A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Purpose: This study evaluated the treatment outcomes of benign and malignant tumors of the foot to establish the treatment guidelines for foot tumors. Materials and Methods: Eighty-three (41 male and 42 female) cases were included in the study. All patients were treated in a single institution from January 2006 to December 2022. The mean age was 43 years (range, 12–92). The mean follow-up period was 91 months (range, 5–208 months). The location of the tumor, recurrence following surgery, histologic diagnosis, overall five-year survival rate, and disease-specific five-year survival rate were evaluated. The oncologic results were analyzed at the final follow-up. Results: Benign tumors were found in 60 cases and malignant tumors were found in 23 cases. The 41 male cases composed 25 cases of benign tumors and 16 cases of malignant tumors. The 42 female cases composed 35 cases of benign tumors and seven cases of malignant tumors. The tumor locations were 61 cases in the forefoot, five in the midfoot, and 17 in the hindfoot. Reoperation was performed in two cases due to recurrence. An un-planned excision was done in two cases, which led to secondary wide resections. The overall five-year survival rate was 65.9% (58.3% in males and 85.7% in females). The disease-specific five-year survival rate was 62.3% (62.5% in males and 66.7% in females). The oncologic outcomes of 23 malignant cases were continuous disease-free in 16 cases and died of disease in seven cases at the final follow-up. Conclusion Benign foot tumors were dominant (72%) in this study. The preferred location was the forefoot, with statistical significance (p<0.05). There were no statistical significant differences between males and females (p>0.05). This study provides the guidelines for treating benign and malignant foot tumors by analyzing the treatment and oncologic outcomes.

Purpose: This study evaluated the treatment outcomes of benign and malignant tumors of the foot to establish the treatment guidelines for foot tumors. Materials and Methods: Eighty-three (41 male and 42 female) cases were included in the study. All patients were treated in a single institution from January 2006 to December 2022. The mean age was 43 years (range, 12–92). The mean follow-up period was 91 months (range, 5–208 months). The location of the tumor, recurrence following surgery, histologic diagnosis, overall five-year survival rate, and disease-specific five-year survival rate were evaluated. The oncologic results were analyzed at the final follow-up. Results: Benign tumors were found in 60 cases and malignant tumors were found in 23 cases. The 41 male cases composed 25 cases of benign tumors and 16 cases of malignant tumors. The 42 female cases composed 35 cases of benign tumors and seven cases of malignant tumors. The tumor locations were 61 cases in the forefoot, five in the midfoot, and 17 in the hindfoot. Reoperation was performed in two cases due to recurrence. An un-planned excision was done in two cases, which led to secondary wide resections. The overall five-year survival rate was 65.9% (58.3% in males and 85.7% in females). The disease-specific five-year survival rate was 62.3% (62.5% in males and 66.7% in females). The oncologic outcomes of 23 malignant cases were continuous disease-free in 16 cases and died of disease in seven cases at the final follow-up. Conclusion Benign foot tumors were dominant (72%) in this study. The preferred location was the forefoot, with statistical significance (p<0.05). There were no statistical significant differences between males and females (p>0.05). This study provides the guidelines for treating benign and malignant foot tumors by analyzing the treatment and oncologic outcomes.

Purpose: This study evaluated the treatment outcomes of benign and malignant tumors of the foot to establish the treatment guidelines for foot tumors. Materials and Methods: Eighty-three (41 male and 42 female) cases were included in the study. All patients were treated in a single institution from January 2006 to December 2022. The mean age was 43 years (range, 12–92). The mean follow-up period was 91 months (range, 5–208 months). The location of the tumor, recurrence following surgery, histologic diagnosis, overall five-year survival rate, and disease-specific five-year survival rate were evaluated. The oncologic results were analyzed at the final follow-up. Results: Benign tumors were found in 60 cases and malignant tumors were found in 23 cases. The 41 male cases composed 25 cases of benign tumors and 16 cases of malignant tumors. The 42 female cases composed 35 cases of benign tumors and seven cases of malignant tumors. The tumor locations were 61 cases in the forefoot, five in the midfoot, and 17 in the hindfoot. Reoperation was performed in two cases due to recurrence. An un-planned excision was done in two cases, which led to secondary wide resections. The overall five-year survival rate was 65.9% (58.3% in males and 85.7% in females). The disease-specific five-year survival rate was 62.3% (62.5% in males and 66.7% in females). The oncologic outcomes of 23 malignant cases were continuous disease-free in 16 cases and died of disease in seven cases at the final follow-up. Conclusion Benign foot tumors were dominant (72%) in this study. The preferred location was the forefoot, with statistical significance (p<0.05). There were no statistical significant differences between males and females (p>0.05). This study provides the guidelines for treating benign and malignant foot tumors by analyzing the treatment and oncologic outcomes.

