Strategy to develop broadly effective multivalent COVID-19 vaccines against emerging variants based on Ad5/35 platform.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron strain has evolved into highly divergent variants with several sub-lineages. These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants. We developed bivalent vaccine AdCLD-CoV19-1 BA.5/BA.2.75 and trivalent vaccines AdCLD-CoV19-1 XBB/BN.1/BQ.1.1 and AdCLD-CoV19-1 XBB.1.5/BN.1/BQ.1.1 using an Ad5/35 platform-based non-replicating recombinant adenoviral vector. We compared immune responses elicited by the monovalent and multivalent vaccines in mice and macaques. We found that the BA.5/BA.2.75 bivalent and the XBB/BN.1/BQ.1.1 and XBB.1.5/BN.1/BQ.1.1 trivalent vaccines exhibited improved cross-neutralization ability compared to their respective monovalent vaccines. These data suggest that the developed multivalent vaccines enhance immunity against circulating Omicron subvariants and effectively elicit neutralizing antibodies across a broad spectrum of SARS-CoV-2 variants.

Boosting with variant-matched adenovirus-based vaccines promotes neutralizing antibody responses against SARS-CoV-2 Omicron sublineages in mice.

Global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron subvariants, such as BA.4, BA.5 and XBB.1.5, has been leading the recent wave of coronavirus disease 2019 (COVID-19). Unique mutations in the spike proteins of these emerging Omicron subvariants caused immune evasion from the pre-existing protective immunity induced by vaccination or natural infection. Previously, we developed AdCLD-CoV19-1, a non-replicating recombinant adenoviral vector that encodes the receptor binding domain of the spike protein of the ancestral SARS-CoV-2 strain. Based on the same recombinant adenoviral vector platform, updated vaccines that cover unique mutations found in each Omicron subvariant, including BA.1, BA.2, BA.4.1 and BA.5, were constructed. Preclinical studies revealed that each updated vaccine as a booster shot following primary vaccination targeting the ancestral strain improved neutralizing antibody responses against the pseudovirus of its respective strain most effectively. Of note, boosting with a vaccine targeting the BA.1 or BA.2 Omicron subvariant was most effective in neutralization against the pseudovirus of the BA.2.75 strain, whereas BA.4.1/5-adapted booster shots were most effective in neutralization against the BQ.1, BQ1.1 and BF.7 strains. Therefore, it is imperative to develop a vaccination strategy that can cover the unique spike mutations of currently circulating Omicron subvariants in order to prevent the next wave of COVID-19.

Unraveling the molecular mechanisms of cell migration impairment and apoptosis associated with steroid sulfatase deficiency: Implications for X-linked ichthyosis.

Steroid sulfatase (STS) deficiency is responsible for X-linked ichthyosis (XLI), a genetic disorder characterized by rough and dry skin caused by excessive keratinization. The impaired keratinization process leads to reduced cell mobility and increased apoptosis, which can cause an excessive buildup of the stratum corneum. In this study, we investigated the mechanisms underlying XLI and found that STS deficiency reduces cell mobility and increases apoptosis in human keratinocyte HaCaT cells. To explore these mechanisms further, RNA-sequencing was conducted on skin tissues from STS transgenic and knockout mice. Our RNA-seq results revealed that STS deficiency plays a critical role in regulating multiple signaling pathways associated with cell mobility and apoptosis, such as Wnt/ß signaling and the Hippo signaling pathway. Knockdown of the STS gene using shRNA in HaCaT cells led to an upregulation of E-cadherin expression and suppression of key factors involved in epithelial-mesenchymal transition (EMT), such as N-cadherin and vimentin. Inhibition of EMT involved the Hippo signaling pathway and reduction of HIF-1α. Interestingly, inhibiting STS with shRNA increased mitochondrial respiration levels, as demonstrated by the extracellular flux oxygen consumption rate. Additionally, we observed a significant increase in ROS production in partial STS knockout cells compared to control cells. Our study demonstrated that the excessive generation of ROS caused by STS deficiency induces the expression of Bax and Bak, leading to the release of cytochrome c and subsequent cell death. Consequently, STS deficiency impairs cell mobility and promotes apoptosis, offering insights into the pathophysiological processes and potential therapeutic targets for XLI.

