Purpose: This study was conducted to explore the core educational components of interprofessional education (IPE) for pediatric emergencies to establish a basis for interprofessional simulation education. Methods: Using Whittemore and Knafl's integrative review method, we searched for studies in PubMed, Embase, Cochrane Library, CINAHL, and four South Korean databases (RISS, NDSL, DBpia, and KISS). Results: We identified 21 studies on the general characteristics of IPE in pediatric emergency situations and integrated the core components of IPE according to a PRISMA flowchart. Three core components were identified (individual - competent professionals, team - cooperative professions, and outcome - optimal achievement), with the subthemes of role and responsibility, clinical judgment, performance, leadership, communication, teamwork, patient safety, and quality improvement. Conclusion We recommend that IPE pediatric emergencies should contain the three dimensions of these core components to enhance individual and team performance and to promote optimal achievement in terms of patient outcomes. IPE programs should consider these characteristics and include a valid tool for evaluating the programs' effectiveness.

PURPOSE: Cancer cells frequently express genes that are specifically or preferentially expressed in male germ cells under normal conditions. The ATPase family AAA domain-containing 2 (ATAD2) is one such and works as an important cofactor for MYC-dependent transcription. In hepatocellular carcinoma (HCC), ATAD2 has been identified as a candidate driver gene located within the amplified 8q24 locus. However, the prognostic significance of ATAD2 protein expression in HCC remains uncertain. MATERIALS AND METHODS: We investigated ATAD2 protein expression by immunohistochemistry in tumor tissue from 182 HCC patients who underwent curative resection. Associations of ATAD2 expression with clinicopathologic variables or prognosis of HCC patients were analyzed. RESULTS: ATAD2 expression was observed in 119 (65.4%) of the 182 HCCs and tended to be independent predictor of early recurrence (p=0.059). ATAD2 expression showed an unfavorable influence on recurrence-free survival (RFS) (p < 0.001). Subgroup analysis among patients with tumor size < or = 5.0 cm (n=109), patients at Barcelona Clinic Liver Cancer stage 0 or A (n=92), and patients with alpha-fetoprotein < or = 20 ng/mL (n=61), the ATAD2-positive groups unfavorably influenced RFS (p=0.008, p=0.009, and p=0.013, respectively). In addition, ATAD2 expression was an independent predictor of shorter RFS (p=0.002). ATAD2 expression showed an unfavorable influence on disease-specific survival (p=0.001), but was not an independent predictor of shorter disease-specific survival (p=0.109). CONCLUSION: ATAD2 protein expression may be a potential predictor of RFS in HCC patients after curative resection and ATAD2 may have prognostic value in patients with early stage HCC or normal serum alpha-fetoprotein level.
Adenosine Triphosphatases ; alpha-Fetoproteins ; Carcinoma, Hepatocellular* ; Germ Cells ; Humans ; Immunohistochemistry ; Liver Neoplasms ; Male ; Prognosis ; Recurrence

PURPOSE: Paternally expressed gene 10 (PEG10), first identified as an imprinted gene, is paternally expressed and maternally silenced. In hepatocellular carcinoma (HCC), PEG10 has been identified as a potential target gene located within the amplified 7q21 locus. The purpose of this study was to investigate the expression of PEG10 protein in HCC and evaluate its prognostic significance. MATERIALS AND METHODS: PEG10 protein expression was examined by immunohistochemistry in tumor tissues from 218 HCC patients undergoing curative resection. Furthermore, the relationships between PEG10 expression and clinicopathologic features or postoperative survival of HCC patients were evaluated. The median follow-up period was 119.8 months for survivors. RESULTS: PEG10 expression was observed in 148 of the 218 HCCs (67.9%) and was significantly correlated with younger age, female, higher Edmondson grade, microvascular invasion, intrahepatic metastasis, higher American Joint Committee on Cancer T-stage, and higher alpha-fetoprotein level. PEG10 expression was an independent predictor of early recurrence (p=0.013), and it showed an unfavorable influence on recurrence-free survival (p < 0.001). A subgroup analysis showed that among patients with alpha-fetoprotein < or = 20 ng/mL (80 patients), the PEG10-positive group also showed an unfavorable influence on recurrence-free survival (p=0.002). Moreover, a multivariate survival analysis identified PEG10 as an independent predictor of shorter recurrence-free survival (p=0.005). PEG10 expression showed an unfavorable influence on overall survival (p=0.007) but was not an independent predictor of shorter overall survival (p=0.128). CONCLUSION: PEG10 protein could be a potential biomarker predicting early recurrence and recurrence-free survival in HCC patients after curative resection, even in those with normal serum alpha-fetoprotein levels.
alpha-Fetoproteins ; Carcinoma, Hepatocellular* ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Joints ; Neoplasm Metastasis ; Recurrence* ; Survivors

