Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Although patients with chronic obstructive pulmonary disease (COPD) experience high morbidity and mortality worldwide, few biomarkers are available for COPD.Here, we analyzed potential biomarkers for the diagnosis of COPD by using word embedding. Methods: To determine which biomarkers are likely to be associated with COPD, we selected respiratory disease-related biomarkers. Degrees of similarity between the 26 selected biomarkers and COPD were measured by word embedding. And we infer the similarity with COPD through the word embedding model trained in the large-capacity medical corpus, and search for biomarkers with high similarity among them. We used Word2Vec, Canonical Correlation Analysis, and Global Vector for word embedding. We evaluated the associations of selected biomarkers with COPD parameters in a cohort of patients with COPD. Results: Cytokeratin 19 fragment (Cyfra 21-1) was selected because of its high similarity and its significant correlation with the COPD phenotype. Serum Cyfra 21-1 levels were determined in patients with COPD and controls (4.3 ± 5.9 vs. 3.9 ± 3.6 ng/mL, P = 0.611). The emphysema index was significantly correlated with the serum Cyfra 21-1 level (correlation coefficient = 0.219,P = 0.015). Conclusion Word embedding may be used for the discovery of biomarkers for COPD and Cyfra 21-1 may be used as a biomarker for emphysema. Additional studies are needed to validate Cyfra 21-1 as a biomarker for COPD.

Background: Although patients with chronic obstructive pulmonary disease (COPD) experience high morbidity and mortality worldwide, few biomarkers are available for COPD.Here, we analyzed potential biomarkers for the diagnosis of COPD by using word embedding. Methods: To determine which biomarkers are likely to be associated with COPD, we selected respiratory disease-related biomarkers. Degrees of similarity between the 26 selected biomarkers and COPD were measured by word embedding. And we infer the similarity with COPD through the word embedding model trained in the large-capacity medical corpus, and search for biomarkers with high similarity among them. We used Word2Vec, Canonical Correlation Analysis, and Global Vector for word embedding. We evaluated the associations of selected biomarkers with COPD parameters in a cohort of patients with COPD. Results: Cytokeratin 19 fragment (Cyfra 21-1) was selected because of its high similarity and its significant correlation with the COPD phenotype. Serum Cyfra 21-1 levels were determined in patients with COPD and controls (4.3 ± 5.9 vs. 3.9 ± 3.6 ng/mL, P = 0.611). The emphysema index was significantly correlated with the serum Cyfra 21-1 level (correlation coefficient = 0.219,P = 0.015). Conclusion Word embedding may be used for the discovery of biomarkers for COPD and Cyfra 21-1 may be used as a biomarker for emphysema. Additional studies are needed to validate Cyfra 21-1 as a biomarker for COPD.

The present study was performed to investigate the infection status with Clonorchis sinensis metacercariae (CsMc) in fishes from 2 sites, the middle and lower reaches, of Tamjin-gang (River) in Jeollanam-do, the Republic of Korea. Total 1,132 fishes in 22 species were collected from the middle reaches in Jangheung-gun for 4 years (2014–2017) and 517 fishes in 17 species were also collected from the lower reaches in Gangjin-gun in 2014 and 2017. They were all individually examined with the artificial digestion method in our laboratory. CsMc were detected in 322 (28.5%) out of 1,132 fishes from Jangheung-gun, and in 161 (31.1%) out of 517 fishes from Gangjin-gun, and their densities were 51 and 57 per fish infected each. In the fish species with CsMc, positive rates were 61.5% in Jangheung-gun and 62.7% in Gangjin-gun. A total of 222 Pungtungia herzi were examined and they were all infected with CsMc. The average intensity was 103 CsMc in the index fish, P. herzi (95 in Jangheung-gun and 121 in Gangjin-gun). In P. herzi bimonthly examined in 2017, the intensity was commonly most higher in March in 2 surveyed sites, however the significant seasonal endemicity was not showed. Conclusively, it was confirmed that CsMc is more or less prevalent in fishes from Tamjin-gang and their endemicity is higher in fish from the lower reaches in Gangjin-gun than the middle reaches in Jangheung-gun in Jeollanam-do, Korea.
Clonorchis sinensis ; Digestion ; Fishes ; Jeollanam-do ; Korea ; Metacercariae ; Methods ; Republic of Korea ; Seasons