Effectiveness of the triglyceride-glucose index and triglyceride-glucose-related indices in predicting cardiovascular disease in middle-aged and older adults: A prospective cohort study.

BACKGROUNDS: Cardiovascular disease (CVD) risk assessment is a crucial component of public health. We aimed to determine the predictive value of the TyG index and TyG-related indices for new-onset CVD. METHODS: This prospective study included 7,808 participants aged 40-69 years from the Ansung-Ansan cohort database. Our analysis was stratified by diabetes status. The hazard ratio (HR) with a 95% confidence interval (CI) for incident CVD was computed using multiple Cox proportional-hazards regression models. To evaluate the predictive performance of these indices for new-onset CVD, we calculated the Harrell's C-index (95% CI). RESULTS: In this study, a total of 6,890 participants did not have diabetes at baseline, while 918 participants had diabetes. In participants without diabetes, compared to the lowest tertile, fully adjusted HR and 95% CI for new-onset CVD in the highest tertile were as follows: TyG (HR 1.42, 95% CI 1.06-1.90), TyG-body mass index (BMI) (HR 1.92, 95% CI 1.19-3.10), TyG-waist circumference (WC) (HR 2.37, 95% CI 1.61-3.49), and TyG-waist-to-height ratio (WHtR) (HR 2.20, 95% CI 1.47-3.28). However, no significant associations were observed between TyG, modified TyG indices, and new-onset CVD in participants with diabetes. Notably, the C-indice of TyG-WC and TyG-WHtR were significantly higher than those of TyG and TyG-BMI in participants without diabetes. CONCLUSIONS: TyG-BMI, TyG-WC, and TyG-WHtR were associated with an increased risk of new-onset CVD in participants without diabetes. Furthermore, TyG-WC and TyG-WHtR showed better predictive performances for new-onset CVD than TyG and TyG-BMI in participants without diabetes.

Feasibility of new patient dose management tool in digital radiography: Using clinical exposure index data of mobile chest radiography in a large university hospital.

The clinical anteroposterior (AP) chest images taken with a mobile radiography system were analyzed in this study to utilize the clinical exposure index (EI) as a patient dose-monitoring tool. The digital imaging and communications in medicine header of 6048 data points exposed under the 90 kVp and 2.5 mAs were extracted using Python for identifying the distribution of clinical EI. Even under the same exposure conditions, the clinical EI distribution was 137.82-4924.38. To determine the cause, the effect of a patient's body shape on EI was confirmed using actual clinical chest AP image data binarized into 0 and 255-pixel values using Python. As a result, the relationship between the direct X-ray area of the chest AP image, the higher the clinical EI, the larger the rate of the direct X-ray area. A conversion equation was also derived to infer entrance surface dose through clinical EI based on the patient thickness. This confirmed the possibility of directly monitoring patient dose through EI without a dosimeter in real-time. Therefore, to use the clinical EI of the mobile radiography system as a patient dose-monitoring tool, the derivation method of clinical EI considers several factors, such as the relationship between patient factors.

YPEL3 expression induces cellular senescence via the Hippo signaling pathway in human breast cancer cells.

The Hippo pathway is a signaling pathway that controls organ size in animals by regulating cell proliferation and apoptosis. Yes-associated protein 1 (YAP1), an oncogene associated with the development and progression of breast cancer, is downregulated by the Hippo pathway and is associated with the development and progression of breast cancer. Yippee-like 3 (YPEL3) is a target gene of the tumor suppressor protein p53, and its activation has been shown to inhibit cell growth, induce cellular senescence, and suppress tumor cell metastasis. In this study, we found that YAP1 inhibits the expression of YPEL3 expression in breast cancer cells. Furthermore, a decrease in lamin B1, a marker protein of cellular senescence, coupled with the activation of senescence-associated ß-galactosidase indicated that upregulating YPEL3 levels through YAP1 downregulation can induce cellular senescence. Additionally, elevated YPEL3 levels resulted in higher levels of oxygen consumption rate in mitochondria, thus promoting apoptosis. This suggests that YPEL3 plays a crucial role in regulating oxidative stress and cell apoptosis in breast cancer cells. Therefore, the interaction between YAP1 and YPEL3 represents a novel mechanism of cellular senescence mediated by the Hippo signaling pathway. Collectively, our findings suggest that the Hippo signaling pathway plays an important role in regulating cellular senescence, which could have implications for the development of new therapeutic strategies for diseases such as cancer.

