Subjective Cognitive Decline in Community-Dwelling Older Adults With Objectively Normal Cognition: Mediation by Depression and Instrumental Activities of Daily Living.

OBJECTIVE: Subjective cognitive decline (SCD) refers to self-reported memory loss despite normal cognitive function and is considered a preclinical stage of Alzheimer's disease. This study aimed to examine the mediating effects of depression and Instrumental Activities of Daily Living (IADL) on the association between the scoring of Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and Subjective Cognitive Decline Questionnaire (SCD-Q). METHODS: A sample of 139 community-dwelling older adults aged 65-79 with normal cognitive function completed the SCD-Q, a comprehensive neuropsychological battery, and functional/psychiatric scales. We conducted 1) a correlation analysis between SCD-Q scores and other variables and 2) a path analysis to examine the mediating effects of depression and IADL on the relationship between CDR-SB and SCD-Q. RESULTS: CDR-SB was found to be indirectly associated with SCD-Q, with depressive symptoms mediating this relationship. However, no direct association was observed between SCD-Q and CDR-SB. Additionally, IADL was not associated with SCD-Q and did not mediate the relationship between CDR-SB and SCD-Q. The model fit was acceptable (minimum discrepancy function by degrees of freedom divided [CMIN/DF]=1.585, root mean square error of approximation [RMSEA]=0.065, comparative fit index [CFI]=0.955, Tucker-Lewis index [TLI]=0.939). CONCLUSION: Our results suggest that SCD-Q is influenced by depressive symptoms, but not by IADL. The role of depressive symptoms as a mediator between CDR-SB and SCD-Q indicates that psychological factors may contribute to the perception of SCD. Therefore, interventions targeting depression may mitigate the concerns associated with SCD and reduce feelings of worse performance compared to others of the same age group.

Self-Management Using eHealth Technologies for Liver Transplant Recipients: Scoping Review.

BACKGROUND: Liver transplantation has become increasingly common as a last-resort treatment for end-stage liver diseases and liver cancer, with continually improving success rates and long-term survival rates. Nevertheless, liver transplant recipients face lifelong challenges in self-management, including immunosuppressant therapy, lifestyle adjustments, and navigating complex health care systems. eHealth technologies hold the potential to aid and optimize self-management outcomes, but their adoption has been slow in this population due to the complexity of post-liver transplant management. OBJECTIVE: This study aims to examine the use of eHealth technologies in supporting self-management for liver transplant recipients and identify their benefits and challenges to suggest areas for further research. METHODS: Following the Arksey and O'Malley methodology for scoping reviews, we conducted a systematic search of 5 electronic databases: PubMed, CINAHL, Embase, PsycINFO, and Web of Science. We included studies that (1) examined or implemented eHealth-based self-management, (2) included liver transplant recipients aged ≥18 years, and (3) were published in a peer-reviewed journal. We excluded studies that (1) were case reports, conference abstracts, editorials, or letters; (2) did not focus on the posttransplantation phase; (3) did not focus on self-management; and (4) did not incorporate the concept of eHealth or used technology solely for data collection. The quality of the selected eHealth interventions was evaluated using (1) the Template for Intervention Description and Replication guidelines and checklist and (2) the 5 core self-management skills identified by Lorig and Holman. RESULTS: Of 1461 articles, 15 (1.03%) studies were included in the final analysis. Our findings indicate that eHealth-based self-management strategies for adult liver transplant recipients primarily address lifestyle management, medication adherence, and remote monitoring, highlighting a notable gap in alcohol relapse interventions. The studies used diverse technologies, including mobile apps, videoconferencing, and telehealth platforms, but showed limited integration of decision-making or resource use skills essential for comprehensive self-management. The reviewed studies highlighted the potential of eHealth in enhancing individualized health care, but only a few included collaborative features such as 2-way communication or tailored goal setting. While adherence and feasibility were generally high in many interventions, their effectiveness varied due to diverse methodologies and outcome measures. CONCLUSIONS: This scoping review maps the current literature on eHealth-based self-management support for liver transplant recipients, assessing its potential and challenges. Future studies should focus on developing predictive models and personalized eHealth interventions rooted in patient-generated data, incorporating digital human-to-human interactions to effectively address the complex needs of liver transplant recipients. This review emphasizes the need for future eHealth self-management research to address the digital divide, especially with the aging liver transplant recipient population, and ensure more inclusive studies across diverse ethnicities and regions.

