An Epidemiological Study on Legionnaires' Disease in Gyeonggi Province, Korea: Occurrence, Infection Routes, and Risk Factors for Mortality (2016-2022).

Background and Objectives: Legionnaires' disease (LD) is an acute respiratory disease with increasing annual numbers of reported domestic and global cases. This study aimed to establish foundational data for the prevention and control of LD by investigating the occurrence and infection routes of reported and suspected cases of LD in Gyeonggi Province, Korea, from January 2016 to December 2022, and by and analyzing the risk factors for death. Materials and Methods: A sex-and-age standardization was performed on LD patients and suspected cases reported in Gyeonggi Province. The monthly average number of confirmed cases was visualized using graphs, and a survival analysis was performed using Kaplan-Meier survival curves. The mortality risk ratio was estimated using the Cox proportional hazards model. Results: The incidence of LD in Gyeonggi Province mirrored the national trend, peaking in July with the highest number of confirmed and suspected cases. While there was no significant difference in survival rates by age, the survival rate was higher for suspected cases when analyzed separately. Comparing the death ratio by infection route, nosocomial infections showed the highest death ratio, and intensive care unit (ICU) admission and the presence of coinfections were significantly correlated with mortality. Factors such as nosocomial infection, admission within 1 to 3 days following diagnosis, and the development of complications were factors contributing to a higher risk of death. Conclusions: The general characteristics of patients with LD were similar to those suggested by previous studies. The proportion of community-acquired infections was lower than in previous studies, but the length of hospital stay was similar for survivors and the deceased, and the mortality rate within 30 days after diagnosis was higher for nosocomial infections. In conclusion, nosocomial infection, a period of up to 3 days from admission to diagnosis, and complications were significantly related to the mortality rate of LD.

Anti-osteoporosis effects of triterpenoids from the fruit of sea buckthorn (Hippophae rhamnoides) through the promotion of osteoblast differentiation in mesenchymal stem cells, C3H10T1/2.

In a previous study, we discovered that the ethanolic extract of sea buckthorn (Hippophae rhamnoides) fruits exhibited anti-osteoporosis effects both in vitro and in vivo. Through bioassay-guided fractionation, we identified the hexane fraction (HRH) as the active fraction, which was further fractionated using preparative HPLC. Among the resulting six fractions, HRHF4 showed significant activity. In the present study, we focused on the bioassay-guided isolation of bioactive compounds from the HRHF4 fraction. We successfully identified the active HRHF43 fraction, which led us to the isolation of potential bioactive compounds (1-6). The chemical structures of these compounds were determined using NMR data, LC-MS analysis, and HR-ESI-MS data as four triterpenes, ursolic acid (1), uvaol (2), oleanolic aldehyde (3), and ursolic aldehyde (4), together with two fatty acids, methyl linoleate (5) and ethyl oleate (6). To evaluate the efficacy of promoting osteoblast differentiation and the expression of mRNA biomarkers related to osteogenesis, we tested the isolated compounds in the mouse mesenchymal stem cell line, C3H10T1/2. Alkaline phosphate staining demonstrated that triterpenes (1-4) displayed osteogenic activity. Particularly noteworthy, ursolic aldehyde (4) exhibited the most potent effect, showing an 11.2-fold higher activity at a concentration of 10 µg/mL compared to the negative control. Moreover, ursolic aldehyde (4) upregulated the gene expression of bone formation-related biomarkers, including Runx2, Osterix, Alp, and Osteopontin. These findings suggest that the fruit extract of H. rhamnoides may have potential as a nutraceutical for promoting bone health, with ursolic aldehyde (4) identified as an active constituent.

Epidemiology of Carbapenem-Resistant Enterobacteriaceae Bacteremia in Gyeonggi Province, Republic of Korea, between 2018 and 2021.

The incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing since 2008, with Gyeonggi Province in South Korea being particularly vulnerable due to its large number of healthcare facilities. This study examines the trends of CRE occurrence in Gyeonggi Province over the past four years and the epidemiological characteristics of the infected patients. Patients with positive CRE blood cultures admitted to healthcare facilities in Gyeonggi Province from January 2018 to December 2021 were evaluated in this study. Risk factors for CRE-related death were analyzed using data from patients who died within 30 days of the last blood sampling. Older adults aged 70 years and above constituted the majority of patients with CRE bacteremia. Antibiotic use did not significantly affect mortality risk. Non-survivors were more common in tertiary hospitals and intensive care units and included patients with hypertension, malignant tumors, and multiple underlying diseases. Klebsiella pneumoniae was the most common CRE strain, with Klebsiella pneumoniae carbapenemase being the predominant carbapenemase. Our study suggests the endemicity of CRE in Gyeonggi Province and highlights the increasing isolation of CRE strains in South Korean long-term care hospitals within the province. Further, infection control measures and government support specific to each healthcare facility type are crucial.

Direct indicators of social distancing effectiveness in COVID-19 outbreak stages: a correlational analysis of case contacts and population mobility in Korea.

