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Soo Min Son,1 Eun-Ju Park,1 Young Hye Cho,1 Sang Yeoup Lee,1 Jung-In Choi,1 Young-In Lee,1 Yun Jin Kim,2 Jeong Gyu Lee,2 Yu Hyeon Yi,2 Young Jin Tak,2 Hye Rim Hwang,2 Seung-Hun Lee,2 Ryuk Jun Kwon,1 Choongrak Kim3 1Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam-do 50612, South Korea; 2Department of Family Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan 626-770, South Korea; 3Department of Statistics Pusan National University, Busan 609-735, South KoreaCorrespondence: Eun-Ju ParkMedical of Family Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612 Tel +82-55-360-2140Fax +82-55-360-2170Email everblue124@hanmail.netBackground: Many researchers have identified that adequate sleep duration is linked to the quality of life and metabolic diseases. Nowadays, it is hard to take enough sleep, so weekend catch-up sleep (CUS) may be an alternative option in modern society. To our knowledge, no previous studies reported the association between weekend CUS and metabolic syndrome, especially in the Korean population.Objective: We investigated the association between weekend CUS and the prevalence of metabolic syndrome in Korean adults (≥ 20 years old) with less than 6 hours of average weekday sleep.Patients and Methods: A total of 1,453 individuals were selected from the Korean National Health and Nutrition Examination Survey. Weekend CUS was divided into four categories: ≤ 0 hour, 0– 1 hour, 1– 2 hours, and ≥ 2 hours. Odds ratios (ORs) with 95% confidence intervals (CIs) were derived by univariate and multivariate logistic regression analyses.Results: Participants with weekend CUS ≥ 1 hour had decreased risk of metabolic syndrome in univariate analysis (CUS 1– 2 hours: OR: 0.413, 95% CI: 0.301– 0.568; CUS ≥ 2 hours: OR: 0.382, 95% CI 0.296– 0.493). Weekend CUS 1– 2 hours reduced the risk of metabolic syndrome in multivariate logistic regression analysis (OR: 0.552, 95% CI: 0.369– 0.823). Based on the age group analysis, weekend CUS ≥ 1 hour reduced the metabolic syndrome among those aged 20– 39 and 40– 65 (20– 39: CUS 1– 2 hours OR: 0.248, 95% CI: 0.078– 0.783, CUS ≥ 2 hours OR: 0.374, 95% CI: 0.141– 0.991; 40– 65: CUS 1– 2 hours OR: 0.507, 95% CI 0.309– 0.832 CUS ≥ 2 hours OR: 0.638, 95% CI: 0.415– 0.981).Conclusion: Weekend CUS was associated with a low risk of metabolic syndrome among Korean adults with sleep restriction.Keywords: sleep recovery, sleep deprivation, metabolic syndrome, insulin sensitivity

Hee Seon Choi,1 Young Hye Cho,1 Sang Yeoup Lee,1 Eun Ju Park,1 Yun Jin Kim,2,3 Jeong Gyu Lee,2,3 Yu Hyeon Yi,2,3 Young Jin Tak,2,3 Hye Rim Hwang,2,3 Seung Hun Lee2,3 1Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam-do 50612, South Korea; 2Department of Family Medicine, Pusan National University School of Medicine, Yangsan 626-780, South Korea; 3Department of Family Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan 626-770, South KoreaCorrespondence: Young Hye ChoFamily Medicine Clinic, Obesity, Metabolism and Nutrition Center and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 626-770, South KoreaTel +82 51 240 7707Fax +82 51 240 7843Email younghey82@naver.comBackground: Obesity is an important risk factor of cardiovascular disease (CVD). Atherosclerosis can be considered an important signal of CVD. Primary physicians can reduce the risk of CVD by preventing and treating obesity. Therefore, finding a tool to diagnose the association of obesity with arteriosclerosis is important. The association between obesity parameters and arterial stiffness remains controversial. To our knowledge, no previous studies reported the relationships between multiple new anthropometric parameters (a body shape index [ABSI], body round index [BRI], and visceral adiposity index [VAI]) and brachial-ankle wave velocity (ba-PWV) as an indicator of CVD risk, especially in the Korean population.Objective: To investigate the relationships between arterial stiffness (assessed using ba-PWV) and anthropometric parameters estimated on the basis of body mass index (BMI), waist circumference (WC), ABSI, BRI, and VAI, and to identify the indicators of obesity that best represents CVD risk.Methods: A total of 2,647 adults (1,474 men and 1,173 women) were recruited for this cross-sectional study. The correlations between the anthropometric indexes (BMI, WC, ABSI, BRI, and VAI) and mean ba-PWV were analyzed. A multivariate linear regression analysis was performed to evaluate the association between each anthropometric and the presence of arterial stiffness.Results: We investigated the relationships between the obesity parameters and ba-PWV by adjusting the covariates (age, diabetes mellitus [DM], hypertension [HTN], and smoking status) related to the mean ba-PWV. In the multivariate regression analysis, ABSI (men: β =0.066, p