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

Background: Lung adenocarcinoma (LUAD) among never-smokers is a public health burden especially prevalent in East Asian (EAS) women. Polygenic risk scores (PRSs), which quanefy geneec suscepebility, are promising for straefying risk, yet have mainly been developed in European (EUR) populaeons. We developed and validated single-and mule-ancestry PRSs for LUAD in EAS never-smokers, using the largest available genome-wide associaeon study (GWAS) dataset. Methods: We used GWAS summary staesecs from both EAS (8,002 cases; 20,782 controls) and EUR (2,058 cases; 5,575 controls) populaeons, as well as independent EAS individual level data. We evaluated several PRSs approaches: a single-ancestry PRS using 25 variants that reached genome-wide significance (PRS-25), a genome-wide Bayesian based approach (LDpred2), and a mule-ancestry approach that models geneec correlaeons across ancestries (CT-SLEB). PRS performance was evaluated based on the associaeon with LUAD and AUC values. We then esemated the lifeeme absolute risk of LUAD (age 30-80) and projected the AUC at different sample sizes using EAS-derived effect-size distribueon and heritability esemates. Findings: The CT-SLEB PRS showed a strong associaeon with LUAD risk (odds raeo=1.71, 95% confidence interval (CI): 1.61, 1.82) with an AUC of 0.640 (95% CI: 0.629, 0.653). Individuals in the 95 th percenele of the PRS had an esemated 6.69% lifeeme absolute risk of LUAD. Comparison of LUAD risk between individuals in the highest and lowest 20% PRS quaneles revealed a 3.92-fold increase. Projeceon analyses indicated that achieving an AUC of 0.70, which approaches the maximized prediceon poteneal of the PRS given the esemated geneec variance, would require a future study encompassing 55,000 EAS LUAD cases with a 1:10 case-control raeo. Interpretations: Our study underscores the poteneal of mule-ancestry PRS approaches to enhance LUAD risk straeficaeon in never-smokers, parecularly in EAS populaeons, and highlights the necessary scale of future research to uncover the geneec underpinnings of LUAD.

High-throughput characterization of functional variants highlights heterogeneity and polygenicity underlying lung cancer susceptibility.

Genome-wide association studies (GWASs) have identified numerous lung cancer risk-associated loci. However, decoding molecular mechanisms of these associations is challenging since most of these genetic variants are non-protein-coding with unknown function. Here, we implemented massively parallel reporter assays (MPRAs) to simultaneously measure the allelic transcriptional activity of risk-associated variants. We tested 2,245 variants at 42 loci from 3 recent GWASs in East Asian and European populations in the context of two major lung cancer histological types and exposure to benzo(a)pyrene. This MPRA approach identified one or more variants (median 11 variants) with significant effects on transcriptional activity at 88% of GWAS loci. Multimodal integration of lung-specific epigenomic data demonstrated that 63% of the loci harbored multiple potentially functional variants in linkage disequilibrium. While 22% of the significant variants showed allelic effects in both A549 (adenocarcinoma) and H520 (squamous cell carcinoma) cell lines, a subset of the functional variants displayed a significant cell-type interaction. Transcription factor analyses nominated potential regulators of the functional variants, including those with cell-type-specific expression and those predicted to bind multiple potentially functional variants across the GWAS loci. Linking functional variants to target genes based on four complementary approaches identified candidate susceptibility genes, including those affecting lung cancer cell growth. CRISPR interference of the top functional variant at 20q13.33 validated variant-to-gene connections, including RTEL1, SOX18, and ARFRP1. Our data provide a comprehensive functional analysis of lung cancer GWAS loci and help elucidate the molecular basis of heterogeneity and polygenicity underlying lung cancer susceptibility.

The Effects of Etchant on via Hole Taper Angle and Selectivity in Selective Laser Etching.

This research focuses on the manufacturing of a glass interposer that has gone through glass via (TGV) connection holes. Glass has unique properties that make it suitable for 3D integrated circuit (IC) interposers, which include low permittivity, high transparency, and adjustable thermal expansion coefficient. To date, various studies have suggested numerous techniques to generate holes in glass. In this study, we adopt the selective laser etching (SLE) technique. SLE consists of two processes: local modification via an ultrashort pulsed laser and chemical etching. In our previous study, we found that the process speed can be enhanced by changing the local modification method. For further enhancement in the process speed, in this study, we focus on the chemical etching process. In particular, we try to find a proper etchant for TGV formation. Here, four different etchants (HF, KOH, NaOH, and NH4F) are compared in order to improve the etching speed. For a quantitative comparison, we adopt the concept of selectivity. The results show that NH4F has the highest selectivity; therefore, we can tentatively claim that it is a promising candidate etchant for generating TGV. In addition, we also observe a taper angle variation according to the etchant used. The results show that the taper angle of the hole is dependent on the concentration of the etchant as well as the etchant itself. These results may be applicable to various industrial fields that aim to adjust the taper angle of holes.

