Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Background/Aims: A comprehensive analysis of trends in the incidence of hepatocellular carcinoma (HCC) is important for planning public health initiatives. We aimed to analyze the trends in HCC incidence in South Korea over 10 years and to predict the incidence for the year 2028. Methods: Data from patients with newly diagnosed HCC between 2008 and 2018 were obtained from Korean National Health Insurance Service database. Age-standardized incidence rates (ASRs) were calculated to compare HCC incidence. A poisson regression model was used to predict the future incidence of HCC. Results: The average crude incidence rate (CR) was 22.4 per 100,000 person-years, and the average ASR was 17.6 per 100,000 person-years between 2008 and 2018. The CR (from 23.9 to 21.2 per 100,000 person-years) and ASR (from 21.9 to 14.3 per 100,000 person-years) of HCC incidence decreased during the past ten years in all age groups, except in the elderly. The ASR of patients aged ≥80 years increased significantly (from 70.0 to 160.2/100,000 person-years; average annual percent change, +9.00%; P<0.001). The estimated CR (17.9 per 100,000 person-years) and ASR (9.7 per 100,000 person-years) of HCC incidence in 2028 was declined, but the number of HCC patients aged ≥80 years in 2028 will be quadruple greater than the number of HCC patients in 2008 (from 521 to 2,055), comprising 21.3% of all HCC patients in 2028. Conclusions The ASRs of HCC in Korea have gradually declined over the past 10 years, but the number, CR, and ASR are increasing in patients aged ≥80 years.

Alternative complement pathway dysregulation plays a key role in glomerulonephritis (GN) and is associated with C3 deposition. Herein, we examined pathological and clinical differences between cases of primary GN with C3-dominant (C3D-GN) and nondominant (C3ND-GN) deposition. Methods: We extracted primary GN data from the Korean GlomeruloNEphritis sTudy (KoGNET). C3D-GN was defined as C3 staining two grades greater than C1q, C4, and immunoglobulin via immunofluorescence analysis. To overcome a large difference in the number of patients between the C3D-GN and C3ND-GN groups (31 vs. 9,689), permutation testing was used for analysis. Results: The C3D-GN group exhibited higher serum creatinine (p ≤ 0.001), a greater prevalence of estimated glomerular filtration rate of <60 mL/min/1.72 m2 (p ≤ 0.001), higher (but not significantly so) C-reactive protein level, and lower serum C3 level (p ≤ 0.001). Serum albumin, urine protein/creatinine ratio, number of patients who progressed to end-stage renal disease, and all-cause mortality were comparable between groups. Interstitial fibrosis and mesangial cellularity were greater in the C3D-GN group (p = 0.04 and p = 0.01, respectively) than in the C3ND-GN group. C3 deposition was dominant in the former group (p < 0.001), in parallel with increased subendothelial deposition (p ≤ 0.001). Conclusion: Greater progression of renal injury and higher mortality occurred in patients with C3D-GN than with C3ND-GN, along with pathologic differences in interstitial and mesangial changes.

BACKGROUND/AIMS: An association between obesity and erosive esophagitis has been reported, but the effects of sarcopenia and obesity on erosive esophagitis are unknown. This study examined the relationship between obesity, sarcopenia, sarcopenic obesity, and erosive esophagitis in a large population of asymptomatic men and women.METHODS: This study analyzed 32,762 subjects who underwent a comprehensive health check-up, which included upper gastrointestinal endoscopy, from August 2006 to December 2011 by a cross-sectional study. Sarcopenia was defined as a decrease in the appendicular skeletal muscle mass (ASM)/body weight value of two SD or more below the normal means for a younger reference group.RESULTS: The study was carried out on four groups according to obesity and sarcopenic status: normal, obesity, sarcopenic, and sarcopenic obese group. In a multivariable model, the risk of erosive esophagitis was higher in the obese (adjusted OR [aOR] 1.35, 95% CI 1.22–1.49), sarcopenic (aOR 2.12, 95% CI 1.40–3.19), and sarcopenic obese groups (aOR 1.54, 95% CI 1.27–1.87) than in the normal group. The risk of erosive esophagitis was higher in the sarcopenic and sarcopenic obese groups than the obese group; the ORs were 1.63 (95% CI 1.08–2.47) and 1.22 (95% CI 1.01–1.46), respectively. In dose-response analysis, increasing sarcopenia severity showed a positive and graded relationship with the overall, Los Angeles (LA)-B or higher grade, and LA-C erosive esophagitis.CONCLUSIONS: This study suggests that sarcopenia is strongly and progressively associated with erosive esophagitis.

BACKGROUND: In order to provide essential scientific evidence on the population's health status and social health determinants as well as the current capacity of the health care system in Vietnam to health policy makers and managers, Vietnam Ministry of Health, Hanoi University of Public Health, Hanoi Medical University, and Ho Chi Minh University of Medicine and Pharmacy collaborated with Seoul National University (Korea) and conducted a health system survey in the Quoc Oai district (of Hanoi capital) that represented northern rural Vietnam. METHODS: The study design was a cross-sectional study. The survey covered different topics (more than 200 questions) and was administered in three separate questionnaires: 1) Basic information of all household members; 2) Household characteristics; and 3) Individual characteristics. Socio-demographic characteristics among the households and individuals were collected from 2,400 households sampled by multi-stage cluster sampling method: more than 200 questions. RESULTS: The household size of Quoc Oai was larger than the national average and there was no significant difference in gender composition. In addition, the proportions of pre-elderly, age 55–64, and elderly group (65 years old and over) were higher than the national population statistics. In this context, demographic transition has begun in Quoc Oai. CONCLUSION: This study design description provides the basic information about a baseline survey of a future prospective cohort (as a part of a collaborative project on strengthening the health system in Vietnam) to the prospective data user of this survey.
Aged ; Cohort Studies ; Cross-Sectional Studies ; Delivery of Health Care ; Family Characteristics ; Health Policy ; Humans ; Methods ; Pharmacy ; Population Characteristics ; Population Dynamics ; Prospective Studies ; Public Health ; Seoul ; Surveys and Questionnaires ; Vietnam