Yu Hyeon Yi,1,2 Young Hye Cho,3 Yun Jin Kim,1,2 Sang Yeoup Lee,3 Jeong Gyu Lee,1,2 Eun Hee Kong,4 Byung Mann Cho,5 Young Jin Tak,1,2 Hye Rim Hwang,1,2 Seung Hun Lee,1,2 Eun Ju Park3 1Department of Family Medicine, Pusan National University School of Medicine, Yangsan 626-780, Korea; 2Department of Family Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan 626-770, Korea; 3Department of Family Medicine, Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 626–780, Korea; 4Department of Family Medicine, College of Medicine, Kosin University, Busan, Korea; 5Department of Preventive Medicine, Pusan National University School of Medicine, Yangsan 626-780, Korea Background: High intraocular pressure (IOP) is well established as the most significant risk factor for both the development and progression of primary open-angle glaucoma. Elevated IOP is more frequently seen in the presence of metabolic disturbances that are associated with the components of metabolic syndrome (MetS). The aim of this study was to investigate the association between ocular hypertension and MetS.Patients and methods: We examined the relationship between ocular hypertension and MetS in 17,160 Korean adults without glaucoma aged >19 years (7,368 men and 9,792 women) who participated in the 2008–2010 Korea National Health and Nutrition Examination Survey. Multivariate logistic regression analysis was used to assess the relationship between MetS and ocular hypertension, after adjusting for age, body mass index, smoking, alcohol consumption, and regular exercise.Results: The prevalence of MetS was 35.1% among males and 30.1% among females. The prevalence of ocular hypertension was 1.3% among males with MetS and 0.7% among females with MetS. Participants with MetS had a significantly higher IOP than those without MetS (P≤0.001), and each component of MetS had a different effect on the IOP. Hypertension was the strongest predictor of an elevated IOP. In multivariate regression analysis, ocular hypertension was significantly associated with MetS (P=0.027 for men; P=0.015 for women).Conclusion: There is a statistically significant relationship between MetS and ocular hypertension. Keywords: intraocular pressure, glaucoma, metabolic syndrome, obesity, hypertension

