Ionic liquid-caged nucleic acids enable active folding-based molecular recognition with hydrolysis resistance.

Beyond storage and transmission of genetic information in cellular life, nucleic acids can perform diverse interesting functions, including specific target recognition and biochemical reaction acceleration; the versatile biopolymers, however, are acutely vulnerable to hydrolysis-driven degradation. Here, we demonstrate that the cage effect of choline dihydrogen phosphate permits active folding of nucleic acids like water, but prevents their phosphodiester hydrolysis unlike water. The choline-based ionic liquid not only serves as a universal inhibitor of nucleases, exceptionally extending half-lives of nucleic acids up to 6 500 000 times, but highly useful tasks of nucleic acids (e.g. mRNA detection of molecular beacons, ligand recognition of aptamers, and transesterification reaction of ribozymes) can be also conducted with well-conserved affinities and specificities. As liberated from the function loss and degradation risk, the presence of undesired and unknown nucleases does not undermine desired molecular functions of nucleic acids without hydrolysis artifacts even in nuclease cocktails and human saliva.

The penultimate step of proteasomal ATPase assembly is mediated by a switch dependent on the chaperone Nas2.

The proteasome holoenzyme is a complex molecular machine that degrades most proteins. In the proteasome holoenzyme, six distinct ATPase subunits (Rpt1 through Rpt6) enable protein degradation by injecting protein substrates into it. Individual Rpt subunits assemble into a heterohexameric "Rpt ring" in a stepwise manner, by binding to their cognate chaperones. Completion of the heterohexameric Rpt ring correlates with release of a specific chaperone, Nas2; however, it is unclear whether and how this event may ensure proper Rpt ring assembly. Here, we examined the action of Nas2 by capturing the poorly characterized penultimate step of heterohexameric Rpt ring assembly. For this, we used a heterologous Escherichia coli system coexpressing all Rpt subunits and assembly chaperones as well as Saccharomyces cerevisiae to track Nas2 actions during endogenous Rpt ring assembly. We show that Nas2 uses steric hindrance to block premature progression of the penultimate step into the final step of Rpt ring assembly. Importantly, Nas2 can activate an assembly checkpoint via its steric activity, when the last ATPase subunit, Rpt1, cannot be added in a timely manner. This checkpoint can be relieved via Nas2 release, when Nas2 recognizes proper addition of Rpt1 to one side of its cognate Rpt5, and ATP hydrolysis by Rpt4 on the other side of Rpt5, allowing completion of Rpt ring assembly. Our findings reveal dual criteria for Nas2 release, as a mechanism to ensure both the composition and functional competence of a newly assembled proteasomal ATPase, to generate the proteasome holoenzyme.

Osteoporotic Bone Regeneration via Plenished Biomimetic PLGA Scaffold with Sequential Release System.

Achieving satisfactory bone tissue regeneration in osteoporotic patients with ordinary biomaterials is challenging because of the decreased bone mineral density and aberrant bone microenvironment. In addressing this issue, a biomimetic scaffold (PMEH/SP), incorporating 4-hexylresorcinol (4HR), and substance P (SP) into the poly(lactic-go-glycolic acid) (PLGA) scaffold with magnesium hydroxide (M) and extracellular matrix (E) is introduced, enabling the consecutive release of bioactive agents. 4HR and SP induced the phosphorylation of p38 MAPK and ERK in human umbilical vein endothelial cells (HUVECs), thereby upregulating VEGF expression level. The migration and tube-forming ability of endothelial cells can be promoted by the scaffold, which accelerates the formation and maturation of the bone. Moreover, 4HR played a crucial role in the inhibition of osteoclastogenesis by interrupting the IκB/NF-κB signaling pathway and exhibiting SP, thereby enhancing the migration and angiogenesis of HUVECs. Based on such a synergistic effect, osteoporosis can be suppressed, and bone regeneration can be achieved by inhibiting the RANKL pathway in vitro and in vivo, which is a commonly known mechanism of bone physiology. Therefore, the study presents a promising approach for developing a multifunctional regenerative material for sophisticated osteoporotic bone regeneration.

Increased risk of incident gout in patients with hyperthyroidism: a nationwide retrospective cohort study.

