Cyber-Physical Modeling of Intelligent Traffic Controllers Using Simulator for Urban Mobility (SUMO)

Transportation problems have always been a global concern. The challenges in traffic congestion were easily observed during pre-pandemic times. However, traffic congestion still persists even during the COVID-19 pandemic (2020 and present) where there has been less number of vehicles because of travel restrictions. The emergence of wireless communication technologies and intelligent transportation systems (ITS) pave the way for solving some of the problems found in the transportation industry. Subsequently, traffic control systems are used at various intersections to manage the flow of traffic and reduce car collisions. However, some intersections are better off without these traffic control systems. The proposed study will analyze a T-junction road in five different setups using different types of traffic controllers. The simulation tool used is SUMO. The study found that an adaptive or vehicle-actuated traffic controller is the ideal method for regulating traffic flow in a T-junction with a one-way or two-way main road. It was observed in the simulation that it reduced the potential car collisions in the non-TL junction. However, the average speed and completion time of the road network was affected by the method. © 2022 IEEE.

Community outreach and engagement to increase colorectal cancer screening in ethnic minority communities

PURPOSE: Colorectal cancer (CRC) is preventable with screening, yet remains the second leading cause of cancer deaths in the U.S. Nationally, CRC screening substantially declined during the COVID-19 pandemic and is underutilized by ethnic minorities and in safety-net systems. Therefore, City of Hope partnered with Federally Qualified Health Centers (FQHCs) and community and faithbased organizations to improve CRC screening among medically underserved communities. METHOD(S): Between October 2020 and October 2022, we implemented a multi-component intervention that included community outreach and education (a multi-ethnic multimedia campaign and community training adapted from the NCI Screen2Save (S2S) program) and clinic-based interventions (provider/staff training and patient education). Intervention reach and training participant surveys were assessed. Within our four FQHC sites, we also compared clinic-level CRC screening rates among age-eligible patients before (June 2021) and after implementation of the clinic-based intervention (June 2022). RESULT(S): Our reach assessment showed that our multi-ethnic multimedia campaign reached 35.4 million impressions, our S2S education training reached 300 diverse community members, and our provider/staff training reached 150 medical providers. Among the 100 providers surveyed, >80% felt confident they could get their patients to complete their CRC screening test and follow-up care. For the clinic-based intervention component, our baseline sample included 11,259 age-eligible patients across the four FQHC sites. Overall CRC screening rates increased from 45% to 52% before vs. after the intervention implementation period. The site with the highest CRC screening rate (>62%) maintained steady rates over the observation period, whereas three sites with lower baseline rates showed greater pre-post improvements (average 15 percentage-point increase). CONCLUSION(S): An overall increase in CRC screening rates was achieved across FQHCs, despite clinic staffing challenges during the COVID-19 pandemic. Intervention implementation is ongoing with attempts to document individual, clinic improvements by race/ethnicity.

Counselling support for the mental health of children in Hong Kong's international schools during the COVID-19 pandemic: parents' perspectives

Objective: This study investigated how school counsellors in international schools in Hong Kong supported the wellbeing of students and families during the period of school closure caused by the COVID-19 pandemic from the perspective of parents. Method: Sixteen parents with children in eleven different international schools in Hong Kong were interviewed and the data were analysed thematically. Results: Strong pre-existing relationships, role clarity, and open communication between counsellors and parents were associated with the effective adaptation of counselling services to the changing needs of parents during the school closure period, but these characteristics were often weak or absent. Conclusions: Parents' perceptions of counselling during the school closure period provide important feedback that schools can use to build more integrated and responsive support services. Counsellors can support students' wellbeing more effectively during crises by communicating their roles clearly, building strong relationships with parents, and helping students to maintain a diverse experience in their schooling. © 2021 Australian Psychological Society.

An International, Multicenter Evaluation of Pharmacist Medication Management in Icu Recovery Centers