Background: The CCDC22 gene plays vital roles in regulating the NF-κB pathway, an essential pathway for neuroinflammation, neurodevelopment, and epileptogenesis. Previously, variants in CCDC22 were reported to be associated with intellectual disability. This study aimed to explore the association between CCDC22 and epilepsy., Methods: Trios-based whole-exome sequencing (WES) was performed in a cohort of patients with epilepsy of unknown cause recruited from the China Epilepsy Gene 1.0 Project. Damaging effects of variants were analysed using protein modelling., Results: Hemizygous missense CCDC22 variants were identified in three unrelated cases. These variants had no hemizygous frequencies in controls. All missense variants identified in this study were predicted to be "damaging" by multiple in silico tools and to alter the hydrogen bonds with surrounding residues and/or protein stability. The three patients presented with focal epilepsy of varying severity, including one with refractory seizures and focal cortical dysplasia (FCD) and two with seizures responding to antiseizure medicine. Notably, the variant associated with the severe phenotype was located in the coiled-coil domain and predicted to alter hydrogen bonding and protein stability, whereas the two variants associated with mild epilepsy were located outside functional domains and had moderate molecular alterations. Analysis of spatiotemporal expression indicated that CCDC22 was expressed in brain subregions with three peaks in the fetal stage, infancy, and early adulthood, especially in the fetal stage, explaining the occurrence of developmental abnormities., Significance: CCDC22 variants are potentially associated with X-linked focal epilepsy and FCD. The molecular subregional effects supported the occurrence of FCD., Competing Interests: Declaration of competing interest All the authors declare that there are no conflicts of interest., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To explore the value of predicting new-onset heart failure events in patients with hypertrophic cardiomyopathy (HCM) using clinical and cardiac magnetic resonance (CMR) features based on machine learning algorithms. Methods: The study was a retrospective cohort study. Patients with a confirmed diagnosis of HCM who underwent CMR examinations at Beijing Anzhen Hospital from May 2017 to March 2021 were selected and randomly divided into the training set and the validation set in a ratio of 7∶3. Clinical data and CMR parameters (including conventional parameters and radiomics features) were collected. The endpoint events were heart failure hospitalization and heart failure death, with follow-up ending in January 2023. Features with high stability and P value<0.05 in univariate Cox regression analysis were selected. Subsequently, three machine learning algorithms-random forest, decision tree, and XGBoost-were used to build heart failure event prediction models in the training set. The model performance was then evaluated using the independent validation set, with the performance assessed based on the concordance index. Results: A total of 462 patients were included, with a median age of 51 (39, 62) years, of whom 332 (71.9%) were male. There were 323 patients in the training set and 139 in the validation set. The median follow-up time was 42 (28, 52) months. A total of 44 patients (9.5% (44/462)) experienced endpoint events (8 cases of heart failure death and 36 cases of heart failure hospitalization), with 31 events in the training set and 13 in the validation set. Univariate Cox regression analysis identified 39 radiomic features, 4 conventional CMR parameters (left ventricular end-diastolic volume index, left ventricular end-systolic volume index, left ventricular ejection fraction, and late gadolinium enhancement ratio), and 1 clinical feature (history of non-sustained ventricular tachycardia) that could be included in the machine learning model. In the prediction models built with the training set, the concordance indices for the random forest, decision tree, and XGBoost models were 0.966 (95% CI 0.813-0.995), 0.956 (95% CI 0.796-0.992), and 0.973 (95% CI 0.823-0.996), respectively. In the validation set, the concordance indices for the random forest, decision tree, and XGBoost models were 0.854 (95% CI 0.557-0.964), 0.706 (95% CI 0.399-0.896), and 0.703 (95%CI 0.408-0.890), respectively. Conclusion: Integrating clinical and CMR features of HCM patients through machine learning aids in predicting heart failure events, with the random forest model showing superior performance.

Background: Renal cell carcinoma (RCC) is a highly aggressive malignancy accounting for the majority of kidney cancers. Despite recent advancements in therapeutic options, the prognosis for advanced-stage RCC remains poor. Niemann-Pick C1-Like 1 (NPC1L1) plays a crucial role in cholesterol absorption and has been implicated in cancer progression across various cancers. However, its expression patterns and prognostic significance in RCC remain unclear., Methods: In this study, NPC1L1 expression in normal and RCC tissues, including subtypes, was compared using TCGA, GEPIA2, and The Human Protein Atlas. Clinical correlations were assessed, and the impact of NPC1L1 on overall survival (OS) and progression-free survival (PFS) was evaluated. Gene effect scores were analyzed using the DepMap tool to determine the involvement of NPC1L1 in RCC progression., Results: NPC1L1 expression was significantly lower in RCC tissues compared to normal tissues, particularly in the clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) subtypes, but increased in advanced tumor stages. Higher NPC1L1 expression was associated with worse OS and PFS in RCC patients. Multivariable Cox regression confirmed NPC1L1 as an independent prognostic marker. Additionally, gene effect scores showed that NPC1L1 is essential for the survival of specific RCC cell lines., Conclusions: This study determines NPC1L1 as an independent prognostic indicator in RCC, with higher expression associated with poor survival outcomes. These findings suggest that NPC1L1 could serve as a valuable marker for identifying high-risk RCC patients. Further research is required to investigate the molecular mechanisms underlying the role of NPC1L1 in RCC progression.

Background and Objectives : This study aimed to investigate the association between insulin resistance, as measured by the triglyceride-glucose index (TyG index), and hearing impairment in middle-aged women in Korea. Materials and Methods : This cross-sectional survey utilized data from the Korea National Health and Nutrition Examination Survey (KNHANES) IV (2007-2009), specifically from the period after July 21, 2009, when hearing test results became available, and from the KNHANES V (2010-2012). This study was conducted on 5416 women aged 40 to 69 who had completed both the health examination survey and audiometric tests, excluding those with missing data on menopausal status and the use of hormone replacement therapy. Results : In the study group, the prevalence of high-frequency hearing loss according to the TyG index was significantly higher in the mild hearing loss group (OR = 1.29; 95% CI: 1.12, 1.49, p < 0.001) and the moderate hearing loss group (OR = 1.27; 95% CI: 1.09, 1.48, p = 0.002). Conversely, the prevalence of low-frequency hearing loss did not show a significant difference in either the mild hearing loss group (OR = 1.17; 95% CI: 0.99, 1.37, p = 0.065) and the moderate hearing loss group (OR = 1.13; 95% CI: 0.94, 1.35, p = 0.199) Conclusions : Since diabetes can induce hearing impairment in women, it is recommended that women with a high TyG index undergo early hearing tests.