Purpose: To assess associations between surveillance intervals in a national hepatocellular carcinoma (HCC) surveillance program and receiving curative treatment and mortality using nationwide cohort data for Korea. Materials and Methods: Using the National Health Insurance Service Database of Korea, we retrospectively identified 3201852 patients, the target population of the national HCC surveillance program, between 2008 and 2017. After exclusion, a total of 64674 HCC patients were divided based on surveillance intervals: never screened, ≤6 months (6M), 7–12 months (1Y), 13–24 months (2Y), and 25–36 months (3Y). Associations for surveillance interval with the chance to receive curative therapy and all-cause mortality were analyzed. Results: The 6M group (51.9%) received curative therapy more often than the other groups (1Y, 48.3%; 2Y, 43.8%; 3Y, 41.3%; never screened, 34.5%). Odds ratio for receiving curative therapy among the other surveillance interval groups (1Y, 0.87; 2Y, 0.76; 3Y, 0.77;never screened, 0.57; p<0.001) were significantly lower than that of the 6M group. The hazard ratios (HRs) of all-cause mortality were 1.07, 1.14, and 1.37 for 2Y, 3Y, and never screened groups. The HR for the 1Y group (0.96; p=0.092) was not significantly different, and it was lower (0.91; p<0.001) than that of the 6M group after adjustment for lead-time bias. Curative therapy was associated with survival benefits (HR, 0.26; p<0.001). Conclusion HCC surveillance, especially at a surveillance interval of 6 months, increases the chance to receive curative therapy.

Purpose: To assess associations between surveillance intervals in a national hepatocellular carcinoma (HCC) surveillance program and receiving curative treatment and mortality using nationwide cohort data for Korea. Materials and Methods: Using the National Health Insurance Service Database of Korea, we retrospectively identified 3201852 patients, the target population of the national HCC surveillance program, between 2008 and 2017. After exclusion, a total of 64674 HCC patients were divided based on surveillance intervals: never screened, ≤6 months (6M), 7–12 months (1Y), 13–24 months (2Y), and 25–36 months (3Y). Associations for surveillance interval with the chance to receive curative therapy and all-cause mortality were analyzed. Results: The 6M group (51.9%) received curative therapy more often than the other groups (1Y, 48.3%; 2Y, 43.8%; 3Y, 41.3%; never screened, 34.5%). Odds ratio for receiving curative therapy among the other surveillance interval groups (1Y, 0.87; 2Y, 0.76; 3Y, 0.77;never screened, 0.57; p<0.001) were significantly lower than that of the 6M group. The hazard ratios (HRs) of all-cause mortality were 1.07, 1.14, and 1.37 for 2Y, 3Y, and never screened groups. The HR for the 1Y group (0.96; p=0.092) was not significantly different, and it was lower (0.91; p<0.001) than that of the 6M group after adjustment for lead-time bias. Curative therapy was associated with survival benefits (HR, 0.26; p<0.001). Conclusion HCC surveillance, especially at a surveillance interval of 6 months, increases the chance to receive curative therapy.

To prevent the spread of the coronavirus disease 2019 (COVID-19) pandemic, vaccines have been authorized for emergency use and implemented worldwide. We present a case of de novo glomerulonephritis (GN) after use of the COVID-19 mRNA vaccine BNT162b2.A 48-year-old man with no relevant medical history was referred for sudden and persistent worsening of renal insufficiency 1.5 months after the second vaccine dose. He had arthralgia and skin rash a week after vaccination. Abdominal pain and diarrhea started 2 weeks later, and he was admitted to the hospital for enteritis treatment. Colonoscopy showed multiple ulcerations and petechiae suggestive of vasculitis in the terminal ileum. After prednisolone therapy, his gastrointestinal symptoms improved, but his renal function continued to deteriorate. Based on kidney biopsy findings and nephrotic-range proteinuria (5,306 mg/24 hours), he was diagnosed with anti-neutrophil cytoplasmic autoantibody (ANCA)-negative pauci-immune crescentic GN (CrGN). He received high-dose steroid pulse therapy and oral cyclophosphamide, and then, gradually underwent steroid tapering, with improvement in proteinuria and renal function over several weeks. Several cases of GN suspected to be related to COVID-19 vaccines have been reported. To our knowledge, this is the first case report of ANCA-negative pauci-immune crescentic CrGN with extrarenal involvement after COVID-19 mRNA vaccination. Our finding expands the spectrum of COVID-19 vaccine-associated GN.

