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Objective: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with several comorbidities, including an increased risk of certain cancers. This study aimed to investigate the potential associations between RA and increased risk of urological cancers-specifically kidney, bladder, prostate and testicular cancers-and the influence of RA serological status on this risk., Methods: This retrospective cohort study used data from the Korean National Health Insurance System database (2010-2020), including patients with RA and a 1:5 matched non-RA population. RA patients were grouped according to serological status. The primary outcome was newly diagnosed urological cancer, and its association with RA was analyzed by Cox proportional hazards regression analyses adjusting for potential confounders., Results: RA patients had an increased risk of kidney cancer compared with the non-RA population (adjusted hazard ratio [aHR], 1.34 [95% confidence interval (CI), 1.04-1.78]). The risk of kidney cancer was even higher in women with RA (aHR 1.57 [95% CI: 1.10, 2.24]). However, the risk of bladder, prostate and testicular cancers was not associated with RA (bladder cancer, aHR 1.24, 95% CI 0.95-1.62; prostate cancer, aHR 1.13, 95% CI 0.94-1.35; testicular cancer, aHR 2.31, 95% CI 0.44-12.20). No significant difference in urological cancer risk was found according to serological status., Conclusions: RA patients have a higher risk of kidney cancer than the general population. Further research is needed to understand the mechanisms underlying the association between RA and kidney cancer to optimize cancer prevention and screening strategies., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Although adolescent and young adult (AYA) cancer survivors have an increased risk of psychiatric disorders, limited evidence has been suggested. We aimed to determine the risk of psychiatric disorders among AYA cancer survivors., Materials and Methods: A retrospective population-based cohort study based on the Korea National Health Insurance Service database was carried out. All men and women aged 15-39 years diagnosed with cancer between 2006 and 2019 (N = 88 965) were included and matched with controls (1 : 4). The prevalence ratios (PRs) of psychiatric disorders were calculated in cancer patients and compared with those in the control group every 6 months before and after cancer diagnosis., Results: The mean age of the participants was 32.2 years and the majority were 30-39 years of age (72.9%). There was no difference in the PRs of psychiatric disorders between AYA cancer patients and the control group before cancer diagnosis, but it increased sharply after cancer diagnosis [PR 2.50, 95% confidence interval (CI) 2.42-2.58 in the first 6 months]. During a median follow-up of 6.5 years, 54 733 participants developed psychiatric disorders. The overall risk of psychiatric disorders among AYA cancer survivors compared with the control group had a sub-distribution hazard ratio of 1.42 (95% CI 1.39-1.45) after considering competing risks., Conclusions: Our study confirmed a 42% increased risk of psychiatric disorders among AYA cancer survivors compared with controls across various cancer types. Our findings suggest that AYA cancer survivors require long-term psychological support following their cancer diagnosis., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

AMPK is a promising target for various chronic illnesses such as diabetes and Alzheimer's disease (AD). We sought to develop a novel small molecule that directly activates AMPK, with the potential to fundamentally modulate the pathogenic mechanisms of the metabolic disorders. To identify a potent novel pharmacophore in an unbiased way, we performed structure-based virtual screening on a commercially available chemical library, and evaluated the actual AMPK activity of 118 compounds selected from 100,000 compounds based on docking scores. Additional iterative molecular docking studies and experimental evaluation of AMPK activity led us to select a hit compound, B1, with a chromone backbone. Using the hit compound and other compounds structurally similar to the hit compound, we identified the chalcone structure as a new scaffold with more efficient interactions with key residues required for AMPK activation. From the newly designed and synthesized chalcone derivatives, we discovered compound 6 as a candidate compound. Compound 6 showed the most efficient interactions with the key residues of AMPK at in silico study and demonstrated significant activation of AMPK in both in vitro and in cellular assays., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kyung-Hwa Jeon has patent issued to Industry-Academic Cooperation Foundation, Yonsei University Ewha University - Industry Collaboration Foundation Cha University Industry Academic Cooperation Foundation. Hyun-Ji Jo has patent issued to Industry-Academic Cooperation Foundation, Yonsei University Ewha University - Industry Collaboration Foundation Cha University Industry Academic Cooperation Foundation. Seojeong Park has patent issued to Industry-Academic Cooperation Foundation, Yonsei University Ewha University - Industry Collaboration Foundation Cha University Industry Academic Cooperation Foundation. Hyunjeong Kim has patent issued to Industry-Academic Cooperation Foundation, Yonsei University Ewha University - Industry Collaboration Foundation Cha University Industry Academic Cooperation Foundation. Eosu Kim has patent issued to Industry-Academic Cooperation Foundation, Yonsei University Ewha University - Industry Collaboration Foundation Cha University Industry Academic Cooperation Foundation. Younghwa Na has patent issued to Industry-Academic Cooperation Foundation, Yonsei University Ewha University - Industry Collaboration Foundation Cha University Industry Academic Cooperation Foundation. Youngjoo Kwon has patent issued to Industry-Academic Cooperation Foundation, Yonsei University Ewha University - Industry Collaboration Foundation Cha University Industry Academic Cooperation Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Masson SAS. All rights reserved.)

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)., Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague-Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis., Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor., Conclusions: CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS., Competing Interests: The authors have nothing to disclose., (Copyright © 2025 Korean Society for Sexual Medicine and Andrology.)

Background: Depression among breast cancer survivors is a significant concern affecting their long-term survivorship and quality of life. This study investigates the incidence of depression among breast cancer survivors and identifies associated risk factors., Methods: This retrospective cohort study used data from the Korean National Health Insurance Service database and included 59,340 breast cancer patients without a history of depression who underwent surgery between January 1, 2010, and December 31, 2016. They were individually matched 1:2 by age with a general population without cancer (n = 99,834). The mean follow-up period was 6.4 ± 2.6 years. Sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) were calculated considering death as a competing risk and adjusting for sociodemographic factors and comorbidities., Results: Breast cancer survivors with a mean (standard deviation) age of 51.5 (9.2) years had a 39% increased risk of depression compared to non-cancer controls (sHR 1.39, 95% CI 1.36-1.42). During the first year post-diagnosis, breast cancer survivors across all ages exhibited a significantly elevated risk of depression, with a sHR of 3.23 (95% CI 3.08-3.37). Notably, younger survivors had a sHR of 4.51 (95% CI 4.19-4.85), and older survivors had a sHR of 2.56 (95% CI 2.42-2.71). One year post-surgery, younger survivors (age ≤ 50 years) showed a 1.16-fold increase in depression risk (sHR 1.16, 95% CI 1.11-1.20), while older survivors (age > 50 years) showed no significant change in risk, which decreased over time. Use of anthracycline, taxane, or endocrine therapy was associated with an increased depression risk (sHR 1.17, 95% CI 1.13-1.22; sHR 1.12, 95% CI 1.07-1.16; and sHR 1.27, 95% CI 1.14-1.41, respectively), with endocrine therapy showing a 41% increased depression risk in older survivors (sHR 1.41, 95% CI 1.23-1.61)., Conclusion: This study demonstrates a significant association between breast cancer and depression, with a particularly heightened risk in younger survivors within the first year post-diagnosis. Special attention is needed to meticulously screen for depressive symptoms during the early follow-up years for breast cancer survivors who are premenopausal or have undergone chemotherapy and endocrine therapy., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of Samsung Medical Center (approval no. NHIS-2023-1-212). The NHIS granted permission to use the NHIS database. Informed consent was waived because all screened populations agreed to transfer their screening results to the NHIS, and the NHIS database was constructed after anonymization of individual identities. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Recent studies have suggested that increased brachial-ankle pulse wave velocity (baPWV) is a risk factor for diabetes. Exploring its relationship with insulin resistance is of interest, necessitating further studies across different sexes and age groups., Methods and Results: This cohort study involved 119 170 Korean adults with an average age of 39.8 years, none of whom had diabetes at baseline. As part of a health screening, baPWV measurements were taken. Over a median follow-up period of 5.6 years, fasting blood glucose, glycated hemoglobin, insulin levels, and questionnaire responses were collected. The risk of developing diabetes was evaluated using a flexible parametric proportional hazards model with data stratified by sex and age group (<40 versus ≥40 years). During the follow-up period, diabetes was diagnosed in 5966 participants (5.0%). A fully adjusted model found that the hazard ratios for diabetes onset associated with baPWV quartiles Q2 (1171.0-1270.5 cm/s), Q3 (1271.0-1376.0 cm/s), and Q4 (≥1376.5 cm/s) compared with Q1 (<1171.0 cm/s) were 1.06 (95% CI, 0.96-1.17), 1.25 (1.14-1.38), and 1.48 (1.34-1.62), respectively ( P for trend <0.001). A significant sex-based interaction was noted in this association, with women showing a higher risk of diabetes development. Furthermore, higher baPWV quartiles were associated with an increased risk of developing insulin resistance, defined as the homeostatic model assessment of insulin resistance., Conclusions: These findings highlight the importance of arterial stiffness, as measured by elevated baPWV, in the development of diabetes and insulin resistance. Notably, this study highlighted a strong association, particularly among women.

HER2 overexpression significantly contributes to the aggressive nature and recurrent patterns observed in various solid tumors, notably gastric cancers. Trastuzumab, HER2-targeting monoclonal antibody drug, has shown considerable clinical success; however, readily emerging drug resistance emphasizes the pressing need for improved interventions in HER2-overexpressing cancers. To address this, we proposed targeting the protein-protein interaction (PPI) between ELF3 and MED23 as an alternative therapeutic approach to trastuzumab. In this study, we synthesized a total of 26 compounds consisting of 10 chalcones, 7 pyrazoline acetyl, and 9 pyrazoline propionyl derivatives, and evaluated their biological activity as potential ELF3-MED23 PPI inhibitors. Upon systematic analysis, candidate compound 10 was selected due to its potency in downregulating reporter gene activity of ERBB2 promoter confirmed by SEAP activity and its effect on HER2 protein and mRNA levels. Compound 10 effectively disrupted the binding interface between the ELF3 TAD domain and the 391-582 amino acid region of MED23, resulting in successful inhibition of the ELF3-MED23 PPI. This intervention led to a substantial reduction in HER2 levels and its downstream signals in the HER2-positive gastric cancer cell line. Subsequently, compound 10 induced significant apoptosis and anti-proliferative effects, demonstrating superior in vitro and in vivo anticancer activity overall. We found that the anticancer activity of compound 10 was not only restricted to trastuzumab-sensitive cases, but was also valid for trastuzumab-refractory clones. This suggests its potential as a viable therapeutic option for trastuzumab-resistant gastric cancers. In summary, compound 10 could be a novel alternative therapeutic strategy for HER2-overexpressing cancers, overcoming the limitations of trastuzumab., Competing Interests: SH, KJ, HL, IM, SJ, SK, HJ, SP, MA, SK, YN, YK No competing interests declared, (© 2024, Hwang, Jeon et al.)