Background: Insulin resistance contributes to the development of cardiovascular disease and type 2 diabetes mellitus. Smoking leads to an increase in triglyceride levels, which, in turn, increases insulin resistance. Although the number of e-cigarette users has increased in recent years, few studies have investigated the association between ecigarette use and insulin resistance. Therefore, this study aimed to determine the association between e-cigarette use and insulin resistance using the triglyceride-glucose (TyG) index in Korean adults., Methods: This study included 4,404 healthy adults aged ≥20 years who participated in the Korea National Health and Nutrition Examination Survey between 2019 and 2020. Participants were categorized as never-smokers or ecigarette users, and the TyG index was categorized into low- and high-TyG index groups according to the median value (9.22). A logistic regression analysis was performed to determine the association between e-cigarette smoking and insulin resistance., Results: E-cigarette users had a higher TyG index than never smokers (e-cigarette: mean=3.95; never: mean=9.18; P<0.001). The e-cigarette users had a higher risk of being in the high TyG index group than never-smokers (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.03-1.84). In the subgroup analysis stratified by sex, age, and body mass index, a higher OR for a high TyG index was observed in men (OR, 1.46; 95% CI, 1.03-2.08) and individuals aged 60 years or older (OR, 3.74; 95% CI, 1.14-12.30)., Conclusion: Our findings suggest that e-cigarette use is significantly associated with insulin resistance.

Elevated uric acid levels are linked with obesity and diabetes. Existing research mainly examines the relationship between sugar-sweetened carbonated beverage (SSB) consumption and uric acid levels. This study explored the association between the quantity and frequency of SSB consumption and elevated uric acid levels in Korean adults. Data from 2881 participants aged 19-64 years (1066 men and 1815 women) in the 2016 Korea National Health and Nutrition Examination Survey were analyzed. Serum uric acid levels were categorized into quartiles, with the highest defined as high uric acid (men, ≥6.7 mg/dL; women, ≥4.8 mg/dL). SSB consumption was classified into quartiles (almost never, <1 cup (<200 mL), 1-3 cups (200-600 mL), ≥3 cups (≥600 mL)) and frequency into tertiles (almost never, ≤1/week, ≥2/week). Multivariate logistic regression assessed the association, with separate analyses for men and women. Increased daily SSB consumption and frequency were significantly associated with high uric acid levels in men but not in women. After adjusting for sociodemographic and health characteristics, consuming ≥3 cups (≥600 mL) of SSBs per day and SSBs ≥ 2/week were significantly associated with high serum uric acid levels in men, but this association was not observed in women. The study concludes that increased SSB intake is linked to elevated uric acid levels in Korean men, but not in women.

Background: Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker., Methods: A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016-2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely "0-2 breakfasts per week" and "3-7 breakfasts per week"; hs-CRP concentrations were measured through blood tests., Results: Comparing between the "infrequent breakfast consumption (0-2 breakfasts per week)" and "frequent breakfast consumption (3-7 breakfasts per week)" groups, the mean hs-CRP was found to be significantly higher in the "infrequent breakfast consumption" group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036)., Conclusion: Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.