Oxidative balance score inversely associated with the prevalence and incidence of metabolic syndrome: analysis of two studies of the Korean population.

Background: Pro-oxidant/antioxidant imbalances leading to chronic inflammation and insulin resistance can contribute to the development of metabolic syndrome (MetS). Oxidative Balance Score (OBS), a comprehensive measure of exposure to pro- and anti-oxidants, represents an individual's total oxidative balance. This study aimed to evaluate the association between OBS and MetS using two large datasets. Methods: We analyzed data from 2,735 adults older than 19 years from the 2021 Korean National Health and Nutritional Examination Survey (KNHANES) and 5,807 adults aged 40-69 years from the Korean Genome and Epidemiology Study (KoGES). In each dataset, OBS was categorized into sex-specific tertiles (T). Results: In KNHANES, the odds ratios and 95% confidence intervals for prevalent MetS in T3, compared to T1, were 0.44 (0.29-0.65) in men and 0.34 (0.23-0.50) in women after adjusting for confounders. In KoGES, the hazard ratios and 95% confidence intervals for incident MetS in T3, compared to T1, were 0.56 (0.48-0.65) in men and 0.63 (0.55-0.73) in women after adjusting for confounders. Conclusion: OBS appears to be inversely related to MetS, which suggests that adopting lifestyle behaviors that decrease oxidative stress could be an important preventive strategy for MetS.

Transcriptomic patterns in early-secretory and mid-secretory endometrium in a natural menstrual cycle immediately before in vitro fertilization and embryo transfer.

OBJECTIVE: This study aimed to evaluate the endometrial transcriptomic patterns in the early secretory phase (ESP) and mid-secretory phase (MSP) of the natural menstrual cycle before in vitro fertilization and embryo transfer (IVF-ET). METHODS: Thirty patients whose endometrial tissues were obtained from the ESP or MSP of a natural menstrual cycle immediately before IVF-ET were included. Endometrial dating was histologically confirmed as ESP (cycle days 16-18) or MSP (cycle days 19-21), according to the noyes criteria. The patients were divided into two groups depending on the IVF-ET outcome: pregnant (n=14; 7 in ESP and 7 in MSP) or non-pregnant (n=16; 8 in ESP and 8 in MSP). Differentially expressed genes (DEGs) in the MSP, compared to the ESP, were identified using NanoString nCounter (NanoString Technologies, Seattle, WA, USA) data for both the pregnant and non-pregnant groups. RESULTS: Thirteen DEGs in the pregnant group and 11 DEGs in the non-pregnant group were identified in the MSP compared to those in the ESP. In both groups, adrenoceptor alpha 2A, interleukin 1 receptor-associated kinase 2, a disintegrin and metalloproteinase with thrombospondin repeats 15 (ADAMTS15), serpin family E member 1, integrin subunit beta 3, transmembrane protein 252 (TMEM252), huntingtin associated protein 1, C2 calcium-dependent domain containing 4A, and integrin subunit alpha 2 were upregulated in the MSP, compared to the ESP. TMEM37, galactosidase beta 1 like 2, Rho family GTPase 3, and cytochrome P450 family 24 subfamily A member 1 were upregulated in the MSP only in the pregnant group. ADAMTS8 was downregulated and monoamine oxidase A was upregulated in the MSP only in the non-pregnant group. CONCLUSION: Transcriptomic patterns in the endometrium immediately before IVF-ET appear to differ according to the IVF-ET outcome. These novel DEGs, which have not been previously studied, may have functional significance during the window of implantation and serve as potential biomarkers of endometrial receptivity.

Formononetin Inhibits Progression of Endometriosis via Regulation of p27, pSTAT3, and Progesterone Receptor: In Vitro and In Vivo Studies.

