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Influenza is an important public health concern. We propose a new real-time influenza-like illness (ILI) surveillance system that utilizes a nationwide prospective drug utilization monitoring in Korea. We defined ILI-related claims as outpatient claims that contain both antipyretic and antitussive agents and calculated the weekly rate of ILI-related claims, which was compared to weekly ILI rates from clinical sentinel surveillance data during 2014–2018. We performed a cross-correlation analysis using Pearson's correlation, time-series analysis to explore actual correlations after removing any dubious correlations due to underlying non-stationarity in both data sets. We used the moving epidemic method (MEM) to estimate an absolute threshold to designate potential influenza epidemics for the weeks with incidence rates above the threshold. We observed a strong correlation between the two surveillance systems each season. The absolute thresholds for the 4-years were 84.64 and 86.19 cases per 1000claims for claims data and 12.27 and 16.82 per 1000 patients for sentinel data. The epidemic patterns were more similar in the 2016–2017 and 2017–2018 seasons than the 2014–2015 and 2015–2016 seasons. ILI claims data can be loaded to a drug utilization review system in Korea to make an influenza surveillance system. [ABSTRACT FROM AUTHOR]

To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodelling. Recently, microglial cells have been shown to be responsible for a portion of synaptic pruning, but the remaining mechanisms remain unknown. Here we report a new role for astrocytes in actively engulfing central nervous system synapses. This process helps to mediate synapse elimination, requires the MEGF10 and MERTK phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to refine their retinogeniculate connections normally and retain excess functional synapses. Finally, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify MEGF10 and MERTK as critical proteins in the synapse remodelling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes. [ABSTRACT FROM AUTHOR]

Fly ash has been regarded as hazardous because of its high adsorption of toxic organic and/or inorganic pollutants. Fly ash is also known to have broad distributions of different chemical and physical properties, such as size and density. In this study, fly ash emitted from a solid waste incinerator was pre-fractionated into six sub-populations by use of gravitational SPLITT fractionation (GSF). The GSF fractions were then analyzed by sedimentation field-flow fractionation (SdFFF) and ICP–AES. SdFFF analysis showed the fly ash has a broad size distribution ranging from a few nanometers up to about 50 µm. SdFFF results were confirmed by electron microscopy. Inductively coupled plasma–atomic emission spectroscopy (ICP–AES) analysis of the GSF fractions showed the fly-ash particles contain a variety of inorganic elements including Ca, Si, Mg, Fe, and Pb. The most abundant in fly ash was Ca, followed by Si then Mg. No correlations were found between trace element concentration and particle size. [ABSTRACT FROM AUTHOR]

Carbon black is one of the most useful particulate materials in the industrial field. Among the various physical properties of carbon black, size and size distribution are the most important properties to affect the quality of a final product. However, it is difficult to measure the exact particle size of carbon black since it suffers unavoidable interference from flocculation. In this study, the effects of various factors on the dispersion of industrial carbon blacks were investigated for the determination of size and size distribution of carbon black particles. Sedimentation and flow field-flow fractionations (FIFFF) were used to determine the size of carbon black, and their optimum analytical conditions were tested by changing surfactant, pH, ionic strength, and method of dispersion. The results showed that surfactant structure and its concentration played significant roles in dispersion stability. Carbon black was dispersed well with a nonionic surfactant with a pH of around 8 and an ionic strength of 0.003 M. The mean diameters measured from two types of FFF and photon correlation spectroscopy are in good agreement. This study demonstrates the potential of sedimentation and flow FFF for analyzing highly adsorptive industrial particles and guides for sample preparation. [ABSTRACT FROM AUTHOR]