Previous studies have reported that thyroid dysfunction is associated with increased serum uric acid levels; however, the relationship between hyperthyroidism and incidence of clinical manifestations of gout has not been fully investigated. Therefore, this study aimed to longitudinally investigate the risk of gout in patients with hyperthyroidism. This nationwide retrospective cohort study used data from the Korean National Health Claims Database. We included 76,494 patients with hyperthyroidism and 76,542 age- and sex-matched controls. A Cox proportional hazard regression model was used to adjust for potential confounders and estimate the risk of incident gout in patients with hyperthyroidism. During a mean follow-up of 9 years, incident gout developed in 3,655 (4.8%) patients with hyperthyroidism and 3251 (4.2%) controls. Hyperthyroidism was significantly associated with increased risk of incident gout [adjusted hazard ratio (HR), 1.12; 95% confidence interval (CI) 1.07-1.18], independent of baseline metabolic profiles. The median time from the diagnosis of hyperthyroidism to the development of gout was 6 years. When stratified by age and sex, the risk of gout was still significant in the < 50-year age group (HR: 1.2, 95% CI 1.12-1.29) and males (HR: 1.21, 95% CI 1.12-1.30), but not in the older age group (> 50 years) and females. Hyperthyroidism is an important risk factor for incident gout, particularly in younger age groups (< 50 years) and males. Our results highlight the importance of continuous screening for gout in patients with hyperthyroidism.

Anithiactin D, a Phenylthiazole Natural Product from Mudflat-Derived Streptomyces sp., Suppresses Motility of Cancer Cells.

Anithiactin D (1), a 2-phenylthiazole class of natural products, was isolated from marine mudflat-derived actinomycetes Streptomyces sp. 10A085. The chemical structure of 1 was elucidated based on the interpretation of NMR and MS data. The absolute configuration of 1 was determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectral data. Anithiactin D (1) significantly decreased cancer cell migration and invasion activities at a concentration of 5 µM via downregulation of the epithelial-to-mesenchymal transition (EMT) markers in A549, AGS, and Caco-2 cell lines. Moreover, 1 inhibited the activity of Rho GTPases, including Rac1 and RhoA in the A549 cell line, suppressed RhoA in AGS and Caco-2 cell lines, and decreased the mRNA expression levels of some matrix metalloproteinases (MMPs) in AGS and Caco-2 cell lines. Thus 1, which is a new entity of the 2-phenylthiazole class of natural products with a unique aniline-indole fused moiety, is a potent inhibitor of the motility of cancer cells.

Software-based interventions for low back pain management: A systematic review and meta-analysis.

INTRODUCTION: Using software for self-management interventions can improve health outcomes for individuals with low back pain, but there is a dearth of research to confirm its effectiveness. Additionally, no known research has evaluated the effective elements of software-based interventions for low back pain self-management components. This study aimed to synthesize the effectiveness of software-based interventions to promote self-management health outcomes among individuals with low back pain. DESIGN: A systematic review and meta-analysis was conducted. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement, relevant studies up to July 2022 were searched via four electronic databases: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Web of Science. RESULTS: 4908 adults with low back pain who participated in 23 studies were included. Software-based interventions were effective in reducing fear avoidance (mean difference [MD] = -0.95, 95% CI: -1.45 to -0.44), pain catastrophizing (MD = -1.31, 95% CI: -1.84 to -0.78), disability (MD = -8.21, 95% CI: -13.02 to -3.39), and pain intensity (MD = -0.86, 95% CI: -1.17 to -0.55). Specifically, interventions that included an exercise component were more effective in reducing pain and disability. Additionally, cognitive behavioral therapy (CBT) intervention significantly reduced fear avoidance and pain catastrophizing but had no noticeable impact on disability and pain compared to standard treatment. The certainty of the evidence in this review varied from very low to high across outcomes. The heterogeneity of the study results was significant, suggesting that future studies in this area could optimize the design, time points, measures, and outcomes to strengthen the evidence. CONCLUSIONS: Low back pain self-management interventions delivered through software-based programs effectively reduce pain intensity, disability, fear avoidance, and pain catastrophizing. CLINICAL RELEVANCE: Low back pain is among the most common reasons for seeking healthcare visits. Combining exercise and counseling through soft-based programs may effectively address this issue and its associated suffering and disability.

SEC22B inhibition attenuates colorectal cancer aggressiveness and autophagic flux under unfavorable environment.

