Identifying risk factors for COVID-19 cluster infections in schools in the Republic of Korea: a case-control study.

Objectives: No study has yet analyzed risk factors to determine whether students with confirmed coronavirus disease 2019 (COVID-19) infections may affect students at neighboring schools. Therefore, this study aimed to determine risk factors for COVID-19 transmission among schools within a community in the Republic of Korea. Methods: An epidemiological investigation was conducted among 696 students and school staff members at 3 schools where COVID-19 clusters began on October 15, 2021. Interviews, visit history surveys, a facility risk assessment, and closed-circuit television were used to identify risk factors. The statistical significance of risk factors was also evaluated. Results: We confirmed 129 cases (18.5%) among the individuals exposed to COVID-19 at the 3 schools, many of whom had a history of visiting the same multi-use facilities. The odds ratio of having visited multi-use facilities such as karaoke rooms was 1.90 (95% confidence interval, 1.03-3.50); the number of visits to a karaoke room and the visit durations were significantly higher among confirmed cases than non-confirmed cases (p=0.02 and p=0.03, respectively). Conclusion: Having a history of visiting karaoke rooms often and spending a long time there were risk factors for COVID-19 infection and inter-school transmission. Thus, it is necessary to investigate the status of multi-use facilities frequently visited by adolescents and consider incorporating them into the scope of school quarantine to prevent infectious diseases at schools in a community.

Evolutionary conservation of receptor compensation for stem cell homeostasis in Solanaceae plants.

Stem cell homeostasis is pivotal for continuous and programmed formation of organs in plants. The precise control of meristem proliferation is mediated by the evolutionarily conserved signaling that encompasses complex interactions among multiple peptide ligands and their receptor-like kinases. Here, we identified compensation mechanisms involving the CLAVATA1 (CLV1) receptor and its paralogs, BARELY ANY MERISTEMs (BAMs), for stem cell proliferation in two Solanaceae species, tomato and groundcherry. Genetic analyses of higher-order mutants deficient in multiple receptor genes, generated via CRISPR-Cas9 genome editing, reveal that tomato SlBAM1 and SlBAM2 compensate for slclv1 mutations. Unlike the compensatory responses between orthologous receptors observed in Arabidopsis, tomato slclv1 mutations do not trigger transcriptional upregulation of four SlBAM genes. The compensation mechanisms within receptors are also conserved in groundcherry, and critical amino acid residues of the receptors associated with the physical interaction with peptide ligands are highly conserved in Solanaceae plants. Our findings demonstrate that the evolutionary conservation of both compensation mechanisms and critical coding sequences between receptor-like kinases provides a strong buffering capacity during stem cell homeostasis in tomato and groundcherry.

In Vitro/In Vivo Correlation of Two Extended-Release Cilostazol Formulations.

This study aims to evaluate and determine the correlation between in vitro release and in vivo pharmacokinetics of two extended-release dosage forms of Cilostazol. In vitro release profiles for two dosage forms, tablet and capsule, were analyzed under physiologically mimicked medium conditions using the paddle and basket USP release apparatus. A single-dose, two-period crossover study design in beagle dogs was applied for the pharmacokinetic study. The fed and fast effects were considered for evaluation. Pseudo gastric release medium transfer setup study from pH 1.2 to pH 6.8 (+0.5% SLS) and pH 1.2 to pH 6.8 (+1.0% SLS) demonstrated that Pletaal® SR 200 mg capsules have higher drug release rates than Cilostan® CR 200 mg tablets. Similarly, in vivo study showed Cilostazol concentration in plasma and AUC was lower under the fast state than the fed state. The ratio of least squared geometric mean values, Cmax, AUC0-t, and AUC0-inf of Cilostazol were 2.53-fold, 2.89-fold, and 2.87-fold higher for Pletaal® SR 200 mg capsules compared with Cilostan® CR 200 mg tablets, respectively. Correlation of in vitro/in vivo data indicated that Pletal® SR 200 mg capsules have better release and pharmacodynamic effect than Cilostan® CR 200 mg tablets.

Why Perfluorocarbon nanoparticles encounter bottlenecks in clinical translation despite promising oxygen carriers?