Genome-wide association study identifies high-impact susceptibility loci for HCC in North America.

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Digital Literacy and Associated Factors in Older Adults Living in Urban South Korea: A Qualitative Study.

This study aimed to explore digital literacy among community-dwelling older adults in urban South Korea. A semistructured interview guide was developed using the Digital Competence ( 2.0 framework, which emphasizes the competencies for full digital participation in five categories: information and data literacy, communication and collaboration, content creation, safety, and problem-solving. The data were analyzed using combined inductive and deductive content analysis. Inductive analysis identified three main categories: perceived ability to use digital technology, responses to digital technology, and contextual factors. In the results of deductive analysis, participants reported varying abilities in using digital technologies for information and data literacy, communication or collaboration, and problem-solving. However, their abilities were limited in handling the safety or security of digital technology and lacked in creating digital content. Responses to digital technology contain subcategories of perception (positive or negative) and behavior (trying or avoidance). Regarding contextual factors, aging-related physical and cognitive changes were identified as barriers to digital literacy. The influence of families or peers was viewed as both a facilitator and a barrier. Our participants recognized the importance of using digital devices to keep up with the trend of digitalization, but their digital literacy was mostly limited to relatively simple levels.

Characteristics of Life-Sustaining Treatment Decisions: National Data Analysis in South Korea.

This study analyzed the national data on life-sustaining treatment decisions from 2018 to 2020 to find out the characteristics of South Korea's end-of-life procedure according to the decision-making approach and process. We collected the data of 84,422 patients registered with the National Agency for Management of Life-sustaining Treatment. We divided the patients into four groups (G1, G2, G3, and G4) according to the decision-making approach. A descriptive analysis of each group was conducted using indicators such as the patient's age, status, diagnosis, and content of forgoing life-sustaining treatment. Additionally, logistic regression analysis was performed by dividing the patients into self-determining (G1, G2) and non-self-determining patients (G3, G4). Cancer was the most common diagnosis for each group. The period from life-sustaining treatment decision to implementation was 10.76, 1.01, 0.86, and 1.19 days for G1, G2, G3, and G4, respectively. In the logistic regression analysis, the self-determination ratio was higher for 40-49 years old and lower for cardiovascular disease and gastrointestinal disease. Age was has a major impact on life-sustaining treatment decisions (LSTD), and with increase in age, the family, and not the patient, made the LSTD. The LSTD method also differed depending on the disease. The self-determination rates of patients with circulatory or digestive diseases were somewhat lower than that of those with neoplastic diseases. The period from decision-making to implementation is short for end-of-life care.

Path analysis of illness uncertainty and psychosocial adaptation of patients with Marfan syndrome.

AIMS: Marfan syndrome (MFS) is a genetic disorder that causes sudden or chronic cardiovascular problems, which can be fatal. Since MFS patients require regular close medical observation, it is important to understand the factors and pathways associated with psychosocial adaptation to the disease. This study aimed to identify the relationships among illness uncertainty, uncertainty appraisal, and psychosocial adaptation in MFS patients using path analysis. METHOD AND RESULTS: This descriptive cross-sectional survey study was conducted from October 2020 to March 2021, in compliance with STROBE guidelines. Using data from 179 participants aged older than 18 years, we constructed a hypothetical path model to identify determinants of illness uncertainty, uncertainty appraisal, and psychosocial adaptation. In the path analysis, disease severity, illness uncertainty, anxiety, and social support were significant factors influencing MFS patients' psychosocial adaptation. Disease severity and illness uncertainty exerted direct effects, while anxiety and social support exerted both direct and indirect (through illness uncertainty) effects. Finally, anxiety showed the greatest total effect. CONCLUSION: These findings are useful for enhancing MFS patients' psychosocial adaptation. Medical professionals should focus on managing disease severity, decreasing anxiety, and increasing social support.

Everyday Digital Literacy Questionnaire for Older Adults: Instrument Development and Validation Study.