Objectives: Electrocardiography (ECG)-based diagnosis by experts cannot maintain uniform quality because individual differences may occur. Previous public databases can be used for clinical studies, but there is no common standard that would allow databases to be combined. For this reason, it is difficult to conduct research that derives results by combining databases. Recent commercial ECG machines offer diagnoses similar to those of a physician. Therefore, the purpose of this study was to construct a standardized ECG database using computerized diagnoses. Methods: The constructed database was standardized using Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) and Observational Medical Outcomes Partnership–common data model (OMOP-CDM), and data were then categorized into 10 groups based on the Minnesota classification. In addition, to extract high-quality waveforms, poor-quality ECGs were removed, and database bias was minimized by extracting at least 2,000 cases for each group. To check database quality, the difference in baseline displacement according to whether poor ECGs were removed was analyzed, and the usefulness of the database was verified with seven classification models using waveforms. Results: The standardized KURIAS-ECG database consists of high-quality ECGs from 13,862 patients, with about 20,000 data points, making it possible to obtain more than 2,000 for each Minnesota classification. An artificial intelligence classification model using the data extracted through SNOMED-CT showed an average accuracy of 88.03%. Conclusions The KURIAS-ECG database contains standardized ECG data extracted from various machines. The proposed protocol should promote cardiovascular disease research using big data and artificial intelligence.

Objective: We investigated the effects of a quick Sequential Organ Failure Assessment (qSOFA)–negative result (qSOFA score <2 points) at triage on the compliance with sepsis bundles among patients with sepsis who presented to the emergency department (ED). Methods: Prospective sepsis registry data from 11 urban tertiary hospital EDs between October 2015 and April 2018 were retrospectively reviewed. Patients who met the Third International Consensus Definitions for Sepsis and Septic Shock criteria were included. Primary exposure was defined as a qSOFA score ≥2 points at ED triage. The primary outcome was defined as 3-hour bundle compliance, including lactate measurement, blood culture, broad-spectrum antibiotics administration, and 30 mL/kg crystalloid administration. Multivariate logistic regression analysis to predict 3-hour bundle compliance was performed. Results: Among the 2,250 patients enrolled in the registry, 2,087 fulfilled the sepsis criteria. Only 31.4% (656/2,087) of the sepsis patients had qSOFA scores ≥2 points at triage. Patients with qSOFA scores <2 points had lower lactate levels, lower SOFA scores, and a lower 28-day mortality rate. Rates of compliance with lactate measurement (adjusted odds ratio [aOR], 0.47; 95% confidence interval [CI], 0.29–0.75), antibiotics administration (aOR, 0.64; 95% CI, 0.52–0.78), and 30 mL/kg crystalloid administration (aOR, 0.62; 95% CI, 0.49–0.77) within 3 hours from triage were significantly lower in patients with qSOFA scores <2 points. However, the rate of compliance with blood culture within 3 hours from triage (aOR, 1.66; 95% CI, 1.33–2.08) was higher in patients with qSOFA scores <2 points. Conclusion A qSOFA-negative result at ED triage is associated with low compliance with lactate measurement, broad-spectrum antibiotics administration, and 30 mL/kg crystalloid administration within 3 hours in sepsis patients.

