Online music education for sustainable development: Analysis of music learning videos in e-Hakseupteo

This study investigates music learning video content at e-Hakseupteo, a government-supported e-learning platform utilized during the COVID-19 pandemic, and provides suggestions for remote music learning in the future. The data from music learning videos in e-Hakseupteo were extracted via each subject to statistically analyze the data in various aspects including provision regions, the content providers, target audiences, video titles, and contents of each music learning video. As a result, this analysis demonstrated that e-Hakseupteo offered students fewer opportunities to learn music than other subjects because of the significant lack of music learning videos. In addition, e-Hakseupteo has provided unequal music educational opportunities and regional discrepancy due to the unintentional access settings. Finally, the music learning videos at e-Hakseupteo were produced by specific agent groups in Seoul with limited experts. Implications and suggestions are provided for the sustainability of remote learning in music education.

An update of the efficacy and comparative characteristics of direct (new) oral anticoagulants (DOACs)

: Direct (New-generation) Oral Anticoagulants (DOACs) have emerged as effective agents which are used in place of vitamin-K antagonists in treatment and prophylaxis of Venous Thromboembolism (VTE), atrial fibrillation and other thrombotic diseases. Among them, the FIIa-direct thrombin inhibitor dabigatran and FXa inhibitors (rivaroxaban, apixaban, edoxaban) are the most broadly used. Anticoagulant dosing may differ under special considerations. The patients’ physiological reserves, organ functional status and failures should be taken into account in clinical decision-making processes. The advantages and drawbacks of each specific agent should be weighed with special regard to metabolism, pharmacokinetics and pharmacodynamics, along with the efficiency of the agents in different indications. This article aims to review the most recent literature to highlight the usage and efficacy of the agents in different clinical conditions.

Chemotherapy-Induced Leukoencephalopathy: A Case Series

Rationale: Leukoencephalopathy, a complication associated with chemotherapy has been reported after giving high doses of methotrexate and cytarabine with no specific risk factors to date. Objectives: To review the prevalence of chemotherapy-induced leukoencephalopathy in children with acute lymphoblastic leukemia (ALL). To present the clinical course, pathogenesis and neuro-imaging findings of chemotherapy-induced leukoencephalopathy in children with ALL. Case: We reported three cases of adolescent ALL precursor B-cell patients who received high doses of methotrexate and presented with neurologic and MRI findings consistent with leukoencephalopathy. Our patients were only placed on supportive measures with adequate hydration, without providing any special intervention. Yet, all of them had complete neurological recovery. Discussion and Summary: Methotrexate is a cell cycle-specific agent that inhibits the enzyme dihydrofolate reductase, preventing the conversion of folic acid to tetrahydrofolic acid and inhibiting cell replication. It is one of the most commonly implicated drug causing leukoencephalopathy.[3] On MRI T2-weighted images, all of them had hyperintensities on the posterior frontal/parietal corona radiata and centrum semiovale consistent with leukoencephalopathy. Complete recovery happened spontaneously in all of the cases. There is no standard treatment for acute and subacute toxicities from methotrexate. Keywords: Leukoencephalopathy, Chemotherapeutic drugs, Neurotoxicity, Case series

A clinical case of anaphylactic shock development after anesthesia induction

The article describes a clinical case when a patient who was supposed to have a planned surgery on the spine developed anaphylactic shock. After 10 minutes of anesthesia introduction, the patient developed severe hypotension (resistant to the administration of adrenomimetics) and tachycardia; a decrease in the partial pressure of carbon dioxide at the end of expiration was noted. Due to the rapid development of a critical condition, the absence of specific skin manifestations and allergic history, as well as a direct association with the administration of a specific agent, it was necessary to carry out a differential diagnosis between acute myocardial infarction, pulmonary embolism, and anaphylactic shock. During the intensive care, the patient had echocardiography and ECG, blood gases were tested; the decisive diagnostic factor was the identification of bronchospasm signs. When the condition was stabilized, angiography of the vessels of the heart and lungs was performed; later, the agent that caused the development of anaphylaxis was established.Identifying the cause of hypotension after induction of anesthesia is critical because therapy can vary significantly. The development of anaphylactic shock during general anesthesia is not common but delayed diagnosis and therapy can be fatal. The article discusses modern approaches to the diagnosis and therapy of perioperative anaphylaxis using the example of the presented clinical case.

Melatonin attenuates growth factor receptor signaling required for SARS-CoV-2 replication

Melatonin has recently been suggested as a non-specific agent to prevent early (asymptomatic or moderate) infections with SARS-CoV-2 virus, the agent responsible for COVID-19, from developing to severe conditions requiring hospitalization. This recommendation was based on the ability of melatonin to suppress excessive inflammatory reactions and to modulate the immune system by attenuating the innate (blind and potentially harmful) response and potentiating the adaptive (selective and helpful) one. Recent data on the molecular mechanism of COVID-19 infection show that growth factor signaling is required for SARS-CoV-2 replication in the infected cells. When confronted with previously published data on the effects of melatonin on epidermal growth factor signaling, these data strongly suggest that melatonin can also act against the virus itself. Taken together, these data represent an additional argument in favor of using melatonin treatment as both a preventive and curative measure against COVID-19.