Background: The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy., Methods: Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy., Results: Compound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth., Conclusion: ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The efficacy and safety of different oral ginkgo-based Chinese patent medicines (CPMs) regimens for hypertension patients were analyzed based on the network meta-analysis of the frequency framework., Methods: We conducted a comprehensive search of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and Chinese Biomedical Literature Database to gather data on randomized controlled trials (RCTs) evaluating the efficacy of 8 ginkgo biloba oral preparations for the treatment of hypertension. The trials included in the analysis were conducted from the inception of the databases up to September 2023. Methodological quality and risk of bias were assessed using the RoB 2.0 evaluation tool, and a reticulated meta-analysis was conducted using STATA MP 14 software. The RCTs included in this study were published studies and therefore did not require ethics committee review or patient consent., Results: We ultimately included 46 RCTs covering 8 CPMs including ginkgo biloba tablet (GBT), GB capsule (GBC), ginkgo biloba drop (GBD), ginkgo biloba ketone ester drop, Fufangyinxing capsule, fufangyinxingtongmai oral liquid, Yinxingmihuan oral liquid, Yindanxinanotong softgel capsule (YDXNT). GBD + CT demonstrated the highest effectiveness in reducing systolic blood pressure (surface under the cumulative ranking [SUCRA] = 78.7%) and improving total effective rate (SUCRA = 86.7%). GBC + CT exhibited the greatest efficacy in reducing diastolic blood pressure (SUCRA = 92.6%). GBT + CT was identified as the most effective in lowering total cholesterol (TC) (SUCRA = 100%). Additionally, YDXNT + CT demonstrated notable improvements in triglyceride levels (SUCRA = 92.2%), Nitric oxide (NO) (SUCRA = 93.9%), and ET-1 (SUCRA = 67.5%). In terms of safety, 14 studies reported the occurrence of adverse reactions with a high degree of clinical heterogeneity, which was only qualitatively analyzed in this study., Conclusion Subsections: We found that a combination of 8 ginkgo-based CPMs + CT was effective in hypertension compared with CT. The evidence showed that GBD + CT were the best in improving systolic blood pressure and total effective rate, GBC + CT improved diastolic blood pressure, GBT + CT were the most effective in improving TC, and YDXNT + CT was the most effective in improving TG, NO, and ET-1. Adverse effects were only analyzed qualitatively, and the number of adverse effects of CPMs treatment was relatively low compared to CT. In addition, the quality of the literature included in the study was low, and further validation through RCTs with larger sample sizes, higher quality, and more rigorously designed is needed., 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. As this study did not involve clinical data, ethics approval was not applicable., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To investigate differences in the incidence of enteropathy or intestinal malabsorption in patients taking angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), and beta blockers (BBs) at a single center in Korea., Methods: In this retrospective study, we utilized data from the Yangsan electronic medical records to identify 129,169 patients. These individuals were prescribed olmesartan, other ARBs, ACEI, CCB, and BBs between November 2008 and February 2021., Results: Of the 44,775 patients, 51 (0.11%) were observed to have enteropathy or intestinal malabsorption. Compared with the ACEI group, the adjusted odds ratios (ORs) for enteropathy and intestinal malabsorption were OR=1.313 (95% confidence interval [CI]: [0.188-6.798], p =0.893) for olmesartan, OR=0.915 (95% CI: [0.525-1.595], p =0.754) for the other ARBs, OR=0.928 (95% CI: [0.200-4.307]; p =0.924) for the CCB, and OR=0.663 (95% CI: [0.151-2.906]; p =0.586) for the BBs group. These findings were adjusted for factors such as age, gender, duration of antihypertensive medication, and comorbidities., Conclusion: In a retrospective cohort study of patients on antihypertensive medications, no significant difference was found in the incidence of enteropathy or intestinal malabsorption when ACEI was compared to olmesartan, other ARBs, CCB, and BBs., (Copyright: © Saudi Medical Journal.)