OBJECTIVES: Formononetin is one of the phytoestrogens that functions like a selective estrogen receptor modulator (SERM). In this study, we evaluated the effects of formononetin on endometriosis progression in vitro and in vivo. MATERIALS AND METHODS: After pathological confirmation, 10 eutopic and ectopic endometria were collected from patients with endometriosis. Ten eutopic endometria samples were collected from patients who did not have endometriosis. To determine the cytotoxic dose and therapeutic dose of formononetin, the concentration of 70% of the cells that survived after formononetin administration was estimated using a Cell counting kit-8 (CCK 8) assay. Western blot analysis was used to determine the relative expression levels of BAX, p53, pAKT, ERK, pERK, p27, and pSTAT3 in the eutopic endometria without endometriosis, eutopic endometria with endometriosis, and ectopic endometria with endometriosis as the formononetin concentration was increased. We confirmed the effect of formononetin on apoptosis and migration in endometriosis using fluorescence-activated cell sorting (FACS) and wound healing assays, respectively. A mouse model of endometriosis was prepared using a non-surgical method, as previously described. The mice were intraperitoneally administered formononetin for four weeks after dividing them into control, low-dose formononetin (40 mg/kg/day) treatment, and high-dose (80 mg/kg/day) formononetin treatment groups. All the mice were euthanized after formononetin treatment. Endometriotic lesions were retrieved and confirmed using hematoxylin and eosin (H&E) staining. Immunohistochemical (IHC) staining of p27 was performed. RESULTS: We set the maximum concentration of formononetin administration to 80 µM through the CCK8 assay. Based on formononetin concentration, the expression levels of BAX, p53, pAKT, ERK, pERK, p27, and pSTAT3 proteins were measured using Western blot analysis (N = 4 per group). The expression level of pERK, p27, and pSTAT3 in eutopic endometrium with endometriosis tended to decrease with increasing formononetin concentration, and a significant decrease was noted at 80 µM. The expression of p27 in ectopic endometrium with endometriosis was also significantly decreased at 80 µM of formononetin. FACS analysis revealed that formononetin did not significantly affect apoptosis. In the wound healing assay, formononetin treatment revealed a more significant decrease in the proliferation of the eutopic endometrium in patients with endometriosis than in the eutopic endometrium without endometriosis. Relative expression of sex hormone receptors decreased with increasing formononetin doses. Although no significant differences were observed in the ER, PR-A, ERß/ERα, and PR-B/PR-A, significant down-regulation of PR-B expression was noted after formononetin treatment at 80 µM. In the in vivo study, endometriotic lesions in the formononetin-treated group significantly decreased compared to those in the control group. The relative expression of p27 using IHC was highest in the control group and lowest in the high-dose formononetin treatment group. CONCLUSIONS: Formononetin treatment was shown to inhibit the proliferation of eutopic and ectopic endometria in patients with endometriosis through the regulation of p27, pSTAT3, and PR-B. In an endometriosis mouse model, formononetin treatment significantly reduced the number of endometriotic lesions with decreased p27 expression. The results of this study suggest that formononetin may be used as a non-hormonal treatment option for endometriosis.

Characterization of seasonal behaviors of naturally occurring radioactive materials in a groundwater borehole using an in situ monitoring system.

Understanding the temporal behaviors of naturally occurring radioactive materials is important for safeguarding groundwater as a secure water resource for drinking, agriculture, and industry usage. This study reports the vertical profiles of 238U concentration and 222Rn activity and the management of in situ monitoring systems during intensive field sampling of a national groundwater-monitoring borehole for seven years (2015-2021). The aim was to capture the seasonal characteristics of the 238U concentrations and 222Rn activity. Both factors were low in the rainy season and high in the winter season, reflecting the dilution effect of rainfall recharge. The 238U and 222Rn behaviors were associated with water-rock interactions of calcite dissolution in fracture zones filled with carbonate minerals. Furthermore, multilayer perceptron models estimated the 238U concentration and 222Rn activity with reasonable regression and classification accuracy. Hydrometeorological indicators (temperature and groundwater-level fluctuations) were more important estimators of 238U concentration and 222Rn activity than geochemical process indicators. The regression accuracy performance was higher at deeper sampling depths, where seasonality in the 238U and 222Rn behaviors dominated. From the predicted distributions of 238U concentrations and 222Rn activities, we could estimate the ranges of 238U concentrations and 222Rn activities emerging from groundwater boreholes. High exposure threats from 238U and 222Rn during groundwater usage were found in the winter season. When the multilayer perceptron models use the entire in situ monitoring data at refined temporal resolution, we can quickly determine the naturally occurring radioactive materials and further develop the national groundwater-monitoring borehole equipped with the in-situ monitoring system, supplementing the occasionally obtained field-measurement data.