Objective: Low-dose computed tomography screening reduces lung cancer and overall mortality, but the participation rate remains low. The objective of this study was to develop a decision aid (DA) that addresses the overabundance of healthcare options and barriers to participation in lung cancer screening (LCS) among the general population aged 40-79 years in Korea., Materials and Methods: The DA was developed by following the International Patient Decision Aid Standards process. To evaluate the DA, participants aged 40-79 years were purposively sampled from four districts of the Seoul metropolitan area, with 25 individuals from each decade of the age range. Participants used the DA for LCS, and pre-post comparison was conducted. The primary outcome was a change in intention to undergo LCS after completing the DA. The secondary outcomes were changes in knowledge and attitude about LCS, decisional conflict, and the perceived usefulness of the DA., Results: The DA prototype contained lung cancer risk assessment and decision-making components that addressed knowledge, risks, benefits, costs, and personal values. In a pilot study of 100 participants (mean age 59.0 [SD 11.1] years, 80 % male, 25 % of whom had undergone LCS), knowledge about LCS increased (mean [SD] score [out of 100] before vs. after: 68.3 [13.4] vs. 73.6 [18.0], p < 0.001). A positive change in attitude was observed (p = 0.004), but the intention to screen remained consistent (70 % before vs. 72 % after; p = 0.650). Eighty-eight participants reported the lowest level of conflict in decision-making, and most reported that the DA was useful (mean [SD] score 78.8 [9.0] out of 100). 72 % reported that the DA facilitated self-decision-making, but 27 % felt the DA recommended LCS., Conclusions: This study highlights the potential of a well-designed DA to enhance knowledge and attitudes about LCS, but those improvements did not translate to a significant change in screening intentions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to investigate the efficacy and safety of extracorporeal shock wave therapy (ESWT) over an 8-week period in individuals diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) compared to a control group., Materials and Methods: This prospective, double-blind, placebo-controlled study enrolled 46 participants diagnosed with CP/CPPS, who were randomly assigned to either the treatment group or the control group in a 2:1 ratio. In the treatment group, ESWT was administered at the perineum once a week for 8 weeks. CP/CPPS-related symptoms were assessed using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). Pain and erectile function were measured using the Visual Analogue Scale (VAS) and the International Index of Erectile Function-Erectile Function (IIEF-EF)., Results: The primary efficacy assessment variable, the change in NIH-CPSI total score at 4 weeks after the end of the 8-week treatment compared to baseline, was significantly improved ( P  = 0.0225) in the treatment group (-11.27 ± 8.39) compared to the control group (-5.44 ± 5.73). Regarding the secondary efficacy assessment variables, the treatment group showed significant decreases compared to the control group in change in NIH-CPSI total score ( P  = 0.0055) at the end of the 8-week treatment compared to baseline, along with significant decreases in pain and quality of life scores, as well as VAS assessments at the end of the 8-week treatment and 4 weeks after the end of treatment ( P  < 0.05). Moreover, in the evaluation conducted to assess improvement in sexual function, the treatment group showed a significant increase compared to baseline than the control group in the IIEF total score at 4 weeks after the end of the treatment ( P  = 0.0364). No patients experienced severe side effects related to ESWT during the therapeutic period or the follow-up duration., Conclusions: The efficacy assessment in this clinical trial indicates that extracorporeal shock wave therapy is expected to have a symptomic improvement effect on CP/CPPS., (© 2024 The Asian Pacific Prostate Society. Published by Elsevier B.V.)

Background: Previous studies have investigated cardiovascular disease (CVD) risks in cancer patients, but there is limited knowledge concerning the CVD risk in adult and young adolescent (AYA) survivors of gastric cancer., Objectives: This study aims to investigate the incidence of CVD in AYA gastric cancer survivors, analyzing it by treatment type and identifying associated risk factors., Methods: We conducted a retrospective cohort study using Korean National Health Insurance Service data collected from 2006 to 2019. Propensity score matching (1:3, caliper < 0.1) was performed using the variables age, sex, income, residential area, and presence of comorbidities, and we classified participants into gastric cancer (n = 6562) and non-cancer control (n = 19,678) groups. Cox regression models were used to calculate hazard ratios (HRs) for CVD incidence. The study assessed CVD incidence by cancer treatment and identified risk factors through multivariable Cox regression., Results: During a median 6.5-year follow-up, AYA gastric cancer survivors consistently exhibited greater CVD incidence. Their risk of CVD was significantly elevated compared to that of controls (HR, 1.18; 95% confidence interval [CI] 1.05-1.33). In particular, deep vein thrombosis (HR, 3.93; 95% CI 3.06-14.67) and pulmonary embolism (HR, 6.58; 95% CI 3.06-14.67) risks were notably increased. Chemotherapy was associated with an increased risk of stroke, heart failure, atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Hypertension (HR, 1.58; 95% CI 1.10-2.26) and dyslipidemia (HR, 1.46; 95% CI 1.06-2.20) emerged as risk factors for CVD development., Conclusion: This study reports elevated risks of CVD in AYA gastric cancer survivors and emphasizes the need for vigilant monitoring of CVD in this population., (© 2024. The Author(s).)

Purpose: The primary goal of this study is to evaluate the effect of the non-invasive radiofrequency hyperthermia (RFHT) device on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) rat model and investigate the underlying mechanism., Materials and Methods: In this study, Sprague-Dawley rats were randomly distributed into three groups: (1) normal control group, (2) CP/CPPS group, and (3) RFHT group. CP/CPPS rat models were induced by 17β-estradiol and dihydrotestosterone for 4 weeks and RFHT was administered for 5 weeks after model establishment. During RFHT administration, core body temperatures were continuously monitored with a rectal probe. After administering RFHT, we assessed pain index for all groups and collected prostate tissues for Western blot analysis, immunofluorescence, and immunohistochemistry. We also collected adjacent organs to the prostate including urinary bladder, testes, and rectum for safety assessment via H&E staining along with a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay., Results: After administering RFHT, pain in rats was significantly alleviated compared to the CP/CPPS group. RFHT reduced high-mobility group box 1 (HMGB1) expression and improved inflammation by downregulating subsequent proinflammatory cytokines through inhibition of the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. In prostate-adjacent organs, no significant histological alteration or inflammatory infiltration was detected. The area of cell death also did not increase significantly after RFHT., Conclusions: In conclusion, RFHT demonstrated anti-inflammatory effects by inhibiting the HMGB1-TLR4-NF-κB pathway in CP/CPPS rat models. This suggests that RFHT could serve as a safe and promising therapeutic strategy for CP/CPPS., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

South Korea and China have implemented increasingly stringent mitigation measures to reduce the health risks from PM 2.5 exposure, jointly conducting a ground-based air quality observation study in Northeast Asia. Dispersion normalized positive matrix factorization (DN-PMF) was used to identify PM 2.5 sources in Seoul and Beijing and assess the effectiveness of the seasonal management programs (SMPs) through a comparative study. Samples were collected during three periods: January-December 2019, September 2020-May 2021, and July 2021-March 2022. In Seoul, ten sources were resolved (Secondary nitrate: 8.67 μg/m 3 , 34 %, Secondary sulfate: 5.67 μg/m 3 , 22 %, Motor vehicle: 1.83 μg/m 3 , 7.2 %, Biomass burning: 2.30 μg/m 3 , 9.1 %, Residual oil combustion: 1.66 μg/m 3 , 6.5 %, Industry: 2.15 μg/m 3 , 8.5 %, Incinerator: 1.39 μg/m 3 , 5.5 %, Coal combustion: 0.363 μg/m 3 , 1.4 %, Road dust/soil: 0.941 μg/m 3 , 3.7 %, Aged sea salt: 0.356 μg/m 3 , 1.4 %). The SMP significantly decreased PM 2.5 mass concentrations and source contributions of motor vehicle, residual oil combustion, industry, coal combustion, and biomass burning sources (p-value < 0.05). For Seoul, the reduction effects of the SMPs were evident even considering the influence of the natural meteorological variations and the responses to COVID-19. In Beijing, nine sources were resolved (Secondary nitrate: 12.6 μg/m 3 , 28 %, Sulfate: 8.27 μg/m 3 , 18 %, Motor vehicle: 3.77 μg/m 3 , 8.4 %, Biomass burning: 2.70 μg/m 3 , 6.0 %, Incinerator: 4.50 μg/m 3 , 10 %, Coal combustion: 3.52 μg/m 3 , 7.8 %, Industry: 5.01 μg/m 3 , 11 %, Road dust/soil: 2.92 μg/m 3 , 6.5 %, Aged sea salt: 1.63 μg/m 3 , 3.6 %). Significant reductions in PM 2.5 mass concentrations and source contributions of industry, coal combustion, and incinerator (p-value < 0.05) were observed, attributed to the SMP and additional measures enforced before the 2022 Beijing Winter Olympics. Unlike comparing PM 2.5 mass concentration variations using conventional methods, investigation of the source contribution variations of PM 2.5 by using DN-PMF can provide a deeper understanding of the effectiveness of the air quality management policies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Coronary computed tomography angiography-derived fractional flow reserve (FFR CT ) is a per-vessel index reflecting cumulative hemodynamic burden while coronary events occur in focal lesions., Objectives: The authors sought to evaluate the additive prognostic value of the local gradient of FFR CT (FFR CT gradient) in addition to FFR CT to predict future coronary events., Methods: The current study included 245 patients (634 vessels) who underwent coronary computed tomography angiography within 6 to 36 months before the index angiography, of which 209 vessels had future coronary events and 425 vessels did not. Future coronary events were defined as a composite of vessel-specific myocardial infarction or urgent revascularization during a mean interval of 1.5 years. Pre-existing disease patterns were classified according to FFR CT of ≤0.80 and FFR CT gradient of ≥0.025/mm., Results: Both FFR CT (per 0.01 decrease; adjusted HR: 1.040; 95% CI: 1.029-1.051; P  < 0.001) and FFR CT gradient (per 0.01 increase; adjusted HR: 1.144; 95% CI: 1.101-1.190; P  < 0.001) were significantly associated with the risk of future coronary events. Lesions with FFR CT gradient of ≥0.025/mm showed significantly higher risk of future coronary events than those with FFR CT gradient of <0.025/mm in both the FFR CT >0.80 (49.2% vs 30.1%; HR: 2.069; 95% CI: 1.265-3.385; P  = 0.004) and FFR CT  ≤0.80 groups (60.9% vs 38.3%; HR: 1.988; 95% CI: 1.317-2.999; P =0 .001). Adding FFR CT gradient into the model with FFR CT alone showed significantly increased predictability of future coronary events (global chi-square: 45.8 vs 39.9; P  = 0.015)., Conclusions: Patients with high FFR CT gradient showed increased risk of future coronary events irrespective of FFR CT . Integrating both FFR CT and FFR CT gradient showed incremental predictability of future coronary events compared with FFR CT alone. (Prediction and Validation of Clinical Course of Coronary Artery Disease With CT-Derived Non-Invasive Hemodynamic Phenotyping and Plaque Characterization [DESTINY Study]; NCT04794868)., Competing Interests: The current study was supported by the internal research funds provided from the Heart Vascular Stroke Institute, Samsung Medical Center (OTX0004011). Other than providing financial support, the sponsors were not involved with design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Dr Hahn has received institutional research grants from the National Evidence-Based Healthcare Collaborating Agency, Ministry of Health and Welfare, Korea; Abbott Vascular; Biosensors; Boston Scientific; Daiichi-Sankyo; Donga-ST; Hanmi Pharmaceutical; and Medtronic Inc. Dr Gwon has received institutional research grants from Boston Scientific, Genoss, and Medtronic Inc. Dr J.-M. Lee has received institutional research grants from Abbott Vascular, Boston Scientific, Philips Volcano, Terumo Corporation, Zoll Medical, and Donga-ST. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