BACKGROUND: The need for digital literacy in aging populations is increasing in the digitalizing society. Digital literacy involves the identification, evaluation, and communication of information through various digital devices or relevant programs. OBJECTIVE: The aims of this study were to develop an Everyday Digital Literacy Questionnaire (EDLQ), a digital literacy assessment scale, and subsequently evaluate its psychometric properties using a population of community-dwelling older adults in South Korea. METHODS: The EDLQ was developed using an instrument development design. A nationwide survey was conducted, and the study included 1016 community-dwelling older adults (age ≥60 years). To evaluate the psychometric properties, the participants were randomly divided into 2 groups (n=508 each), and the internal consistency (Cronbach α and McDonald ω), structural validity (exploratory factor analysis and confirmatory factor analysis), hypothesis-testing construct validity using the eHealth Literacy Scale (eHEALS), and measurement invariance were analyzed. RESULTS: Among the initial 30 items of the EDLQ, 22 items with a 3-factor solution had a total explained variance of 77%. The domains included "information and communication" (9 items), "content creation and management" (4 items), and "safety and security" (9 items). Confirmatory factor analysis was conducted with this 3-factor solution (χ2206=345.1; normed χ2206=1.7; comparative fit index=0.997; Tucker-Lewis index=0.997; root-mean-square error of approximation=0.036; standardized root-mean-square residual=0.050; composite reliability=0.903-0.959; average variance extracted=0.699-0.724; R2=0.616-0.773). Hypothesis-testing construct validity with the eHEALS revealed a strong correlation (r=0.75). Cronbach α and McDonald ω coefficients were .98 and 0.98, respectively. The fit indices for measurement invariance, including the configural, metric, and scalar invariance models, demonstrated a satisfactory fit to the data. Our findings suggest that the psychometric properties of the 22-item EDLQ are valid and reliable for assessing digital literacy among older Korean adults. CONCLUSIONS: In this study, we developed a digital literacy measure with strong psychometric properties that made it suitable for assessing the digital literacy of community-dwelling older adults in Korea. To broaden its applicability, however, further assessment of its feasibility for use with different languages and cultures is necessary. Moreover, more empirical research on digital literacy and related factors in older adults can facilitate the development of personalized digital health care services and educational interventions in the digital society.

The Effects of an Order-Assist Mobile Application on Pediatric Anesthesia Safety: An Observational Study.

Pediatric anesthesia requires the rapid creation, communication, and execution of anesthesia orders, and there is a risk of human error. The authors developed an order-assisted mobile application (app) to reduce human error during pediatric anesthesia preparation. The authors conducted an observational study that compared the effects of the application by comparing anesthesiologists' errors, nurses' errors, nurses leaving the operating room, and delays in surgery, between the Conventional group (n = 101) and the App group (n = 101). The app was associated with reduced human error by anesthesiologists and nurses, and it lowered the frequency and duration of nurses leaving the operating room during anesthesia. In addition, the authors surveyed anesthesia nurses regarding the effectiveness of the app. The nurses confirmed that the app was convenient and reduced human error. This study revealed that the order-assisted mobile app developed by a pediatric anesthesiologist could reduce human errors by anesthesiologists and nurses during pediatric anesthesia preparation.

Acidification-based direct electrolysis of treated wastewater for hydrogen production and water reuse.

This report describes the direct electrolysis of treated wastewater (as a catholyte) to produce hydrogen and potentially reuse the water. To suppress the negative shift of the cathodic potential due to an increase in pH by the hydrogen evolution reaction (HER), the treated wastewater is acidified using the synergetic effect of protons generated from the bipolar membrane and inorganic precipitation occurred at the surface of the cathode during the HER. Natural seawater, as an accessible source for Mg2+ ions, was added to the treated wastewater because the concentration of Mg2+ ions contained in the original wastewater was too low for acidification to occur. The mixture of treated wastewater with seawater was acidified to pH 3, allowing the initial cathode potential to be maintained for more than 100 h. The amount of inorganic precipitates formed on the cathode surface is greater than that in the control case (adding 0.5 M NaCl instead of seawater) but does not adversely affect the cathodic potential and Faradaic efficiency for H2 production. Additionally, it was confirmed that less organic matter was adsorbed to the inorganic deposits under acidic conditions. These indicate that acidification plays an important role in improving the performance and stability of low-grade water electrolysis. Considering that the treated wastewater is discharged near the ocean, acidification-based electrolysis of the effluent with seawater can be a water reuse technology for green hydrogen production, enhancing water resilience and contributing to the circular economy of water resources.

