Traditional epidemiological studies have identified a number of risk factors for various diseases using regression-based methods that examine the association between an exposure and an outcome (i.e., one-to-one correspondences). One of the major limitations of this approach is the “black-box” aspect of the analysis, in the sense that this approach cannot fully explain complex relationships such as biological pathways. With high-throughput data in current epidemiology, comprehensive analyses are needed. The network approach can help to integrate multi-omics data, visualize their interactions or relationships, and make inferences in the context of biological mechanisms. This review aims to introduce network analysis for systems epidemiology, its procedures, and how to interpret its findings.

Traditional epidemiological studies have identified a number of risk factors for various diseases using regression-based methods that examine the association between an exposure and an outcome (i.e., one-to-one correspondences). One of the major limitations of this approach is the “black-box” aspect of the analysis, in the sense that this approach cannot fully explain complex relationships such as biological pathways. With high-throughput data in current epidemiology, comprehensive analyses are needed. The network approach can help to integrate multi-omics data, visualize their interactions or relationships, and make inferences in the context of biological mechanisms. This review aims to introduce network analysis for systems epidemiology, its procedures, and how to interpret its findings.

OBJECTIVES: Lifestyles, including exercise behaviors, change continually over time. This study examined whether the clinical biomarkers (CBs) related to cardiometabolic diseases (CMDs) and their relationships differed with changes in exercise behavior. METHODS: The Ansan-Ansung cohort study (third to fifth phases; n=2,668) was used in the current study. Regular exercise behavior was investigated using a yeso questionnaire. Changes in exercise behavior were classified into 4 groups: Y-N, N-Y, Y-Y, and N-N, with “Y” indicating that a participant regularly engaged in exercise at a given time point and “N” indicating that he or she did not. Fourteen CBs related to CMDs were used, and the associations between changes in exercise behavior and relative changes in CBs were examined. CB networks were constructed and topological comparisons were conducted. RESULTS: Y-N was associated with increases in fasting blood sugar and insulin levels in men, and increased total cholesterol and low-density lipoprotein cholesterol levels in women. Meanwhile, N-Y was inversely associated with body fat percentage, visceral fat percentage, fasting insulin, and triglyceride level. Waist circumference played a central role in most networks. In men, more edges were found in the N-Y and Y-Y groups than in the N-N and Y-N groups, whereas women in the N-Y and Y-Y groups had more edges than those in the N-N and Y-N groups. CONCLUSIONS Consistent exercise or starting to engage in regular exercise had favorable effects on CBs related to CMDs, although their network patterns differed between the sexes.

Gene-modified replication-competent adenoviruses (Ads) are emerging as a promising new modality for the treatment of cancer. We have previously shown that E1B 19kDa and E1B 55kDa gene deleted Ad (Ad-deltaE1B19/55) exhibits improved tumor-specific replication and cell lysis, leading to potent anti-tumor effect. As an additional effort to increase cancer cell-selectivity of replicating adenovirus, we have first generated eleven E1A-mutant Ads (Ad-mt#1~#11) with deletion or substitution in retinoblastoma (Rb) binding sites of E1A. Of these viruses, Ad-mt#7 demonstrated significantly improved cytopathic effect (CPE) and viral replication in a cancer cell-specific manner. To further increase the cancer cell-specific killing effect of Ad-mt#7, both E1B 19kDa and E1B 55kDa genes were deleted, resulting in an Ad-deltaE1Bmt7. As assessed using CPE assay, MTT assay, and immunoblot analysis for Ad fiber expression, Ad-deltaE1Bmt7 exerted markedly enhanced cancer cell-specific killing effect as well as viral replication in comparison to either Ad-mt#7 or Ad-deltaE1B19/55. Furthermore, the growth of established human cervical carcinoma in nude mice was significantly suppressed by intratumoral injection of Ad-deltaE1Bmt7. In summary, we have developed an oncolytic adenovirus with significantly improved therapeutic profiles for cancer treatment.
Adenoviridae* ; Animals ; Apoptosis ; Binding Sites ; Homicide ; Humans ; Mice ; Mice, Nude ; Retinoblastoma

BACKGROUND: Abdominal pain is a common complaint seen at emergency centers. Various diseases can cause abdomin al pain making it difficult to make a correct diagnosis. In the elderly, however, the consequences of an incorrect or delayed diagnosis can be more critical. We investigated the accuracy of initial diagnoses in the emergency center and analyzed the associations among medical factors including age. METHODS: We compared the ICD 10 codes of initial diagnoses to the codes of final diagnoses, defined the 'degree of agreement' using a 5 point scale, and classified patients into 'high degree of agreement' or 'low degree of agreement' groups. According to the severity of illness, we classified patients as 'admission' or 'out patient follow up'. According to their illness, we classified them as 'surgical' or 'medical'. According to age, we classified them as 'elderly' or 'adult'. Finally, we analyzed the statistical significance of each association. RESULTS: Overall, admitted patients and surgical diagnoses had higher degrees of agreement. 'Elderly' patients had no significant difference in 'degree of agreement' from 'adult' patients. CONCLUSION: Among patients presenting with acute abdominal pain to the emergency center, the degree of agreement between initial diagnosis and final diagnosis is dependent on the diagnostic characteristics of the disease, and not on the age of the patients. Further studies on the diagnostic accuracy of individual diseases are needed. Additional diagnosis associated variables, for example comorbidity and prognosis, needs to be studied regarding relationship to diagnostic accuracy.
Abdominal Pain ; Aged ; Comorbidity ; Delayed Diagnosis ; Emergencies ; Humans ; Prognosis

