVATION PATHWAYS

Objective: COVID19-associated immunopathology is associated with increased production of interferon (IFN)-alpha (IFNα) and lambda3 (IFNL3). Effects of IFNs are mediated by interferon-stimulated genes (ISGs) and influence expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. Increasing evidence indicates vascular inflammation in cardiovascular sequelae of COVID19. We hypothesized that S1P-induced immune/inflammatory responses in endothelial cells (EC) are mediated via IFNα and IFNL3. Design and method: Human ECs were stimulated with S1P (1 μg/mL), IFNα (100ng/mL) or IFNL3 (100IU/mL). Because ACE2, metalloproteinase domain-17 (ADAM17) and type-II transmembrane serine protease (TMPRSS2) are important for SARS-CoV-2 infection, cells were treated with inhibitors of ADAM17 (marimastat, 3.8 nM), ACE2 (MLN4760, 440pM), and TMPRSS2 (camostat, 50 μM). Gene and protein expression was investigated by real-time PCR immunoblotting, respectively. Vascular function was assessed in mesenteric arteries from wild-type (WT) normotensive and hypertensive mice and in ISG15-deficient (ISG15KO) mice. Results: EC stimulated with S1P increased expression of IFNα (3-fold), IFNL3 (4-fold) and ISG (2-fold)(p < 0.05). EC exhibited higher responses to IFNα (ISG15: 16-fold) than to IFNL3 (ISG15: 1.7-fold)(p < 0.05). S1P increased gene expression of IL-6 (1.3-fold), TNFα (6.2-fold) and IL-1β (3.3-fold), effects that were maximized by IFNs. Only marimastat inhibited S1P effects. IL-6 was increased by IFNα (1,230pg/mL) and IFNL3 (1,124pg/mL) vs control (591pg/ mL). This was associated with increased phosphorylation of Stat1 (134%), Stat2 (102%), ERK1/2 (42%). Nitric oxide production and eNOS phosphorylation (Ser1177) were reduced by IFNα and (40%) and IFNL3 (40%). Reduced endothelium relaxation maximal response (%Emax) was observed in vessels from WTmice stimulated with IFNα (67%) and IFNL3 (71%) vs control (82%)(p < 0.05) but not in vessels from ISG15KO mice. Increased contraction was observed only in vessels from hypertensive mice treated with IFNα (9.1 ± 0.5mN vs control: 7.3 ± 0.3mN, p < 0.05). Conclusions: In ECs, S1P, IFNα and IFNL3 increased ISG15 and IL-6, processes that involve ADAM17. Inflammation induced by S1P was amplified by IFNs. IFNs induce vascular dysfunction through ISG15-dependent mechanisms, with augmented effects in hypertension. Our findings demonstrate that S1P induces immune/inflammatory responses that may be important in endotheliitis associated with COVID-19. This is especially important in the presence of cardiovascular risk factors, including hypertension.

A STUDY OF PERCEPTION AND READINESS OF MANAGEMENT STUDENTS TOWARDS ONLINE TEACHING

The current study proposes a comprehensive structural model to determine whether online learning perceptions and online learning readiness affect students' online learning performance and course satisfaction. A questionnaire was voluntarily completed by 75 management students Furthermore, it was found that students' computer/Internet self-efficacy for online learning readiness had a mediated effect not only on online learning perceptions and online discussion score but also on online learning perceptions and course satisfaction, Significance of online learning is widely recognized as a means to enhance accessibility and quality of teaching learning process in the world. Therefore, the current paper has its objective to explore perception and readiness of education students for online learning.

A RANDOMIZED CLINICAL TRIAL OF SCREENING FOR ATRIAL FIBRILLATION WITH A 14-DAY PATCH MONITOR: ANALYSIS OF ECG RECORDINGS FROM THE GUARD-AF STUDY

