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Plasma protein-based identification of neuroimage-driven subtypes in mild cognitive impairment via protein-protein interaction aware explainable graph propagational network
No full textAs an early indicator of dementia, mild cognitive impairment (MCI) requires specialized treatment according to its subtypes for the effective prevention and management of dementia progression. Based on the neuropathological characteristics, MCI can be classified into Alzheimer's disease (AD)-related cognitive impairment (ADCI) and subcortical vascular cognitive impairment (SVCI), being more likely to progress to AD and subcortical vascular dementia (SVD), respectively. For identifying MCI subtypes, plasma protein biomarkers are recently seen as promising tools due to their minimal invasiveness and cost-effectiveness in diagnostic procedures. Furthermore, the application of machine learning (ML) has led the preciseness in the biomarker discovery and the resulting diagnostics. Nevertheless, previous ML-based studies often fail to consider interactions between proteins, which are essential in complex neurodegenerative disorders such as MCI and dementia. Although protein-protein interactions (PPIs) have been employed in network models, these models frequently do not fully capture the diverse properties of PPIs due to their local awareness. This limitation increases the likelihood of overlooking critical components and amplifying the impact of noisy interactions. In this study, we introduce a new graph-based ML model for classifying MCI subtypes, called eXplainable Graph Propagational Network (XGPN). The proposed method extracts the globally interactive effects between proteins by propagating the independent effect of plasma proteins on the PPI network, and thereby, MCI subtypes are predicted by estimation of the risk effect of each protein. Moreover, the process of model training and the outcome of subtype classification are fully explainable due to the simplicity and transparency of XGPN's architecture. The experimental results indicated that the interactive effect between proteins significantly contributed to the distinct differences between MCI subtype groups, resulting in an enhanced classification performance with an average improvement of 10.0 % compared to existing methods, also identifying key biomarkers and their impact on ADCI and SVCI
Trends in the incidence of young-adult-onset diabetes by diabetes type: a multi-national population-based study from an international diabetes consortium
No full textBackground: Population-based incidence data on young-adult-onset type 1 diabetes and type 2 diabetes are limited. We aimed to examine secular trends in the incidence of diagnosed type 1 diabetes and type 2 diabetes with an age of onset between 15 and 39 years. Methods: In this multicountry aggregate data analysis, we assembled eight administrative datasets from high-income jurisdictions and countries (Australia, Denmark, Finland, Hungary, Japan, Scotland, South Korea, and Spain [Catalonia]) that had appropriate data available from an international diabetes consortium (GLOBODIAB) describing incidence by diabetes type among people aged 15–39 years from 2000 to 2020. We modelled type 1 diabetes and type 2 diabetes incidence rates using Poisson regression including age and calendar time by sex. Findings: During the years 2000–20, there were 349 591 incident diabetes (both types) cases from 346 million person-years of follow-up among people aged 15–39 years. Over time, there was no statistically significant change in the incidence of type 1 diabetes in Hungary and Japan. The incidence of type 1 diabetes significantly increased in Australia, Denmark, Finland, Scotland, South Korea, and Spain, with annual changes ranging from 0·5% to 6·0%. The incidence of type 2 diabetes significantly increased in four of eight jurisdictions (Denmark, Finland, Japan, and South Korea), with annual increases from 2·0% to 8·5%. The magnitude of increase in incidence of type 2 diabetes was greater in Asian than non-Asian jurisdictions. There was no statistically significant change in type 2 diabetes incidence in Australia and Hungary. The incidence of type 2 diabetes significantly decreased in Scotland and Spain, with annual changes of –0·7% and –1·5%, respectively. Interpretation: There is variability in the trajectory of the incidence of young-adult-onset type 2 diabetes among high-income countries or jurisdictions, with a greater evidence of increase in Asian than non-Asian countries. Evolving trends in the incidence of type 1 and type 2 diabetes in young adults call for the ongoing surveillance of diabetes incidence and a greater research focus on this population. Funding: US Centers for Disease Control and Prevention, Diabetes Australia Research Programme, and Victoria State Government Operational Infrastructure Support Programme
국내 간호대학(학과)의 학사편입학 과정 현황 분석과 발전전략