Artificial Oxygen Carriers (AOCs) have emerged as ground-breaking biomedical solutions, showcasing tremendous potential for enhancing human health and saving lives. Perfluorocarbon (PFC)-based AOCs, in particular, have garnered significant interest among researchers, leading to numerous clinical trials since the 1980 s. However, despite decades of exploration, the success rate has remained notably limited. This comprehensive review article delves into the landscape of clinical trials involving PFC compounds, shedding light on the challenges and factors contributing to the lack of clinical success with PFC nanoparticles till date. By scrutinizing the existing trials, the article aims to uncover the underlying issues like pharmacological side effects of the PFC and the nanomaterials used for the designing, complex formulation strategy and poor clinical trial designs of the formulation. More over each generation of the PFC formulation were discussed with details for their failure in the clinical trials limitations that block the path of PFC-based AOCs' full potential. Furthermore, the review emphasizes a forward-looking approach by outlining the future pathways and strategies essential for achieving success in clinical trials. AOCs require advanced yet biocompatible single-componentformulations. The new trend might be a novel drug delivery technique, like gel emulsion or reverse PFC emulsion with fluoro surfactants. Most importantly, well-planned clinical trials may end in a success story.

Risk factors for SARS-CoV-2 transmission during a movie theater outbreak in Incheon in the Republic of Korea, November 2021: a retrospective study.

BACKGROUND: We examined factors contributing to the transmission of an acute respiratory virus within multi-use facilities, focusing on an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a movie theater in the Republic of Korea. METHODS: This retrospective cohort study involved a descriptive analysis of 48 confirmed cases. Logistic regression was applied to a cohort of 80 theater attendees to identify risk factors for infection. The infection source and transmission route were determined through gene sequencing data analysis. RESULTS: Of the 48 confirmed cases, 35 were theater attendees (72.9%), 10 were family members of attendees (20.8%), 2 were friends (4.2%), and 1 was an employee (2.1%). Among the 80 individuals who attended the 3rd to 5th screenings of the day, 35 became infected, representing a 43.8% attack rate. Specifically, 28 of the 33 third-screening attendees developed confirmed SARSCoV-2, constituting an 84.8% attack rate. Furthermore, 11 of the 12 cases epidemiologically linked to the theater outbreak were clustered monophyletically within the AY.69 lineage. At the time of the screening, 35 individuals (72.9%) had received 2 vaccine doses. However, vaccination status did not significantly influence infection risk. Multivariate analysis revealed that close contacts had a 15.9-fold higher risk of infection (95% confidence interval, 4.37-78.39) than casual contacts. CONCLUSION: SARS-CoV-2 transmission occurred within the theater, and extended into the community, via a moviegoer who attended the 3rd screening during the viral incubation period after contracting the virus from a family member. This study emphasizes the importance of adequate ventilation in theaters.

Environmentally adaptive reshaping of plant photomorphogenesis by karrikin and strigolactone signaling.

Coordinated morphogenic adaptation of growing plants is critical for their survival and propagation under fluctuating environments. Plant morphogenic responses to light and warm temperatures, termed photomorphogenesis and thermomorphogenesis, respectively, have been extensively studied in recent decades. During photomorphogenesis, plants actively reshape their growth and developmental patterns to cope with changes in light regimes. Accordingly, photomorphogenesis is closely associated with diverse growth hormonal cues. Notably, accumulating evidence indicates that light-directed morphogenesis is profoundly affected by two recently identified phytochemicals, karrikins (KARs) and strigolactones (SLs). KARs and SLs are structurally related butenolides acting as signaling molecules during a variety of developmental steps, including seed germination. Their receptors and signaling mediators have been identified, and associated working mechanisms have been explored using gene-deficient mutants in various plant species. Of particular interest is that the KAR and SL signaling pathways play important roles in environmental responses, among which their linkages with photomorphogenesis are most comprehensively studied during seedling establishment. In this review, we focus on how the phytochemical and light signals converge on the optimization of morphogenic fitness. We also discuss molecular mechanisms underlying the signaling crosstalks with an aim of developing potential ways to improve crop productivity under climate changes.

