ABSTRACT
Toll-like receptor 7 (TLR7) is an attractive target for developing immune modulators to enhance innate immunity against ssRNA virus infections, including hepatitis C and COVID-19. Ten 3-(5-hydroxyphenyl)-5-phenyl-2-pyrazolines were tested using TLR7 reporter cells, overexpressing TLR7 and the NF-B-inducible SEAP reporter gene to discover a novel TLR7 agonist enhancing innate immunity. Of these, 2-(3-(2-hydroxynaphthalen-1-yl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (compound 6) showed the best TLR7 agonistic activity, and further experiments were carried out to study the immune-modulatory capability of compound 6. Treatment with compound 6 rapidly induced phosphorylation of IRAK4, IKKα/β, IBα, and p65/RelA in THP1 monocytic cells. In addition, it increased the expression of NF-B-regulated innate cytokines, such as TNFα and IL1β, in THP1 monocytic cells. These data suggest that compound 6 induces an innate immune response by agonizing TLR7 activity in THP1 human monocytic cells. Therefore, compound 6 can be used as an innate immune modulator to develop antiviral agents and vaccine adjuvants. © 2023 Ji Hwan Kim et al.
ABSTRACT
Group testing was conceived during World War II to identify soldiers infected with syphilis using as few tests as possible, and it has attracted renewed interest during the COVID-19 pandemic. A long-standing assumption in the probabilistic variant of the group testing problem is that individuals are infected by the disease independently. However, this assumption rarely holds in practice, as diseases often spread through interactions between individuals and therefore cause infections to be correlated. Inspired by characteristics of COVID-19 and other infectious diseases, we introduce an infection model over networks which generalizes the traditional i.i.d. model from probabilistic group testing. Under this model, we ask whether knowledge of the network structure can be leveraged to perform group testing more efficiently, focusing specifically on community-structured graphs drawn from the stochastic block model. We prove that a simple community-aware algorithm outperforms the baseline binary splitting algorithm when the model parameters are conducive to “strong community structure.”Moreover, our novel lower bounds imply that the community-aware algorithm is order-optimal in certain parameter regimes. We extend our bounds to the noisy setting and support our results with numerical experiments. IEEE
ABSTRACT
Background. COVID-19 increase the risk of invasive pulmonary aspergillosis. However, the risk factors and fungal origin of COVID-19 associated pulmonary aspergillosis (CAPA) is not fully defined yet. We aim to identify the risk factors for CAPA in severe COVID-19 and evaluate association between fungal contamination within the air of negative pressure rooms and diagnosis of CAPAs. Methods. We performed a retrospective case-control study to identify risk factors for CAPA with 420 severe COVID-19 patients from March 2020 to January 2022 who admitted to a tertiary care hospital in South Korea. CAPA was defined with modified AspICU criteria. Control, matched by admission date and severity of COVID-19 at admission, was selected for each case. Air sampling and fungal culture was done on Jan 2022 with a microbial air sampler (MAS-100NT) at 11 spaces in the COVID-19 designated isolation ward including 9 negative pressure isolation rooms (IRs). A cross-sectional comparison between rooms with and without airborne fungal contamination was performed. Results. A total of 420 COVID-19 patients were hospitalized during the study period, and 51 patients were diagnosed with CAPA (prevalence 12.14%, incidence 6.26 per 1000 patient.day). Multivariate analysis showed that older age (odds ratio [OR] 1.051, 95% confidence intervals [CI] 1.006-1.009, p=0.025), mechanical ventilator use (OR 2.692, 95% CI 1.049-6.911, p=0.04), and lymphopenia (OR 4.353, 95% CI 1.727-10.975, p=0.02) were independent risk factors for CAPA. (Table 1, 2) Aspergillus spp. was identified within the air from 7 out of 11 spaces including 6 IRs and 1 doctors' room. (Figure 1). All 6 IRs with positive aspergillus culture were being occupied by patients at least 8 days. Among 6 patients, 3 had already been diagnosed with CAPA whereas the other 3 were not diagnosed with CAPA through the observation period. Among 4 patients in isolation rooms without airborne aspergillus contamination, one patient had been diagnosed as CAPA before air sampling. (Table 3). Conclusion. Association between CAPA and airborne aspergillus contamination within the negative pressure room could not be demonstrated in this study. Rather than environmental factors, patient factors such as older age, ventilator care, and lymphopenia were found to be associated with CAPA diagnosis.