Context-aware single-cell multiome approach identified cell-type specific lung cancer susceptibility genes.

Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, the genetic mechanisms and target genes underlying these loci are largely unknown, as most risk-associated-variants might regulate gene expression in a context-specific manner. Here, we generated a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Accessible chromatin peak detection identified cell-type-specific candidate cis-regulatory elements (cCREs) from each lung cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs prioritized the variants for 68% of the GWAS loci, a subset of which was also supported by transcription factor abundance and footprinting. cCRE colocalization and single-cell based trait relevance score nominated epithelial and immune cells as the main cell groups contributing to lung cancer susceptibility. Notably, cCREs of rare proliferating epithelial cell types, such as AT2-proliferating (0.13%) and basal cells (1.8%), overlapped with CCVs, including those in TERT. A multi-level cCRE-gene linking system identified candidate susceptibility genes from 57% of lung cancer loci, including those not detected in tissue- or cell-line-based approaches. cCRE-gene linkage uncovered that adjacent genes expressed in different cell types are correlated with distinct subsets of coinherited CCVs, including JAML and MPZL3 at the 11q23.3 locus. Our data revealed the cell types and contexts where the lung cancer susceptibility genes are functional.

Digital literacy among Korean older adults: A scoping review of quantitative studies.

Background: While digital literacy has become an essential competency for individuals across generations and sectors of society, supporting digital literacy in older adults is particularly challenging. South Korea is among the many countries undergoing rapid digitalization and population aging. Therefore, it is timely to identify the current understanding of digital literacy among older adults in South Korea. Aim: To identify prior studies that quantitatively measure digital literacy among older adults in South Korea and to identify and evaluate how digital literacy was measured in the reviewed studies. Methods: The study followed Arksey and O'Malley's scoping review framework, searching through four international (PubMed, CINAHL, Embase, and Cochrane Library) and four Korean (RISS, KISS, KCI, and KMBase) databases. Results: Among 42 studies included in the final analysis, 38 were cross-sectional studies, and 21 employed primary data. Digital literacy was assessed in various scopes, including digital literacy, e-health literacy, Internet use, and smartphone use. Of the 25 identified measures, three were validated; the rest varied greatly, from using a few items from large surveys to employing investigator-developed measures. Based on the European Commission's Digital Competence Framework, the most commonly addressed components were "information and data literacy" and "communication and collaboration." Conclusions: In recent years, attention toward digital literacy among South Korean older adults has grown rapidly. However, the level of digital literacy among older adults in South Korea remains inconclusive given measurement heterogeneity. Developing and validating more robust measures are warranted to evaluate digital literacy among older adults with diverse functions and circumstances.

Large-scale whole exome sequencing studies identify two genes,CTSL and APOE, associated with lung cancer.

Common genetic variants associated with lung cancer have been well studied in the past decade. However, only 12.3% heritability has been explained by these variants. In this study, we investigate the contribution of rare variants (RVs) (minor allele frequency <0.01) to lung cancer through two large whole exome sequencing case-control studies. We first performed gene-based association tests using a novel Bayes Factor statistic in the International Lung Cancer Consortium, the discovery study (European, 1042 cases vs. 881 controls). The top genes identified are further assessed in the UK Biobank (European, 630 cases vs. 172 864 controls), the replication study. After controlling for the false discovery rate, we found two genes, CTSL and APOE, significantly associated with lung cancer in both studies. Single variant tests in UK Biobank identified 4 RVs (3 missense variants) in CTSL and 2 RVs (1 missense variant) in APOE stongly associated with lung cancer (OR between 2.0 and 139.0). The role of these genetic variants in the regulation of CTSL or APOE expression remains unclear. If such a role is established, this could have important therapeutic implications for lung cancer patients.

Study of Through Glass Via (TGV) Using Bessel Beam, Ultrashort Two-Pulses of Laser and Selective Chemical Etching.

Selective laser etching is a promising candidate for the mass production of glass interposers. It comprises two steps: local modification by an ultrashort-pulsed laser and chemical etching of the modified volume. According to previous studies, when an ultrashort-pulsed laser beam is irradiated on the sample, electron excitation occurs, followed by phonon vibration. In general, the electron excitation occurs for less than a few tens of picoseconds and phonon vibration occurs for more than 100 picoseconds. Thus, in order to compare the electric absorption and thermal absorption of photons in the commercial glass, we attempt to implement an additional laser pulse of 213 ps and 10 ns after the first pulse. The modified glass sample is etched with 8 mol/L KOH solution with 110 °C to verify the effect. Here, we found that the electric absorption of photons is more effective than the thermal absorption of them. We can claim that this result helps to enhance the process speed of TGV generation.