A Randomized, Open-Label, Single-Dose, Crossover Study of the Comparative Bioavailability of EPA and DHA in a Novel Liquid Crystalline Nanoparticle-Based Formulation of ω-3 Acid Ethyl Ester Versus Omacor® Soft Capsule among Healthy Adults.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well known for their capacity to lower triglyceride levels, but the clinical effectiveness is hindered by limited bioavailability and patient adherence. To address this challenge, we introduce a novel liquid crystalline nanoparticle-based formulation, the innovative medicine and drug delivery (IMD)-Omega soft capsule (cap), designed to optimize the pharmacokinetics (PK) and safety of EPA and DHA. This randomized, open-label, crossover study engages a cohort of 24 healthy adult subjects, utilizing key PK parameters like Cmax, AUC, Tmax, t½, and Ke to conduct a comprehensive evaluation. The trial compares the performance of the IMD-Omega soft cap with the well-established Omacor® soft cap. The IMD-Omega soft cap exhibited an impressive 110% increase in bioavailability for EPA and a remarkable 134% surge for DHA in comparison to the Omacor® soft cap over a span of 72 h. The key success can be attributed to the innovative liquid crystalline nanoparticle design, bolstering the dissolution and permeability of these essential fatty acids. Intriguingly, intra-participant variability for AUC0-72 h and Cmax were calculated at 45.04% and 34.26%, respectively. It is noteworthy that the parameters of Tmax for EPA (≈6.00 h) and DHA (≈5.00 h), t½ for both EPA and DHA ≈ 30-40 h, and Kel around 0.18-0.22 h-1 for EPA and ≈0.008-0.02 h-1 for DHA, displayed comparability between the IMD-Omega and Omacor® formulations. Encouragingly, the IMD-Omega soft cap showed excellent tolerability. The promise of optimized patient compliance and reduced dosages adds further weight to its potential significance.

Evaluation of COVID-19 vaccine effectiveness in different high-risk facility types during a period of Delta variant dominance in the Republic of Korea: a cross-sectional study.

BACKGROUND: We evaluated the effectiveness of coronavirus disease 2019 vaccination in high-risk facilities in the Republic of Korea during the period when the highly transmissible Delta variant was prevalent. Additionally, we aimed to explore any disparities in vaccine effectiveness (VE) across various types of institutions, specifically distinguishing between non-medical and medical establishments. METHODS: We examined 8 outbreak clusters covering 243 cases and 895 contacts from 8 high-risk facilities divided into 2 groups: group A (4 non-medical institutions) and group B (4 medical institutions). These clusters were observed from July 27, 2021 to October 16, 2021 for the attack rate (AR) and VE with respect to disease severity. A generalized linear model with a binomial distribution was used to determine the odds ratio (OR) for disease severity and death. RESULTS: AR was notably lower in group B (medical institutions). Furthermore, VE analysis revealed that group A exhibited higher effectivity for disease severity and death than group B. The OR for disease severity was 0.24 (95% confidence interval [CI], 0.03-2.16) for group A and 0.27 (95% CI, 0.12-0.64) for group B, with the OR for death at 0.12 (95% CI, 0.01-1.32) in group A and 0.34 (95% CI, 0.14-0.87) in group B. CONCLUSION: Although VE may vary across institutions, our findings underscore the importance of implementing vaccinations in high-risk facilities. Customized vaccination programs, tailored response plans, and competent management personnel are essential for effectively addressing and mitigating public health challenges.

Accuracy of Rapid Antigen Screening Tests for SARS-CoV-2 Infection at Correctional Facilities in Korea: March - May 2022.