Objectives: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy., Methods: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations., Results: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation., Significance: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity., Competing Interests: Declaration of Competing Interest The authors have stated that they had no interests which might be perceived as posing a conflict or bias., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: To provide an updated list of epilepsy-associated genes based on clinical-genetic evidence., Methods: Epilepsy-associated genes were systematically searched and cross-checked from the OMIM, HGMD, and PubMed databases up to July 2023. To facilitate the reference for the epilepsy-associated genes that are potentially common in clinical practice, the epilepsy-associated genes were ranked by the mutation number in the HGMD database and by case number in the China Epilepsy Gene 1.0 project, which targeted common epilepsy., Results: Based on the OMIM database, 1506 genes were identified to be associated with epilepsy and were classified into three categories according to their potential association with epilepsy or other abnormal phenotypes, including 168 epilepsy genes that were associated with epilepsies as pure or core symptoms, 364 genes that were associated with neurodevelopmental disorders as the main symptom and epilepsy, and 974 epilepsy-related genes that were associated with gross physical/systemic abnormalities accompanied by epilepsy/seizures. Among the epilepsy genes, 115 genes (68.5%) were associated with epileptic encephalopathy. After cross-checking with the HGMD and PubMed databases, an additional 1440 genes were listed as potential epilepsy-associated genes, of which 278 genes have been repeatedly identified variants in patients with epilepsy. The top 100 frequently reported/identified epilepsy-associated genes from the HGMD database and the China Epilepsy Gene 1.0 project were listed, among which 40 genes were identical in both sources., Significance: Recognition of epilepsy-associated genes will facilitate genetic screening strategies and be helpful for precise molecular diagnosis and treatment of epilepsy in clinical practice., Competing Interests: Declaration of Competing Interest The authors have stated that they had no interests that might be perceived as posing a conflict or bias., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The GABRA1 gene, encoding the GABR A R subunit α1, plays vital roles in inhibitory neurons. Previously, the GABRA1 gene has been identified to be associated with developmental and epileptic encephalopathy (DEE) and idiopathic generalized epilepsy (IGE). This study aims to explore the phenotypic spectrum of GABRA1 and molecular subregional effect analysis., Methods: Trios-based whole-exome sequencing was performed in patients with epilepsy. Previously reported GABRA1 mutations were systematically reviewed to analyze the molecular subregional effects., Results: De novo GABRA1 mutations were identified in six unrelated patients with heterogeneous epilepsy, including three missense mutations (p.His83Asn, p.Val207Phe, and p.Arg214Cys) and one frameshift mutation (p.Thr453Hisfs*47). The two missense mutations, p.His83Asn and p.Val207Phe, were predicted to decrease the protein stability but no hydrogen bond alteration, with which the two patients also presented with mild genetic epilepsy with febrile seizures plus and achieved seizure-free status by monotherapy. The missense variant p.Arg214Cys was predicted to decrease protein stability and destroy hydrogen bonds with surrounding residues, which was recurrently identified in three cases with severe DEE. The frameshift variant p.Thr453Hisfs*47 was located in the last fifth residue of the C-terminus and caused an extension of 47 amino acids, with which the patients presented with moderated epilepsy with generalized tonic-clonic seizures alone (GTCA) but achieved seizure-free status by four drugs. The four variants were not presented in gnomAD and were evaluated as "pathogenic/likely pathogenic" according to ACMG criteria. Analysis of all reported cases indicated that patients with mutations in the N-terminal extracellular region presented a significantly higher percentage of FS and DEE, and the patients with variants in the transmembrane region presented earlier seizure onset ages., Significance: This study suggested that GABRA1 variants were potentially associated with a spectrum of epilepsies, including EFS+, DEE, and GTCA. Phenotypic severity may be associated with the damaging effect of variants. The molecular subregional effects help in understanding the underlying mechanism of phenotypic variation., 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 © 2024 Liu, Luo, Zhang, Lin, Lan, Li, Shi, Su, Yi, Zhou and Li.)

Purpose: This study aimed to develop a direct breastfeeding protocol for premature infants admitted to neonatal intensive care units (NICUs) and investigate its efficacy., Background: Direct breastfeeding increases the amount and duration of breastfeeding. However, NICUs have low direct feeding rates owing to medical staff anxiety, lack of knowledge and experience, and fear of overwork. Accordingly, this study developed a protocol for direct breastfeeding in the NICU and evaluated its effect., Methods: The protocol was developed through a literature review, expert validation, and preliminary investigation. Its application effects were identified using a nonexperimental, evidence-based research design targeting premature infants, their mothers, and NICU nurses., Results: The protocol comprised 5 areas and 23 items. Application of the protocol resulted in continuous weight gain of the infants and increased self-efficacy in the mothers' direct breastfeeding ( t = 3.219, P = .004). Significant increases were noted in NICU nurses' direct breastfeeding activities ( t = 3.93, P < .001), breastfeeding rates in the NICU ( P = .037), and direct breastfeeding rates ( P = .007)., Conclusions: Results underscore the value of an evidence-based protocol for improving breastfeeding rates in premature infants. This study highlights the need for continuous nursing education on protocol applications and human resource support., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Neutrophil extracellular traps (NETs) play an important role in sepsis-related acute lung injury (ALI). Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and miRNA are becoming promising agents for the treatment of ALI. The current study aimed to elucidate the mechanism by BMSCs-derived exosomes carrying miR-127-5p inhibiting to the formation of NETs in sepsis-related ALI. We successfully isolated exosomes from BMSCs and confirmed that miR-127-5p was enriched in the exosomes. ALI mice treated with BMSCs-derived exosomes histologically improved, and the release of NETs and inflammatory factors in lung tissue and peripheral blood of mice also decreased compared with LPS group, while the protective effect of exosomes was attenuated after the knockdown of miR-127-5p. Using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay, we identified CD64 as a direct target of miR-127-5p. Meanwhile, BMSCs-derived exosomes can synergize with anti-CD64 mab in ALI mice to reduce tissue damage, inhibit the release of inflammatory factors and NETs formation. The synergistic effect of exosomes was attenuated when miR-127-5p was down-regulated. These findings suggest that exosomal miR-127-5p derived from BMSCs is a potential therapeutic agent for treatment of sepsis-induced ALI through reducing NETs formation by targeting CD64., 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 Elsevier B.V. All rights reserved.)