Inverse Association between Oxidative Balance Score and Incident Type 2 Diabetes Mellitus.

Mitigating the risk of type 2 diabetes mellitus (T2DM) can be achieved through the maintenance of a healthy weight, the adoption of a healthy diet, and engaging in regular physical activity. The oxidative balance score (OBS), an integrated measure of pro- and antioxidant exposure conditions, represents an individual's overall oxidative balance status. This study aimed to evaluate the association between OBS and T2DM incidence using data from a large, community-based, prospective cohort study. Data from 7369 participants aged 40-69 years who engaged in the Korean Genome and Epidemiology Study (KoGES) were analyzed. The hazard ratio (HR) and 95% confidence interval (CI) for T2DM incidence of sex-specific OBS tertile groups were calculated using univariable and multivariable Cox proportional hazard regression analyses. During the mean 13.6-year follow-up period, 908 men and 880 women developed T2DM. The fully-adjusted HR (95% CI) for incident T2DM of the middle and highest tertile groups, compared with the referent lowest tertile group, were 0.86 (0.77-1.02) and 0.83 (0.70-0.99) in men and were 0.94 (0.80-1.11) and 0.78 (0.65-0.94) in women, respectively. Individuals with a high OBS are at lower risk for the development of T2DM. This implies that lifestyle modification with more antioxidant properties could be a preventive strategy for T2DM.

Adaptive Beam Divergence Control to Mitigate Scintillation Effect Caused by Pointing Error in Vertical FSO Transmissions.

Free-space optical (FSO) communication has been studied for next-generation network systems. Because an FSO system establishes point-to-point communication links, maintaining alignment among the transceivers is a critical challenge. In addition, atmospheric turbulence causes significant signal loss in FSO vertical links. Even in clear weather conditions, transmitted optical signals suffer significant scintillation losses due to random variations. Thus, the effect of atmospheric turbulence should be considered in vertical links. In this paper, we analyze the relationship between pointing error and scintillation from the aspect of beam divergence angle. Furthermore, we propose an adaptive beam that optimizes its divergence angle according to the pointing error between the communicating optical transceivers to mitigate the effect of scintillation due to pointing error. We performed a beam divergence angle optimization and compared it with adaptive beamwidth. The proposed technique was demonstrated using simulations, which revealed an enhanced signal-to-noise ratio and the mitigation of the scintillation effect. The proposed technique would be useful in minimizing the scintillation effect in vertical FSO links.

Corrigendum: Understanding students' problem-solving patterns: evidence from an allotted response time in a PISA 2012 item.

[This corrects the article DOI: 10.3389/fpsyg.2022.1050435.].

Nationwide epidemiologic study for fibrosing interstitial lung disease (F-ILD) in South Korea: a population-based study.

BACKGROUND: Fibrosing interstitial lung disease (F-ILD) is a major public health concern due to its poor prognosis. Recent clinical evidence shows that antifibrotic approaches such as pirfenidone and nintedanib provide better clinical outcome prediction in idiopathic pulmonary fibrosis (IPF) as well as selected progressive fibrosing ILD (PF-ILD) patients. Having epidemiologic insight into these diseases will be essential for the efficient utilization of these therapeutic resources. This study aimed to estimate the current prevalence, incidence, and mortality of F-ILD classified as idiopathic pulmonary fibrosis (IPF), PF-ILD other than IPF, and non-progressive F-ILD and their temporal trend in Korea. METHODS: Population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment (HIRA) database (2011-2018). Patients with IPF were identified using ICD-10 code, RID code, and differential diagnosis approach. By leveraging medical records available from claim data and referencing those used in clinical trials, rigorous diagnostic criteria for PF-ILD detection were implemented. RESULTS: For the past eight years, the prevalence of IPF and PF-ILD has progressively increased, while non-progressive F-ILD has remained stable. IPF, PF-ILD, and non-progressive F-ILD prevalence per 100,000 in 2018 were 16.9, 10.4, and 11.7, respectively. The incidence of IPF in 2018 was more than twice that of 2012. The incidence of PF-ILD in 2018 was 1.5 times higher than that in 2012. In 2018, the mortalites were 10.3% and 12.2% for IPF and PF-ILD, respectively. The mortality rate of PF-ILD was greater than that of IPF in all years. Unclassifiable PF-ILD and rheumatoid arthritis-PF-ILD had the highest proportion and mortality among the PF-ILD subtypes. CONCLUSION: The prevalence and incidence of IPF and PF-ILD have been steadily increasing in recent years. The mortality rate of PF-ILD remained consistently high and exceeded those of IPF in all years.