OBJECTIVES: The effectiveness of social distancing during the coronavirus disease 2019 (COVID-19) pandemic has been evaluated using the magnitude of changes in population mobility. This study aimed to investigate a direct indicator-namely, the number of close contacts per patient with confirmed COVID-19. METHODS: From week 7, 2020 to week 43, 2021, population movement changes were calculated from the data of two Korean telecommunication companies and Google in accordance with social distancing stringency levels. Data on confirmed cases and their close contacts among residents of Gyeonggi Province, Korea were combined at each stage. Pearson correlation analysis was conducted to compare the movement data with the change in the number of contacts for each confirmed case calculated by stratification according to age group. The reference value of the population movement data was set using the value before mid-February 2020, considering each data's characteristics. RESULTS: In the age group of 18 or younger, the number of close contacts per confirmed case decreased or increased when the stringency level was strengthened or relaxed, respectively. In adults, the correlation was relatively low, with no correlation between the change in the number of close contacts per confirmed case and the change in population movement after the commencement of vaccination for adults. CONCLUSIONS: The effectiveness of governmental social distancing policies against COVID-19 can be evaluated using the number of close contacts per confirmed case as a direct indicator, especially for each age group. Such an analysis can facilitate policy changes for specific groups.

ICARUS-Q: Integrated control and readout unit for scalable quantum processors.

We present a control and measurement setup for superconducting qubits based on the Xilinx 16-channel radio-frequency system-on-chip (RFSoC) device. The proposed setup consists of four parts: multiple RFSoC boards, a setup to synchronize every digital to analog converter (DAC) and analog to digital converter (ADC) channel across multiple boards, a low-noise direct current supply for tuning the qubit frequency, and cloud access for remotely performing experiments. We also designed the setup to be free of physical mixers. The RFSoC boards directly generate microwave pulses using sixteen DAC channels up to the third Nyquist zone, which are directly sampled by its eight ADC channels between the fifth and the ninth zones.

Anti-Osteoporosis Effects of the Fruit of Sea Buckthorn (Hippophae rhamnoides) through Promotion of Osteogenic Differentiation in Ovariectomized Mice.

The fruit of Hippophae rhamnoides has been widely used for medicinal purposes because of its anti-inflammatory, antioxidant, antiplatelet, and antimicrobial effects. Since there are no clear reports on the therapeutic efficacy of H. rhamnoides in osteoporosis, this study aimed to confirm the potential use of H. rhamnoides for the treatment of osteoporosis through its osteogenic differentiation-promoting effect in ovariectomized mice. Through an in vitro study, we compared the effects of the EtOH extract of H. rhamnoides fruits (EHRF) on the differentiation of C3H10T1/2, a mouse mesenchymal stem cell line, into osteoblasts based on alkaline phosphatase (ALP) staining and the relative expression of osteogenesis-related mRNAs. The EHRF significantly stimulated the differentiation of mesenchymal stem cells into osteoblasts and showed 7.5 times (* p < 0.05) higher osteogenesis than in the untreated control. A solvent fractionation process of EHRF showed that the hexane-soluble fraction (HRH) showed 10.4 times (** p < 0.01) higher osteogenesis than in the untreated control. Among the subfractions derived from the active HRH by preparative HPLC fractionation, HRHF4 showed 7.5 times (* p < 0.05) higher osteogenesis than in the untreated naïve cells, and HRH and HRHF4 fractions showed 22.6 times (*** p < 0.001) stronger osteogenesis activity than in the negative control. Osteoporosis was induced by excision of both ovaries in 9-week-old female ICR mice for in vivo analysis, and two active fractions, HRH and HRHF4, were administered orally for three months. During the oral administration period, body weight was measured weekly, and bone mineral density (BMD) and body fat density were measured simultaneously using a DEXA machine once a month. In particular, during the in vivo study, the average BMD of the ovariectomized group decreased by 0.0009 g/cm2, whereas the average BMD of the HRH intake group increased by 0.0033 g/cm2 (* p < 0.05) and that of the HRHF4 intake group increased by 0.0059 g/cm2 (** p < 0.01). The HRH and HRHF4 intake groups significantly recovered the mRNA and protein expression of osteogenic genes, including ALP, Osteopontin, Runx2, and Osterix, in the osteoporosis mouse tibia. These findings suggest that the active fractions of H. rhamnoides fruit significantly promoted osteoblast differentiation in mesenchymal stem cells and increased osteogenic gene expression, resulting in an improvement in bone mineral density in the osteoporosis mouse model. Taken together, H. rhamnoides fruits are promising candidates for the prevention and treatment of osteoporosis.

Phytochemical Investigation of Bioactive Compounds from White Kidney Beans (Fruits of Phaseolus multiflorus var. Albus): Identification of Denatonium with Osteogenesis-Inducing Effect.

