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In pixel-based deep reinforcement learning (DRL), learning representations of states that change because of an agent's action or interaction with the environment poses a critical challenge in improving data efficiency. Recent data-efficient DRL studies have integrated DRL with self-supervised learning (SSL) and data augmentation to learn state representations from given interactions. However, some methods have difficulties in explicitly capturing evolving state representations or in selecting data augmentations for appropriate reward signals. Our goal is to explicitly learn the inherent dynamics that change with an agent's intervention and interaction with the environment. We propose masked and inverse dynamics modeling (MIND), which uses masking augmentation and fewer hyperparameters to learn agent-controllable representations in changing states. Our method is comprised of a self-supervised multitask learning that leverages a transformer architecture, which captures the spatiotemporal information underlying in the highly correlated consecutive frames. MIND uses two tasks to perform self-supervised multitask learning: masked modeling and inverse dynamics modeling. Masked modeling learns the static visual representation required for control in the state, and inverse dynamics modeling learns the rapidly evolving state representation with agent intervention. By integrating inverse dynamics modeling as a complementary component to masked modeling, our method effectively learns evolving state representations. We evaluate our method by using discrete and continuous control environments with limited interactions. MIND outperforms previous methods across benchmarks and significantly improves data efficiency. The code is available at https://github.com/dudwojae/MIND.
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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.
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BACKGROUND: With a rapid decrease in tuberculosis (TB) incidence, the significance of latent tuberculosis infection (LTBI) has been underscored in South Korea. Although South Korea does not have a high proportion of immigrants compared to other countries, there is a growing argument that it should actively embrace immigrants as a solution to address issues of low birth rates and population aging. This study aimed to assess TB incidence among immigrants who participated a pilot LTBI screening program in South Korea. METHODS: Records of immigrants participated in a pilot LTBI screening program in South Korea between 2018 and 2019 were linked with Korean National TB Surveillance System to determine TB development. Participants underwent interferon-gamma release assay (IGRA) and chest X-rays. Standardized incidence ratios (SIRs) stratified by age, country of origin's TB burden was calculated with a reference group of general South Korean population. RESULTS: Of a total of 9,517 participants, 14 TB cases were identified. Participants with positive IGRA results who did not initiate LTBI treatment showed TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio of 9.08 (95% confidence interval [CI], 2.50-32.99). SIR of TB among total participants including those with negative IGRA results was 2.60 (95% CI, 1.54-4.38; P < 0.001), whereas SIR among those with positive IGRA results was 5.86 (95% CI, 3.15-10.89; P < 0.001). In the calculation of SIR among participants with positive IGRA results, those aged under 35 from high TB-burden countries or intermediate TB-burden countries showed a high SIR (18.08; 95% CI, 2.55-128.37; P = 0.004), and 11.30 (95% CI, 2.82-45.16; P < 0.001), respectively). Contrary to previous reports that suggest the majority of elderly population with a positive IGRA result were due to remote infection and had a lower TB risk compared to younger ages, SIR among those aged 65 or over from intermediate TB-burden countries was 6.15 (95% CI, 0.87-43.69; P = 0.069), which was comparable to that in younger participants aged between 35 and 49 (SIR, 4.87; 95% CI, 1.22-19.49; P = 0.025) or those aged between 50 and 64 (SIR, 4.62; 95% CI, 1.73-12.31; P = 0.002). CONCLUSION: Young immigrants with positive IGRA results from countries with high or intermediate TB burden showed a relatively high TB risk compared to a general South Korea population. In addition, unexpected high TB risk was observed among elderly immigrants with positive IGRA results. In establishing future policies for LTBI in immigrants in South Korea, screenings should primarily focus on younger age group (who aged under 35). Additionally, further research is needed on the high TB risk observed in elderly immigrants.
Subject(s)
Emigrants and Immigrants , Interferon-gamma Release Tests , Latent Tuberculosis , Mass Screening , Humans , Republic of Korea/epidemiology , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Adult , Incidence , Emigrants and Immigrants/statistics & numerical data , Female , Male , Middle Aged , Young Adult , Adolescent , Aged , Child , Child, Preschool , InfantABSTRACT
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.