Secondary cytoreductive surgery with and without hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer.

Background: Secondary cytoreductive surgery (CRS) can afford promising results in patients with recurrent ovarian cancer; however, the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) remains unclear. We compared the outcomes of secondary CRS combined with and without HIPEC in patients with recurrent ovarian cancer. Methods: We retrospectively evaluated patients with recurrent ovarian cancer who underwent secondary CRS, with or without HIPEC (n=46), at the Yonsei Cancer Center between January 2006 and February 2021. Of the 46 included patients, 20 underwent secondary CRS-plus-HIPEC, while 26 underwent secondary CRS without HIPEC (henceforth referred to as secondary CRS-only). Results: Of the 46 patients, 84.8% and 89.1% had undergone optimal surgery and platinum-based chemotherapy, respectively, as the initial treatment before the first relapse. Overall, 32.6% of patients received maintenance therapy, such as bevacizumab or polyadenosine diphosphate ribose polymerase inhibitors. The median follow-up period was 15.9 months. The median progression-free survival (PFS) was 32.7 and 25.1 months in the secondary CRS-plus-HIPEC and secondary CRS-only groups, respectively; however, both groups failed to reach the median overall survival (OS). Based on the Kaplan-Meier analysis, there was no difference in PFS (P=0.587) or OS (P=0.239) between the two groups. We identified patients with epithelial ovarian cancer and found that the median PFS was 25.1 months in the secondary CRS-only group; this was not achieved in the secondary CRS-plus-HIPEC group (P=0.244). Conclusions: In patients with recurrent ovarian cancer, secondary CRS with HIPEC did not improve survival when compared with CRS without HIPEC. However, on subgrouping patients with epithelial ovarian cancer, the addition of HIPEC to secondary CRS tended to improve PFS.

Pure copper nanoparticles prepared by coating-assisted vapor phase synthesis without agglomeration.

Modern electronic devices, such as smartphones and electric vehicles, require multilayer ceramic capacitors (MLCCs), which comprise highly pure Cu terminations and Ni electrodes. Vapor-phase synthesis (VPS) is a promising method for synthesizing nanoparticles (NPs) with high purity and crystallinity. However, the agglomeration of the NPs occurs during their synthesis, which degrades the performance of the MLCC electrodes owing to several factors, including electrical shorts and low packing density. This paper proposes a coating-assisted VPS to inhibit agglomeration using potassium chloride (KCl) as the coating agent. The agglomeration ratio of the Cu NPs synthesized by in-flight coating with KCl at 950 °C significantly decreased from 48.20% to 3.80%, compared to without KCl coating. Furthermore, X-ray fluorescence and X-ray diffraction analyses confirmed that the KCl coating agent and residual copper chloride were removed by washing with ammonium hydroxide.

Updated National Diagnostic Reference Levels and Achievable Doses for CT Protocols: A National Survey of Korean Hospitals.

Background: In 2021, the Korean government proposed a new CT diagnostic reference level. This study performed a nationwide survey and developed new DRLs and AD for 13 common CT examinations. We compared other countries' DRLs for CT examinations. Methods: This study investigated the CTDIvol and DLP of the 12 types of CT protocols for adults and brain CT protocol for pediatrics. A total of 7829 CT examinations were performed using 225 scanners. We defined the DRLs values in the distribution of radiation exposure levels to determine the nationwide patient dose and distribution status of the dose. Results: This study showed that the new Korean national CT DRLs are slightly higher or similar to those of previous surveys and are similar or lower than those of other countries. In some protocols, although the DLP value increased, the CTDIvol decreased; therefore, it can be concluded that the patient's dose in CT examinations was well managed. Conclusions: The new CT DRLs were slightly higher than or similar to that of the previous survey and were evaluated to be similar or lower than CT DRLs of other countries. These DRLs will be used for radiation optimization and effective dose calculation for an individual.