BACKGROUND: In spite of the improvement in the quality of artificial heart valves and surgical techniques, the incidence of the complications following valve replacement is still high. We reviewed the clinical results of the valve replacements performed in Korean University Anam Hospital during the last 26 years. MATERIAL AND METHOD: The data of 571 patients who received valve replacement between December 1976 and December 2003 were reviewed. RESULT: There were 304 cases of MVR which was the most common procedure performed. There were 122 cases of AVR, and 111 cases of AVR with MVR. Among the 47 patients who received redo operation 38 cases were redo cases including 31 cases of MVR. 32.5% of the patients who had tissue valve replacement had second valve replacement with 10.2+/-3.9 years interval. 24.3% (139/571) of the patients developed valve related complications and cerebral infarction was the highest in frequency. Atrial fibrillation was related with increased complication rates and the mechanical valve replaced group had higher hemorrhagic complication rate than tissue valve replaced group. The operative mortality was 3.68% and the most common cause of the failure was low output syndrome. The operative mortality was higher in the patient group who had valve replacement before the year 1990. The patient group who had mechanical valve replacement had higher operative mortality rate than the tissue valve group. The 5-year survival rate was 92.2% and 10 year survival rate was 85.7%. CONCLUSION: The operative mortality of valve replacement has been improved. The mechnical valve replaced patients had higher hemorrhagic complication rate than the tissue valve replaced patients and more tissue valve replaced patients received redo valve replacement.
Atrial Fibrillation ; Cerebral Infarction ; Heart Valve Diseases ; Heart Valves* ; Heart* ; Heart, Artificial ; Humans ; Incidence ; Mortality ; Survival Rate

Background: This study assessed the relationship between non-participation in health checkups and all-cause mortality and morbidity, considering socioeconomic status. Methods: Healthy, middle-aged (35–54 years) working individuals who maintained either self-employed or employee status from 2006–2010 were recruited in this retrospective cohort study from the National Health Insurance Service in Korea. Health check-up participation was calculated as the sum of the number of health check-ups in 2007–2008 and 2009–2010.Adjusted hazard ratio (HR) and 95% confidence interval (CI) of all-cause mortality were estimated for each gender using multivariable Cox proportional hazard models, adjusting for age, income, residential area, and employment status. Interaction of non-participation in health check-ups and employment status on the risk of all-cause mortality was further analyzed. Results: Among 4,267,243 individuals with a median 12-year follow-up (median age, 44;men, 74.43%), 89,030 (2.09%) died. The proportion (number) of deaths of individuals with no, one-time, and two-time participation in health check-ups was 3.53% (n = 47,496), 1.66% (n = 13,835), and 1.33% (n = 27,699), respectively. The association between health checkup participation and all-cause mortality showed a reverse J-shaped curve with the highest adjusted HR (95% CI) of 1.575 (1.541–1.611) and 1.718 (1.628–1.813) for men and women who did not attend any health check-ups, respectively. According to the interaction analysis, both genders showed significant additive and multiplicative interaction, with more pronounced additive interaction among women who did not attend health check-ups (relative excess risk due to interaction, 1.014 [0.871−1.158]). Conclusion Our study highlights the significant reverse J-shaped association between health check-up participation and all-cause mortality. A pronounced association was found among self-employed individuals, regardless of gender.

PURPOSE: The high mobility group box 1 (HMGB1) protein has roles in apoptosis and immune responses by acting as a ligand for receptor for advanced glycation end products (RAGE), Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 1. In particular, HMGB1/RAGE is involved in tumor metastasis by inducing matrix metalloproteinase 2 (MMP2) and MMP9 expression. We investigated the associations between genetic variations in HMGB1-related genes and disease-free survival (DFS) and overall survival (OS) in Korean female breast cancer patients. METHODS: A total of 2,027 patients in the Seoul Breast Cancer Study were included in the analysis. One hundred sixteen single nucleotide polymorphisms (SNPs) were extracted from eight genes. A multivariate Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) of each SNP. The effects of the SNPs on breast cancer prognosis were assessed at cumulative levels with polygenic risk scores. RESULTS: The SNPs significantly associated with DFS were rs243867 (hazard ratio, 1.26; 95% CI, 1.05–1.50) and rs243842 (hazard ratio, 1.24; 95% CI, 1.03–1.50); both SNPs were in MMP2. The SNPs significantly associated with OS were rs243842 in MMP2 (hazard ratio, 1.33; 95% CI 1.03–1.71), rs4145277 in HMGB1 (hazard ratio, 1.29; 95% CI, 1.00–1.66), rs7656411 in TLR2 (hazard ratio, 0.76; 95% CI, 0.60–0.98), and rs7045953 in TLR4 (hazard ratio, 0.50; 95% CI, 0.29–0.84). The polygenic risk score results for the DFS and OS patients showed third tertile hazard ratios of 1.72 (95% CI, 1.27–2.34) and 2.75 (95% CI, 1.79–4.23), respectively, over their first tertile references. CONCLUSION: The results of the present study indicate that genetic polymorphisms in HMGB1-related genes are related to breast cancer prognosis in Korean women.
Advanced Glycosylation End Product-Specific Receptor ; Apoptosis ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Female ; Genetic Predisposition to Disease* ; Genetic Variation ; HMGB1 Protein ; Humans ; Matrix Metalloproteinase 2 ; Myeloid Cells ; Neoplasm Metastasis ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Prognosis* ; Proportional Hazards Models ; Seoul ; Toll-Like Receptors

Background/Aims: The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrence Methods: Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed. Results: TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010). Conclusions The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.