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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.
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Bartholin's Glands , Melanoma , Humans , Melanoma/pathology , Melanoma/diagnosis , Diagnosis, Differential , Bartholin's Glands/pathology , Female , Cysts/pathology , Cysts/diagnosis , Vulvar Diseases/pathology , Vulvar Diseases/diagnosis , Vulvar Neoplasms/pathology , Vulvar Neoplasms/diagnosis , Middle AgedABSTRACT
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.
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Fluorocarbons , Nanoparticles , Oxygen , Fluorocarbons/chemistry , Humans , Nanoparticles/chemistry , Oxygen/administration & dosage , Oxygen/chemistry , Animals , Clinical Trials as Topic/methods , Translational Research, Biomedical/methods , Drug Carriers/chemistryABSTRACT
Purpose: Early intervention of surgical scars with a pulsed dye laser is known to effectively prevent pathologic scars. Despite multiple reports on the effectiveness of the treatment, very few studies have demonstrated its appropriate initiation timing. In this study, our objective was to determine the optimal timing for initiating laser treatment following thyroidectomy. Methods: This study retrospectively analyzed 91 patients undergoing pulsed dye laser treatment post-thyroidectomy, grouping them by treatment initiation timing. The patients underwent treatment at intervals of 3-4 weeks with at least five sessions. Those with a high pliability score were injected with intralesional corticosteroids. The Antera 3D® skin imaging analyzer was used to assess biophysical parameters. Results: The total Vancouver Scar Scale score significantly reduced after treatment in all groups. The Vancouver Scar Scale score reduction rate was significantly higher after treatment in the group for which the treatment was initiated within 3 weeks of surgery. The pigmentation and erythema score analyzed by Antera 3D® was also lower in this group. Conclusion: Early intervention using a pulsed dye laser within 3 weeks of thyroidectomy can substantially inhibit pathological scar development, providing physicians with a guide for optimal treatment commencement.
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BACKGROUND: Psoriasis is a chronic inflammatory disorder characterized by pathogenic hyperproliferation of keratinocytes and immune dysregulation. Currently, objective evaluation tools reflecting the severity of psoriasis are insufficient. MicroRNAs in extracellular vesicles (EV miRNAs) have been shown to be potential biomarkers for various inflammatory diseases. Our objective was to investigate the possibility of plasma-derived EV miRNAs as a marker for the psoriasis disease severity. METHODS: EVs were extracted from the plasma of 63 patients with psoriasis and 12 with Behçet's disease. We performed next-generation sequencing of the plasma-derived EV miRNAs from the psoriasis patients. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the level of EV miRNA expression. In situ hybridization was used to discern the anatomical location of miRNAs. qRT-PCR, western blotting, and cell counting kits (CCKs) were used to investigate IGF-1 signaling in cells transfected with miRNA mimics. RESULTS: We identified 19 differentially expressed EV miRNAs and validated the top three up-and down-regulated EV miRNAs. Among these, miR-625-3p was significantly increased in patients with severe psoriasis in both plasma and skin and most accurately distinguished moderate-to-severe psoriasis from mild-to-moderate psoriasis. It was produced and secreted by keratinocytes upon stimulation. We also observed a significant intensification of IGF-1 signalling and increased cell numbers in the miR-625-3p mimic transfected cells. CONCLUSIONS: We propose keratinocyte-derived EV miR-625-3p as a novel and reliable biomarker for estimating the severity of psoriasis. This biomarker could objectively evaluate the severity of psoriasis in the clinical setting and might serve as a potential therapeutic target. Trial registration None.
Subject(s)
Circulating MicroRNA , Extracellular Vesicles , MicroRNAs , Psoriasis , Humans , Circulating MicroRNA/genetics , Insulin-Like Growth Factor I , MicroRNAs/genetics , Keratinocytes , Psoriasis/genetics , BiomarkersABSTRACT
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.