From function to translation: Decoding genetic susceptibility to human diseases via artificial intelligence.

While genome-wide association studies (GWAS) have discovered thousands of disease-associated loci, molecular mechanisms for a considerable fraction of the loci remain to be explored. The logical next steps for post-GWAS are interpreting these genetic associations to understand disease etiology (GWAS functional studies) and translating this knowledge into clinical benefits for the patients (GWAS translational studies). Although various datasets and approaches using functional genomics have been developed to facilitate these studies, significant challenges remain due to data heterogeneity, multiplicity, and high dimensionality. To address these challenges, artificial intelligence (AI) technology has demonstrated considerable promise in decoding complex functional datasets and providing novel biological insights into GWAS findings. This perspective first describes the landmark progress driven by AI in interpreting and translating GWAS findings and then outlines specific challenges followed by actionable recommendations related to data availability, model optimization, and interpretation, as well as ethical concerns.

Comparison of cardiovascular disease risk in women with and without breast cancer: secondary data analysis with the 2014-2018 korean national health and nutrition examination survey.

BACKGROUND: Aging breast cancer survivors may be at an elevated risk of cardiovascular disease (CVD), but little is known about CVD risk assessment and breast cancer in Korean women. We hypothesized that Korean breast cancer survivors would have higher risks of future CVD within the next 10 years (i.e., Framingham Risk Score [FRS]) than women without cancer. OBJECTIVES: (1) To compare FRS-based CVD risks in women with and without breast cancer based on propensity score matching; and (2) To explore adiposity-related measures in relation to FRS in Korean women with breast cancer. METHODS: Using the cross-sectional data from the 2014-2018 Korean National Health and National Survey (KNHANES), we identified 136 women with breast cancer aged 30-74 years who had no other cancer and no CVD. The comparison group of 544 women with no cancer were selected by 1:4 nearest-neighbor propensity score matching based on breast cancer diagnosis. CVD risk was assessed by FRS based on multiple traditional risk factors (e.g., cholesterol, blood pressure, diabetes, and smoking). Adiposity was measured by physical examination, including body mass index (BMI) and waist-to-height ratio (WHtR). Physical activity and health behaviors were assessed by self-reports. RESULTS: Women with breast cancer (mean age of 57 years) had similar FRS levels at a low-risk category (< 10%) to women with no cancer (4.9% vs. 5.5%). Breast cancer survivors (mean 8.5 survival years) presented at significantly lower levels of total cholesterol, BMI, and WHtR (all p values < 0.05) than their counterpart. Within the breast cancer group, WHtR ≥ 0.5 was associated with higher FRS, compared to WHtR < 0.5. FRS was not different by survival < 5 years or ≥ 5 years after breast cancer diagnosis. CONCLUSIONS: FRS-based CVD risks were not different in Korean, mostly postmenopausal, women by breast cancer status. Whereas breast cancer survivors had even lower levels of lipid and adiposity measures than women without cancer, those values indicating borderline cardiometabolic risk suggest continued screening and management efforts for these aging women. Future studies are needed to examine longitudinal trajectories of CVD risk factors and CVD outcomes among Korean breast cancer survivors.

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Synthesis and biological evaluation of flavonoid-based IP6K2 inhibitors.

Inositol polyphosphates (IPs) are a group of inositol metabolites that act as secondary messengers for external signalling cues. They play various physiological roles such as insulin release, telomere length maintenance, cell metabolism, and aging. Inositol hexakisphosphate kinase 2 (IP6K2) is a key enzyme that produces 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-IP7), which influences the early stages of glucose-induced exocytosis. Therefore, regulation of IP6Ks may serve as a promising strategy for treating diseases such as diabetes and obesity. In this study, we designed, synthesised, and evaluated flavonoid-based compounds as new inhibitors of IP6K2. Structure-activity relationship studies identified compound 20s as the most potent IP6K2 inhibitor with an IC50 value of 0.55 µM, making it 5-fold more potent than quercetin, the reported flavonoid-based IP6K2 inhibitor. Compound 20s showed higher inhibitory potency against IP6K2 than IP6K1 and IP6K3. Compound 20s can be utilised as a hit compound for further structural modifications of IP6K2 inhibitors.