This study investigated the effects of lairage conditions on the welfare and meat quality of pigs during lairage periods. A total of 3070 finishing pigs were assigned to one of six groups arranged in two trials in a 2 × 3 factorial design according to the illuminance (under 40 lux (LX), over 40 lux (HX)) and stocking density (low density (LD), higher than 0.83 m 2 /100 kg; normal density (ND), 0.50-0.83 m 2 /100 kg; high density (HD), lower than 0.50 m 2 /100 kg) with high temperature (HT), higher than 24 °C; low temperature (LT), lower than 10 °C. Pigs stocked with HD showed lower aggression behavior and overlap behavior than those stocked with LD at LT. Pigs stocked with HD showed higher standing, sitting, and aggression behavior than those stocked with LD at HT. Pigs stocked with HD showed higher pH than those stocked with LD at LT. At HT, pigs stocked with LD showed higher pH, WHC, DL, and CL than those stocked with HD. At LT, pigs stocked with LD showed higher cortisol levels than those stocked with HD. However, pigs stocked with LD showed lower cortisol levels than those stocked with HD at HT. Based on the obtained results, stocking of too-high (lower than 0.50 m 2 /100 kg) density at HT and stocking of too-low (higher than 0.83 m 2 /100 kg) density at LT are generally not good for meat quality and animal welfare.

Electrocardiogram (ECG) changes after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients are associated with prognosis. This study investigated the feasibility of predicting left ventricular (LV) dysfunction in STEMI patients using an artificial intelligence (AI)-enabled ECG algorithm developed to diagnose STEMI. Serial ECGs from 637 STEMI patients were analyzed with the AI algorithm, which quantified the probability of STEMI at various time points. The time points included pre-PCI, immediately post-PCI, 6 h post-PCI, 24 h post-PCI, at discharge, and one-month post-PCI. The prevalence of LV dysfunction was significantly associated with the AI-derived probability index. A high probability index was an independent predictor of LV dysfunction, with higher cardiac death and heart failure hospitalization rates observed in patients with higher indices. The study demonstrates that the AI-enabled ECG index effectively quantifies ECG changes post-PCI and serves as a digital biomarker capable of predicting post-STEMI LV dysfunction, heart failure, and mortality. These findings suggest that AI-enabled ECG analysis can be a valuable tool in the early identification of high-risk patients, enabling timely and targeted interventions to improve clinical outcomes in STEMI patients., (© 2024. The Author(s).)

Background: There are limited clinical data on drug-coated balloon (DCB)-based percutaneous coronary intervention (PCI) compared with drug-eluting stent (DES)-only PCI in patients with complex coronary artery lesions., Objectives: The goal of the current study was to investigate the efficacy of DCB in patients undergoing PCI for complex coronary artery lesions., Methods: From an institutional registry of patients with de novo complex coronary artery lesions, 126 patients treated with DCB-based PCI were compared with 234 propensity score-matched patients treated with DES-only PCI. Complex coronary artery lesions were defined as the presence of at least 1 of the following: bifurcation, chronic total occlusion, unprotected left main disease, long lesion ≥38 mm, multivessel disease, lesion requiring ≥3 devices, or severe calcification. The primary endpoint was target vessel failure (TVF) at 2 years, a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization., Results: Baseline characteristics were comparable between the 2 groups. DCB-based PCI showed a comparable risk of TVF vs DES-based PCI (7.6% vs 8.1%; HR: 0.81; 95% CI: 0.33-1.99; P  = 0.638). The risks of cardiac death (5.0% vs 5.7%; HR: 0.78; 95% CI: 0.24-2.49), target vessel-related myocardial infarction (0.9% vs 1.3%; HR: 2.65; 95% CI: 0.26-27.06), and target vessel revascularization (3.5% vs 2.0%; HR: 1.30; 95% CI: 0.30-5.67) were also comparable between the 2 groups., Conclusions: DCB-based PCI showed comparable risks of TVF vs those of DES-only PCI in patients with complex coronary artery lesions. DCB might be considered as a suitable alternative device to DES in patients undergoing complex PCI. (Long-term Outcomes and Prognostic Factors in Patient Undergoing CABG or PCI; NCT03870815)., Competing Interests: Dr J.M. Lee has received an institutional research grant from Abbott Vascular, Boston Scientific, Philips Volcano, Terumo Corporation, Zoll Medical, and Donga-ST. Dr Hahn has received an institutional research grant from the National Evidence-based Healthcare Collaborating Agency, Ministry of Health & Welfare of the Republic of Korea, Abbott Vascular, Biosensors, Boston Scientific, Daiichi-Sankyo, Donga-ST, Hanmi Pharmaceutical, and Medtronic Inc. Dr Gwon has received an institutional research grant from Boston Scientific, Genoss, and Medtronic Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Triple-negative breast cancer (TNBC) patients harboring wild-type breast cancer susceptibility gene 1 (BRCA1) account for most TNBC patients but lack adequate targeted therapeutic options. Although radiotherapy (RT) is the primary treatment modality for TNBC patients, radioresistance is one of the major challenges. RT-induced increase in cathepsin S (CTSS) causes radioresistance through suppressing BRCA1-mediated apoptosis of tumor cells, which was induced by CTSS-mediated degradation of BRCA1. Targeting CTSS may provide a novel therapeutic opportunity for TNBC patients. Publicly available data and human tissue microarray slides were analyzed to investigate the relationship between CTSS and BRCA1 in breast cancer patients. A CTSS enzyme assay and in silico docking analysis were conducted to identify a novel CTSS inhibitor. RO5461111 was used first to confirm the concept of targeting CTSS for radiosensitizing effects. The MDA-MB-231 TNBC cell line was used for in vitro and in vivo assays. Western blotting, promoter assay, cell death assay, clonogenic survival assay, and immunohistochemistry staining were conducted to evaluate novel CTSS inhibitors. CTSS inhibitors were further evaluated for their additional benefit of inhibiting cell migration. A novel CTSS inhibitor, TS-24, increased BRCA1 protein levels and showed radiosensitization in TNBC cells with wild-type BRCA1 and in vivo in a TNBC xenograft mouse model. These effects were attributed by BRCA1-mediated apoptosis facilitated by TS-24. Furthermore, TS-24 demonstrated the additional effect of inhibiting cell migration. Our study suggests that employing CTSS inhibitors for the functional restoration of BRCA1 to enhance RT-induced apoptosis may provide a novel therapeutic opportunity for TNBC patients harboring wild-type BRCA1., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: The aim of this study was to investigate the level of satisfaction of parent caregivers of childhood cancer survivors (CCSs) with currently provided survivorship care and their preferences for survivorship care provider., Methods: Study subjects were parent caregivers recruited at three hospitals in Korea. Study data were collected from self-administered questionnaires and medical records. We assessed parent caregivers' levels of satisfaction with specific survivorship care contents and preferred types of survivorship care provider among oncologists, primary care physicians (PCPs), and institutional general physicians (IGPs). Factors associated with parent caregivers' preferences for survivorship care provider were evaluated by multiple logistic regression analysis., Results: 680 parent caregivers (mother 62.1% and father 37.9%) of 487 CCSs (mean age at diagnosis: 6.9 ± 5.1 years; mean time since treatment completion 5.4 ± 4.4 years) were included. Parent caregivers' dissatisfaction was the highest with screening for second primary cancer, followed by psychosocial problem management. Higher educational level of parent caregiver, parent caregiver's higher level of dissatisfaction with currently provided care, higher age of CCSs at cancer diagnosis, history of receiving hematopoietic stem cell transplant, and longer time lapse after cancer treatment were significantly associated with parent caregivers' higher preference for PCPs or IGPs than oncologists. Parent caregiver's multiple comorbidities and higher fear of cancer recurrence were associated with parent caregivers' higher preference for oncologists than PCPs or IGPs. Around 80% of parent caregivers recognized that a shared care system was helpful for promoting the health of CCSs., Conclusion: Parent caregivers were substantially dissatisfied with currently provided care, especially regarding the health issues not directly associated with the primary cancer. Parent caregivers' preferences for survivorship care provider is influenced by multiple factors, including age and survival time of CCSs, characteristics of parent caregivers, satisfaction level with care, and specific survivorship care contents., Implications for Cancer Survivors: The findings of our study suggest that shared survivorship care for CCSs with consideration of specific care contents can complement the current oncologist-led survivorship care system., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Depression is among the most common comorbidities in rheumatoid arthritis (RA). There is a lack of data regarding the association of RA seropositivity and biologic agents with depression risk among individuals with RA., Objective: To investigate the risk of depression following RA diagnosis among patients in South Korea., Design, Setting, and Participants: This retrospective cohort study included 38 487 patients with RA and a comparison group of 192 435 individuals matched 1:5 for age, sex, and index date. Data were from the Korean National Health Insurance Service database. Participants were enrolled from 2010 to 2017 and were followed up until 2019. Participants who had previously been diagnosed with depression or were diagnosed with depression within 1 year after the index date were excluded. Statistical analysis was performed in May 2023., Exposures: Seropositive RA (SPRA) was defined with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes M05 and enrollment in the Korean Rare and Intractable Diseases program. Seronegative RA (SNRA) was defined with ICD-10 codes M06 (excluding M06.1 and M06.4) and a prescription of any disease-modifying antirheumatic drugs (DMARDs) for 270 days or more., Main Outcomes and Measures: Newly diagnosed depression (ICD-10 codes F32 or F33)., Results: The mean (SD) age of the total study population was 54.6 (12.1) years, and 163 926 individuals (71.0%) were female. During a median (IQR) follow-up of 4.1 (2.4-6.2) years, 27 063 participants (20 641 controls and 6422 with RA) developed depression. Participants with RA had a 1.66-fold higher risk of depression compared with controls (adjusted hazard ratio [aHR], 1.66 [95% CI, 1.61-1.71]). The SPRA group (aHR, 1.64 [95% CI, 1.58-1.69]) and the SNRA group (aHR, 1.73 [95% CI, 1.65-1.81]) were associated with an increased risk of depression compared with controls. Patients with RA who used biologic or targeted synthetic DMARDs (aHR, 1.33 [95% CI, 1.20-1.47]) had a lower risk of depression compared with patients with RA who did not use these medications (aHR, 1.69 [95% CI, 1.64-1.74])., Conclusions and Relevance: This nationwide cohort study found that both SPRA and SNRA were associated with a significantly higher risk of depression. These results suggest the importance of early screening and intervention for mental health in patients with RA.