BACKGROUND: The number of confirmed cases of individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increased rapidly due to the Omicron variant. Correctional facilities are vulnerable to infectious diseases, and they introduced rapid antigen tests (RATs) to allow for early detection and rapid response. We aimed to evaluate the diagnostic performance and usefulness of SARS-CoV-2 RATs in newly incarcerated people. MATERIALS AND METHODS: We conducted a cross-sectional study at correctional facilities in Korea from 9 March to 22 May 2022. The study population was newly incarcerated people who were divided into two groups. In one group, 799 paired SARS-CoV-2 RATs and real-time polymerase chain reaction (RT-PCR) were conducted simultaneously in 522 individuals in March 2022. In the other group, 4,034 paired RATs and RT-PCR consecutively in 4,034 participants; only individuals with negative RATs results underwent RT-PCR from April to May 2022. We analyzed data using descriptive statistics and a logistic regression model. RESULTS: Among the 799 specimens in March, RT-PCR was positive in 72 (9.0%), and among the 4,034 specimens in April - May 2022, RT-PCR was positive in 40 (1.0%). Overall, the RATs had a sensitivity of 58.3%, specificity of 100.0%, positive predictive value (PPV) of 100.0%, and negative predictive value (NPV) of 96.0%. Asymptomatic individuals constituted 98.2% of the study group, and symptomatic individuals 1.8%. In asymptomatic cases, the sensitivity of RATs was 52.5%, specificity was 100.0%, PPV was 100.0%, and NPV was 96.3%. In symptomatic cases, the sensitivity of RATs was 84.6%, specificity was 100.0%, PPV was 100.0%, and NPV was 33.3%. Sensitivity (P = 0.034) and NPV (P = 0.004) differed significantly according to the presence and absence of symptoms, and the F1 score was the highest at 0.9 in symptomatic individuals in March. There was a positive linear trend in the proportion of false-negative RATs in newly incarcerated people following the weekly incidence of SARS-CoV-2 (P = 0.033). The best-associated predictors of RATs for SARS-CoV-2 infection involved symptoms, timing of sample collection, and repeat testing. CONCLUSION: Sensitivity and NPV significantly depend on whether symptoms are present, and the percentage of false negatives is correlated with the incidence. Thus, using RATs should be adjusted according to the presence or absence of symptoms and the incidence of SARS-CoV-2 infection in the community. RATs could be a useful screening tool as an effective first-line countermeasure because they can rapidly identify infectious patients and minimize SARS-CoV-2 transmission in correctional facilities.

Comparative Effectiveness of COVID-19 Bivalent Versus Monovalent mRNA Vaccines in the Early Stage of Bivalent Vaccination in Korea: October 2022 to January 2023.

BACKGROUND: This retrospective observational matched-cohort study of 2,151,216 individuals from the Korean coronavirus disease 2019 (COVID-19) vaccine effectiveness cohort aimed to evaluate the comparative effectiveness of the COVID-19 bivalent versus monovalent vaccines in providing additional protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, critical infection, and death in Korea. METHODS: Among individuals, those vaccinated with COVID-19 bivalent vaccines were matched in a 1:1 ratio with those who were vaccinated with monovalent vaccines (bivalent vaccines non-recipients) during the observation period. We fitted a time-dependent Cox proportional-hazards model to estimate hazard ratios (HRs) of COVID-19 outcomes for infection, critical infection, and death, and we defined vaccine effectiveness (VE) as 1-HR. RESULTS: Compared with the bivalent vaccination group, the incidence proportions in the monovalent vaccination group were approximately three times higher for infection, nine times higher for critical infection, and 11 times higher for death. In the early stage of bivalent vaccination, relative VE of bivalent vaccine against monovalent vaccine was 42.4% against SARS-CoV-2 infection, 81.3% against critical infection, and 85.3% against death. In addition, VE against critical infection and death according to the elapsed period after bivalent vaccination was maintained at > 70%. CONCLUSION: The bivalent booster dose provided additional protection against SARS-CoV-2 infections, critical infections, and deaths during the omicron variant phase of the COVID-19 pandemic.

Polo-like Kinase 4: A Multifaceted Marker Linking Tumor Aggressiveness and Unfavorable Prognosis, and Insights into Therapeutic Strategies.

(1) Background: This study investigated whether polo-like kinase 4 (PLK4) is a suitable therapeutic target or biomarker for lung adenocarcinoma (LUAD). (2) Methods: We acquired LUAD data from The Cancer Genome Atlas (TCGA) database through the UCSC Xena data portal. Gene expression, clinical, survival, and mutation data from multiple samples were analyzed. Gene enrichment analysis, unsupervised clustering of PLK4-related pathways, and differential gene expression analyses were performed. Additionally, correlations, t-tests, survival analyses, and statistical analyses were performed. (3) Results: PLK4 expression was higher in LUAD tissues than in normal tissues and was associated with poor prognosis for both overall and progression-free survival in LUAD. PLK4 was highly correlated with cell-proliferation-related pathways using Gene Ontology (GO) biological process terms. PLK4 expression and pathways that were highly correlated with PLK4 expression levels were upregulated in patients with LUAD with the TP53 mutation. (4) Conclusions: PLK4 expression affects the survival of patients with LUAD and is a potential therapeutic target for LUAD with TP53 mutations.