Classical term-modal logics

We introduce classical term-modal logics and argue that they are useful for modelling agent-relative notions of obligation, evidence and abilities, and their interaction with properties of and relations between the agents in question. We spell out the semantics of these logics in terms of neighborhood models, provide sound and strongly complete axiomatizations and establish the decidability of specific (agent-finite) variants.

Kawasaki disease with tsutsugamushi disease: two case reports

A number of microorganisms were hypothesised as an aetiology of the Kawasaki disease. Unfortunately, no specific agent that provides reproducible evidence has yet been reported. We report two cases of extremely rare Kawasaki disease with tsutsugamushi disease. These case reports suggest that Kawasaki disease can rarely occur concurrently or immediately after a rickettsial illness such as tsutsugamushi disease.

Chemical, physical and biological triggers of evolutionary conserved Bcl-xL-mediated apoptosis

ABSTRACTThe evidence that pan-Bcl-2 or Bcl-xL-specific inhibitors prematurely kill virus-infected or RNA/DNA-transfected cells provides rationale for investigating these apoptotic inducers further. Here, we show that Bcl-xL-specific agent A-1155463 prematurely kills cells of different origins and the small roundworms (C. elegans), when combined with DNA-damaging agent 4-nitroquinoline-1-oxide (4NQO). The synergistic effect of 4NQO-A-1155463 combination was p53-dependent, was associated with the release of Bad and Bax from Bcl-xL, which triggered mitochondrial outer membrane permeabilization (MOMP). Combinations of Bcl-xL-specific inhibitors with certain anticancer compounds or physical insults also killed cells. Collectively, our results suggest that biological, chemical and physical factors trigger evolutionary conserved Bcl-xL-mediated apoptotic pathway.

Evaluation of adjunctive mycophenolate for large vessel giant cell arteritis

Objectives GCA patients with large vessel involvement (LV-GCA) experience greater CS requirements and higher relapse rates compared with classical cranial GCA. Despite the distinct disease course, interventions in LV-GCA have yet to be investigated specifically. This study aimed to evaluate the CS-sparing effect and tolerability of first-line mycophenolate in LV-GCA. Methods A retrospective cohort study was conducted in patients with LV-GCA identified from a regional clinical database between 2005 and 2019. All cases were prescribed mycophenolate derivatives (MYC; MMF or mycophenolic acid) at diagnosis and were followed up for ≥2 years. The primary outcome was the cumulative CS dose at 1 year. Secondary outcomes included MYC tolerance, relapse rates and CRP levels at 1 and 2 years. Results A total of 37 patients (65% female; mean age 69.4 years, SD 7.9 years) were identified. All cases demonstrated large vessel involvement via CT/PET (n = 34), CT angiography (n = 5) or magnetic resonance angiography (n = 2). After 2 years, 31 patients remained on MYC, whereas 6 had switched to MTX or tocilizumab owing to significant disease relapse. The mean (±SD) cumulative prednisolone dose at 1 year was 4960 (±1621) mg. Relapse rates at 1 and 2 years were 16.2 and 27%, respectively, and CRP levels at 1 and 2 years were 4 [interquartile range (IQR) 4–6] and 4 (IQR 4–4) mg/l, respectively. Conclusion To our knowledge, this is the first attempt to assess the effectiveness of any specific agent in LV-GCA. MYC might be both effective in reducing CS exposure and well tolerated in this subpopulation. A future randomized controlled trial is warranted.

Reactivation of Epstein–Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function

Epstein–Barr nuclear antigen 1 (EBNA1) plays a vital role in the maintenance of the viral genome and is the only viral protein expressed in nearly all forms of Epstein–Barr virus (EBV) latency and EBV-associated diseases, including numerous cancer types. To our knowledge, no specific agent against EBV genes or proteins has been established to target EBV lytic reactivation. Here we report an EBNA1- and Zn2+-responsive probe (ZRL5P4) which alone could reactivate the EBV lytic cycle through specific disruption of EBNA1. We have utilized the Zn2+chelator to further interfere with the higher order of EBNA1 self-association. The bioprobe ZRL5P4can respond independently to its interactions with Zn2+and EBNA1 with different fluorescence changes. It can selectively enter the nuclei of EBV-positive cells and disrupt the oligomerization andoriP-enhanced transactivation of EBNA1. ZRL5P4can also specifically enhance Dicer1 and PML expression, molecular events which had been reported to occur after the depletion of EBNA1 expression. Importantly, we found that treatment with ZRL5P4alone could reactivate EBV lytic induction by expressing the early and late EBV lytic genes/proteins. Lytic induction is likely mediated by disruption of EBNA1 oligomerization and the subsequent change of Dicer1 expression. Our probe ZRL5P4is an EBV protein-specific agent that potently reactivates EBV from latency, leading to the shrinkage of EBV-positive tumors, and our study also suggests the association of EBNA1 oligomerization with the maintenance of EBV latency.