Background: Screening for atrial fibrillation (AF) is attractive because AF can remain undiagnosed and AF-related stroke can be prevented by anticoagulants (OAC). Methods: A randomized trial of screening for AF in individuals ≥70 years old without AF. Stroke and major bleeding are the efficacy and safety outcomes, ascertained from claims databases and electronic health records. Screening is done using a Zio®XT 14-day continuous cardiac rhythm patch monitor and compared, 1:1, to usual care. Use of OAC for detected AF is decided by patients and their physicians. The planned sample size was 52,000 recruited from U.S. primary care practices. Enrollment was severely hampered by the COVID-19 pandemic and stopped May 31, 2021 with 11,931 participants. Follow-up for stroke and bleeding events continues. Here, we report patch monitor findings from the 5,965 participants randomized to the screening arm. Results: 5,720 (96%) participants returned patches with analyzable data, the largest sample of patch monitor AF screening to date. Median (IQR) age was 75 (72, 79) years;57% were women. Median wear time was 13.9 (13.7, 14.0) days and median analyzable time was 98.4% (95.6, 99.5). 255 (4.5%) participants had AF, including 30 (0.5%) with 100% AF. 100% AF was more common in those age ≥80 (1.0%) than among younger participants (0.40%), p<.01. In the 225 participants with paroxysmal AF (PAF), median AF “burden” was 0.48% (0.016-2.5) of time monitored [78 (3.2, 454) minutes]. Median number of AF episodes during monitoring was 3 (1, 19). Median longest single AF episode was 60 (3-278) minutes. AF burden and length of longest episode were highly correlated (r=0.79, p<.001). Neither of these measures of PAF were associated with either age or sex. Conclusion: In GUARD-AF’s older primary care population, 0.5% of screened participants had persistent AF and 4% had PAF detected within 2 weeks of monitoring. In those with PAF, average AF burden was low but >25% had an episode of ≥4.6 hours of continuous AF, suggesting increased stroke risk. The need for stroke-preventive interventions (e.g., OAC) for screen-detected PAF remains a critically important research question.

Infection in asymptomatic carriers of SARS-CoV-2 can interfere with the achievement of robust immunity on a population scale

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide as a severe pandemic, and a significant portion of the infected population may remain asymptomatic. Given this, five surveys were carried out between May and September 2020 with a total of 3585 volunteers in the municipality of Foz do Igua..u, State of Paran.., a triple border region between Brazil/Argentina/Paraguay. Five months after the first infection, volunteers were re-analysed for the production of IgG anti-Spike and anti-RBD-Spike, in addition to analyses of cellular immunity. Seroconversion rates ranged from 4.4% to a peak of 37.21% followed by a reduction in seroconversion to 21.1% in September, indicating that 25% of the population lost their circulating anti-SARS-CoV-2 antibodies 3 months after infection. Analyses after 5 months of infection showed that only 17.2% of people still had anti-RBD-Spike antibodies, however, most volunteers had some degree of cellular immune response. The strategy of letting people become naturally infected with SARS-CoV-2 to achieve herd immunity is flawed, and the first contact with the virus may not generate enough immunogenic stimulus to prevent a possible second infection.

Management of renin-angiotensinaldosterone system blockade in patients admitted in hospital with confirmed coronavirus disease (Covid-19) infection: The mcgill raas-covid-19 randomized controlled trial

Background: More data is needed on the cardiovascular impact of discontinuing versus continuing renin-angiotensin aldosterone system inhibitors (RAASi) among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Methods: The McGill RAAS-COVID-19 trial was a randomized, open label trial in adult patients hospitalized with COVID-19, who were previously treated with RAASi (angiotensin converting enzyme inhibitors [ACEi]/angiotensin receptor blocker [ARB]) (NCT04508985;10/2020-03/2021). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]). All analyses were conducted using the intention-to-treat principle. Results: Overall, 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a similar mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5);p= 0.60), but the negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.7 [95% CI 1.1 to 2.6];p=0.03). Particularly, RAASi discontinuation increased brain natriuretic peptide (BNP) levels (% change from baseline: +16.7% vs.-27.5%;p= 0.02) and increased the incidence of acute heart failure (33% vs. 4.2%, p=0.03). Conclusion: Discontinuation of RAASi increased BNP levels and risk of acute heart failure in participants hospitalized with COVID-19;where possible, RAASi should be continued.

St Andrew's COVID-19 surgery safety (StACS) study: The Burns Centre experience.

BACKGROUND: The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has the potential to significantly impact burns patients both directly through infective complications of an immunocompromised cohort, and indirectly through disruption of care pathways and resource limitations. The pandemic presents new challenges that must be overcome to maintain patient safety; in particular, the potential increased risks of surgical intervention, anaesthesia and ventilation. This study comprehensively reviews the measures implemented to adapt referral pathways and mitigate the risk posed by COVID-19 during the height of the pandemic, within a large Burns Centre. METHODS: A prospective cohort study was designed to assess patients treated at the Burns Centre during the UK COVID-19 pandemic peak (April-May 2020), following implementation of new safety measures. All patients were analysed for 30-day mortality. In addition, a prospective controlled cohort study was undertaken on all inpatients and a random sample of outpatients with telephone follow-up at 30 days. These patients were divided into three groups (operative inpatients, non-operative inpatients, outpatients). COVID-19 related data collected included test results, contact with proven cases, isolation status and symptoms. The implemented departmental service COVID-19 safety adaptations are described. RESULTS: Of 323 patients treated at the Burns Centre during the study period, no 30-day COVID-19 related deaths occurred (0/323). Of the 80 patients analysed in the prospective controlled cohort section of the study, 51 underwent COVID-19 testing, 3.9% (2/51) were positive. Both cases were in the operative group, however in comparison to the non-operative and outpatient groups, there was no significant increase in COVID-19 incidence in operative patients. CONCLUSIONS: We found no COVID-19 related mortality during the study period. With appropriate precautions, burns patients were not exposed to an increased COVID-19 risk. Similarly, burns patients undergoing operative management were not at a significantly increased risk of contracting COVID-19 in comparison to non-operative groups.