Objectives: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy., Methods: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations., Results: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation., Significance: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity., Competing Interests: Declaration of Competing Interest The authors have stated that they had no interests which might be perceived as posing a conflict or bias., (Copyright © 2023. Published by Elsevier Ltd.)

A structural mechanics and energy storage difunctional supercapacitor based on a geopolymer membrane injected with a 0.5 M Na 2 SO 4 electrolyte and a pseudocapacitive electrode Mn 7 O 13 is designed and assembled. The geopolymer membrane is prepared as a structural electrolyte with metakaolin and alkaline activator solution. The wide channels in the geopolymer matrix provide paths for ion movement. The Mn 7 O 13 electrode is prepared by different hydrothermal treatments at different temperatures and times, and assembled with activated carbon and a geopolymer with different moduli to form a difunctional supercapacitor. The results show that the electrode sample annealed at 300 °C for 45 min after hydrothermal treatment at 160 °C for 24 h exhibits the best comprehensive performance. The specific capacitance of the electrode is 175.5 F g -1 (2392.6 F m -2 ) at 1 A g -1 , and the specific capacitance of the difunctional structure supercapacitor assembled with a geopolymer with a modulus of 1.2 and cured for 28 days is 144.12 F g -1 (1960.0F m -2 ) at 1 A g -1 under 15 MPa.

Background: Considering the prolongation of the COVID-19 pandemic, the lack of studies on burnout, particularly in healthcare workers, needs to be addressed. This report aimed to identify the risk factors of burnout by comparing the level of burnout between nurses in general wards and those in COVID-19-dedicated wards in a national university hospital., Methods: A survey based on the Korean version of Burnout Assessment Tool (BAT-K) was conducted on nurses between 10 January and 31 January 2022. The BAT-K consists of exhaustion, mental distance, cognitive impairment, emotional impairment and secondary symptoms., Results: A total of 165 nurses, including 81 nurses from the COVID-19-dedicated ward, completed the questionnaire. The percentage of general-ward nurses with an emotional impairment score above the clinical cutoff was higher than that of COVID-19 ward nurses. General ward compared to the COVID-19 ward increased the risk of presenting with total-core symptoms. Two factors increased the risk regarding mental distance: short career length and underlying disease., Conclusions: In contrast to previous studies, the risk of burnout in the COVID-19-ward nurses was lower than that of the general ward nurses. The risk regarding mental distance was correlated with short career length and presence of an underlying disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cell-cell interaction (CCI) is a crucial event in the development and function of multicellular organisms. The development of CCI databases is beneficial for researchers who want to analyze single-cell sequencing data or study CCI through molecular experiments. CCIs are known to act differently according to cellular and biological contexts such as cell types, gene mutations or disease status; however, previous CCI databases do not completely provide this contextual information pertaining to CCIs. We constructed a cell-cell interaction database (CCIDB) containing the biological and clinical contexts involved in each interaction. To build a database of cellular and tissue contexts, we collected 38 types of context features, which were categorized into seven categories, including 'interaction', 'cell type', 'cofactor', 'effector', 'phenotype', 'pathology' and 'reference'. CCIs were manually retrieved from 272 studies published recently (less than 6 years ago). In the current version of CCIDB, 520 CCIs and their 38 context features have been manually collected and curated by biodata engineers. We suggest that CCIDB is a manually curated CCI resource that is highly useful, especially for analyzing context-dependent alterations in CCIs. Database URL https://ccidb.sysmed.kr/., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: Hyperuricemia is associated with metabolic and cardiovascular diseases and mortality. Efforts to lower the risk of hyperuricemia in various ways are needed as the prevalence of these diseases increases in postmenopausal women. Studies have shown that one of these methods is associated with adequate sleep duration, which is related to a low risk of hyperuricemia. Considering that it is difficult for people to get enough sleep in modern society, this study hypothesized that weekend catch-up sleep could be an alternative. To our knowledge, no past study has investigated the relation between weekend catch-up sleep and hyperuricemia in postmenopausal women. Hence, the aim of this research was to estimate the relation between weekend catch-up sleep and hyperuricemia with insufficient sleep in postmenopausal women during weekday or workday., Methods: This study included 1,877 participants extracted from the Korea National Health and Nutrition Examination Survey VII. The study population was divided into weekend catch-up sleep and non-weekend catch-up sleep groups. Odds ratios with 95% confidence intervals were derived using multiple logistic regression analysis., Results: Weekend catch-up sleep had a significantly lower prevalence of hyperuricemia after adjusting for confounders (odds ratio, 0.758 [95% confidence interval, 0.576-0.997]). In a subgroup analysis, weekend catch-up sleep of 1 to 2 hours was significantly correlated with a lower prevalence of hyperuricemia after adjusting for confounders (odds ratio: 0.522 [95% confidence interval, 0.323-0.845])., Conclusions: Weekend catch-up sleep had a decreased prevalence of hyperuricemia in postmenopausal women with sleep deprivation., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.)