Hepatic fibrosis exacerbates mortality and complications in progressive metabolic dysfunction-associated steatohepatitis (MASH). The role of the adenosine 2A receptor (A2aAR) in hepatic fibrosis within the context of MASH remains uncertain. This study aims to elucidate the involvement of the A2aAR signaling pathway and the efficacy of a novel potent A2aAR antagonist in treating hepatic fibrosis in MASH-induced mice fed a chlorine-deficient, L-amino acid-defined, high fat diet (CDAHFD). A2aAR overexpression in LX-2 cells increased fibrosis markers, whereas the known A2aAR antagonist, ZM241385, decreased these markers. A novel A2aAR antagonist, RAD11, not only attenuated fibrosis progression but also exhibited greater inhibition of the A2aAR signaling pathway compared to ZM241385 in mice with MASH, activated primary hepatocytes, and LX-2 cells. RAD11 exhibited a dual antifibrotic mechanism by targeting both activated HSCs and hepatocytes. Its superior antifibrotic efficacy over ZM241385 in the MASH condition stems from its ability to suppress A2aAR-mediated signaling, inhibit HSC activation, reduce hepatic lipogenesis in hepatocytes, and mitigate lipid accumulation-induced oxidative stress-mediated liver damage. This study has shed light on the relationship between A2aAR signaling and hepatic fibrosis, presenting RAD11 as a potent therapeutic agent for managing MASH and hepatic fibrosis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: The purpose of this study was to evaluate the efficacy and safety of red ginseng oil (RXGIN) in men with lower urinary tract symptoms., Materials and Methods: Men aged between 40 and 75 years with a total International Prostate Symptom Score (IPSS) of 8 to 19 points were recruited from April 2020 to December 2020. Subjects were randomly assigned to either the RXGIN group or the control group in a 1:1 ratio and received either RXGIN or placebo daily for 12 weeks. For the primary outcome, changes in IPSS scores at 6 and 12 weeks from baseline were analyzed. The secondary outcomes were changes in International Index of Erectile Function (IIEF), maximum urinary flow rate, and post-void residual volume at weeks 6 and 12 compared to baseline. Urine analysis and blood tests were additionally performed for safety assessment., Results: A total of 88 subjects (RXGIN group, 46; control group, 42) completed the study. The total IPSS and IPSS subscores (residual urine sensation, frequency, intermittency, urgency, weak stream, straining, nocturia, and quality of life) were significantly improved in the RXGIN group compared to the control group at weeks 6 and 12. Total IIEF and sexual desire were significantly improved in the RXGIN group at week 6 and week 12, respectively, but there were no significant changes in the level of serum testosterone or dihydrotestosterone. The serum prostate-specific antigen showed significant decrease at weeks 12. No serious adverse events leading to discontinuation of the study drug were observed in the RXGIN group., Conclusions: Red ginseng oil (RXGIN) appears to be safe and effective in improving lower urinary tract symptoms in men and may also improve some aspects of sexual function., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

In-stent restenosis (ISR) after percutaneous coronary intervention is a major reason for limited long-term patency due to complex neointimal proliferation caused by vascular injury. Drug-coated balloon (DCB) has been developed to treat various cardiovascular diseases including ISR by providing anti-proliferative drugs into blood vessel tissues. However, a significant proportion of the drug is lost during balloon tracking, resulting in ineffective drug delivery to the target region. In this study, we report an everolimus-coated balloon (ECB) using everolimus-loaded gelatin-hydroxyphenyl propionic acid microgel (GM) with enhanced everolimus delivery to vascular walls for long-term patency. GM with high drug loading (> 97%) was simply prepared by homogenizing enzyme-mediated crosslinked hydrogels. The optimal condition to prepare GM-coated ECB (GM-ECB) was established by changing homogenization time and ethanol solvent concentration (30 ∼ 80%). In vitro sustained everolimus release for 30 d, and cellular efficacy using smooth muscle cells and vascular endothelial cells were evaluated. Additionally, an in vivo drug transfer levels of GM-ECB using rabbit femoral arteries were assessed with reduced drug loss and efficient drug delivery capability. Finally, using ISR-induced porcine models, effective in vivo vascular patency 4 weeks after treatment of ECBs was also confirmed. Thus, this study strongly demonstrates that GM can be used as a potential drug delivery platform for DCB application. STATEMENT OF SIGNIFICANCE: We report an ECB using everolimus-loaded GM prepared by homogenization of enzymatic cross-linked hydrogel. GM showed efficient drug loading (> 97 %) and controllable size. GM-ECB exhibited potential to deliver everolimus in a sustained manner to target area with drug efficacy and viability against SMC and EC. Although GM-ECB had much lower drug content compared to controls, animal study demonstrated enhanced drug transfer and reduced drug loss of GM-ECB due to the protection of encapsulated drugs by GM, and the possible interaction between GM and endothelium. Finally, vascular patency and safety were assessed using ISR-induced porcine models. We suggest an advanced DCB strategy to alleviate rapid drug clearance by bloodstream while improving drug delivery for a long-term vascular patency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: To evaluate the efficacy and safety of Cervi Parvum Cornu , Angelicae Gigantis Radix and Glycyrrhizae Radix complex (CAG) in men with moderate lower urinary tract symptoms (LUTS)., Materials and Methods: From November 2020 to January 2022, participants with International Prostate Symptom Score (IPSS) of 12-19 in two centers were recruited and randomize into three groups: a CAG 500 mg/day group (CAG 500), a CAG 1000 mg/day group (CAG 1000), and a placebo group (PG). They were treated for 12 weeks. The primary endpoint was change of IPSS at the end of study from baseline. Secondary end points included change of prostate specific antigen (PSA), testosterone, dihydrotestosterone (DHT), maximum urinary flow rate (Q max), post-void residual volume (PVR), International Index of Erectile Function (IIEF), and drug safety., Results: A total of 103 patients were able to finish the study according to the study protocol. Total IPSS and sub-scores (residual urine sensation, frequency, weak stream, hesistancy, nocturia, and quality of life) in CAG 500 and CAG 1000 were significantly improved at the 12 th week compared to those of the PG. Changes of serum PSA, DHT, and testosterone levels at the 12 th week from baseline did not show significant differences among the three groups. Q max and PVR changes did not show significant differences among the three groups either. Total IIEF and sub-scores (erectile function, orgasmic function, sexual desire, intercourse satisfaction) in CAG 1000 were significantly improved at 12 th week compared to those in PG. No significant adverse events were found., Conclusions: CAG is well tolerated in patients with moderate LUTS. Treatment with CAG for 12 weeks has a therapeutic effect on moderate LUTS., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Asian Pacific Prostate Society. Published by Elsevier B.V.)