PURPOSE: Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research. MATERIALS AND METHODS: We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues. RESULTS: Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor–overexpressing PDX with clear cell histology (p=0.023). CONCLUSION: PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.
Animals ; Biology ; Cell Line ; Drug Therapy, Combination ; Eosine Yellowish-(YS) ; Epidermal Growth Factor ; Erlotinib Hydrochloride ; Female ; Hematoxylin ; Heterografts* ; Humans ; Mice ; Microsatellite Repeats ; Molecular Targeted Therapy ; Ovarian Neoplasms* ; Precision Medicine ; Translational Medical Research ; Tumor Burden

OBJECTIVE: This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary CT angiography in healthy subjects. MATERIALS AND METHODS: Volunteers were randomized to receive 420 mgI/kg of either iohexol-350 or iohexol-380 using a flow rate of 4 mL/sec. All adverse events were recorded. Two blinded readers independently reviewed the CT images and conflicting results were resolved by a third reader. Luminal attenuations (ascending aorta, left main coronary artery, and left ventricle) in Hounsfield units (HUs) and image quality on a 4-point scale were calculated. RESULTS: A total of 225 subjects were given contrast media (115 with iohexol-380 and 110 with iohexol-350). There was no difference in number of adverse drug reactions between groups: 75 events in 56 (48.7%) of 115 subjects in the iohexol-380 group vs. 74 events in 51 (46.4%) of 110 subjects in the iohexol-350 group (p = 0.690). No severe adverse drug reactions were recorded. Neither group showed an increase in serum creatinine. Significant differences in mean density between the groups was found in the ascending aorta: 375.8 ± 71.4 HU with iohexol-380 vs. 356.3 ± 61.5 HU with iohexol-350 (p = 0.030). No significant differences in image quality scores between both groups were observed for all three anatomic evaluations (all, p > 0.05). CONCLUSION: Iohexol-380 provides improved enhancement of the ascending aorta and similar attenuation of the coronary arteries without any increase in adverse drug reactions, as compared with iohexol-350 using an identical amount of total iodine.
Angiography* ; Aorta ; Contrast Media ; Coronary Vessels ; Creatinine ; Drug-Related Side Effects and Adverse Reactions ; Image Enhancement ; Iodine ; Phenobarbital ; Volunteers

BACKGROUND: Cognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear. We examined the role of FOXO transcription factors and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt and apoptosis-related signaling pathways in PC-12 cells exposed to repeated glucose deprivation/reperfusion. METHODS: PC-12 cells were exposed to control (Dulbecco's Modified Eagle Medium [DMEM] containing 25 mM glucose) or glucose deprivation/reperfusion (DMEM with 0 mM glucose for 6 hours and then DMEM with 25 mM glucose for 18 hours) for 5 days. MTT assay and Western blot analysis were performed for cell viability, apoptosis, and the expression of survival signaling pathways. FOXO3/4',6-diamidino-2-phenylindole staining was done to ascertain the involvement of FOXO transcription factors in glucose deprivation/reperfusion conditions. RESULTS: Compared to PC-12 cells not exposed to hypoglycemia, cells exposed to glucose deprivation/reperfusion showed a reduction of cell viability, decreased expression of phosphorylated Akt and Bcl-2, and an increase of cleaved caspase-3 expression. Of note, FOXO3 protein was localized in the nuclei of glucose deprivation/reperfusion cells but not in the control cells. CONCLUSION: Repeated glucose deprivation/reperfusion caused the neuronal cell death. Activated FOXO3 via the PI3K/Akt pathway in repeated glucose deprivation/reperfusion was involved in genes related to apoptosis.
Apoptosis ; Blotting, Western ; Brain ; Caspase 3 ; Cell Death* ; Cell Survival ; Cognition Disorders ; Eagles ; Glucose* ; Hypoglycemia ; Neurons ; Phosphatidylinositol 3-Kinase ; Reperfusion ; Reperfusion Injury ; Transcription Factors*