Autophagy has bidirectional functions in cancer by facilitating cell survival and death in a context-dependent manner. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a large family of proteins essential for numerous biological processes, including autophagy; nevertheless, their potential function in cancer malignancy remains unclear. Here, we explored the gene expression patterns of SNAREs in tissues of patients with colorectal cancer (CRC) and discovered that SEC22B expression, a vesicle SNARE, was higher in tumor tissues than in normal tissues, with a more significant increase in metastatic tissues. Interestingly, SEC22B knockdown dramatically decreased CRC cell survival and growth, especially under stressful conditions, such as hypoxia and serum starvation, and decreased the number of stress-induced autophagic vacuoles. Moreover, SEC22B knockdown successfully attenuated liver metastasis in a CRC cell xenograft mouse model, with histological signs of decreased autophagic flux and proliferation within cancer cells. Together, this study posits that SEC22B plays a crucial role in enhancing the aggressiveness of CRC cells, suggesting that SEC22B might be an attractive therapeutic target for CRC.

Mesoscopic Stacking Reconfigurations in Stacked van der Waals Film.

Mesoscopic-scale stacking reconfigurations are investigated when van der Waals (vdW) films are stacked. A method to visualize complicated stacking structures and mechanical distortions simultaneously in stacked atom-thick films using Raman spectroscopy is developed. In the rigid limit, it is found that the distortions originate from the transfer process, which can be understood through thin film mechanics with a large elastic property mismatch. In contrast, with atomic corrugations, the in-plane strain fields are more closely correlated with the stacking configuration, highlighting the impact of atomic reconstructions on the mesoscopic scale. It is discovered that the grain boundaries do not have a significant effect while the cracks are causing inhomogeneous strain in stacked polycrystalline films. This result contributes to understanding the local variation of emerging properties from moiré structures and advancing the reliability of stacked vdW material fabrication.

Progressive resolution optimizer (PRO) predominates over photon optimizer (PO) in sparing of spinal cord for spine SABR VMAT plans.

BACKGROUND: we assessed the performance of the optimization algorithms by comparing volumetric modulated arc therapy generated by a progressive resolution optimized (VMATPRO) and photon optimizer (VMATPO) in terms of plan quality, MU reduction, sparing of the spinal cord (or cauda equina), and plan complexity. METHODS: Fifty-seven patients who received spine stereotactic ablative radiotherapy (SABR) with tumors located in the cervical, thoracic, and lumbar spine were retrospectively selected. For each patient, VMATPRO and VMATPO with two full arcs were generated with using the PRO and PO algorithms. For dosimetric evaluation, the dose-volumetric (DV) parameters of the planning target volume (PTV), organs at risk (OARs), the corresponding planning organs at risk (PRV), and 1.5-cm ring structure surrounding the PTV (Ring1.5 cm) were calculated for all VMAT plans. The total number of monitor units (MUs) and the modulation complexity score for the VMAT (MCSv) were compared. To investigate the correlations of OAR sparing to plan complexity, Pearson's and Spearman's correlation tests were conducted between the two algorithms (PO - PRO, denoted as Δ) in the DV parameters for normal tissues, total MUs, and MCSv. RESULTS: For the PTVs, Target conformity and dose homogeneity in the PTVs of VMATPRO were better than those of VMATPO with statistical significance. For the spinal cords (or cauda equine) and the corresponding PRVs, all of the DV parameters for VMATPRO were markedly lower than those for VMATPO, with statistical significance (all p < 0.0001). Among them, the difference in the maximum dose to the spinal cord between VMATPRO and VMATPO was remarkable (9.04 Gy vs. 11.08 Gy with p < 0.0001). For Ring1.5 cm, no significant difference in V115% for VMATPRO and VMATPO was observed. CONCLUSIONS: The use of VMATPRO resulted in improved coverage and uniformity of dose to the PTV, as well as OARs sparing, compared with that of VMATPO for cervical, thoracic, and lumbar spine SABR. Better dosimetric plan quality generated by the PRO algorithm was observed to result in higher total MUs and plan complexity. Therefore, careful evaluation of its deliverability should be performed with caution during the routine use of the PRO algorithm.

Nationwide-incidence and trends of fibromyalgia in South Korea: a population-based study.