Background: Prostate-specific antigen-based routine screening is not recommended for the general population due to conflicting results with mortality reduction. We aimed to develop a web-based decision aid (DA) for informed decision making for prostate cancer screening., Methods: Using the International Patient Decision Aid Standards (IPDAS) development process model, we developed our DA based on patient and clinician interviews and multidisciplinary expert discussions. The prototype consisted of predicting individual prostate cancer risk and informed decision-making, including knowledge, risk and benefit, cost, personal value, and decision making. We conducted a pilot study on 101 healthy men, evaluating the effectiveness of DA by measuring knowledge, attitude, and intention to screen before and after using the DA, as well as decisional conflict and usefulness after using the DA., Results: Of the 101 participants (median age 60 [50-69] years), 84% had not undergone screening for prostate cancer in the past two years. After using the DA, knowledge on prostate cancer screening increased (mean score [of 10] before versus after: 6.85 ± 1.03 versus 7.57 ± 1.25; P < 0.001), and intention to not screen increased from 27.7% to 51.5% ( P < 0.001), but attitude toward screening did not change ( P = 0.564). After use of the DA, 79 participants reported no decisional conflict, and the usefulness score was high (mean score [of 100] 77.35 ± 7.69), with 85% of participants reporting that the DA helped with decision making., Conclusion: Our web-based DA yielded increased knowledge, decreased screening intention, and high perceived usefulness. These findings indicate potential clinical relevance, especially among younger individuals., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background and Objectives: Paroxysmal atrial fibrillation (AF) is a major potential cause of embolic stroke of undetermined source (ESUS). However, identifying AF remains challenging because it occurs sporadically. Deep learning could be used to identify hidden AF based on the sinus rhythm (SR) electrocardiogram (ECG). We combined known AF risk factors and developed a deep learning algorithm (DLA) for predicting AF to optimize diagnostic performance in ESUS patients., Methods: A DLA was developed to identify AF using SR 12-lead ECG with the database consisting of AF patients and non-AF patients. The accuracy of the DLA was validated in 221 ESUS patients who underwent insertable cardiac monitor (ICM) insertion to identify AF., Results: A total of 44,085 ECGs from 12,666 patient were used for developing the DLA. The internal validation of the DLA revealed 0.862 (95% confidence interval, 0.850-0.873) area under the curve (AUC) in the receiver operating curve analysis. In external validation data from 221 ESUS patients, the diagnostic accuracy of DLA and AUC were 0.811 and 0.827, respectively, and DLA outperformed conventional predictive models, including CHARGE-AF, C2HEST, and HATCH. The combined model, comprising atrial ectopic burden, left atrial diameter and the DLA, showed excellent performance in AF prediction with AUC of 0.906., Conclusions: The DLA accurately identified paroxysmal AF using 12-lead SR ECG in patients with ESUS and outperformed the conventional models. The DLA model along with the traditional AF risk factors could be a useful tool to identify paroxysmal AF in ESUS patients., Competing Interests: Medical AI Inc. provided support in the form of salaries for authors (Jong-Hwan Jang, Sora Kang, Hak Seung Lee, Min Sung Lee, Jeong Min Son, Yong-Yeon Jo, Tae Jun Park, and Joon-myoung Kwon). Joon-myoung Kwon is the founder and stakeholder in Medical AI Inc., a medical artificial intelligence company. There are no patents, products in development of marketed products to declare. This does not alter our adherence to Korean Circulation Journal policies. Ki-Hyun Jeon, Il-Young Oh and Ji Hyun Lee have no financial conflict of interest., (Copyright © 2023. The Korean Society of Cardiology.)

Ticagrelor-based dual antiplatelet therapy (DAPT) provides potent antiplatelet inhibition but may increase the bleeding risk in Asian populations. We investigated the influence of early ticagrelor dose reduction (120 mg) on clinical outcomes in Korean patients undergoing percutaneous coronary intervention (PCI). A multicenter prospective clinical cohort study was conducted with patients who received standard-dose ticagrelor-based DAPT (180 mg) after PCI for complex lesions. Major adverse cardiovascular event (MACE: a composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization), bleeding, and net adverse clinical events (NACE: a composite of MACE and bleeding) were assessed. Among the 772 patients on standard-dose ticagrelor-based DAPT, 115 (14.8%) switched to low-dose ticagrelor-based DAPT (120 mg) within 6 months. Common reasons for the regimen changes were switching as planned (38.8%), dyspnea (25.5%), and bleeding (23.6%). A multivariable Cox proportional hazard model (CPH) showed that the risks of MACE, bleeding, and NACE were not different between the low-dose and standard-dose groups throughout the entire follow-up period and the period beyond 6 months post-PCI. Time-varying multivariable CPH models of the ticagrelor dose reduction yielded similar results. A reduction of the ticagrelor dose within 6 months after PCI is feasible and safe even in patients with complex lesions harboring a high ischemic event risk., (© 2023. Springer Nature Limited.)

Background: While conventional electrocardiogram monitoring devices are useful for detecting atrial fibrillation, they have considerable drawbacks, including a short monitoring duration and invasive device implantation. The use of patch-type devices circumvents these drawbacks and has shown comparable diagnostic capability for the early detection of atrial fibrillation., Objective: We aimed to determine whether a patch-type device (AT-Patch) applied to patients with a high risk of new-onset atrial fibrillation defined by the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex scale (CHA 2 DS 2 -VASc) score had increased detection rates., Methods: In this nonrandomized multicenter prospective cohort study, we enrolled 320 adults aged ≥19 years who had never experienced atrial fibrillation and whose CHA 2 DS 2 -VASc score was ≥2. The AT-Patch was attached to each individual for 11 days, and the data were analyzed for arrhythmic events by 2 independent cardiologists., Results: Atrial fibrillation was detected by the AT-Patch in 3.4% (11/320) of patients, as diagnosed by both cardiologists. Interestingly, when participants with or without atrial fibrillation were compared, a previous history of heart failure was significantly more common in the atrial fibrillation group (n=4/11, 36.4% vs n=16/309, 5.2%, respectively; P=.003). When a CHA 2 DS 2 -VASc score ≥4 was combined with previous heart failure, the detection rate was significantly increased to 24.4%. Comparison of the recorded electrocardiogram data revealed that supraventricular and ventricular ectopic rhythms were significantly more frequent in the new-onset atrial fibrillation group compared with nonatrial fibrillation group (3.4% vs 0.4%; P=.001 and 5.2% vs 1.2%; P<.001), respectively., Conclusions: This study detected a moderate number of new-onset atrial fibrillations in high-risk patients using the AT-Patch device. Further studies will aim to investigate the value of early detection of atrial fibrillation, particularly in patients with heart failure as a means of reducing adverse clinical outcomes of atrial fibrillation., Trial Registration: ClinicalTrials.gov NCT04857268; https://classic.clinicaltrials.gov/ct2/show/NCT04857268., (©Ju-Seung Kwun, Jang Hoon Lee, Bo Eun Park, Jong Sung Park, Hyeon Jeong Kim, Sun-Hwa Kim, Ki-Hyun Jeon, Hyoung-won Cho, Si-Hyuck Kang, Wonjae Lee, Tae-Jin Youn, In-Ho Chae, Chang-Hwan Yoon. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 18.09.2023.)

Background: Diabetes mellitus (DM) is associated with thrombogenicity, clinically manifested with atherothrombotic events after percutaneous cutaneous intervention (PCI). This study aimed to investigate association between DM status and platelet reactivity, and their prognostic implication in PCI-treated patients., Methods: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test (PTRG-PFT) cohort was established to determine the linkage of platelet function test (PFT) with long-term prognosis during dual antiplatelet therapy including clopidogrel in patients treated with drug-eluting stent (DES). We assessed platelet reactivity using VerifyNow and 'high platelet reactivity (HPR)' was defined as ≥ 252 P2Y12 reaction unit (PRU). Major adverse cardiac and cerebrovascular event (MACCE) was a composite of all-cause death, myocardial infarction, stent thrombosis or stroke., Results: Between July 2003 and Aug 2018, DES-treated patients with available PFT were enrolled (n = 11,714). Diabetic patients demonstrated significant higher levels of platelet reactivity (DM vs. non-DM: 225.7 ± 77.5 vs. 213.6 ± 79.1 PRU, P < 0.001) and greater prevalence of HPR compared to non-diabetic patients (38.1% vs. 32.0%, P < 0.001). PRU level and prevalence of HPR were significantly associated with insulin requirement and Hb A1c level, as well as diabetic status. DM status and HPR phenotype had a similar prognostic implication, which showed the synergistic clinical impact on MACCE. Association between PRU level and MACCE occurrence seemed higher in diabetic vs. non-diabetic patients. In non-DM patients, HPR phenotype did not significantly increase the risk of MACCE (adjusted hazard ratio [HR adj ]: 1.073; 95% confidence interval [CI]: 0.869-1.325; P = 0.511), whereas HPR was an independent determinant for MACCE occurrence among diabetic patients (HR adj : 1.507; 95% CI: 1.193-1.902; P < 0.001)., Conclusion: The levels of on-clopidogrel platelet reactivity are determined by diabetic status and the severity of DM. In addition, HPR phenotype significantly increases the risk of MACCE only in diabetic patients., Clinical Trial Registration: URL: https://www., Clinicaltrials: gov . Unique identifier: NCT04734028., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This study used observational data and a chemical transport model to investigate the contributions of several factors to the recent change in air quality in China and South Korea from 2016 to 2020. We focused on observational data analysis, which could reflect the annual trend of emission reduction and adjust existing emission amounts to apply it into a chemical transport model. The observation data showed that the particulate matter (PM 2.5 ) concentrations during winter 2020 decreased by -23.4 % (-14.68 μg/m 3 ) and - 19.5 % (-5.73 μg/m 3 ) in China and South Korea respectively, compared with that during winter 2016. Meteorological changes, the existing national plan for a long-term emission reduction target, and unexpected events (i.e., Coronavirus disease 2019 (COVID-19) in China and South Korea and the newly introduced special winter countermeasures in South Korea from 2020) are considered major factors that may affect the recent change in air quality. The impact of different meteorological conditions on PM 2.5 concentrations was assessed by conducting model simulations by fixing the emission amounts; the results indicated changes of +7.6 % (+4.77 μg/m 3 ) and + 9.7 % (+2.87 μg/m 3 ) in China and South Korea, respectively, during winter 2020 compared to that during winter 2016. Due to the existing and pre-defined long-term emission control policies implemented in both countries, PM 2.5 concentration significantly decreased from winter 2016-2020 in China (-26.0 %; -16.32 μg/m 3 ) and South Korea (-9.1 %; -2.69 μg/m 3 ). The unexpected COVID-19 outbreak caused the PM 2.5 concentrations in China to decrease during winter 2020 by another -5.0 % (-3.13 μg/m 3 ). In South Korea, the winter season special reduction policy, which was introduced and implemented in winter 2020, and the COVID-19 pandemic may have contributed to -19.5 % (-5.92 μg/m 3 ) decrease in PM 2.5 concentrations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluated the efficacy and safety of gelatinized Maca ( Lepidium meyenii ) for eugonadal patients with late onset hypogonadism symptoms (LOH)., Materials and Methods: Participants were instructed to receive 1,000 mg of Maca or placebo, two pills at a time, three times per day for 12 weeks before food intake. To evaluate the efficacy of the drug, Aging Males' Symptoms scale (AMS), Androgen Deficiency in the Aging Males (ADAM), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF) questionnaires, serologic tests (total testosterone and free testosterone, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride), body weight, and waist circumference were assessed at 4 and 12 weeks after treatment., Results: A total of 80 participants were enrolled and randomly assigned to Maca treated group (n=41) or the placebo group (n=39). AMS, IIEF, and IPSS were significantly (p<0.05) improved in Maca treated group than in the placebo group. ADAM positive rate was also significantly (p<0.0001) decreased in Maca treated group., Conclusions: Maca may be considered an effective and safe treatment for eugonadal patients with late onset hypogonadism symptoms., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Background: The ultrathin-strut drug-eluting stent (DES) has shown better clinical results than thin- or thick-strut DES. We investigated if re-endothelialization was different among three types of DES: ultrathin-strut abluminal polymer-coated sirolimus-eluting stent (SES), thin-strut circumferential polymer-coated everolimus-eluting stent (EES), and thick-strut polymer-free biolimus-eluting stent (BES) to gain insight into the effect of stent design on promoting vascular healing. Methods: After implanting three types of DES in the coronary arteries of minipigs, we performed optical coherence tomography (OCT) at weeks 2, 4, and 12 ( n = 4, each). Afterward, we harvested the coronary arteries and performed immunofluorescence for endothelial cells (ECs), smooth muscle cells (SMCs), and nuclei. We obtained 3D stack images of the vessel wall and reconstructed the en face view of the inner lumen. We compared re-endothelialization and associated factors among the different types of stents at different time points. Results: SES showed significantly faster and denser re-endothelialization than EES and BES at weeks 2 and 12. Especially in week 2, SES elicited the fastest SMC coverage and greater neointimal cross-sectional area (CSA) compared to EES and BES. A strong correlation between re-endothelialization and SMC coverage was observed in week 2. However, the three stents did not show any difference at weeks 4 and 12 in SMC coverage and neointimal CSA. At weeks 2 and 4, SMC layer morphology showed a significant difference between stents. A sparse SMC layer was associated with denser re-endothelialization and was significantly higher in SES. Unlike the sparse SMC layer, the dense SMC layer did not promote re-endothelialization during the study period. Conclusion: Re-endothelialization after stent implantation was related to SMC coverage and SMC layer differentiation, which were faster in SES. Further investigation is needed to characterize the differences among the SMCs and explore methods for increasing the sparse SMC layer in order to improve stent design and enhance safety and efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hahn, Lee, Hyun, Cho, Yoon, Jeon, Kang, Youn and Chae.)

