Design and evaluation of a remote synchronous gamified mathematics teaching activity that integrates multi-representational scaffolding and a mind tool for gamified learning.

Gamified learning is an instructional strategy that motivates students to learn, and the use of multiple representations assists learning by promoting students' thinking and advanced mathematical problem-solving skills. In particular, emergency distance learning caused by the COVID-19 pandemic may result in a lack of motivation and effectiveness in learning. This study designed an online gamified learning activity incorporating multi-representational scaffolding and compared the differences in the learning achievement and motivation for the gamified activity and general synchronous distance learning. In addition, for the group that conducted the gamified learning activity, we measured the participants' flow, anxiety, and emotion during the activity. A total of 36 high school students participated in the experiment. The results indicated that the gamified learning activity was not significantly effective in terms of enhancing learning achievement. In terms of learning motivation, a significant decrease in motivation was found for the group using general synchronous learning, while a significant increase in motivation was found for the group using synchronous gamified learning. This indicates that despite the negative impact of the pandemic on learning, gamified learning still enhances students' learning motivation. The results of flow, anxiety, and emotion showed that the participants had a positive and engaged experience. Participants provided feedback that the multi-representational scaffolding facilitates learning.

A 30-Year-Old Woman with an 8-Week History of Anxiety, Depression, Insomnia, and Mild Cognitive Impairment Following COVID-19 Who Responded to Accelerated Bilateral Theta-Burst Transcranial Magnetic Stimulation Over the Prefrontal Cortex.

BACKGROUND This report is of a 30-year-old woman with an 8-week history of anxiety, depression, insomnia, and mild cognitive impairment following COVID-19 infection, who responded to accelerated bilateral theta-burst transcranial magnetic stimulation (TBS) over the prefrontal cortex. CASE REPORT A previously healthy 30-year-old woman visited our psychiatric clinic for symptoms including anxiety, depression, insomnia, and brain fog (mild cognitive impairment) for more than 8 weeks after being diagnosed with COVID-19 on May 9, 2022. Continuous TBS of the right dorsolateral prefrontal cortex (DLPFC), followed by intermittent TBS of the left DLPFC, was performed twice daily over 5 days for a total of 10 sessions. The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), and subsets of the Wechsler Memory Scale (WMS)-Third Edition were administered at baseline and at the end of treatment. After 10 sessions of treatment, her BAI, BDI, HAMD, PSQI, WMS-Logical Memory, WMS-Faces, WMS-Verbal Paired Associates, and WMS-Family Pictures scores had improved from 4, 18, 10, 14, 8, 10, 12, and 8, respectively, to 0, 7, 1, 10, 15, 15, 15, and 10, respectively. CONCLUSIONS Accelerated TBS over the bilateral DLPFC may ameliorate long-COVID-associated neuropsychiatric symptoms. Additional trials are warranted to evaluate the effect of neuropsychiatric symptoms following COVID-19.

Modeling SARS-CoV-2 and influenza infections and antiviral treatments in human lung epithelial tissue equivalents.

There is a critical need for physiologically relevant, robust, and ready-to-use in vitro cellular assay platforms to rapidly model the infectivity of emerging viruses and develop new antiviral treatments. Here we describe the cellular complexity of human alveolar and tracheobronchial air liquid interface (ALI) tissue models during SARS-CoV-2 and influenza A virus (IAV) infections. Our results showed that both SARS-CoV-2 and IAV effectively infect these ALI tissues, with SARS-CoV-2 exhibiting a slower replication peaking at later time-points compared to IAV. We detected tissue-specific chemokine and cytokine storms in response to viral infection, including well-defined biomarkers in severe SARS-CoV-2 and IAV infections such as CXCL10, IL-6, and IL-10. Our single-cell RNA sequencing analysis showed similar findings to that found in vivo for SARS-CoV-2 infection, including dampened IFN response, increased chemokine induction, and inhibition of MHC Class I presentation not observed for IAV infected tissues. Finally, we demonstrate the pharmacological validity of these ALI tissue models as antiviral drug screening assay platforms, with the potential to be easily adapted to include other cell types and increase the throughput to test relevant pathogens.

Development of human-derived, three-dimensional respiratory epithelial tissue constructs with perfusable microvasculature on a high-throughput microfluidics screening platform.

The COVID-19 pandemic has highlighted the need for human respiratory tract-based assay platforms for efficient discovery and development of antivirals and disease-modulating therapeutics. Physiologically relevant tissue models of the lower respiratory tract (LRT), including the respiratory bronchioles and the alveolar sacs, are of high interest because they are the primary site of severe SARS-CoV-2 infection and are most affected during the terminal stage of COVID-19. Current epithelial lung models used to study respiratory viral infections include lung epithelial cells at the air-liquid interface (ALI) with fibroblasts and endothelial cells, but such models do not have a perfusable microvascular network to investigate both viral infectivity and viral infection-induced thrombotic events. Using a high throughput, 64-chip microfluidic plate-based platform, we have developed two novel vascularized, LRT multi-chip models for the alveoli and the small airway. Both models include a perfusable microvascular network consisting of human primary microvascular endothelial cells, fibroblasts and pericytes. The established biofabrication protocols also enable the formation of differentiated lung epithelial layers at the ALI on top of the vascularized tissue bed. We validated the physiologically relevant cellular composition, architecture and perfusion of the vascularized lung tissue models using fluorescence microscopy, flow cytometry, and electrical resistance measurements. These vascularized, perfusable microfluidic lung tissue on high throughput assay platforms will enable the development of respiratory viral infection and disease models for research investigation and drug discovery.

Pharmacological activation of STING blocks SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, resulting millions of infections and deaths with few effective interventions available. Here, we demonstrate that SARS-CoV-2 evades interferon (IFN) activation in respiratory epithelial cells, resulting in a delayed response in bystander cells. Since pretreatment with IFNs can block viral infection, we reasoned that pharmacological activation of innate immune pathways could control SARS-CoV-2 infection. To identify potent antiviral innate immune agonists, we screened a panel of 75 microbial ligands that activate diverse signaling pathways and identified cyclic dinucleotides (CDNs), canonical STING agonists, as antiviral. Since CDNs have poor bioavailability, we tested the small molecule STING agonist diABZI, and found that it potently inhibits SARS-CoV-2 infection of diverse strains including variants of concern (B.1.351) by transiently stimulating IFN signaling. Importantly, diABZI restricts viral replication in primary human bronchial epithelial cells and in mice in vivo. Our study provides evidence that activation of STING may represent a promising therapeutic strategy to control SARS-CoV-2.