A New Epigenetic Crosstalk: Chemical Modification Information Flow.

Central dogma is the most fundamental hypothesis in the field of molecular biology and explains the genetic information flow from DNA to protein. Beyond residue-by-residue transmission of sequential information, chemical modifications of DNA, RNA, and protein are also relayed in the course of gene expression. Here, this work presents recent evidence supporting bidirectional interplay between chromatin modifications and RNA modifications. Furthermore, several RNA modifications likely affect chemical modifications of proteins. The relay of chemical modifications occurs co-transcriptionally or co-translationally, ensuring crosstalk among chemical modifications at the DNA, RNA, and protein levels. Overall, this work proposes a hypothetical framework that represents transmission of chemical modification information among chromatin, RNA, and proteins.

Epidemiological Characteristics of a COVID-19 Outbreak in a Psychiatric Hospital in Chung-buk.

This study investigated the causes and risks for infection spread in three psychiatric hospitals in Chung-buk, South Korea, to strategize measures to block transmission and prevent a large-scale epidemic. From December 2020 to January 2021, 358 inpatients of Psychiatric Hospitals A, B, and C were enrolled to identify the epidemiological characteristics of confirmed patients. Epidemic curves and propagation relationships were constructed and a genotype analysis was conducted. The index case inpatient from Hospital A transmitted the infection to patients in Hospitals B and C; the infection was confirmed in 47, 193, and 118 patients in Hospitals A, B, and C, respectively. The patient characteristics hampered communication and the close identification of symptom onset. The incidence rate was 10 (2.9%) among employees and 348 (35.8%) among inpatients. The relative risk was 12.1 (95% CI: 6.6-22.5) times higher among inpatients than employees. Next-generation sequencing confirmed the probable infection source as a genotype identical to that of two different outbreaks, although the infection spread was undetermined. Direct risk factors emerged from patient characteristics, wherein cohort isolation was meaningless due to uncontrolled communication. Indirect risk factors included hospital-specific problems due to external factors (non-patient system deficiencies or employee negligence). Prior inspections, a confirmation of non-infection, and institutional emergent measures are needed.

Risk factors for transmission in a COVID-19 cluster infection in a high school in the Republic of Korea.

BACKGROUND: This study aimed to examine the scale, characteristics, risk factors, and modes of transmission in a coronavirus disease 2019 (COVID-19) outbreak at a high school in Seoul, Republic of Korea. METHODS: An epidemiological survey was conducted of 1,118 confirmed cases and close contacts from a COVID-19 outbreak at an educational facility starting on May 31, 2021. In-depth interviews, online questionnaires, flow evaluations, and CCTV analyses were used to devise infection prevention measures. Behavioral and spatial risk factors were identified, and statistical significance was tested. RESULTS: Among 3rd-year students, there were 33 confirmed COVID-19 cases (9.6%). Students who used a study room in the annex building showed a statistically significant 4.3-fold elevation in their relative risk for infection compared to those who did not use the study room. Moreover, CCTV facial recognition analysis confirmed that 17.8% of 3rd-year students did not wear masks and had the lowest percentage of mask-wearers by grade. The air epidemiological survey conducted in the study room in the annex, which met the 3 criteria for a closed space, confirmed that there was only 10% natural ventilation due to the poor ventilation system. CONCLUSION: To prevent and manage the spread of COVID-19 in educational facilities, advance measures that consider the size, operation, and resources of each school are crucial. In addition, various survey methodologies should be used in future studies to quickly analyze a wider range of data that can inform an evidence-based quarantine response.

Results of contact tracing for SARS-CoV-2 Omicron sub-lineages (BA.4, BA.5, BA.2.75) and the household secondary attack risk.