Get PDFPurpose: This study examines the current status of a second-degree Bachelor of Science in Nursing (BSN) program in South Korea, identifies its advantages and limitations, and provides future directions for improving the program. Methods: A mixed-methods, sequential explanatory design was employed. A cross-sectional survey (n=28 faculty members, 122 enrolled students, 20 graduates) was conducted, followed by focus group interviews (n=six faculty members, 13 enrolled students, six graduates). Results: Among the 28 nursing colleges, 19 had a second-degree BSN program enrollment capacity of less than 10% of their total student capacity, whereas six colleges had a capacity ranging from 20% to 30%. The advantages of the program included producing nurses with diverse backgrounds, demonstrating a strong aspiration for the nursing profession, diligent attitude, and mature interpersonal skills among the second-degree BSN students. The limitations included inadequate support and resources for program operations, difficulties in ensuring the quality of classes and clinical practice, and limited opportunities for interaction with other students. Conclusion: This study highlights the importance of establishing clear policies and guidelines for such programs and developing standardized curricula to ensure high-quality nursing education while accommodating an increasing number of students
Exploring 3D Printed Implants with Anti-Dropout Function to Overcome Time Constraints in Acute Orbital Fractures for Patient-Specific Implants
Get PDFOrbital wall reconstruction and implant insertion are crucial procedures for temporarily replacing the orbital walls in cases of significant fractures. Traditional methods using planar orbital implants have faced challenges owing to their flat shape, which increases the risk of dislocation from improper cuts and necessitates the use of screws in the orbital rim. This study aims to improve outcomes by employing customized 3-dimensional implants, thereby reducing complications and risk of dislocation resulting from external shock or implant weight postinsertion. This prospective study included 12 Korean individuals diagnosed with facial fractures (orbital wall injuries). Surgeries were performed on 12 patients, and follow-up CT scans were conducted on 10 of them. Therefore, the authors could only address the results for the 10 patients. The authors used bioactive glass ceramics and medical-grade poly-e-caprolactone to 3D print personalized implants, completing the manufacturing process in an average of 4.6 days. Computed tomography scans guided measurements of orbital volumes and exophthalmos. After surgery, we found that the difference values for bone orbital volumes (<0.1 mL) and exophthalmos (<1 mm except one) decreased compared with presurgery values. Independent t tests and Pearson correlation analysis revealed no significant changes between normal and affected sides in both phases. However, R-values increased in the postsurgery phase. Patients monitored postsurgery at 2 weeks, 3 months, and 6 months showed no complications. The 3D-printed patient-specific implants, customized to individual fracture shapes and featuring distinct implants and locking parts with notches, effectively restore bony orbital volumes and reduce exophthalmos. They have been proven feasible and applicable for reconstructing acute orbital wall fractures
Ethnic differences in the prevalence of amyloid positivity and cognitive trajectories
Get PDFINTRODUCTION: We investigated the prevalence of amyloid beta (Aβ) positivity (+) and cognitive trajectories in Koreans and non-Hispanic Whites (NHWs). METHODS: We included 5121 Koreans from multiple centers across South Korea and 929 NHWs from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants underwent Aβ positron emission tomography and were categorized into cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia stages. Age, sex, education, and apolipoprotein E. genotype were adjusted using multivariable logistic regression and stabilized inverse probability of treatment weights based on the propensity scores to mitigate imbalances in these variables. RESULTS: The prevalence of Aβ+ was lower in CU Koreans than in CU NHWs (adjusted odds ratio 0.60). Aβ+ Koreans showed a faster cognitive decline than Aβ+ NHWs in the CU (B = −0.314, p =.004) and MCI stages (B = −0.385, p <.001). DISCUSSION: Ethnic characteristics of Aβ biomarkers should be considered in research and clinical application of Aβ-targeted therapies in diverse populations. Highlights: Koreans have a lower prevalence of Aβ positivity compared to NHWs in the CU stage. The effects of Alzheimer's risk factors on Aβ positivity differ between Koreans and NHWs. Aβ-positive (Aβ+) Koreans show faster cognitive decline than Aβ+ NHWs in the CU and MCI stages
Real-world safety and effectiveness of lenvatinib in unresectable hepatocellular carcinoma in Korea: post-marketing study
Get PDFAim: This post-marketing surveillance study evaluated the safety and effectiveness of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma in Korea. Materials & methods: Adverse drug reactions (ADRs) and other safety and effectiveness end points were assessed in patients who initiated lenvatinib according to the approved label in republic of Korea. Results: Among 658 lenvatinib-treated patients, ADRs were reported in 57.8%; ADRs grade ≥3 in 13.5%. The most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Physician-reported tumor responses (n = 511) were complete (1.0%) or partial (12.9%) response and stable (45.2%) or progressive disease (40.9%); objective response rates were higher with longer lenvatinib treatment duration (p < 0.001). Conclusion: Lenvatinib was generally well tolerated and effective in real-world clinical practice in Korea. Clinical trial registration:ClinicalTrials.govNCT05225207
Sex-specific risk factors and clinical dementia outcomes for white matter hyperintensities in a large South Korean cohort