INTRODUCTION: Post Intensive Care Syndrome (PICS) is a new or worsening impairment in physical, cognitive, or mental health following critical illness. Similar to PICS, survivors of critical illness due to COVID-19 may develop Post Acute Sequelae of SARS-CoV-2 Infection (PASC) or Long COVID. ICU recovery centers (ICU-RC) are suggested as an interprofessional approach to treat patients with PICS or PASC. Currently, over 40 different ICU-RC worldwide report having a clinical pharmacist. The purpose of this study was to describe the role of pharmacists in identifying and treating medication-related problems in survivors of critical illness. METHOD(S): This prospective, observational study was conducted in 12 ICU-RC between September 2019 and July 2021. A full medication review comprising of medication reconciliation, a patient interview, and counseling session was conducted by a clinical pharmacist on patients seen at the ICU-RC. Baseline demographic and hospital course data were obtained from the electronic health record and at the ICU-RC appointment. Data are reported using descriptive statistics. RESULT(S): A total of 507 patients were referred to an ICU-RC, of which 474 attended and 472 had a full medication review performed by a pharmacist. 237 (47%) of referred patients had a diagnosis of COVID-19. Pharmacy interventions were made in 397 (84%) patients. The median number of pharmacy interventions per patient was 2 (IQR 1,3). Medications were stopped and started in 124 (26%) and 91 (19%) patients, respectively. There was no difference in median total number of medications prescribed at the start and end of the patient visit (10, IQR = 5, 15). The number of patients that had a dose decreased and a dose increased was 51 (11%) and 43 (9%) patients, respectively. Adverse drug event (ADE) preventive measures were implemented in 115 (24%) patients and ADEs were identified in 69 (15%) patients. Drug interactions were identified in 30 (6%) patients. CONCLUSION(S): Pharmacists play an integral role in ICURC resulting in identification, prevention, and treatment of numerous medication-related problems. This paper should serve as a call to action on the importance of including a pharmacist on the interprofessional team in ICU-RC.

GALECTIN-9 PROTECTS HUMANIZED ACE2-IMMUNOCOMPETENT MICE from SARS-CoV-2 INFECTION

Background: Coronavirus disease 2019 (COVID19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) remains a global health emergency even with effective vaccines and limited FDA-approved therapies. To limit mortality and morbidity across the spectrum of disease, the need for therapeutics remains critical. Galectin9 (gal9) is a beta-galactoside binding protein that modulates cell-cell and cell-matrix interactions. In response to SARS-CoV2 infection, it has been shown that circulating gal9 levels are elevated in patient sera with moderate to severe disease. Additionally, it has been reported that gal9 unexpectedly may competitively bind the host ACE2 receptor, potentially impeding viral entry. Therefore, we hypothesized that early recombinant gal-9 treatment post infection may prevent binding of the virus to susceptible host cells resulting in decreased severity of SARS-CoV2-associated disease. Methods: To determine the therapeutic potential of gal9 for treating COVID19, we infected K18-hACE2 transgenic mice intranasally with 104 particle forming units (PFU) of SARS-CoV2. 6 hours post infection (hpi), mice were treated with a single dose of 30 ug of recombinant human gal9 (rhgal9) or PBS intraperitoneally and subsequently monitored 12 days for morbidity. Subgroups of mice were humanely euthanized at 2 and 5 days pi (dpi) for viral plaque assay, flow cytometry, and protein analysis from lung tissue and bronchial alveolar lavage (BAL). Results: We found that mice treated with rhgal9 during the acute phase of infection exhibit improved survival compared to PBS treated animals (25%, p<0.0001). We found that at 5 dpi, rhgal9 treated mice exhibited enhanced viral clearance in the BAL but not in the lung parenchyma. Additionally, we found increased CD8 T cell (p<0.001) and decreased neutrophil (p<0.05) frequencies in the lung at 5 dpi. Finally, we found that BAL fluid had elevated levels of Type 1 Interferon [IFNa (p<0.01) and IFNb (p<0.01)] at 2 dpi and increased MyD88 proinflammatory cytokines [IL1a (p<0.05), IL1b (p<0.01), TNFa (p<0.05), and MIP1a (p<0.05) at 5 dpi. Conclusion: Our study suggests that rhgal9 treatment may be potentially therapeutic for treating acute COVID19. Our data suggest that rhgal9 treatment in combination with other anti-inflammatory mediators may curtail damaging inflammation associated with SARS-CoV2 disease. Further studies are required to determine the optimal time, combination and duration of treatment pi to effectively target the gal9 pathways.