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Melasma relapse is almost common after discontinuation of conventional treatment. Recent studies suggesting that photoaging dermis is the main pathomechanism of melasma, emphasize the dermal targeting therapy. We investigated maintenance effect of microneedling radiofrequency (RF) for melasma treatment. Subjects with melasma were administered oral tranexamic acid and triple combination cream for 2 months and a randomly assigned half face was treated with RF. After discontinuation of conventional therapy, the half face RF continued monthly over 6 months. Modified melasma area severity index (mMASI) score and L* value by a chromameter were collected monthly. Fifteen subjects were enrolled and eleven completed the 8-month study. At 2nd month of conventional therapy, all subjects showed improvement with a 64% reduction in mMASI score. With continuous RF treatment, the improvement was well maintained; whereas in untreated side, the Δ L* gradually decreased, returning to the baseline after the conventional therapy ended. The continuous microneedling RF therapy is beneficial in maintaining the conventional therapy of melasma suggesting the protective effect of dermal targeting therapy in melasma development.(Clinical Trial registration number: NCT05710068, date of first registration: 02/02/2023).
Subject(s)
Melanosis , Orobanchaceae , Radiofrequency Therapy , Humans , Food , Melanosis/therapy , DermisSubject(s)
COVID-19 , Camping , Humans , COVID-19/epidemiology , Japan , Disease Outbreaks , Republic of Korea/epidemiologyABSTRACT
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.
Subject(s)
Lactones , Signal Transduction , Lactones/metabolism , Light , Pyrans/metabolism , Pyrans/pharmacology , Furans/metabolism , Furans/pharmacology , Plant Development/radiation effects , Plant Development/drug effects , Morphogenesis/radiation effects , Morphogenesis/drug effects , Adaptation, Physiological/geneticsABSTRACT
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.
Subject(s)
Eicosapentaenoic Acid , Fatty Acids, Omega-3 , Adult , Humans , Docosahexaenoic Acids , Cross-Over Studies , Biological Availability , EstersABSTRACT
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.
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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.
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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.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Cohort Studies , Pandemics , Retrospective Studies , Vaccination , COVID-19 Vaccines , Vaccines, Combined , Republic of Korea/epidemiologyABSTRACT
Granulomatous rosacea (GR) is a rare and distinct variant of rosacea. We report three cases of recalcitrant GR successfully treated with pulsed-dye laser (PDL) and provide experimental evidence supporting its potential as a treatment option. PDL treatment demonstrated remarkable efficacy in the three clinical cases, despite their resistance to conventional therapies. Chemokine ligand 9 (CXCL9), a key chemokine involved in inflammation and granuloma formation, was found to be increased in skin sections from all three patients. In vitro experiments using human monocytes and dermal fibroblasts demonstrated that PDL treatment significantly reduced CXCL9 expression in fibroblasts. These findings suggest that PDL may modulate CXCL9 secretion in fibroblasts, potentially limiting the recruitment of immune cells to the lesion. Although further research is needed to fully understand the precise mechanisms underlying the role of CXCL9 in GR, PDL may be a promising therapeutic approach for refractory GR.
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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.
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Rationale: Senescent melanocytes accumulate in photoaged skin and are closely related to skin aging. A better understanding of the molecular characteristics of senescent melanocytes may be the key to controlling skin aging. Methods: We have developed an in vitro model of senescence in melanocytes using UV irradiation and investigated the functional characteristics and molecular mechanisms underlying senescence in UV-irradiated melanocytes. Results: We have highlighted that in vitro senescent melanocytes are characterized by melanosome transport dysfunction resulting in melanin accumulation. The defective melanosome transport was confirmed with the ultrastructural characterization of both in vitro UV-induced senescent melanocytes and in vivo melanocytes of hypopigmented aging skin. A single-cell transcriptomic analysis revealed that the glycolytic metabolism pathway appeared to be significantly upregulated in most senescent phenotypes. Furthermore, the inhibition of glycolysis by pharmacological compounds mitigates the pro-aging effects of melanocytes senescence, suggesting that alterations in cellular glucose metabolism act as a driving force for senescence in melanocytes. Conclusion: These results demonstrate that senescent melanocytes are characterized by glycolytic metabolism changes and a defective melanosome transport process, which may be related to impaired mitochondrial function, highlighting the importance of metabolic reprogramming in regulating melanocyte senescence.