Get PDFObjective: White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH’s impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods: Participants aged 49–89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1–2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results: The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion: Older females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration: The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14
Prediction of menstrual recovery patterns in premenopausal women with breast cancer taking tamoxifen after chemotherapy: an ASTRRA Substudy
Get PDFBackground: Chemo-endocrine therapy can lead to various side effects associated with ovarian dysfunction. Predicting menstrual recovery is necessary to discuss the treatment-related issues regarding fertility and premature menopause with patients. Methods: In the ASTRRA trial, patients who resumed ovarian function within 2 years after chemotherapy were randomized to receive tamoxifen for 5 years or OFS with tamoxifen for 2 years. With these 1298 patients, we developed a model that predicts when menstrual recovery will occur within a 3-year period after chemotherapy using variables including age, body mass index, chemotherapy regimen and duration, and serum estradiol and follicle-stimulating hormone levels. Results: The data of 957 patients were used to develop the prediction model, and those of 341 patients were used for validation. In the development group, menstruation resumed in 450 patients (47.0%) within 5 years. In multivariable analysis, younger age (< 35 vs. 45, HR 7.85, 95% CI 4.63–13.30, p < 0.0001), anthracycline-based chemotherapy without taxane (vs. with taxane, HR 1.81, 95% CI 1.37–2.38, p < 0.0001), and chemotherapy duration (≤ 90 days vs. > 90 days, HR 1.32, 95% CI 1.01–1.72, p = 0.045) correlated with menstrual recovery. Using combined age, regimen, and duration of chemotherapy, we developed a simplified scoring system to estimate recovery chances and used a concordance index of 0.679 overall and 0.744 at 3 years for validation. Conclusion: This model predicted timing and probability of menstrual recovery, based on their individual age, type and duration of chemotherapy in premenopausal women diagnosed with breast cancer who received tamoxifen after chemotherapy
Integrative Metabolome and Proteome Analysis of Cerebrospinal Fluid in Parkinson’s Disease
Get PDFParkinson’s disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Recent studies have highlighted the significant role of cerebrospinal fluid (CSF) in reflecting pathophysiological PD brain conditions by analyzing the components of CSF. Based on the published literature, we created a single network with altered metabolites in the CSF of patients with PD. We analyzed biological functions related to the transmembrane of mitochondria, respiration of mitochondria, neurodegeneration, and PD using a bioinformatics tool. As the proteome reflects phenotypes, we collected proteome data based on published papers, and the biological function of the single network showed similarities with that of the metabolomic network. Then, we analyzed the single network of integrated metabolome and proteome. In silico predictions based on the single network with integrated metabolomics and proteomics showed that neurodegeneration and PD were predicted to be activated. In contrast, mitochondrial transmembrane activity and respiration were predicted to be suppressed in the CSF of patients with PD. This review underscores the importance of integrated omics analyses in deciphering PD’s complex biochemical networks underlying neurodegeneration
Combined impact of prediabetes and hepatic steatosis on cardiometabolic outcomes in young adults
Get PDFObjectives: This study aimed to investigate the impact of hepatic steatosis on cardiometabolic outcomes in young adults with prediabetes. Methods: A nationwide cohort study was conducted with 896,585 young adults under 40 years old without diabetes or previous history of cardiovascular disease. Hepatic steatosis was identified using a fatty liver index of ≥ 60. The outcomes of this study were incident diabetes (DM) and composite major adverse cardiovascular events (MACE), including myocardial infarction, stroke, or cardiovascular death. Results: During a median follow-up of 11.8 years, 27,437 (3.1%) incident DM cases and 6,584 (0.7%) MACE cases were recorded. Young adults with prediabetes had a significantly higher risk of incident DM (hazard ratio [HR]: 2.81; 95% confidence interval [CI]: 2.74–2.88; P-value: <0.001) and composite MACE risk (HR: 1.10; 95% CI: 1.03–1.17; P-value: 0.003) compared to individuals with normoglycemia, after adjusting for relevant covariates. Stratification based on hepatic steatosis showed that the combination of prediabetes and hepatic steatosis posed the highest risk for these outcomes, after adjusting for relevant covariates. For incident DM, the HRs (95% CI; P-value) were: 3.15 (3.05–3.26; <0.001) for prediabetes without hepatic steatosis, 2.89 (2.78–3.01; <0.001) for normoglycemia with hepatic steatosis, and 6.60 (6.33–6.87; <0.001) for prediabetes with hepatic steatosis. For composite MACE, the HRs (95% CI; P-value) were 1.05 (0.97–1.13; 0.235) for prediabetes without hepatic steatosis, 1.39 (1.27–1.51; <0.001) for normoglycemia with hepatic steatosis, and 1.60 (1.44–1.78; <0.001) for prediabetes with hepatic steatosis. Conclusions: Prediabetes and hepatic steatosis additively increased the risk of cardiometabolic outcomes in young adults. These findings hold significance for physicians as they provide insights into assessing high-risk individuals among young adults with prediabetes