Introduction: HER2 overexpression induces cancer aggression and frequent recurrences in many solid tumors. Because HER2 overproduction is generally followed by gene amplification, inhibition of protein-protein interaction (PPI) between transcriptional factor ELF3 and its coactivator MED23 has been considered an effective but challenging strategy., Objectives: This study aimed to determine the hotspot of ELF3-MED23 PPI and further specify the essential residues and their key interactions in the hotspot which are controllable by small molecules with significant anticancer activity., Methods: Intensive biological evaluation methods including SEAP, fluorescence polarization, LC-MS/MS-based quantitative, biosensor, GST-pull down assays, and in silico structural analysis were performed to determine hotspot of ELF3-MED23 PPI and to elicit YK1, a novel small molecule PPI inhibitor. The effects of YK1 on possible PPIs of MED23 and the efficacy of trastuzumab were assessed using cell culture and tumor xenograft mouse models., Results: ELF3-MED23 PPI was found to be specifically dependent on H-bondings between D400, H449 of MED23 and W138, I140 of ELF3 for upregulating HER2 gene transcription. Employing YK1, we confirmed that interruption on these H-bondings significantly attenuated the HER2-mediated oncogenic signaling cascades and exhibited significant in vitro and in vivo anticancer activity against HER2-overexpressing breast and gastric cancers even in their trastuzumab refractory clones., Conclusion: Our approach to develop specific ELF3-MED23 PPI inhibitor without interfering other PPIs of MED23 can finally lead to successful development of a drug resistance-free compound to interrogate HER2 biology in diverse conditions of cancers overexpressing HER2., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

For multifunctional wearable sensing systems, problems related to wireless and continuous communication and soft, noninvasive, and disposable functionality issues should be solved for precise physiological signal detection. To measure the critical transitions of pressure, temperature, and skin impedance when continuous pressure is applied on skin and tissue, we developed a sensor for decubitus ulcers using conventional analog circuitry for wireless and continuous communication in a disposable, breathable fabric-based multifunctional sensing system capable of conformal contact. By integrating the designed wireless communication module into a multifunctional sensor, we obtained sensing data that were sent sequentially and continuously to a customized mobile phone app. With a small-sized and lightweight module, our sensing system operated over 24 h with a coin-cell battery consuming minimum energy for intermittent sensing and transmission. We conducted a pilot test on healthy subjects to evaluate the adequate wireless operation of the multifunctional sensing system when applied to the body. By solving the aforementioned practical problems, including those related to wireless and continuous communication and soft, noninvasive, and disposable functionality issues, our fabric-based multifunctional decubitus ulcer sensor successfully measured applied pressure, skin temperature, and electrical skin impedance., (© 2023. The Author(s).)

Background: To assess the association between the reproductive factors of age at menarche, age at menopause, and reproductive span and the incidence of myocardial infarction (MI) and ischemic stroke (IS)., Methods: We used a population-based retrospective cohort study from the National Health Insurance Service database of Korea including a total of 1,224,547 postmenopausal women. Associations between age at menarche (≤ 12, 13-14 [reference], 15, 16, and ≥ 17 years), age at menopause (< 40, 40-45, 46-50, 51-54 [reference], and ≥ 55 years), and reproductive span (< 30, 30-33, 34-36, 37-40 [reference], and ≥ 41 years) and the incidence of MI and IS were assessed by Cox proportional hazard models with adjustment for traditional cardiovascular risk factors and various reproductive factors., Results: During a median follow-up of 8.4 years, 25,181 MI and 38,996 IS cases were identified. Late menarche (≥ 16 years), early menopause (≤ 50 years), and short reproductive span (≤ 36 years) were linearly associated with a 6%, 12-40%, and 12-32% higher risk of MI, respectively. Meanwhile, a U-shaped association between age at menarche and risk of IS was found, with a 16% higher risk in early menarche (≤ 12 years) and a 7-9% higher risk in late menarche (≥ 16 years). Short reproductive span was linearly associated with an increased risk of MI, whereas both shorter and longer reproductive spans were associated with an increased risk of IS., Conclusions: This study demonstrated different patterns of association between age at menarche and incidence of MI and IS: a linear association for MI versus a U-shaped association for IS. Female reproductive factors in addition to traditional cardiovascular risk factors should be considered when assessing overall cardiovascular risk in postmenopausal women., (© 2023. The Author(s).)

Background: Although the morbidity and mortality of cardiovascular diseases (CVD) are rising in young women, the risk factors of CVD among Korean pre-menopausal women have not been intensively investigated., Aims: To determine how age at menarche and other female reproductive factors are associated with the risk of CVD in pre-menopausal women., Methods and Results: A total of 1 088 992 pre-menopausal women who participated in health screening in 2009 were included. The study outcomes were myocardial infarction (MI) and ischaemic stroke. Cox proportional hazards regression analysis was conducted with adjustment of traditional CVD risk factors and reproductive factors., Results: Mean age was 43.8 ± 5.3 years (98.9%, < 55 years), 3.5% were current smokers, and 1.2% were heavy drinkers. During a mean follow-up of 8.3years [9 032 685.9 person-years (PY)], there were 10 876 CVD events (1.0 per 1000 PY).With later menarche, the risk of CVD increased; ≤12 years [adjusted hazard ratio (HR) 1.04, 95% confidence interval 0.93-1.16], 13 years (reference), 14 years (1.06, 0.98-1.14), 15 years (1.15, 1.07-1.24), 16 years (1.23, 1.14-1.34), and ≥17 years (1.33, 1.24-1.44). Compared with non-users, oral contraceptives (OC) users (≥1 year) had an increased risk of CVD (1.11, 1.01-1.22) (P for trend = 0.007)., Conclusions: Later menarche than the mean age at menarche (13 years old) and the use of OC (≥1 year) were associated with a higher risk of CVD, after adjusting for traditional cardiovascular risk factors. This study suggests that female reproductive factors could be unique risk factors for CVD in pre-menopausal women., Competing Interests: Conflict of interest: The Authors declare that there is no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cannabidiol (CBD) is one of the most abundant components of Cannabis and has long been used in Cannabis-based preparations. Recently, CBD has become a promising pharmacological agent because of its beneficial properties in the pathophysiology of several diseases. Although CBD is a kind of cannabinoid and acts on cannabinoid receptors (CB1 and CB2), molecular targets involved in diverse therapeutic properties of CBD have not been identified because CBD also interacts with other molecular targets. Considering that CBD alters the intracellular calcium level by which calpain activity is controlled, and both CBD and calpain are associated with various diseases related to calcium signaling, including neurological disorders, this review provides an overview of calpain and calcium signaling as possible molecular targets of CBD. As calpain is known to play an important role in the pathophysiology of neurological disease, a deeper understanding of its relationship with CBD will be meaningful. To understand the role of CBD as a calpain regulator, in silico structural analysis on the binding mode of CBD with calpain was performed.

Importance: The impact of serial changes in alcohol consumption on dementia risk has rarely been investigated to date., Objective: To investigate the association of comprehensive patterns of changes in alcohol consumption with the incidence of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD)., Design, Setting, and Participants: This is a retrospective cohort study. Data were obtained from the Korean National Health Insurance Service database. Adults aged 40 years and older underwent 2 health examinations in 2009 and 2011. The cohort was assessed until December 31, 2018, and statistical analysis was performed in December 2021., Exposures: Alcohol consumption level was categorized into none (0 g per day), mild (<15 g per day), moderate (15-29.9 g per day), and heavy (≥30 g per day) drinking. On the basis of changes in alcohol consumption level from 2009 to 2011, participants were categorized into the following groups: nondrinker, quitter, reducer, sustainer, and increaser., Main Outcomes and Measures: The primary outcome was newly diagnosed AD, VaD, or other dementia., Results: Among 3 933 382 participants (mean [SD] age, 55.0 [9.6] years; 2 037 948 men [51.8%]), during a mean (SD) follow-up of 6.3 (0.7) years, there were 100 282 cases of all-cause dementia, 79 982 cases of AD, and 11 085 cases of VaD. Compared with sustained nondrinking, sustained mild (adjusted hazard ratio [aHR], 0.79; 95% CI, 0.77-0.81) and moderate (aHR, 0.83; 95% CI, 0.79-0.88) drinking were associated with a decreased risk of all-cause dementia, whereas sustained heavy drinking was associated with an increased risk of all-cause dementia (aHR, 1.08; 95% CI, 1.03-1.12). Compared with sustained levels of drinking, reducing alcohol consumption from a heavy to a moderate level (aHR, 0.92; 95% CI, 0.86-0.99) and the initiation of mild alcohol consumption (aHR, 0.93; 95% CI, 0.90-0.96) were associated with a decreased risk of all-cause dementia. Increasers and quitters exhibited an increased risk of all-cause dementia compared with sustainers. The trends in AD and VaD remained consistent., Conclusions and Relevance: In this cohort study of a Korean population, decreased risk of dementia was associated with maintaining mild to moderate alcohol consumption, reducing alcohol consumption from a heavy to a moderate level, and the initiation of mild alcohol consumption, suggesting that the threshold of alcohol consumption for dementia risk reduction is low.