BACKGROUND: This study aimed to assess the contact tracing outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sub-lineages BA.4, BA.5, and BA.2.75 within Republic of Korea, and to generate foundational data for responding to future novel variants. METHODS: We conducted investigations and contact tracing for 79 confirmed BA.4 cases, 396 confirmed BA.5 cases, and 152 confirmed BA.2.75 cases. These cases were identified through random sampling of both domestically confirmed and imported cases, with the goal of evaluating the pattern of occurrence and transmissibility. RESULTS: We detected 79 instances of Omicron sub-lineage BA.4 across a span of 46 days, 396 instances of Omicron sub-lineage BA.5 in 46 days, and 152 instances of Omicron sub-lineage BA.2.75 over 62 days. One patient with severe illness was confirmed among the BA.5 cases; however, there were no reports of severe illness in the confirmed BA.4 and BA.2.75 cases. The secondary attack risk among household contacts were 19.6% for BA.4, 27.8% for BA.5, and 24.3% for BA.2.75. No statistically significant difference was found between the Omicron sub-lineages. CONCLUSION: BA.2.75 did not demonstrate a higher tendency for transmissibility, disease severity, or secondary attack risk within households when compared to BA.4 and BA.5. We will continue to monitor major SARS-CoV-2 variants, and we plan to enhance the disease control and response systems.

Effectiveness of Heterologous COVID-19 Vaccine Booster in Korean Elderly Population, 2022.

We conducted a cohort study to assess vaccine effectiveness (VE) of coronavirus disease 2019 vaccine combinations on severe acute respiratory syndrome coronavirus 2 critical infection and death among elderly population in Korea. From January to August 2022, VE against death for 4 doses mRNA recipients was 96.1%, whereas 1-dose viral vector + 3-dose mRNA recipients had VE of 90.8%.

Age-specific Risk of SARS-CoV-2 Reinfection During Omicron Outbreaks, South Korea.

We assessed the risk of reinfection among all residents in South Korea who tested positive for coronavirus disease 2019 from January to August 2022. Children 5-11 years [adjusted hazard ratio (aHR) = 2.20], and 12-17 years old (aHR = 2.00), were at higher risk; whereas 3-dose vaccination (aHR = 0.20) lowered the risk of reinfection.

Analysis of pregnant women with critically severe COVID-19 in Republic of Korea from February 2020 and December 2021.

OBJECTIVES: This study aimed to describe the characteristics and risk factors for severe disease in pregnant women infected with coronavirus disease 2019 (COVID-19) from the early days of the COVID-19 epidemic in Korea to the predominant period of the Delta variant. METHODS: A retrospective cohort study was conducted among pregnant women diagnosed with COVID-19 between February 2020 and December 2021. Logistic regression analysis was performed to compare severe and mild cases after adjusting for pregnant women's age, nationality, infection route, outbreak area, infection period, symptoms, underlying disease, smoking status, trimester, and COVID-19 vaccination status. RESULTS: In total, 2,233 pregnant women were diagnosed with COVID-19 by December 2021. Among these, 96.7% had mild symptoms, 3.3% had severe symptoms, and 0.04% died. The risk factors for severe disease in pregnant women with confirmed COVID-19 were being in the age group of 35 to 45 years, having hyperlipidemia, being in the second or third trimester of pregnancy at the time of COVID-19 diagnosis, being infected during the Delta-predominant period, and having a fever (≥38 °C) at diagnosis. Furthermore, 47.1% of patients in the mild group and 84.9% of patients in the severe group had 3 or more risk factors. CONCLUSION: Pregnant women with COVID-19 mainly experienced mild symptoms, but those with risk factors were at a higher risk of developing severe symptoms. Therefore, treatment and follow-up management should be thoroughly implemented.

Effectiveness of A Fourth Dose of COVID-19 mRNA Vaccine in the Elderly Population During the Omicron BA.2 and BA.5 Circulation: A Nationwide Cohort Study in Korea (K-COVE).

We estimate the effectiveness of a fourth dose booster of coronavirus disease 2019 mRNA vaccine in individuals aged ≥60 years during Omicron BA.2 and BA.5 circulation in Korea. The effectiveness against critical infection was 67.7% (95% confidence interval, 50.7%-78.8%) at 31-60 days and 62.1% (95% confidence interval, 45.5%-73.7%) at 61-90 days.