Background: Insulin resistance (IR) and inflammation are closely related to each other and share common pathophysiological and metabolic mechanisms. We aimed to investigate the combined effect of IR and inflammation on comorbidities of type 2 diabetes mellitus (T2DM). Methods: A total 3,758 patients with T2DM were recruited through Huh’s Diabetes Center from January 2003 to June 2009. Insulin sensitivity was measured by a rate constant for plasma glucose disappearance (Kitt , %/min) using short insulin tolerance test. High sensitivity C-reactive protein (hs-CRP) was used as a surrogate for inflammation. Results: Patients with the lowest tertile of Kitt (IR group) showed worse cardio-metabolic parameters while those with the highest tertile of hs-CRP levels had worse cardio-metabolic parameters. The prevalence of metabolic syndrome, fatty liver, albuminuria, and carotid atherosclerosis decreased with Kitt tertile, but increased with hs-CRP tertile. In multiple regression analysis, both Kitt and hs-CRP were independent risk factors for comorbidities of T2DM. In addition, they showed synergistic effects on these comorbidities. Conclusion Both IR and inflammation were significantly associated with comorbidities of T2DM in a dose dependent manner. In addition, the coexistence of IR and inflammation may synergistically contribute to increased comorbidities of T2DM.

Objective: Prior studies have explored the relationship between initial body temperature (BT) and mortality in patients with sepsis in the emergency department (ED). However, there has been no study on whether or not changes in BT are associated with prognosis in these patients. We hypothesize that BT measured upon ED arrival and septic shock registry enroll time are related to the prognosis of patients with septic shock. Methods: We conducted a prospective, observational, registry-based study. Each patient was assigned to 1 of 4 groups according to BT upon ED arrival and registry enrollment. Odds ratios for 28-day mortality according to the patient group were estimated using multivariable logistic regression. We also conducted logistic regression sensitivity analysis, except for patients whose time interval between arrival and enrollment was less than 1 hour. Results: A total of 2,138 patients with septic shock were included. The 28-day mortalities were 13.7%, 11.2%, 13.0%, and 25.8% in groups 1, 2, 3, and 4, respectively (P<0.001). After adjusting for age, sex, mean atrial pressure, respiratory rate, Sequential Organ Failure Assessment score, lactate concentration, comorbidity, and suspicious infection focus, the risk of mortality was significantly low in patients from group 1 (adjusted odds ratio [aOR], 0.433; 95% confidence interval [CI], 0.310-0.604) and group 2 (aOR, 0.540; 95% CI, 0.336-0.868) compared with group 4. In the sensitivity analysis, group based on BT measured upon ED arrival and registry enrollment also remained an independent predictor of mortality. Conclusion Afebrile status upon ED arrival and registry enrollment were strongly associated with higher 28-day mortality in patients with septic shock.

Background: Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM. Methods: We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography. Results: LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002). Conclusions Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.

OBJECTIVE: Endotracheal intubation (ETI) is the most reliable way to manage the airway. Stepwise deliberate practice and mastery training is essential in maintaining and promoting the skill of intubation. This study was conducted to identify differences in examiners' expectations regarding competent skill performance and to develop learner-adjusted assessment tools with appropriate levels according to student and resident learners based on the expectations and limited observation of performance by examiners. METHODS: This was an exploratory, psychometric study using a simple airway part task trainer. The draft ETI assessment tool from the literatures, previous tools, and the preliminary learner-adjusted assessment tool for students and residents were developed and analyzed. Knowledge-based and competence-based items for each learner group were identified based on experts' expectations. The final learner-adjusted tools were refined through analyzing the content validity, internal consistency, and interrater reliability based on assessing the observed performance of 14 students and 12 residents by ten experts. RESULTS: The preliminary student-adjusted assessment tool and resident-adjusted assessment tool had 12 items on the checklist with a ternary scoring system and a ternary scoring checklist including 15 items, and an overall Global Rating Scale. The final student-adjusted assessment tool was composed of a ternary scoring checklist including 9 items (total CVI, 86.6%; Cronbach's α, 0.83; interrater reliability, 0.64). The resident-adjusted assessment, on the other hand, was also composed of a ternary scoring checklist including 12 items (total CVI, 86.4%; Cronbach's α, 0.7; interrater reliability, 0.78), in addition to global rating scale including ‘rating of the overall process’. CONCLUSION: The experts had different expectations regarding the level of competence in each step according to learner groups with different levels of difficulty. Understanding the factors influencing assessments can provide a guide for teaching and objectively assessing to the examiner.
Checklist ; Hand ; Humans ; Intubation ; Intubation, Intratracheal ; Mental Competency ; Psychometrics