ABSTRACT
For a long time, gift packaging has been a means of conveying the sender’s feeling and message just as important as the gift itself. This has been a part of social communication mean for a long time especially in East Asian societies. Therefore, packaging used to be a form of cultural communication which carries much personal and social meaning by using all kinds of material. In the twenty-first century, under the social atmosphere of sustainability, such cultural communication is regarded as vain, and the use of recycled packaging materials or the omission of packaging itself is increasingly common. Also, due to the COVID-19 pandemic, it is even more difficult to meet face-to-face and convey thankful and beloved feelings. The aim of this research is to study how non-material communication can contribute to people’s emotional satisfaction within the object exchange. The purpose is to develop a virtual packaging service using augmented reality (AR) technology, while reflecting people’s cultural and personal needs, as a sustainable user experience (UX) approach. This research analyzes user perceptions and attitudes towards virtual packaging through a quantitative study of 200 participants and evaluates users’ acceptability and cultural needs for immaterial packaging. Based on this, a new AR packaging service is developed which can bring psychological and spiritual satisfaction to people, unlike virtual messages and material packaging which have simple delivery purposes. This research will promote the use of AR technology as a cultural bridge between physical packaging and virtual communication delivering people’s hopes and cheerful minds, as well as a factor for sustainable development and the green economy. © 2022, Springer Nature Switzerland AG.
ABSTRACT
Digital literacy is not based solely on an understanding of technology, but is highly influenced by social and cultural context. This study focused on developing mobile applications for medication allergy care for respiratory-related patients in daily life, which is based on inclusiveness and digital literacy. With COVID-19, there are growing needs to share the role of primary care hospitals, with, for example GPs, and self-care symptom records applications, in order to supplement the saturated medical service of general hospitals. The mobile application of ‘medication-allergy record for respiratory-related patients’ which is developed in this study considers cultural digital literacy and provides the solutions to the local people’s needs. For these objectives this study has conducted field research and analyzed the influential factors and needs in digital interaction, by interviewing 120 outpatients of respiratory and allergic internal medicine department in general hospital in Cheongju. Based on this, the direction of the mobile application has developed new information architecture and relevant wire-frames. This study will contribute to the future direction of non-face communication in health-care service by suggesting a self-data-producing digital health care service by bridging the personal culture and user-centered technology. © Springer Nature Switzerland AG 2021.
ABSTRACT
A few months after the onset of the coronavirus Disease 2019 (COVID-19) pandemic, the worse prognoses of acute myocardial infarction, ischemic and hemorrhagic stroke, and cardiac arrest were reported. This study aimed to investigate the changes in the characteristics and prognoses of these diseases in the emergency department (ED) over a year after pandemic’s onset. This was a retrospective observational study. The year 2019 was defined as the pre-period, while the year from February 2020 to January 2021 was defined as the post-period. Adult patients diagnosed with acute myocardial infarction, ischemic stroke, hemorrhagic stroke, or cardiac arrest during the study period were included. The primary outcome was in-hospital mortality. Time series analyses using autoregressive integrated moving average (ARIMA)(p,d,q) model were performed to evaluate the changes between periods. A multivariable logistic regression analysis of factors affecting in-hospital mortality was performed. The proportions of patients with acute myocardial infarction (0.8% vs. 1.1%, p < 0.001), hemorrhagic stroke (1.0% vs. 1.2%, p = 0.011), and cardiac arrest (0.9% vs. 1.1%, p = 0.012) increased in the post-period. The post-period was independently associated with in-hospital mortality in acute myocardial infarction (adjusted odds ratio (aOR) 2.54, 95% confidence interval (95% CI) 1.06–6.08, p = 0.037) and hemorrhagic stroke (aOR 1.74, 95% CI 1.11–2.73, p = 0.016), but not for ischemic stroke or cardiac arrest. Over a year after onset of the COVID-19 pandemic in Korea, the number of patients with acute myocardial infarction, hemorrhagic stroke, and cardiac arrest in the ED increased. An independent association between the post-period and mortality was observed for acute myocardial infarction, and hemorrhagic stroke. This study provides important information for future studies and policies. ©2022 The Author(s). Published by MRE Press.