Phaseolus multiflorus var. albus (Leguminosae), commonly known as "white kidney bean", is a twining perennial vine whose fruit has been used as a popular food worldwide owing to its high nutritional content, in terms of proteins, carbohydrates, fats, and vitamins. As part of our ongoing study to investigate novel bioactive components from various natural resources, a phytochemical investigation of the extract of P. multiflorus var. albus fruits resulted in the isolation of three phenolic compounds (1-3) and one dipeptide (4). The chemical structures of the compounds (1-4) were determined through 1D and 2D nuclear magnetic resonance spectroscopy and high-resolution-liquid chromatography-mass spectrometry; they were identified as denatonium (1), trans-ferulic acid ethyl ester (2), eugenin (3), and α-L-glutamyl-L-Leucine (4). Intriguingly, denatonium (1) is known to be the most bitter chemical compound. To the best of our knowledge, denatonium (1) was identified from natural sources for the first time, and compounds 2-4 were reported for the first time from P. multiflorus var. albus in this study; however, compound 2 turned out to be an artifact produced by an extraction with ethanol. The isolated compounds 1-4 were tested for their regulatory effects on the differentiation between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs). Compound 4 slightly suppressed the adipogenic differentiation of MSCs, and compounds 1 and 4 stimulated osteogenic differentiation, unlike the negative control. These findings provide experimental evidence that compounds 1 and 4 may induce the osteogenesis of MSCs and activate bone formation.

Ginkgonitroside, a new nitrophenyl glycoside and bioactive compounds from Ginkgo biloba leaves controlling adipocyte and osteoblast differentiation.

Eight compounds (1-8) including one novel nitrophenyl glycoside, ginkgonitroside (1) were isolated from the leaves of Ginkgo biloba, a popular medicinal plant. The structure of the new compound was characterized using extensive spectroscopic analyses via 1D and 2D NMR data interpretations, HR-ESIMS, and chemical transformation. To the best of our knowledge, the present study is the first to report the presence of nitrophenyl glycosides, which are relatively unique phytochemicals in natural products, in G. biloba. The isolated compounds (1-8) were examined for their effects on the regulation of mesenchymal stem cell (MSC) differentiation. Compounds 1-3 and 8 were able to suppress MSC differentiation toward adipocytes. In contrast, compounds 5 and 8 showed activity promoting osteogenic differentiation of MSCs. These findings demonstrate that the active compounds showed regulatory activity on MSC differentiation between adipocytes and osteocytes.

Solving the inverse problem of time independent Fokker-Planck equation with a self supervised neural network method.

The Fokker-Planck equation (FPE) has been used in many important applications to study stochastic processes with the evolution of the probability density function (pdf). Previous studies on FPE mainly focus on solving the forward problem which is to predict the time-evolution of the pdf from the underlying FPE terms. However, in many applications the FPE terms are usually unknown and roughly estimated, and solving the forward problem becomes more challenging. In this work, we take a different approach of starting with the observed pdfs to recover the FPE terms using a self-supervised machine learning method. This approach, known as the inverse problem, has the advantage of requiring minimal assumptions on the FPE terms and allows data-driven scientific discovery of unknown FPE mechanisms. Specifically, we propose an FPE-based neural network (FPE-NN) which directly incorporates the FPE terms as neural network weights. By training the network on observed pdfs, we recover the FPE terms. Additionally, to account for noise in real-world observations, FPE-NN is able to denoise the observed pdfs by training the pdfs alongside the network weights. Our experimental results on various forms of FPE show that FPE-NN can accurately recover FPE terms and denoising the pdf plays an essential role.

Phytochemical Analysis of the Fruits of Sea Buckthorn (Hippophae rhamnoides): Identification of Organic Acid Derivatives.

Hippophae rhamnoides L. (Elaeagnaceae), commonly known as "Sea buckthorn" and "Vitamin tree", is a spiny deciduous shrub whose fruit is known for its nutritional composition, such as vitamin C, and is consumed as a dietary supplement worldwide. As part of our ongoing efforts to identify structurally new and bioactive constituents from natural resources, the phytochemical investigation of the extract of H. rhamnoides fruits led to the isolation of one malate derivative (1), five citrate derivatives (2-6), and one quinate derivative (7). The structures of the isolated compounds were elucidated by analysis of 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data and high-resolution electrospray ionization (HR-ESI) liquid chromatography-mass spectrometry (LC/MS) data. Three of the citrate derivatives were identified as new compounds: (S)-1-butyl-5-methyl citrate (3), (S)-1-butyl-1'-methyl citrate (4), and (S)-1-methyl-1'-butyl citrate (6), which turned out to be isolation artifacts. The absolute configurations of the new compounds were established by quantum chemical electronic circular dichroism (ECD) calculation, which is an informative tool for verifying the absolute configuration of organic acid derivatives. The isolated compounds 1-7 were evaluated for their stimulatory effects on osteogenesis. Compounds 1, 3, 4, 6, and 7 stimulated osteogenic differentiation up to 1.4 fold, compared to the negative control. These findings provide experimental evidence that active compounds 1, 3, 4, 6, and 7 induce the osteogenesis of mesenchymal stem cells and activate bone formation.