Open education resources in the global scenario: Highlights and challenges

Given the recognition of the Open Education Resources (OER) movement in the global scenario, this paper provides an overview of the OER implementation efforts, based on two documents: OER Global Report 2017 and Ljubljana OER Action Plan 2017. The first analyses the OER progress from 2012 to 2017. The second presents recommended actions and strategies to harness the potential of open-licensed resources. We argue that these documents helped to compose the actions and strategies for the 2019 UNESCO OER Recommendation, which, in turn, motivated UNESCO and partnerships to produce an OER Guide under the Pandemic COVID-19 in 2020. Aligned with the OER experiences brought by the Guide, we underscore the importance of openly creating and sharing teaching and learning materials to support educational practices during Covid-19. © 2021 Universidade Federal de Santa Catarina. All rights reserved.

Efficacy of ixekizumab vs. IL-2 vs. colchicine vs. Standard of care for the treatment of hospitalized patients with COVID-19: Preliminary results of a randomized clinical trial (struck: Survival trial using cytokine inhibitors)

Introduction: There are currently scarce approved treatments for Covid-19 and new options are needed. Objectives: To evaluate the efficacy of an IL-17 inhibitor vs. low-dose IL-2 vs. colchicine vs. standard of care for the treatment of hospitalized patients with Covid-19. Methods: This is an on-going multicenter, open-label, prospective, randomized, active-controlled, adaptive 4-arm study. Patients hospitalized with moderate to severe presentation of Covid-19 are being recruited according to predetermined eligibility criteria. Patients are randomized to one of the trial arms: ixekizumab (IL-17 inhibitor), low dose IL-2, colchicine (indirect IL-6 inhibitor), or standard treatment, each according to the pre-established periods and doses. The primary study outcome is the proportion of patients with clinical improvement, defined by an increase of two points on the WHO's ordinal scale at day 28. Secondary study outcome is in-hospital mortality. Results: Until May 27, 30 patients with similar baseline clinical and demographic features have been enrolled in the study. Table 1 describes the main efficacy outcomes for each of the study arms. Ixekizumab arm presented the greatest improvement in the WHO scale (71.4%), while colchicine arm presented the lowest mortality rate (0%), but no statistically significant differences have been observed, so far. Conclusion: These preliminary results suggest that Ixekizumab and colchicine should be further studied as potential therapeutic drugs for treating patients with moderate to severe Covid-19. (Figure Presented).

VR training for critical tasks - assembling the INSPIRE emergency pulmonary ventilator for COVID-19 treatment

This paper describes a VR system designed to train health professionals and volunteers to properly assemble the replaceable pneumatic circuit of the Inspire emergency pulmonary ventilator. The simulator's primary goal is to internalize a mindful attitude in the trainee, as even minor mistakes may lead to disastrous consequences during the machine's operation, such as sequels and even patient death. The system was based on the state of the art of medical VR training and proposes innovative ways to communicate and demonstrate instructions, possible repercussions of mistakes, and feedback mechanisms to portray step completion and execution accuracy. The main challenge was dealing with standard VR systems' limitations, particularly the absence of force feedback.

Unity in diversity: between utopias and concretion in research from popular education

This study addresses the theme of social isolation resulting from the Coronavirus pandemic (COVID19) from an intervention carried out by master students in education with male and female students in a technical course class in human resources and administration of a vocational school located in Limeira/SP. With a view to provoking reflections and generating subsidies for new discussions about the epochal moment that involves everyone, the intervention started with an invitation to students to build and share messages of solidarity, peace and good practices among themselves within a social coexistence in a pandemic scenario of insecurities and uncertainties. The study was developed based on a theoretical framework and on the contributions of Popular Education and its conclusion occurred with the disclosure of the constructions made through audiovisual resources and through this article report. We intend that, among the positive impacts produced by this study, we find the inspiration for the implementation of actions in favor of a culture of peace and solidarity and of transformation, alterity and empathy as well as indignation in face of inequalities that imposes a lesser or greater degree suffering to some people at the expense © 2020, Estudios Pedagogicos. All Rights Reserved.