Introduction: To estimate herpes zoster (HZ) incidence rate (IR) and economic burden in individuals with immunocompromised conditions and autoimmune diseases (IC/AID) in the Republic of Korea (ROK). Methods: The nationwide Health Insurance Review and Assessment Service database was used to identify HZ cases from 2016 to 2020 in ROK. HZ and non-HZ IC/AID cases were matched 1:3 using age, sex, institution, Charlson comorbidity index, IC/AID, and index date. Annual HZ IRs/1000 persons and 1-year HZ-associated all-cause direct medical costs for IC/AID cases were calculated. Results: Among 65,976 individuals with IC/AID (mean age 57.14 years [standard deviation 14.1]; 64.94% female), annual HZ IR (95% confidence interval) fluctuated from 2016 to 2020, averaging 23.41/1000 persons (22.21–24.62) and was higher in women (26.85 [25.40–28.31]) than men (18.96 [18.03–19.89]). IRs were highest in individuals aged ≥ 50 years, and in those with transplants (including solid organ and hematopoietic stem cell transplants; 37.12 [35.45–38.79]) and hemato-oncology conditions (35.5 [31.6–39.3]). Mean 12-month all-cause direct medical costs were higher in individuals with IC/AID and HZ (4,759,671 Korean Republic won [KRW]; approximately 4046 United States dollar [USD; according to the 2020 conversion rate from UNCTAD; 1 KRW = 0.00085 USD]) than those without HZ (3,786,658 KRW; 3219 USD). Conclusion: Individuals with IC/AID have a substantial disease and economic burden from HZ in ROK, highlighting the need for appropriate HZ prevention measures in the IC/AID population. Plain Language Summary: [ABSTRACT FROM AUTHOR]

Although several biomarkers can be used to distinguish cholangiocarcinoma (CCA) from healthy controls, differentiating the disease from benign biliary disease (BBD) or pancreatic cancer (PC) is a challenge. CCA biomarkers are associated with low specificity or have not been validated in relation to the biological effects of CCA. In this study, we quantitatively analyzed 15 biliary bile acids in CCA (n = 30), BBD (n = 57) and PC (n = 17) patients and discovered glycocholic acid (GCA) and taurochenodeoxycholic acid (TCDCA) as specific CCA biomarkers. Firstly, we showed that the average concentration of total biliary bile acids in CCA patients was quantitatively less than in other patient groups. In addition, the average composition ratio of primary bile acids and conjugated bile acids in CCA patients was the highest in all patient groups. The average composition ratio of GCA (35.6%) in CCA patients was significantly higher than in other patient groups. Conversely, the average composition ratio of TCDCA (13.8%) in CCA patients was significantly lower in all patient groups. To verify the biological effects of GCA and TCDCA, we analyzed the gene expression of bile acid receptors associated with the development of CCA in a CCA cell line. The gene expression of transmembrane G protein coupled receptor (TGR5) and sphingosine 1-phosphate receptor 2 (S1PR2) in CCA cells treated with GCA was 8.6-fold and 3.4-fold higher compared with control (untreated with bile acids), respectively. Gene expression of TGR5 and S1PR2 in TCDCA-treated cells was not significantly different from the control. Taken together, our study identified GCA and TCDCA as phenotype-specific biomarkers for CCA. [ABSTRACT FROM AUTHOR]

The disease burden of respiratory syncytial virus (RSV) infection in the adult population has not been well characterized compared to children. Investigation of the clinical characteristics and disease burden of adult RSV infection would help to establish public health policy and a future vaccine strategy. We retrospectively collected medical records of hospitalized adult patients who were diagnosed with RSV infection from January 2012 to December 2015 from three tertiary hospitals. Baseline characteristics, clinical outcomes and economic charge during hospitalization were compared by age groups (19–49 years, 50–64 years, and ≥ 65 years) using Chi-square test. The odds of risk factors of RSV pneumonia were calculated using binary logistic regression. A total of 204 patients from three hospitals were enrolled. Patients who older than 65 years were 132 (64.7%). 118 (57.8%) patients had clinically confirmed pneumonia and 22 (10.8%) died in a hospital. The median medical cost of RSV pneumonia was 2,855.26 USD (interquartile range, 1,561.85–5,379.55) per each admission. Solid cancer (adjusted OR, 3.85; 95% CI, 1.65–9.02, p = 0.002) and hematologic malignancy (all patients had pneumonia) were shown to be risk factors for RSV pneumonia. RSV infection in South Korea seemed to have a significant burden among adults as pneumonia, care in the intensive care unit and mortality. Nationwide awareness and further effort to recognize the current burden, prepare specific treatment, and prevent adult RSV infection would be necessary. [ABSTRACT FROM AUTHOR]