GALECTIN-9 INDUCES SARS-CoV-2 REPLICATION and INFLAMMATION in AIRWAY EPITHELIAL CELLS

Background: Galectin-9 (Gal-9) is a β-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis. Multiple recent reports demonstrate that plasma levels of Gal-9 are elevated in the setting of severe COVID-19 disease. However, a causal role of Gal-9 in SARS-CoV-2 pathology remains to be elucidated. Here, we determined the impact of Gal-9 on SARS-CoV-2 replication and pro-inflammatory signaling in immortalized and primary human airway epithelial cells (AECs). Methods: Dose-dependent cytotoxicity of recombinant human Gal-9 in the Calu-3 AEC line was determined by MTT assay. Calu-3 cells were infected with SARS-CoV-2 isolate USA-WA1/2020 (MOI=0.01). Primary AECs were isolated from healthy donor lung transplant tissue, cultured at air liquid interface (ALI), and infected with SARS-CoV-2 lineage P.1 (MOI=0.1). SARS-CoV-2 replication was assessed by RT-PCR quantitation of the nucleocapsid (N) gene, immunofluorescence assay (IFA) of N protein, and titration of supernatant (TCID50). Viral entry was measured using luciferase activity of VSV-SARS-CoV-2 S-ΔG-Luciferase reporter pseudovirus. ACE2 and TMPRSS2 cell-surface expression were measured by flow cytometry. Pro-inflammatory factors (IL-6, IL-8, and TNFα) were detected by RT-PCR. Total RNA-seq was used to evaluate Gal-9 effects on the host transcriptome. Groups were compared by Student's t-test, and differential expression analyses were performed using DESeq2. Results: Gal-9 reached 50% cytotoxicity in Calu-3 cells at 597 nM. Gal-9 significantly increased SARS-CoV-2 expression (8.1 to 25.5 fold;p<0.0001) and infectious virus release (1.9 to 17.8 fold;p<0.038) in a dose-dependent manner in Calu-3 cells. Pseudovirus entry into Calu-3 cells was enhanced by Gal-9 (2.4 to 5.6 fold;p<0.0016), and the enhanced entry was inhibited by anti-ACE2 antibody (p<0.0027). Cell surface ACE2 and TMPRSS2 expression were unaffected by Gal-9. Gal-9 treatment accelerated virus-induced expression of IL-6, IL-8, and TNFα (p<0.018) in Calu-3 cells. Gal-9 increased SARS-CoV-2 production (p=0.03) and pro-inflammatory factor expression (p<0.05) in primary AECs (N=5 donors). RNA-seq data revealed that Gal-9 significantly induced IL-17, EIF2, IL-8 and IL-6 signaling pathways in the setting of SARS-CoV-2 infection. Conclusion: Gal-9 facilitates SARS-CoV-2 entry, replication, and virus-induced pro-inflammatory signaling in AECs ex vivo. Our data suggest that pharmacologic manipulation of Gal-9 should be explored as a SARS-CoV-2 therapeutic strategy.

Subjective wellbeing and emotion regulation strategies: How are they associated with student engagement in online learning during Covid-19?

BACKGROUND: The COVID-19 pandemic has brought unprecedented challenges to the world, creating significant impact on people's lives and subjective wellbeing. While previous studies have shown that students' wellbeing and how they manage their emotions are critical to students' learning, less research has considered their specific impacts on student engagement in online learning. AIMS: The aim of this study is to examine how students' subjective wellbeing and emotion regulation strategies (viz cognitive reappraisal and expressive suppression) are associated with student engagement in online learning during the pandemic. SAMPLE: A total of 965 students from a university in China participated in the study. METHODS: The data were collected online during the COVID-19 from March to July 2020, which included measures of wellbeing, emotion regulation strategie, and online learning engagement. RESULTS: Structural equation modelling results showed that wellbeing was positively associated with both the use of reappraisal and suppression. Moreover, mediation analysis showed that reappraisal partially mediated the relationship between wellbeing and all types of online learning engagement (including cognitive, emotional and behavioural engagements). Conversely, suppression was found to have a small mediating effect between wellbeing and behavioural engagement of online learning only. No such effect was found on cognitive and emotional engagements. CONCLUSIONS: The findings provide evidence on the positive relationship between wellbeing and both the strategies of suppression and reappraisal during the pandemic. However, only reappraisal has positive impact on learning, suggesting the importance of effective regulation strategies on students' online engagement. Theoretical and practical implications of the findings are discussed.

Interleukin-18 and COVID-19.