Reports of the incidence of fibromyalgia (FM) in Asia are uncommon. Therefore, this study used nationwide representative data to investigate the age- and sex-specific incidence and annual trends of FM in South Korea. This nationwide population-based study used data from the Korean National Health Claims Database. From 2012 to 2021, patients with FM diagnosed according to the ACR 2010 criteria from the entire Korean population aged 20-70 years were included in the enrolment database. Age- and sex-specific cumulative and annual incidences were analyzed and incident cases from 2014 to 2021 were included, considering the 2-year washout period. Among the total cohort of 42 million in the entire Korean population, 270,160 had FM during the study period. The incidence in the general population aged 20-70 years was 751.25 (95% confidence interval [CI] 751.10-751.40) per 100,000 persons (men: 95% CI 608.45-608.98; women: 95% CI 898.02-898.69). The incidence of FM increased with advancing age, peaking at 50-54 years both in men and women. The annual incidence was 88.07 (95% CI 88.02-88.13) in 2014; it increased from 2014 to 2019 and peaked in 2019 (109.20; 95% CI 101.65-101.76). The incidence of FM in South Korea was about twice the global average, with a gradual increase over the study period. These detailed estimates can help with proper planning within the healthcare system.

A unified computational view of DNA duplex, triplex, quadruplex and their donor-acceptor interactions.

DNA can assume various structures as a result of interactions at atomic and molecular levels (e.g., hydrogen bonds, π-π stacking interactions, and electrostatic potentials), so understanding of the consequences of these interactions could guide development of ways to produce elaborate programmable DNA for applications in bio- and nanotechnology. We conducted advanced ab initio calculations to investigate nucleobase model structures by componentizing their donor-acceptor interactions. By unifying computational conditions, we compared the independent interactions of DNA duplexes, triplexes, and quadruplexes, which led us to evaluate a stability trend among Watson-Crick and Hoogsteen base pairing, stacking, and even ion binding. For a realistic solution-like environment, the influence of water molecules was carefully considered, and the potassium-ion preference of G-quadruplex was first analyzed at an ab initio level by considering both base-base and ion-water interactions. We devised new structure factors including hydrogen bond length, glycosidic vector angle, and twist angle, which were highly effective for comparison between computationally-predicted and experimentally-determined structures; we clarified the function of phosphate backbone during nucleobase ordering. The simulated tendency of net interaction energies agreed well with that of real world, and this agreement validates the potential of ab initio study to guide programming of complicated DNA constructs.

Marinobazzanan, a Bazzanane-Type Sesquiterpenoid, Suppresses the Cell Motility and Tumorigenesis in Cancer Cells.

Marinobazzanan (1), a new bazzanane-type sesquiterpenoid, was isolated from a marine-derived fungus belonging to the genus Acremonium. The chemical structure of 1 was elucidated using NMR and mass spectroscopic data, while the relative configurations were established through the analysis of NOESY data. The absolute configurations of 1 were determined by the modified Mosher's method as well as vibrational circular dichroism (VCD) spectra calculation and it was determined as 6R, 7R, 9R, and 10R. It was found that compound 1 was not cytotoxic to human cancer cells, including A549 (lung cancer), AGS (gastric cancer), and Caco-2 (colorectal cancer) below the concentration of 25 µM. However, compound 1 was shown to significantly decrease cancer-cell migration and invasion and soft-agar colony-formation ability at concentrations ranging from 1 to 5 µM by downregulating the expression level of KITENIN and upregulating the expression level of KAI1. Compound 1 suppressed ß-catenin-mediated TOPFLASH activity and its downstream targets in AGS, A549, and Caco-2 and slightly suppressed the Notch signal pathway in three cancer cells. Furthermore, 1 also reduced the number of metastatic nodules in an intraperitoneal xenograft mouse model.

Erratum: Correction of Funding in the Article "Rates of COVID-19 Infection Among Healthcare Workers in Designated COVID-19 Wards and General Wards".

This corrects the article on p. e308 in vol. 37, PMID: 36345254.

Structured Electrode Additive Manufacturing for Lithium-Ion Batteries.

As the world increasingly swaps fossil fuels, significant advances in lithium-ion batteries have occurred over the past decade. Though demand for increased energy density with mechanical stability continues to be strong, attempts to use traditional ink-casting to increase electrode thickness or geometric complexity have had limited success. Here, we combined a nanomaterial orientation with 3D printing and developed a dry electrode processing route, structured electrode additive manufacturing (SEAM), to rapidly fabricate thick electrodes with an out-of-plane aligned architecture with low tortuosity and mechanical robustness. SEAM uses a shear flow of molten feedstock to control the orientation of the anisotropic materials across nano to macro scales, favoring Li-ion transport and insertion. These structured electrodes with 1 mm thickness have more than twice the specific capacity at 1 C compared to slurry-cast electrodes and have higher mechanical properties (compressive strength of 0.84 MPa and modulus of 5 MPa) than other reported 3D-printed electrodes.