Emergence of a highly pathogenic avian influenza (HPAI) H5N8 virus in Asia and its spread to Europe and North America has caused great concern for human health. Although the H5N8 virus has been only moderately pathogenic to mammalian hosts, virulence can still increase. We evaluated the pathogenic potential of several H5N8 strains via the mouse-adaptation method. Two H5N8 viruses were sequentially passaged in BALB/c mice and plaque-purified from lung samples. The viruses rapidly obtained high virulence (MLD50, up to 0.5 log10 PFU/mL) within 5 passages. Sequence analysis revealed the acquisition of several virulence markers, including the novel marker P708S in PB1 gene. Combinations of markers synergistically enhanced viral replication and polymerase activity in human cell lines and virulence and multiorgan dissemination in mice. These results suggest that H5N8 viruses can rapidly acquire virulence markers in mammalian hosts; thus, rapid spread as well as repeated viral introduction into the hosts may significantly increase the risk of human infection and elevate pandemic potential. [ABSTRACT FROM AUTHOR]

There were few data regarding the association of volume status with sarcopenia using muscle mass, strength, and physical performance in non-dialysis chronic kidney disease (ND-CKD) patients. We aimed to evaluate the association between volume status and sarcopenia in ND-CKD patients. Our retrospective study analyzed data from a previous study which included ND-CKD patients who had stable renal function. Our study used its baseline data alone. The edema index and muscle mass were measured using a multi-frequency bioimpedance analysis machine. The edema index was calculated using extracellular water/total body water ratio. The skeletal muscle index (SMI, kg/m2) was calculated using appendicular muscle mass per height squared. Handgrip strength (HGS, kg) was measured during the standing position in all patients. Dynamic gait speed (GS, m/s) was evaluated using 6-m walking speed. Patients with both low muscle mass (SMI < 7.0 kg/m2 for men and < 5.7 kg/m2 for women using bioimpedance analysis) and low HGS (< 28 kg for men and < 18 kg for women) or low GS (< 1.0 m/s) were classified as having sarcopenia. The patients (n = 147) were divided into tertiles based on the edema index level. The mean edema index in the low, middle, and high tertiles was 0.377 ± 0.006, 0.390 ± 0.003, and 0.402 ± 0.006, respectively. The edema index was significantly correlated with SMI, HGS, and GS (r = − 0.343 for SMI, − 0.492 for HGS, and − 0.331 for GS; P < 0.001 for three indicators). The SMI, HGS, and GS values were 8.1 ± 1.0 kg/m2, 33.0 ± 9.4 kg, and 1.2 ± 0.2 m/s in the low tertile,7.8 ± 1.2 kg/m2, 30.0 ± 7.5 kg, and 1.0 ± 0.3 m/s in the middle tertile, and 7.2 ± 1.4 kg/m2, 23.7 ± 7.4 kg, and 1.0 ± 0.3 m/s in the high tertile, respectively. Univariate analyses revealed that SMI was lower in patients in the high tertile than in those in the low tertile. HGS was lowest in high tertile, and GS was greatest in the low tertile. The high tertile for predicting sarcopenia had an odds ratio of 6.03 (95% CI, 1.78–20.37; P = 0.004) compared to low or middle tertiles. The results of multivariate analyses were similar to those of the univariate analyses. The subgroup analyses showed that statistical significance was greater in < 65 years and men than ≥ 65 years and women. The present study showed that the edema index is inversely associated with sarcopenia, muscle mass index, strength, and physical performance in ND-CKD patients. However, considering the limitations of our study such as its small sample size, this association was not strong. Further studies that include volume-independent measurements, data on physical activity and diet, and a larger number of patients are warranted to overcome these limitations. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Established fear memory becomes vulnerable to disruption after memory retrieval and extinction; this labile state is critical for inhibiting the return of fear memory. However, the labile state has a very narrow time window after retrieval, and underlying molecular mechanisms are not well known. To that end, we isolated the hippocampus immediately after fear memory retrieval and performed proteomics. We identified Neurobeachin (NBEA), an autism-related regulator of synaptic protein trafficking, to be upregulated after contextual fear memory retrieval. NBEA protein expression was rapid and transient after fear memory retrieval at the synapse. Nbea mRNA was enriched at the synapses, and the rapid induction of NBEA expression was blocked by inhibition of the mammalian target of rapamycin (mTOR)-dependent signaling pathway. Mice with cornu ammonis 1 (CA1)-specific Nbea shRNA knockdown showed normal fear acquisition and contextual fear memory but impaired extinction, suggesting an important role of Nbea in fear memory extinction processes. Consistently, Nbea heterozygotes showed normal fear acquisition and fear memory recall but showed impairment in extinction. Our data suggest that NBEA is necessary either for induction of memory lability or for the physiological process of memory extinction. [ABSTRACT FROM AUTHOR]