Vulnerability to coronavirus disease (COVID)-19 varies due to differences in interferon gamma (IFNγ) immunity. We investigated whether a key modifiable interferon precursor, interleukin-18, was related to COVID-19, overall and by severity, using Mendelian randomisation. We used four established genome-wide significant genetic predictors of interleukin-18 applied to the most recent genome-wide association study of COVID-19 (June 2021) to obtain Mendelian randomisation inverse variance weighted estimates by severity, i.e. any (cases = 112 612, non-cases = 2 474 079), hospitalised (cases = 24 274, non-cases = 2 061 529) and very severe (cases = 8779, non-cases = 1 001 875) COVID-19. To be comprehensive, we also conducted an exploratory analysis for IFNγ and two related cytokines with less well-established genetic predictors, i.e. interleukin-12 and interleukin-23. Genetically predicted interleukin-18 was associated with lower risk of any COVID-19 (odds ratio (OR) 0.96 per standard deviation, 95% confidence interval (0.94-0.99, P-value 0.004)) and of very severe COVID-19 (OR 0.88, 95% CI 0.78-0.999, P-value 0.048). Sensitivity analysis and a more liberal genetic instrument selection gave largely similar results. Few genome-wide significant genetic predictors were available for IFNγ, interleukin-12 or interleukin-23, and no associations with COVID-19 were evident. Interleukin-18 could be a modifiable target to prevent COVID-19 and should be further explored in an experimental design.

Design and rationale for an open-label multicenter phase 4 study assessing Immune response to COVID-19 vaccine in patients with relapsing multiple sclerosis treated with ofatumumab

Introduction: Ofatumumab (OMB), a fully human anti-CD20 monoclonal antibody, is indicated for the treatment of adults with relapsing multiple sclerosis (RMS) in the US. Given the ongoing COVID-19 global pandemic, it is important to assess if OMBtreated patients can mount a protective immune response to the COVID-19 vaccine. Objectives/Aims: To assess immune response to non-live COVID-19 mRNA vaccines (Pfizer or Moderna) in RMS patients treated with subcutaneous OMB 20 mg monthly compared to those on interferon or glatiramer acetate. Methods: This is a 3-cohort, multicenter, prospective study in RMS patients (aged 18-55) receiving the mRNA COVID-19 vaccine (NCT04878211). Patients with prior COVID-19 diagnosis, recent infections, and prior treatment with other immunomodulatory disease-modifying therapies will be excluded. Cohort 1 will receive full course (2 doses) of vaccine ≥2 weeks prior to starting OMB. Cohort 2 will receive the full course of vaccine ≥4 weeks after starting OMB. Cohort 3 will receive the full course of vaccine ≥4 weeks after starting interferon or glatiramer acetate. Patients will continue taking their prescribed therapy per their current dosing schedule throughout treatment period (360 days after completion of full course vaccine). All groups will undergo serologic testing prior to vaccination and 14 days after 2nd vaccine dose. Primary endpoint is positive SARS-CoV-2 qualitative IgG antibody assay 14 days after full course vaccination. Key secondary endpoints include immune response to vaccine at other timepoints, immune conversion to vaccine (SARS-CoV-2 qualitative/ quantitative IgG antibody assay), SARS-CoV-2 neutralizing IgG antibody development, and adverse events (AEs) and serious AEs associated with OMB treatment. Exploratory endpoints include frequency of IFNγ positive CD4+ or CD8+ T cells, and T cell reactivity, after stimulation with SARS-CoV-2 peptide. Results: This study plans to enroll up to 66 RMS patients (up to 22 per cohort) at up to 30 US centers. The planned first patient first visit is on May 31, 2021 and study completion is expected by Q4 2022. An interim analysis will be performed once Cohorts 2 and 3 each have ≥10 patients that have had serum drawn 14 days after full course vaccination. Conclusions: This study will contribute to a better understanding of immune responses that occur in OMB-treated RMS patients given a COVID-19 mRNA vaccine.

Future learning mode under post-covid-19: Innovations, transformations, engagement

A blended learning culture is both a challenge and opportunity under post-COVID-19 for knowledge transfer and sustainable development, with the aim of maintaining social distancing policy and social interaction among learners, teachers, and invited industry guest speakers. In this paper, we review documents in blended learning from Asia, America, and Europe with the key elements in blended learning for faculty development in higher education (HE) institutions. The objective was to identify the key elements in blended learning with innovations and research technology capabilities for a way normal of learning and teaching under COVID-19. Based on the qualitative results of NVivo, it has been identified that the key elements of blended learning are: 1) technology for projects and 2) technology for engagement. These two elements are proposed to relate to Kolb’s experiential learning cycle of active experiment and concrete experience and reflective observation of the new learning experience for sustainable development. © 2021 The Author.