BACKGROUND/OBJECTIVES: Citrus flavonoids have a variety of physiological properties such as anti-oxidant, anti-inflammation, anti-cancer, and anti-obesity. We investigated whether bioconversion of Citrus unshiu with cytolase (CU-C) ameliorates the anti-adipogenic effects by modulation of adipocyte differentiation and lipid metabolism in 3T3-L1 cells. MATERIALS/METHODS: Glycoside forms of Citrus unshiu (CU) were converted into aglycoside forms with cytolase treatment. Cell viability of CU and CU-C was measured at various concentrations in 3T3L-1 cells. The anti-adipogenic and lipolytic effects were examined using Oil red O staining and free glycerol assay, respectively. We performed real time-polymerase chain reaction and western immunoblotting assay to detect mRNA and protein expression of adipogenic transcription factors, respectively. RESULTS: Treatment with cytolase decreased flavanone rutinoside forms (narirutin and hesperidin) and instead, increased flavanone aglycoside forms (naringenin and hesperetin). During adipocyte differentiation, 3T3-L1 cells were treated with CU or CU-C at a dose of 0.5 mg/ml. Adipocyte differentiation was inhibited in CU-C group, but not in CU group. CU-C markedly suppressed the insulin-induced protein expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) as well as the mRNA levels of CEBPalpha, PPARgamma, and sterol regulatory element binding protein 1c (SREBP1c). Both CU and CU-C groups significantly increased the adipolytic activity with the higher release of free glycerol than those of control group in differentiated 3T3-L1 adipocytes. CU-C is particularly superior in suppression of adipogenesis, whereas CU-C has similar effect to CU on stimulation of lipolysis. CONCLUSIONS: These results suggest that bioconversion of Citrus unshiu peel extracts with cytolase enhances aglycoside flavonoids and improves the anti-adipogenic metabolism via both inhibition of key adipogenic transcription factors and induction of adipolytic activity.
3T3-L1 Cells* ; Adipocytes ; Adipogenesis ; Blotting, Western ; Cell Survival ; Citrus* ; Flavonoids ; Glycerol ; Lipid Metabolism ; Lipolysis ; Metabolism ; PPAR gamma ; RNA, Messenger ; Sterol Regulatory Element Binding Protein 1 ; Transcription Factors

Background: Liver fibrosis is an early stage of liver cirrhosis. As a reversible lesion before cirrhosis, liver failure, and liver cancer, it has been a target for drug discovery. Many antifibrotic candidates have shown promising results in experimental animal models; however, due to adverse clinical reactions, most antifibrotic agents are still preclinical. Therefore, rodent models have been used to examine the histopathological differences between the control and treatment groups to evaluate the efficacy of anti-fibrotic agents in non-clinical research. In addition, with improvements in digital image analysis incorporating artificial intelligence (AI), a few researchers have developed an automated quantification of fibrosis. However, the performance of multiple deep learning algorithms for the optimal quantification of hepatic fibrosis has not been evaluated. Here, we investigated three different localization algorithms, mask R-CNN, DeepLabV3+, and SSD, to detect hepatic fibrosis. Results: 5750 images with 7503 annotations were trained using the three algorithms, and the model performance was evaluated in large-scale images and compared to the training images. The results showed that the precision values were comparable among the algorithms. However, there was a gap in the recall, leading to a difference in model accuracy. The mask R-CNN outperformed the recall value (0.93) and showed the closest prediction results to the annotation for detecting hepatic fibrosis among the algorithms. DeepLabV3+ also showed good performance; however, it had limitations in the misprediction of hepatic fibrosis as inflammatory cells and connective tissue. The trained SSD showed the lowest performance and was limited in predicting hepatic fibrosis compared to the other algorithms because of its low recall value (0.75). Conclusions We suggest it would be a more useful tool to apply segmentation algorithms in implementing AI algorithms to predict hepatic fibrosis in non-clinical studies.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.