We investigated whether stem cells (MDSC) from primary cultures of rat skeletal muscle can differentiate into the smooth muscle lineage in response to vascular endothelial growth factor (VEGF) and co-culture with bladder smooth muscle cells. The MDSC were isolated from gastrocnemius muscle biopsies of normal 3-6 week- old Sprague-Dawley rats and purified by the preplate technique. Cells that took approximately 6 days to adhere to the collagen-coated flasks were termed late preplate (LP) cells, and were used in all the experiments. The early plate (EP) cells (pp1-pp4) contained some myogenic cells but were mostly fibroblasts (< 15% desmin+ cells) whereas the LP cells (pp5-pp6) were highly purified muscle-derived cells (pp6) (> 90% desmin+ cells). The muscle-derived stem cells (LP cells) were CD34+ or Sca-1+, CD45- and desmin+ by immunohistochemical staining. After two days of co-culture with bladder smooth muscle cells, about 25% of the muscle-derived stem cells were positive for alpha-smooth muscle actin (α- SM)+. RT-PCR for α-SMA was positive in the VEGF stimulated MDSC, but negative in the absence of VEGF. ln conclusion, rat muscle-derived stem cells exhibited stem cell properties (CD34+ or Sca-1+), and were not of hematogeous (CD45-) but of myogenic origin (desmin+). RT-PCR of α-SMA was positive in the VEGE stimulated muscle-derived stem cells. [ABSTRACT FROM AUTHOR]

Although colorectal cancer is one of the most lethal cancer types in the world, its metastasis to the ovary is rare, compared to metastasis to other organs. Consequently, the genomic basis for colon-to-ovary metastasis remains unstudied, due to limited available patients, and thus there have been no attempts to construct individual-specific networks. Due to its rarity, the small sample size makes common mutations difficult to find. To overcome this problem, we herein attempted to apply a biological connectivity map called a sample-specific network (SSN), to reveal common biological functions in three samples. Our three samples were compared to a clinical dataset contained in The Cancer Genome Atlas (TCGA) Colorectal Adenocarcinoma (COAD), showing different mutational spectra, compared to matched samples based on age, gender, microsatellite instability (MSI) status, and tumor, node, metastasis (TNM) stage. The SSNs for the three samples revealed significant correlations of the mutation statuses of several apoptosis genes, in contrast to the TCGA-matched samples. Further analysis of a targeted-gene panel sequencing dataset for colon-to-ovary metastasis of primary tumor samples also confirmed significant correlations of the mutational statuses among apoptosis genes. In summary, using SSN, we successfully identified a common function (apoptosis) among our three patients having colon-to-ovary metastasis, despite no common mutations in the three patients. Such computational analyses could facilitate productive study of rare cancers and other diseases. [ABSTRACT FROM AUTHOR]