ABSTRACT
Background: There is still controversy about the efficacy of COVID-19 vaccination and its extent in lowering immunogenicity of Rheumatoid Arthritis (RA) patients. The guideline in whether immunosuppressive agents need to be discontinued before the vaccination is continuously updated because it is considered to lower immunogenicity. Furthermore, there is great discussion on the effectiveness of the COVID-19 booster vaccine and interest in antibody generation in different types of vaccine, as in South Korea there are many patients who were prescribed the mRNA booster vaccine after two doses of ChAdOx1-S nCoV-19 vaccine. Objectives: Thus, we investigated the differences of antibody production between patients who received only two doses of ChAdOx1-S nCoV-19 and those who received the mRNA booster vaccine. Also, antibody production under different types of immunosuppressive agents was analyzed. Methods: From October 14, 2021 to January 21, 2022 at a tertiary referral center, two patient groups diagnosed with RA were studied prospectively;one group that completed 1st and 2nd doses of ChAdOx1-S nCoV-19 vaccine, second group that completed mRNA booster vaccine as well as two doses of ChAdOx1-S nCoV-19 vaccine. SARS-CoV-2 antibody testing on the semiquantitative anti-SARS-CoV-2 S enzyme immunoassay was done, and differences in antibody titers were analyzed in patients who received different immunosup-pressive agents such as csDMARD, TNF inhibitor, JAK inhibitor, Tocilizumab, Abatacept and Corticosteroid. Statistical analysis with a multivariate logistic regression model was performed. Results: In a total of 261 patients, 153 patients had completed two doses of ChAdOx1-S nCoV-19, 108 patients had completed third mRNA booster vaccine. Anti-SARS-CoV-2 RBD antibody positive rate (titer>0.8U/mL) was 97%(149/153) and 99%(107/108) respectively, and only 5 patients showed negative result. In the aspect of high antibody titer(>250U/mL), which is the upper limit of the RBD antibody immunoassay, the result showed rate of 31% (47/153) in the non-booster group and 94%(102/108) in the booster group respectively. Among the different immunosuppressive agents and other clinical aspects, multivariate analysis revealed that corticosteroid use (OR 0.91;95% CI: 0.86-0.98), older age(OR 4.33;95% CI: 1.34-13.91), and male gender(OR 0.35;95% CI 0.16-0.75) were signifcantly associated with low rate of high antibody titer. Furthermore, out of 14 patients who underwent antibody test twice before and after the mRNA booster vaccine, other than four patients who already showed high titer of >250U/mL before the mRNA booster vaccine, 10 patients showed an increase in titer after the booster vaccine and 7 patients were acquired high titer of >250U/mL. Conclusion: Anti-SARS-CoV-2 RBD antibody positive rate was 97% or more regardless of the mRNA booster vaccination. However, patients who received the mRNA booster vaccine after two doses of ChAdOx1-S nCoV-19 vaccine showed high antibody titer (>250U/mL) three times more than those who did not receive the booster shot. Our fndings also showed that corticosteroid use, old age, and male gender is signifcantly associated with low rate of acquiring high antibody titer.
ABSTRACT
Background: In Korea, it has been reported that the incidence of some respiratory diseases and Kawasaki diseases has decreased compared to the previous year along with active non-pharmaceutical interventions in the early stages of the COVID-19 pandemic. Autoimmune infammatory rheumatic disease (AIIRD) is mainly affected musculoskeletal organs and connective tissues due to impaired immune regulation. Although gout and osteoarthritis are rheumatic diseases, they are not a disease of the immune system, and are not included in the AIIRD. Objectives: In this study, we investigated the change and difference in the incidence rate of various rheumatic diseases during the COVID-19 pandemic after 2020. Methods: The number of patients for each disease from January 2016 to December 2020 was obtained from the Korea Health Insurance Review and Assessment Service database. We compared the incidence of 9 rheumatic diseases [systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), Sjogren syndrome (SJS), Behcet's disease (BD), infammatory myositis (IIM), scleroderma, polymyalgia rheumatica (PMR), and gout] and hypertension before and after the COVID-19 outbreak. The incidence rates of patients before and after the COVID-19 outbreak were compared using the Poisson test. Results: From 2016 to 2019, the prevalence of rheumatic diseases showed gradually increased. In 2020, the incidence of SLE, AS, SJS, BD, and IIM were signif-cantly decreased compared to the previous 4 years. In contrast, the incidences of gout and hypertension during the COVID-19 pandemic period were signifcantly increased from the predicted values. Conclusion: In conclusion, we found that the incidence of many AIIRDs, including SLE, AS, SJS, BD, and IIM decreased despite the increased incidence of hypertension and gout during the COVID-19 pandemic.