BACKGROUND: The question of which type of prosthetic aortic valve leads to the best outcomes in patients in their 60s remains controversial. We examined the hemodynamic and clinical outcomes of aortic valve replacement in sexagenarians according to the type of prosthesis. METHODS: We retrospectively reviewed 270 patients in their 60s who underwent first-time aortic valve replacement from 1995 to 2011. Early and late mortality, major adverse valve-related events, anticoagulation-related events, and hemodynamic outcomes were assessed. The mean follow-up duration was 58.7±44.0 months. RESULTS: Of the 270 patients, 93 had a mechanical prosthesis (mechanical group), and 177 had a bioprosthesis (tissue group). The tissue group had a higher mean age and prevalence of preoperative stroke than the mechanical group. The groups had no differences in the aortic valve mean pressure gradient (AVMPG) or the left ventricular mass index (LVMI) at 5 years after surgery. In a sub-analysis limited to prostheses in the supra-annular position, the AVMPG was higher in the tissue group, but the LVMI was still not significantly different. There was no early mortality. The 10-year survival rate was 83% in the mechanical group and 90% in the tissue group. The type of aortic prosthesis did not influence overall mortality, cardiac mortality, or major adverse valve-related events. Anticoagulation-related events were more common in the mechanical group than in the tissue group (p=0.034; hazard ratio, 4.100; 95% confidence interval, 1.111–15.132). CONCLUSION: The type of aortic prosthesis was not associated with hemodynamic or clinical outcomes, except for anticoagulation-related events.
Aortic Valve ; Bioprosthesis ; Follow-Up Studies ; Hemodynamics* ; Humans ; Mortality ; Prevalence ; Prostheses and Implants* ; Retrospective Studies ; Stroke ; Survival Rate

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection has been known to cause various extra-gastric diseases, which may be mediated by an increase in systemic inflammation. Thus, we examined the association between H. pylori infection and various markers of systemic inflammation in a large sample of asymptomatic adults. METHODS: Cross-sectional data were obtained from 17,028 adults who completed routine health check-ups. H. pylori infection status was determined using a serum immunoglobulin G test, and systemic inflammation was assessed using the C-reactive protein (CRP) levels, neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR). RESULTS: Multiple linear regression model-adjusted for potential confounders-revealed that H. pylori infection was not associated with CRP levels (coefficient: −0.012, 95% confidence interval [CI]: −0.037, 0.012, p=0.319), NLR (coefficient: 0.055, 95% CI: −0.027, 0.138, p=0.192), or PLR (coefficient: 1.798, 95% CI: −1.979, 5.574, p=0.351). In a multivariable logistic regression model, H. pylori infection was not associated with the risk of CRP levels being elevated to ≥0.1 mg/dL (odds ratio: 0.96, 95% CI: 0.81, 1.08) or ≥0.3 mg/dL (odds ratio: 1.02, 95% CI: 0.84, 1.19). In the multivariable model, CRP levels elevated to ≥0.1 mg/dL were significantly associated with body mass index, current smoking status, hypertension, and diabetes mellitus. Regular exercise and high-density lipoprotein cholesterol were factors that minimized the elevation of CRP levels. CONCLUSIONS: Chronic infection with H. pylori was not associated with various inflammatory markers. Further investigation is needed to clarify the interaction between H. pylori infection, systemic inflammation, and extra-gastric disease.
Adult* ; Body Mass Index ; C-Reactive Protein ; Cholesterol ; Diabetes Mellitus ; Helicobacter pylori* ; Helicobacter* ; Humans ; Hypertension ; Immunoglobulin G ; Inflammation* ; Linear Models ; Lipoproteins ; Logistic Models ; Smoke ; Smoking

BACKGROUND AND PURPOSE: Perfusion-diffusion mismatch has been evaluated to determine whether the presence of a target mismatch helps to identify patients who respond favorably to recanalization therapies. We compared the impact on infarct growth of collateral status and the presence of a penumbra, using magnetic resonance perfusion (MRP) techniques. METHODS: Consecutive patients who were candidates for recanalization therapy and underwent serial diffusion-weighted imaging (DWI) and MRP were enrolled. A collateral flow map derived from MRP source data was generated by automatic post-processing. The impact of a target mismatch (Tmax>6 s/apparent diffusion coefficient (ADC) volume≥1.8, ADC volume<70 mL; and Tmax>10 s for ADC volume<100 mL) on infarct growth was compared with MR-based collateral grading on day 7 DWI, using multivariate linear regression analysis. RESULTS: Among 73 patients, 55 (75%) showed a target mismatch, whereas collaterals were poor in 14 (19.2%), intermediate in 36 (49.3%), and good in 23 (31.5%) patients. After adjusting for initial severity of stroke, early recanalization (P<0.001) and the MR-based collateral grading (P=0.001), but not the presence of a target mismatch, were independently associated with infarct growth. Even in patients with a target mismatch and successful recanalization, the degree of infarct growth depended on the collateral status. Perfusion status at later Tmax time points (beyond the arterial phase) was more closely correlated with collateral status. CONCLUSIONS: Patients with good collaterals show a favorable outcome in terms of infarct growth, regardless of the presence of a target mismatch pattern. The presence of slow blood filling predicts collateral status and infarct growth.
Collateral Circulation ; Diffusion ; Humans ; Linear Models ; Magnetic Resonance Imaging ; Perfusion ; Stroke