Military Doctors' and Nurses' Perceptions of Telemedicine and the Factors Affecting Use Intention.

Purpose: This study investigated military doctors' and nurses' perceptions of telemedicine and the factors influencing their intention to use it based on the unified theory of acceptance and use of technology. Method: This study adopted a questionnaire-based, cross-sectional descriptive approach. It used a web questionnaire for data collection over a 5-week period, starting in June 2021. Results: A total of 72.6% of participants indicated that telemedicine is required in the military. The intention to use telemedicine was significantly higher among women, younger individuals (<30 years), and military nurses. In addition, factors such as voluntariness of use, performance expectancy, social influence, and facilitating conditions positively affected the intention to use telemedicine. Conclusions: To improve military doctors' and nurses' use and understanding of telemedicine, consensus must be reached regarding its use in military contexts. Discussions that incorporate opposing views should be encouraged as well. Moreover, the voluntariness of use significantly affected respondents' intention to use telemedicine. There is an urgent need, therefore, for in-depth analyses of the various factors associated with voluntariness of use of telemedicine; the resulting insights could be used to encourage military doctors and nurses to adopt telemedicine. Finally, along with promoting the use of smartphones for medical consultation among military personnel, military nurses' role should be extended to include health consultation using smartphones. This could promote the active use of telemedicine in military nursing, which could contribute to health promotion among military personnel.

Computational design of a thermolabile uracil-DNA glycosylase of Escherichia coli.

Polymerase chain reaction (PCR) is a powerful tool to diagnose infectious diseases. Uracil DNA glycosylase (UDG) is broadly used to remove carryover contamination in PCR. However, UDG can contribute to false negative results when not inactivated completely, leading to DNA degradation during the amplification step. In this study, we designed novel thermolabile UDG derivatives by supercomputing molecular dynamic simulations and residual network analysis. Based on enzyme activity analysis, thermolability, thermal stability, and biochemical experiments of Escherichia coli-derived UDG and 22 derivatives, we uncovered that the UDG D43A mutant eliminated the false negative problem, demonstrated high efficiency, and offered great benefit for use in PCR diagnosis. We further obtained structural and thermodynamic insights into the role of the D43A mutation, including perturbed protein structure near D43; weakened pairwise interactions of D43 with K42, N46, and R80; and decreased melting temperature and native fraction of the UDG D43A mutant compared with wild-type UDG.

Cyclohumulanoid Sesquiterpenes Induced by the Noncompetitive Coculture of Phellinus orientoasiaticus and Xylodon flaviporus.

Microbial cocultivation has been applied as a strategy to induce the biosynthesis of specialized metabolites. However, most previous studies have focused on competitive interactions between test strains. During our LC-MS-based chemical screening of randomized cocultures of Basidiomycetous fungi, we discovered that the coculture of Phellinus orientoasiaticus (Hymenochaetaceae) and Xylodon flaviporus (Schizoporaceae) induces multiple metabolites, although they did not show any competitive morphology. Targeted isolation yielded three new sesquiterpenes (1-3) along with five known analogues (4-8). The structures of the isolates were determined by MS and NMR experiments as well as electronic circular dichroism analysis. LC-MS analysis suggested that cyclohumulanoids of illudane-, sterpurane-, and tremulane-type scaffolds (1-7) were produced by P. orientoasiaticus, whereas a drimane-type sesquiterpene (8) was produced by X. flaviporus. None of the isolates exhibited antifungal activity or cytotoxicity, and compounds 1-7 exhibited NO production of LPS-treated RAW276.4 cells in a range of 15.9% to 38.0% at 100 µM.

Delay in psychiatric hospitalization from the diagnosis of first-episode schizophrenia and its association with clinical outcomes and direct medical costs: a nationwide, health insurance data-based study.