ABSTRACT
Background: SB5, an adalimumab (ADL) biosimilar, was developed in a low-concentration (40 mg/0.8 mL, SB5-LC) aligned with the reference ADL product. Pharmacokinetics (PK) equivalence of SB5 and reference ADL was demonstrated in a Phase I study conducted in healthy subjects1. Equivalent efficacy and comparable safety between 40 mg/0.8 mL SB5 and 40 mg/0.8 mL reference ADL were demonstrated in a Phase III study conducted in patients with rheumatoid arthritis2. High-concentration, low-volume, citrate-free SB5 (40 mg/0.4 mL, SB5-HC) has been developed as a part of life cycle management in line with the reference ADL formulation. Objectives: To compare the PK, safety, and tolerability of the newly developed SB5-HC (40 mg/0.4 mL) to prior SB5-LC (40 mg/0.8 mL) in healthy male subjects. Methods: This study was a randomised, single-blind, two-arm, parallel group, single-dose study in healthy male subjects. Subjects were randomised in a ratio of 1:1 to receive a single dose of either SB5-HC or SB5-LC by subcutaneous injection on Day 1 and then observed for 57 days during which the PK, safety, and immunogenicity were evaluated. The serum concentration of ADL was measured using an enzyme-linked immunosorbent assay. The primary PK parameters were area under the concentration-time curve from time zero to infnity (AUCinf) and maximum serum concentration (Cmax). Equivalence for the primary PK parameters was to be concluded if the 90% confdence intervals (CIs) for the ratio of geometric least squares means (LSMeans) of the treatment groups compared were completely contained within the pre-defned equivalence margin of 0.80 to 1.25 using an analysis of variance. Results: Of 188 randomised subjects, 187 subjects were analysed as PK Analysis Set (PKS) (n=93 in SB5-HC and n=94 in SB5-LC). One subject was excluded from the PKS in SB5-HC group (major protocol deviation for not being withdrawn in the event of confrmed COVID-19). The geometric LSMeans ratios for the comparison of SB5-HC and SB5-LC for AUCinf and Cmax were 0.920 and 0.984, respectively, and the corresponding 90% CIs were within the pre-defned equivalence margin of 0.80 to 1.25 (Table 1), indicating the two treatment groups are bioequivalent. There were no deaths, serious adverse events or discontinuation of the study due to treatment-emergent adverse events (TEAEs) during the study. The proportions of subjects who experienced TEAEs were comparable between the two treatment groups (44.7% in SB5-HC vs 51.1% in SB5-LC). The most frequent TEAEs were headache (10.6% in SB5-HC vs 12.8% in SB5-LC). Conclusion: This study demonstrated PK equivalence between SB5-HC and SB5-LC in healthy subjects. Both SB5-HC and SB5-LC were generally well tolerated with similar safety profiles.
ABSTRACT
As the COVID-19 pandemic continues, the role of facility managers in controlling and limiting the spread of the virus among facility occupants is critical. To enable facility managers to design and evaluate the effectiveness of facility operational measures (e.g., limiting room occupancy, staggering schedules), researchers have developed simulation models that can predict the physical distancing behaviors of occupants in a given facility layout and facility operational policies. However, these models do not take into consideration the impacts of spatial and temporal constraints in a facility, which can limit occupants' ability to physical distance. To this end, this study examines whether and how such constraints affect occupants' physical distancing behaviors in the context of K-12 educational facilities, where physical distancing is extremely important. A survey to examine students' physical distancing behaviors in educational facilities was designed and conducted in four educational facilities (n=527). The results indicate that occupants' physical distancing behaviors are significantly affected by crowdedness of space (i.e., spatial constraint) given that spatial density impacts the perceived risk of infection. On the other hand, it appears that time pressure due to limited time to meet occupancy schedules (i.e., temporal constraints) does not much influence physical distancing behaviors. These findings are expected to provide a basis upon which to enhance occupant behavior simulation efforts by deepening our understanding of physical distancing behaviors of children and adolescents in educational facilities. © 2022 American Society of Civil Engineers.
ABSTRACT
Since the inception of the group testing problem in World War II, one of the prevailing assumptions in the probabilistic variant of the problem has been that individuals in the population are infected by a disease independently. However, this assumption rarely holds in practice, as diseases typically spread through interactions between individuals and therefore cause infections to be correlated. Inspired by characteristics of COVID-19 and similar diseases, we consider an infection model over networks which generalizes the traditional i.i.d. model from probabilistic group testing. Under this infection model, we ask whether knowledge of the network structure can be leveraged to perform group testing more efficiently, focusing specifically on community-structured graphs drawn from the stochastic block model. We prove that when the network and infection parameters are conducive to 'strong community structure;' our proposed adaptive, graph-aware algorithm outperforms the baseline binary splitting algorithm, and is even order-optimal in certain parameter regimes. A full version of this paper is accessible at http://arxiv.org/abs/2101.0240S. Omitted proofs and numerical experiments are provided in the full version © 2021 IEEE.