Background and Aims: Although many angiotensin receptor blockers (ARBs) are widely used, comparative data regarding their impact on clinical outcomes are limited. We aimed to compare the clinical effectiveness of seven ARBs on long-term cardiovascular outcomes in Korean patients with hypertension., Methods: Using the Korean National Health Insurance Service database, the data of 780,785 patients with hypertension without cardiovascular disease (CVD) who initiated ARB treatment (candesartan, fimasartan, irbesartan, losartan, olmesartan, telmisartan, or valsartan) in 2014 and underwent this treatment for more than 6 months, were analyzed. Cox-regression analysis was performed using Losartan as a comparator, as it was the most widely used drug, by adjusting age, sex, diabetes, dyslipidemia, smoking, alcohol drinking, exercise, body mass index, systolic blood pressure, albuminuria, estimated glomerular filtration rate, and concomitant medications. The occurrence of mortality and the rate of major adverse cardiovascular events (MACEs) of the six ARBs was compared with that of losartan., Results: The median follow-up duration was 5.94 (interquartile range, 5.87-5.97) years. In the crude analysis of all-cause mortality and MACEs, fimasartan exhibited the lowest event rates. In the Cox-regression analysis with adjustment, there was no significant difference in all-cause mortality among ARBs. The risk of MACEs with ARBs was similar to that with losartan, although the risks with irbesartan (hazard ratio [HR], 1.079; 95% confidence interval [CI], 1.033-1.127; p  = 0.007) and candesartan (HR: 1.066; 95% CI, 1.028-1.106; p  = 0.015) were slightly higher., Conclusion: In a Korean population of patients with hypertension without CVD, six different ARBs showed similar efficacy to losartan in terms of long-term mortality and MACEs. Further well-designed prospective studies are required to confirm our findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Prostate cancer patients primarily receive androgen receptor (AR)-targeted drugs as a primary treatment option because prostate cancer is associated with highly activated AR signaling. AR amplification made prostate cancer cells viable under treatment of AR-targeted therapy, leading to castration resistance. AR amplification was more common in enzalutamide-resistant patients. As a strategy to overcome castration resistance and to improve the efficacy of enzalutamide, second-generation nonsteroidal antiandrogen drugs for castration-resistant prostate cancer (CRPC) including topoisomerase II (topo II) poisons such as etoposide and mitoxantrone, have been administered in combination with enzalutamide. In the present study, it was confirmed that amplification of topo IIα, but not I and IIβ, was directly and proportionally associated with poor clinical outcome of Prostate cancer. Among a novel series of newly designed and synthesized 7-(3-aminopropyloxy)-substituted flavone analogues, compound 6, the most potent derivative, was further characterized and identified as a topo IIα catalytic inhibitor that intercalates into DNA and binds to the DNA minor groove with better efficacy and less genotoxicity than etoposide, a topo II poison. Compound 6 showed remarkable efficacy in inhibiting AR-negative CRPC cell growth and sensitizing activity to enzalutamide in AR-positive CRPC cells, thus confirming the potential of topo IIα catalytic inhibitor to overcome resistance to androgen deprivation therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Youngjoo Kwon reports financial support was provided by National Research Foundation (NRF) (Ministry of SIT). Youngjoo Kwon reports financial support was provided by Korea Basic Science Institute (Ministry of Education)., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

This study was conducted to investigate the effects of supplementing different ratios of phytogenic feed additives (PFA) to weaned pigs challenged with pathogenic Escherichia coli on growth performance, nutrient digestibility, intestinal barrier integrity, and immune response, and to determine the optimal mixing ratio for post-weaning diarrhea (PWD) prevention. A total of 48 4-wk-old weaned pigs with initial body weight of 8.01 ± 0.39 kg were placed in individual metabolic cages, and then randomly assigned to eight treatment groups. The eight treatments were as follows: a basal diet without E. coli challenge (negative control, NC), a basal diet with E. coli challenge (positive control, PC), PC with supplementing 0.1% mixture of 20% bitter citrus extract (BCE), 10% microencapsulated blend of thymol and carvacrol (MEO), and 70% excipient (T1), PC with supplementing 0.1% mixture of 10% MEO, 20% premixture of grape seed and grape marc extract, green tea, and hops (PGE), and 60% excipient (T2), PC with supplementing 0.1% mixture of 10% BCE, 10% MEO, 10% PGE, and 70% excipient (T3), PC with supplementing 0.1% mixture of 20% BCE, 20% MEO, and 60% excipient (T4), PC with supplementing 0.1% mixture of 20% MEO, 20% PGE, and 60% excipient (T5), and PC with supplementing 0.1% mixture of 10% BCE, 20% MEO, 10% PGE, and 60% excipient (T6). The experiments progressed in 16 days, including 5 days before and 11 days after the first E. coli challenge (day 0). In the E. coli challenge treatments, all pigs were orally inoculated by dividing a total of 10 mL of E. coli F 18 for three consecutive days from day 0 postinoculation (PI). Compared with the PC group, the PFA2 and PFA6 groups significantly increased (P < 0.05) feed efficiency and decreased (P < 0.05) diarrhea during the entire period. At day 11 PI, the PFA6 group significantly improved (P < 0.05) gross energy digestibility compared to the PFA1 group. The PFA6 group significantly decreased (P < 0.05) tumor necrosis factor α (TNF-α) and interleukin-6 in serum and increased (P < 0.05) the villus height to crypt depth ratio (VH:CD). The PFA2 significantly decreased (P < 0.05) the relative protein expression of calprotectin in the ileum. In conclusion, improvements in growth performance, diarrhea reduction, and immunity enhancement are demonstrated when 10% BCE, 20% MEO, 10% PGE, and 60% excipient are mixed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The clinical value of residual quantitative flow ratio (rQFR), a novel function of QFR technique, is unknown., Aim: We investigated the clinical value of rQFR, aimed to predict residual ischemia after virtual percutaneous coronary intervention (vPCI)., Methods: This is a substudy of the COE-PERSPECTIVE registry, which investigated the prognostic value of post-PCI fractional flow reserve (FFR). From pre-PCI angiograms, QFR and rQFR were analyzed and their diagnostic performance was assessed at blinded fashion using pre-PCI FFR and post-PCI FFR as reference, respectively. The prognostic value of rQFR after vPCI was assessed according to vessel-oriented composite outcome (VOCO) at 2 years., Results: We analyzed 274 patients (274 vessels) with FFR-based ischemic causing lesions (49%) from 555 screened patients. Pre-PCI QFR and FFR were 0.63 ± 0.10 and 0.66 ± 0.11 (R = 0.756, p < 0.001). rQFR after vPCI and FFR after real PCI were 0.93 ± 0.06 and 0.86 ± 0.07 (R = 0.528, p < 0.001). The mean difference between rQFR and post-PCI FFR was 0.068 (95% limit of agreement: -0.05 to 0.19). Diagnostic performance of rQFR to predict residual ischemia after PCI was good (area under the curve [AUC]: 0.856 [0.804-0.909], p < 0.001). rQFR predicted well the incidence of 2-year VOCO after index PCI (AUC: 0.712 [0.555-0.869], p = 0.041), being similar to that of actual post-PCI FFR (AUC: 0.691 [0.512-0.870], p = 0.061). rQFR ≤0.89 was associated with increased risk of 2-year VOCO (hazard ratio [HR]: 12.9 [2.32-71.3], p = 0.0035). This difference was mainly driven by a higher rate of target vessel revascularization (HR: 16.98 [2.33-123.29], p = 0.0051)., Conclusions: rQFR estimated from pre-PCI angiography and virtual coronary stenting mildly overestimated functional benefit of PCI. However, it well predicted suboptimal functional result and long-term vessel-related clinical events., Clinical Trial Registration: Influence of fractional flow reserve on the Clinical OutcomEs of PERcutaneouS Coronary Intervention (COE-PESPECTIVE) Registry, NCT01873560., (© 2022 Wiley Periodicals LLC.)