Evaluation of the airway viral load in acute sars-cov2 infection as a predictor of clinical outcome

Rationale: Throughout recent studies, data suggests high viral load in the plasma and nasopharynx of patients with severe SARS-CoV2 infection is associated with disease severity (mortality, length of hospitalization, and risk of intubation). Here, we evaluated whether viral load in the airway is associated with poor clinical outcomes in patients with SARS-CoV2. Methods: Lower airway samples in 148 patients from an academic center that were admitted to the ICU (dates: March 10th to May 10th, 2020) with severe respiratory failure requiring mechanical ventilation and underwent bronchoscopy for airway clearance and/or tracheostomy. Clinical outcome was defined as ≤ 28 Day mechanical ventilation vs. > 28 Day mechanical ventilation vs. death. Post-admission followup time was 232 [IQR 226-237] days. RNA was isolated in parallel using zymoBIOMICS™ DNA/RNA Miniprep Kit (Cat: R2002) as per manufacturer's instructions. Viral load was measured by quantitative real-time reverse transcription polymerase chain reaction (rRT -PCR) targeting the virus nucleocapsid (N) gene and an additional primer/probe set to detect the human RNase P gene (RP). Results: Among this bronchoscopy cohort, n=58 39% of the subjects were successfully extubated within 28 days of initiation of mechanical ventilation, n=56 38% required prolonged mechanical ventilation and n=34 23% died. We evaluated the viral load by rRT-PCR for SARSCoV2 N gene adjusted by human RP gene throughout the respiratory tract using supraglottic samples and bronchoalveolar lavage (BAL) samples obtained during bronchoscopy. Paired analysis of upper and lower airway samples shows that there is a subset of subjects (n=31, 21%) where there is greater viral load in the BAL than in the supraglottic area supporting topographical differences in viral replication (Fig 1A). BAL samples from subjects that died had higher viral load in their lower airways than patients that survived, even after adjusting for confounders such as age, gender, BMI and timing of sample collection (Fig 1B magenta dots (deceased) vs. yellow/green dots (alive)). Conclusions: Using samples obtained via bronchoscopy we identified that in a subset of subjects with acute SARS-CoV2 infection, the lower airways are the predominant site for viral replication. From our study, it is unclear if the higher viral load reflects host co-morbidies (e.g., diabetes or immunosuppression) or viral factors favoring higher replication. High viral load can be used as a predictor for disease severity upon hospital admission as viral load in the lower airways correlated with poor outcomes.

Evaluation of the lower airway microbiota in patients with severe sars-cov2

RATIONALE:Secondary infections with bacterial pathogens are thought to be responsible for poor outcomes in the 1918 Spanish and H1N1 pandemics. We postulate that poor prognosis in patients with SARS-CoV2 may be associated with uncontrollable viral replication, co-infection with a secondary pathogen, and over exuberant host immune response. We seek to evaluate whether there is an association between distinct features of the lower airway microbiota and poor clinical outcome in patients with SARS-CoV2. METHODS:We collected lower airway samples in 148 patients from NYU admitted between 3/10/2020 and 5/10/2020 with severe respiratory failure requiring mechanical ventilation and that underwent bronchoscopy for airway clearance and/or tracheostomy. Clinical outcome was defined as dead vs alive. DNA was isolated in parallel using zymoBIOMICS™ DNA/RNA Miniprep Kit (Cat: R2002) as per manufacturer's instructions. The V4 region of the 16S rRNA gene marker was sequenced using Illumina MiSeq. Sequences were analyzed using the Quantitative Insights into Microbial Ecology (QIIME version 1.9.1) pipeline. Total bacterial load was evaluated in lower airway samples using digital droplet PCR targeting the 16S rRNA gene. RESULTS:Of the 148 patients included, 114 survived (77%) and 34 (23%) died. Among those with poor clinical outcome, there was a non-statistically significant trend towards higher age and BMI. Patients who died more commonly had chronic kidney disease and prior cerebrovascular accidents, and more often required dialysis. There was no statistically significant difference in the rate of positive bacterial respiratory or blood cultures among those that survived vs. those that died (75 vs. 73% and 43 vs 38%, respectively). Topographical analysis of the 16S RNA microbiome shows compositional differences between the upper and lower airways based on β diversity comparisons. When comparing across clinical outcomes, the α diversity was lower in the dead group but there was no statistically significant difference in overall community composition (β diversity). Taxonomic differential enrichment analysis using DESeq analysis showed that oral commensals were enriched in the group that survived. Patients that died had a higher bacterial load in their lower airways than those who survived. CONCLUSION:Using samples obtained via bronchoscopy we identified lower airway microbiota signatures associated with mortality among critical patients infected with SARS-CoV2. Taxonomic signals identified as associated with poor prognosis did not reveal bacterial taxa commonly classified as respiratory pathogens. This data is not supportive of the hypothesis that secondary untreated bacterial co-infections are responsible for increased mortality in patients with severe SARS-CoV-2.