ABSTRACT
Learning methodologies and experiences have changed over the recent years thanks to the incorporation of digital technology in education, among many of this technologies are Serious Games, however the process of designing and incorporating this technologies is not easy and there are very few available tools, this paper focus is to give some guidelines from real experiences and its results in order to improve the incorporation of this new tools. With modern gadgets and interfaces, now one can initiate learning experiences based on students needs, preferences, and increase the engagement among students, this last period with COVID 19 impacting our institutions and the abrupt incorporation of full online programs and hybrid mode has made us search for new ways to improve the learning experience, young students and millennials are use to playing with games and the results indicates that they are more likely to enjoy learning experiences with them. There has been use of digital simulation environments since many years ago and gamification is more recently, but new technology has made available new ways of developing experiential learning trough games and Edutainment, gamification and more serious games have been recently developed. The empirical results lead to the conclusion that games have a very positive impact in the students learning process in higher education and adds a very good component of experiential teaching to students that can simulate complex environments and decision making through these tools and platforms. © 2021, Springer Nature Switzerland AG.
ABSTRACT
Background: Patients with coronavirus disease 2019 (COVID-19) and cancer have worse clinical outcomes compared to those without cancer. Primary studies have examined this population, but most had small sample sizes and conflicting results. Prior meta-analyses exclude most US and European data or only examine mortality. The present meta-analysis evaluates the prevalence of several clinical outcomes in cancer patients with COVID-19, including new emerging data from Europe and the US. Methods: A systematic search of PubMED, medRxiv, JMIR and Embase by two independent investigators included peer-reviewed papers and preprints up to July 8, 2020. The primary outcome was mortality. Other outcomes were ICU and non-ICU admission, mild, moderate and severe complications, ARDS, invasive ventilation, stable, and clinically improved rates. Study quality was assessed through the Newcastle-Ottawa scale. Random effects model was used to derive prevalence rates, their 95% confidence intervals (CI) and 95% prediction intervals (PI). Results: Thirty-four studies (N = 4,371) were included in the analysis. The mortality prevalence rate was 25.2% (95% CI: 21.1-29.7;95% PI: 9.8-51.1;I2= 85.4), with 11.9% ICU admissions (95% CI: 9.2-15.4;95% PI: 4.3- 28.9;I2= 77.8) and 25.2% clinically stable (95% CI: 21.1-29.7;95% PI: 9.8-51.1;I2= 85.4). Furthermore, 42.5% developed severe complications (95% CI: 30.4-55.7;95% PI: 8.2- 85.9;I2= 94.3), with 22.7% developing ARDS (95% CI: 15.4-32.2;95% PI: 5.8-58.6;I2= 82.4), and 11.3% needing invasive ventilation (95% CI: 6.7-18.4;95% PI: 2.3-41.1;I2= 79.8). Post-follow up, 49% clinically improved (95% CI: 35.6-62.6;95% PI: 9.8-89.4;I2= 92.5). All outcomes had large I2 , suggesting high levels of heterogeneity among studies, and wide PIs indicating high variability within outcomes. Despite this variability, the mortality rate in cancer patients with COVID-19, even at the lower end of the PI (9.8%), is higher than the 2% mortality rate of the non-cancer with COVID-19 population, but not as high as what other meta-analyses conclude, which is around 25%. Conclusions: Patients with cancer who develop COVID-19 have a higher probability of mortality compared to the general population with COVID-19, but possibly not as high as previous studies have shown. A large proportion of them developed severe complications, but a larger proportion recovered. Prevalence of mortality and other outcomes published in prior meta-analyses did not report prediction intervals, which compromises the clinical utilization of such results.
ABSTRACT
The COVID-19 pandemic in the spring of 2020 resulted high levels of unemployment, higher food prices, and loss of business sales. This deterioration in households' financial status likely increased food insecurity in the US, but by how much? While the US government will not measure food insecurity until December of 2020, previous research has developed a methodology whereby internet surveys that can be rapidly deployed using opt-in panels can approximate government numbers. We employ this methodology to measure food insecurity in May of 2020. Results suggest that while there is little to no detectable rise in food insecurity for all households, the percent of households with children classified as food insecure is about three percentage points higher than it was in 2016 and 2017.
ABSTRACT
The COVID-19 pandemic in the spring of 2020 resulted high levels of unemployment, higher food prices, and loss of business sales. This deterioration in households' financial status likely increased food insecurity in the US, but by how much? While the US government will not measure food insecurity until December of 2020, previous research has developed a methodology whereby internet surveys that can be rapidly deployed using opt-in panels can approximate government numbers. We employ this methodology to measure food insecurity in May of 2020. Results suggest that while there is little to no detectable rise in food insecurity for all households, the percent of households with children classified as food insecure is about three percentage points higher than it was in 2016 and 2017.