Monitoring biosignals at the skin interface is necessary to suppress the potential for decubitus ulcers in immobile patients confined to bed. We develop conformally contacted, disposable, and breathable fabric-based electronic devices to detect skin impedance, applied pressure, and temperature, simultaneously. Based on the experimental evaluation of the multifunctional sensors, a combination of robust AgNW electrodes, soft ionogel capacitive pressure sensor, and resistive temperature sensor on fabric provides alarmed the initiation of early-stage decubitus ulcers without signal distortion under the external stimulus. For clinical verification, an animal model is established with a pair of magnets to mimic a human decubitus ulcers model in murine in vivo. The evidence of pressure-induced ischemic injury is confirmed with the naked eye and histological and molecular biomarker analyses. Our multifunctional integrated sensor detects the critical time for early-stage decubitus ulcer, establishing a robust correlation with the biophysical parameters of skin ischemia and integrity, including temperature and impedance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Caregivers of childhood cancer survivors (CCS) have diverse needs, which should be addressed to provide comprehensive cancer care. We aimed to evaluate the unmet needs of caregivers of CCS., Methods: The subjects were 700 caregivers recruited at three major hospitals in South Korea. We collected study data using self-administered questionnaires and a thorough review of medical records. We assessed the unmet needs of caregivers using the comprehensive needs assessment tool for cancer caregivers and evaluated factors associated with the highest tertile range of unmet needs by multiple logistic regression analysis., Results: The greatest unmet needs of caregivers had to do with healthcare staff, followed by information. Compared with father-caregivers, mother-caregivers had greater unmet needs related to health and psychological problems, family/social support, and religious/spiritual support, with odds ratios (95% confidence interval) of 3.79 (2.52-5.69), 3.17 (2.09-4.81), and 1.69 (1.14-2.50), respectively. Compared with caregivers of the youngest CCS (< 6 years), caregivers of CCS aged 12-18 years and caregivers of the oldest CCS (≥ 19 years) respectively showed 2.62 (1.24-5.52) and 3.18 (1.34-7.55) times greater unmet needs for information. Caregivers of CCS who received haematopoietic stem-cell transplantation had a 2.01-fold (1.14-3.57) greater need for practical support., Conclusion: Caregivers of CCS had substantial unmet needs required for comprehensive care for CCS. Several individual characteristics of caregivers and their children were significantly associated with greater unmet needs of the caregivers., Implications for Cancer Survivors: Personalized support based on the characteristics of both CCS and their caregivers is required to provide comprehensive care for CCS., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hearing loss (HL) has been suggested to be associated with impaired microcirculation of the inner ear. This cross-sectional study aimed to evaluate an association between HL and serum lipid levels., Methods: The study comprised 10,356 Korean adults who participated in the fifth Korea National Health and Nutrition Examination Survey (2010-2012). We defined HL as the average hearing thresholds exceeding 25 dB at predetermined frequency levels by pure tone audiometry. Serum lipid levels were measured using an enzymatic assay. The associations between lipid levels and HL were evaluated using a multiple logistic regression model after adjusting for covariates including age, sex, hypertension, diabetes, smoking status, alcohol, physical activity, educational level, household income, and noise exposure. Stratified analyses were performed to examine the effect of the covariates on the association between lipid levels and HL., Results: The high-density lipoprotein cholesterol (HDL-C) level was inversely associated with high-frequency (HF)-HL, with an odds ratio (95% confidence interval) of 0.78 (0.64-0.96) for 1-mmol/L increase in the HDL-C level. Neither the triglyceride nor the low-density lipoprotein cholesterol level was associated with HF-HL. For low-frequency HL, association with any of the serum lipid components was absent. A stratified analysis showed that the inverse association between HDL-C levels and HF-HL was evident (P trend <0.05) in some subjects with specific characteristics such as older age (≥65 years), female sex, non-hypertensive state, and non-regular physical activity. However, a significant interaction between HDL-C levels and all of the stratified variables was absent (P for interaction >0.05)., Conclusion: The HDL-C level has a linear inverse association with the risk of HF-HL. Given the known protective role of HDL-C against atherosclerotic changes, this finding seems to support the concept of impaired microcirculation in the inner ear as a mechanism for HF-HL.

Background: The effect of serial change in alcohol consumption on stroke risk has been limitedly evaluated. We investigated the association of change in alcohol consumption with risk of stroke., Methods: This study is a population-based retrospective cohort study from National Health Insurance Service database of all Koreans. Four lakh five hundred thirteen thousand seven hundred forty-six participants aged ≥40 years who underwent 2 subsequent national health examinations in both 2009 and 2011. Alcohol consumption was assessed by average alcohol intake (g/day) based on self-questionnaires and categorized into non-, mild, moderate, and heavy drinking. Change in alcohol consumption was defined by shift of category from baseline. Cox proportional hazards model was used with adjustment for age, sex, smoking status, regular exercise, socioeconomic information, and comorbidities, Charlson Comorbidity Index, systolic blood pressure, and laboratory results. Subgroup analysis among those with the third examination was conducted to reflect further change in alcohol consumption., Results: During 28 424 497 person-years of follow-up, 74 923 ischemic stroke events were identified. Sustained mild drinking was associated with a decreased risk of ischemic stroke (adjusted hazard ratio, 0.88 [95% CI, 0.86-0.90]) compared with sustained nondrinking, whereas sustained heavy drinking was associated with an increased risk of ischemic stroke (adjusted hazard ratio, 1.06 [95% CI, 1.02-1.10]). Increasing alcohol consumption was associated with an increased risk of ischemic stroke (adjusted hazard ratio, 1.11 [95% CI, 1.06-1.17] from mild to moderate; adjusted hazard ratio, 1.28 [95% CI, 1.19-1.38] from mild to heavy) compared with sustained mild drinkers. Reduction of alcohol consumption from heavy to mild level was associated with 17% decreased risk of ischemic stroke through 3× of examinations., Conclusions: Light-to-moderate alcohol consumption is associated with a decreased risk of ischemic stroke, although it might be not causal and could be impacted by sick people abstaining from drinking. Reduction of alcohol consumption from heavy drinking is associated with a decreased risk of ischemic stroke.

Importance: Although numerous studies have shown an association between alcohol consumption and cancer, how changes in drinking behavior increase or decrease the incidence of cancer is not well understood., Objective: To investigate the association between the reduction, cessation, or increase of alcohol consumption and the development of alcohol-related cancers and all cancers., Design, Setting, and Participants: This population-based cohort study analyzed adult beneficiaries in the Korean National Health Insurance Service. Participants (aged ≥40 years) included those who underwent a national health screening in both 2009 and 2011 and had available data on their drinking status. Data were analyzed from April 16 to July 6, 2020., Exposures: Alcohol consumption level, which was self-reported by participants in health screening questionnaires, was categorized into none (0 g/d), mild (<15 g/d), moderate (15-29.9 g/d), and heavy (≥30 g/d) drinking. Based on changes in alcohol consumption level from 2009 to 2011, participants were categorized into the following groups: nondrinker, sustainer, increaser, quitter, and reducer., Main Outcomes and Measures: The primary outcome was newly diagnosed alcohol-related cancers (including cancers of the head and neck, esophagus, colorectum, liver, larynx, and female breast), and the secondary outcome was all newly diagnosed cancers (except for thyroid cancer)., Results: Among the 4 513 746 participants (mean [SD] age, 53.6 [9.6] years; 2 324 172 [51.5%] men), the incidence rate of cancer was 7.7 per 1000 person-years during a median (IQR) follow-up of 6.4 (6.1-6.6) years. Compared with the sustainer groups at each drinking level, the increaser groups had a higher risk of alcohol-related cancers and all cancers. The increased alcohol-related cancer incidence was associated with dose; those who changed from nondrinking to mild (adjusted hazard ratio [aHR], 1.03; 95% CI, 1.00-1.06), moderate (aHR, 1.10; 95% CI, 1.02-1.18), or heavy (aHR, 1.34; 95% CI, 1.23-1.45) drinking levels had an associated higher risk than those who did not drink. Those with mild drinking levels who quit drinking had a lower risk of alcohol-related cancer (aHR, 0.96; 95% CI, 0.92-0.99) than those who sustained their drinking levels. Those with moderate (aHR, 1.07; 95% CI, 1.03-1.12) or heavy (aHR, 1.07; 95% CI, 1.02-1.12) drinking levels who quit drinking had a higher all cancer incidence than those who sustained their levels, but when quitting was sustained, this increase in risk disappeared. Compared with sustained heavy drinking, reduced heavy drinking levels to moderate levels (alcohol-related cancer: aHR, 0.91 [95% CI, 0.86-0.97]; all cancers: aHR, 0.96 [95% CI, 0.92-0.99]) or mild levels (alcohol-related cancer: aHR, 0.92 [95% CI, 0.86-0.98]; all cancers: aHR, 0.92 [95% CI, 0.89-0.96]) were associated with decreased cancer risk., Conclusions and Relevance: Results of this study showed that increased alcohol consumption was associated with higher risks for alcohol-related and all cancers, whereas sustained quitting and reduced drinking were associated with lower risks of alcohol-related and all cancers. Alcohol cessation and reduction should be reinforced for the prevention of cancer.

Recent studies have revealed the possible association between serum cholesterol levels and hematologic malignancy (HM). However, limited information is available about how reproductive factors interact with this association. Therefore, we investigated the roles of serum cholesterol in the risk of HM according to the menopausal status. We finally identified 1,189,806 premenopausal and 1,621,604 postmenopausal women who underwent a national health screening program in 2009 using data from the Korean National Health Insurance Service database. Overall, 5449 (0.19%) developed HM. Among postmenopausal women, the inverse associations were observed between total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) levels, and the risk of overall HM. In premenopausal women, the highest quartile of HDL-C was associated with a reduced risk of HM compared with the lowest quartile of HDL-C consistent with results in postmenopausal women (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] [0.68-0.95]), whereas the highest quartile of triglyceride (TG) showed an increased risk of HM compared to the lowest quartile of TG, (aHR 1.22, 95% CI [1.02,1.44]) only in premenopausal women. Our finding suggests that lipid profiles are differently associated with HM risk by menopausal status.

Background: Acute myocardial infarction may be associated with new-onset arrhythmias. Patients with myocardial infarction may manifest serious arrhythmias such as ventricular tachyarrhythmias or atrial fibrillation. Frequent, prolonged electrocardiogram (ECG) monitoring can prevent devastating outcomes caused by these arrhythmias., Objective: We aimed to investigate the incidence of arrhythmias in patients following myocardial infarction using a patch-type device-AT-Patch (ATP-C120; ATsens)., Methods: This study is a nonrandomized, single-center, prospective cohort study. We evaluated 71 patients who had had a myocardial infarction and had been admitted to our hospital. The ATP-C120 device was attached to the patient for 11 days and analyzed by 2 cardiologists for new-onset arrhythmic events., Results: One participant was concordantly diagnosed with atrial fibrillation. The cardiologists diagnosed atrial premature beats in 65 (92%) and 60 (85%) of 71 participants, and ventricular premature beats in 38 (54%) and 44 (62%) participants, respectively. Interestingly, 40 (56%) patients showed less than 2 minutes of sustained paroxysmal atrial tachycardia confirmed by both cardiologists. Among participants with atrial tachycardia, the use of β-blockers was significantly lower compared with patients without tachycardia (70% vs 90%, P=.04). However, different dosages of β-blockers did not make a significant difference., Conclusions: Wearable ECG monitoring patch devices are easy to apply and can correlate symptoms and ECG rhythm disturbances in patients following myocardial infarction. Further study is necessary regarding clinical implications and appropriate therapies for arrhythmias detected early after myocardial infarction to prevent adverse outcomes., (©Ju-Seung Kwun, Chang-Hwan Yoon, Sun-Hwa Kim, Ki-Hyun Jeon, Si-Hyuck Kang, Wonjae Lee, Tae-Jin Youn, In-Ho Chae. Originally published in JMIR Cardio (https://cardio.jmir.org), 09.06.2022.)