BACKGROUND: Early intervention is essential for improving the prognosis in patients with first-episode schizophrenia (FES). The Mental Health Act limits involuntary hospitalization in South Korea to cases where an individual exhibits both a mental disorder and a potential for harming themselves or others, which could result in a delay in the required treatment in FES. We investigated the effect of delay in the first psychiatric hospitalization on clinical outcomes in FES. METHODS: The South Korean Health Insurance Review Agency database (2012-2019) was used. We identified 15,994 patients with FES who had a record of at least one psychiatric hospitalization within 1 year from their diagnosis. A multivariate linear regression model and a generalized linear model with a gamma distribution and log link were used to examine associations between the duration from the diagnosis to the first psychiatric admission and clinical outcomes as well as direct medical costs after 2 and 5 years. RESULTS: Within both the 2-year and the 5-year period, longer durations from the diagnosis to the first psychiatric admission were associated with an increase in the number of psychiatric hospitalizations (2-y: B = 0.003, p = 0.003, 5-y: B = 0.007, p = 0.001) and an increase in direct medical costs (total: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.005; inpatient care: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.017). CONCLUSIONS: Earlier psychiatric admission from the diagnosis is associated with a decrease in the number of psychiatric admissions as well as in direct medical costs in patients with FES.

Development of an integrated fatigue measurement system for construction workers: a feasibility study.

BACKGROUND: Construction workers working in physically and mentally challenging environments experience high levels of occupational fatigue, which is the primary cause of industrial accidents and illnesses. Therefore, it is very important to measure fatigue in real time to manage the safety and health of construction workers. This study presents a novel approach for simultaneously measuring the subjective and objective fatigue of construction workers using ecological momentary assessment (EMA) and smartwatches. Due to the complexity and diversity of construction site environments, it is necessary to examine whether data collection using smartwatches is suitable in actual construction sites. This study aims to examine the feasibility of the integrated fatigue measurement method. METHODS: This study comprised two phases: (1) development of an integrated fatigue measurement system for construction workers, and (2) a validation study to evaluate the method's feasibility based on sensor data acquisition, EMA compliance, and feedback from construction workers in the field (N = 80). Three days of biometric data were collected through sensors embedded in the smartwatches for objective fatigue measurement, including heart rate, accelerometer, and gyroscope data. Two types of self-reported data regarding each worker's fatigue were collected through a researcher-developed EMA application. The acceptability and usability of this system were examined based on the researchers' observations and unstructured interviews. RESULTS: Based on the standardized self-report questionnaire scores, participants were classified into high (n = 35, 43.75%) and low (n = 45, 56.25%) fatigue groups for comparison. The quantitative outcomes did not show a statistically significant difference between the two fatigue groups. Both groups experienced positive emotions and were able to recognize their health condition at the time of self-reporting, but stated that responding to this measurement system could be burdensome. CONCLUSIONS: This feasibility study provides a unique understanding of the applications of EMA and smartwatches for safety management in the construction workforce. The developed measurement system shows potential for monitoring fatigue based on the real-time collection of relevant data. It is expected that by expanding this integrated system through further research and onsite application, the health and safety of construction workers can be improved.

Two Case Reports of Life-Threatening Croup Caused by the SARS-CoV-2 Omicron BA.2 Variant in Pediatric Patients.

Croup is a common upper airway infection characterized by a barking cough, stridor, and hoarseness. It is usually caused by viral infection. A small number of croup caused by coronavirus disease 2019 (COVID-19) has been reported in children before the omicron variant surge. Previously reported cases indicated that croup caused by COVID-19 can be treated in the same manner as those with other viral causes. We describe two cases (9-month-old girl and 11-month-old boy) of previously healthy infants who presented with a barking cough and chest retraction and required endotracheal intubation and cardiopulmonary resuscitation. Despite receiving dexamethasone and nebulized racemic epinephrine (NRE) treatment for croup in the emergency department, these patients still developed acute respiratory failure. Reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal samples revealed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron BA.2 variant (Stealth omicron) and no other common respiratory viral pathogens. Both patients were treated with mechanical ventilation, dexamethasone, and NRE in the pediatric intensive care unit. The duration of intubation was 112 hours and 80 hours, respectively. Both patients were discharged without complications. To the best of our knowledge, this is the first report of life-threatening croup produced by the omicron BA.2 variant and confirmed by RT-PCR. We suggest that this SARS-CoV-2 variant may cause severe croup that may not improve with conventional treatment, even in children without underlying diseases.