New markers in metabolic syndrome.

Metabolic syndrome (MetS) is increasing globally and is clinically significant due to its association with cardiovascular disease, type 2 diabetes and cancer. Although the pathogenesis of MetS has not been clearly elucidated, insulin resistance and chronic low-grade inflammation derived from central obesity are the most widely accepted as underlying pathophysiology. Accordingly, insulin resistance indices, adipokines and various inflammatory markers have been suggested as reliable biomarkers for MetS. Others, such as uric acid, alkaline phosphatase, γ-glutamyl transferase, are also known to positively correlate with MetS and could be diagnostically useful. In this review, we provide a comprehensive overview of MetS biomarkers and the development of a systematic approach to laboratory analysis.

Implementation of a massive transfusion protocol: A single trauma center experience from South Korea.

BACKGROUND: Massive transfusion (MT) is traditionally defined as transfusion of more than 10 units of red blood cells (RBCs) within the first 24 h after admission. The aim of this study is to analyze the trend of MT in regional trauma center including ratio of fresh frozen plasma (FFP) and packed RBC. METHODS: Retrospective data were driven from 2014 to 2016. A total of 185 patients who received more than 10 packed RBC units within the first 24 h after admission were included in the study. We analyzed transfusion requirements for each time interval 4 h and 24 h after admission. Moreover, we compared transfusion characteristics between survival and non-survival group, between high FFP: RBC group (≥1: 2) and low FFP: RBC group (<1: 2), and between the first half and latter half period. RESULTS: There was a trend for improvement in the FFP: RBC ratio after applying the MT protocol. The FFP: RBC ratio increased from 1: 1.7 to 1: 1.4 within 24 h after arrival. The time to first transfusion was shortened (137-106 min). Mortality was lower in high FFP: RBC group than that of low FFP: RBC group. CONCLUSION: In our study, the MT protocol improved the FFP: RBC ratio. A higher FFP: RBC ratio also led to an improvement in the mortality rate in MT patients.

Efficient production of retinol in Yarrowia lipolytica by increasing stability using antioxidant and detergent extraction.

The demand for bio-based retinol (vitamin A) is currently increasing, however its instability represents a major bottleneck in microbial production. Here, we developed an efficient method to selectively produce retinol in Yarrowia lipolytica. The ß-carotene 15,15'-dioxygenase (BCO) cleaves ß-carotene into retinal, which is reduced to retinol by retinol dehydrogenase (RDH). Therefore, to produce retinol, we first generated ß-carotene-producing strain based on a high-lipid-producer via overexpressing genes including heterologous ß-carotene biosynthetic genes, GGS1F43I mutant of endogenous geranylgeranyl pyrophosphate synthase isolated by directed evolution, and FAD1 encoding flavin adenine dinucleotide synthetase, while deleting several genes previously known to be beneficial for carotenoid production. To produce retinol, 11 copies of BCO gene from marine bacterium 66A03 (Mb.Blh) were integrated into the rDNA sites of the ß-carotene overproducer. The resulting strain produced more retinol than retinal, suggesting strong endogenous promiscuous RDH activity in Y. lipolytica. The introduction of Mb.Blh led to a considerable reduction in ß-carotene level, but less than 5% of the consumed ß-carotene could be detected in the form of retinal or retinol, implying severe degradation of the produced retinoids. However, addition of the antioxidant butylated hydroxytoluene (BHT) led to a >20-fold increase in retinol production, suggesting oxidative damage is the main cause of intracellular retinol degradation. Overexpression of GSH2 encoding glutathione synthetase further improved retinol production. Raman imaging revealed co-localization of retinol with lipid droplets, and extraction of retinol using Tween 80 was effective in improving retinol production. By combining BHT treatment and extraction using Tween 80, the final strain CJ2104 produced 4.86 g/L retinol and 0.26 g/L retinal in fed-batch fermentation in a 5-L bioreactor, which is the highest retinol production titer ever reported. This study demonstrates that Y. lipolytica is a suitable host for the industrial production of bio-based retinol.