Purpose: For the dignity of patients nearing the end of their lives, it is essential to provide end-of-life (EoL) care in a separate, dedicated space. This study investigated the utilization of specialized rooms for dying patients within a hospice unit., Methods: This retrospective study examined patients who died in a single hospice unit between January 1, 2017, and December 31, 2021. Utilizing medical records, we analyzed the circumstances surrounding death, the employment of specialized rooms for terminally ill patients, and the characteristics of those who received EoL care in a shared room., Results: During the 1,825-day survey period, deaths occurred on 632 days, and 799 patients died. Of these patients, 496 (62.1%) received EoL care in a dedicated room. The average duration of using this dedicated space was 1.08 days. Meanwhile, 188 patients (23.5%) died in a shared room. Logistic regression analysis revealed that a longer stay in the hospice unit was associated with a lower risk of receiving EoL care in a shared room (odds ratio [OR]=0.98, 95% confidence interval [CI] 0.97~0.99; P=0.002). Furthermore, a higher number of deaths on the day a patient died was associated with a greater risk of receiving EoL care in a shared room (OR=1.66, 95% CI 1.33~2.08; P<0.001)., Conclusion: To ensure that more patients receive EoL care for an adequate duration in a private setting, additional research is necessary to increase the number of dedicated rooms and incorporate them into the hospice unit at an early stage., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by Korean Society for Hospice and Palliative Care.)

Background: HCFC1 encodes transcriptional co-regulator HCF-1, which undergoes an unusual proteolytic maturation at a centrally located proteolysis domain. HCFC1 variants were associated with X-linked cobalamin metabolism disorders and mental retardation-3. This study aimed to explore the role of HCFC1 variants in common epilepsy and the mechanism underlying phenotype heterogeneity., Methods: Whole-exome sequencing was performed in a cohort of 313 patients with idiopathic partial (focal) epilepsy. Functional studies determined the effects of the variants on the proteolytic maturation of HCF-1, cell proliferation and MMACHC expression. The role of HCFC1 variants in partial epilepsy was validated in another cohort from multiple centers., Results: We identified seven hemizygous HCFC1 variants in 11 cases and confirmed the finding in the validation cohort with additional 13 cases and six more hemizygous variants. All patients showed partial epilepsies with favorable outcome. None of them had cobalamin disorders. Functional studies demonstrated that the variants in the proteolysis domain impaired the maturation by disrupting the cleavage process with loss of inhibition of cell growth but did not affect MMACHC expression that was associated with cobalamin disorder. The degree of functional impairment was correlated with the severity of phenotype. Further analysis demonstrated that variants within the proteolysis domain were associated with common and mild partial epilepsy, whereas those in the kelch domain were associated with cobalamin disorder featured by severe and even fatal epileptic encephalopathy, and those in the basic and acidic domains were associated with mainly intellectual disability., Conclusion: HCFC1 is potentially a candidate gene for common partial epilepsy with distinct underlying mechanism of proteolysis dysfunction. The HCF-1 domains played distinct functional roles and were associated with different clinical phenotypes, suggesting a sub-molecular effect. The distinct difference between cobalamin disorders and idiopathic partial epilepsy in phenotype and pathogenic mechanism, implied a clinical significance in early diagnosis and management., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Studies have identified platelet-rich plasma (PRP) as a novel adjuvant therapy in androgenetic alopecia (AGA). However, the efficacy of PRP still needs to be improved. The purpose of this study was to assess the efficacy of PRP plus basic fibroblast growth factor (PRPF) for the treatment of AGA., Methods: This was a prospective randomized, double-blind, placebo-controlled, half-head study. Eighty patients whose AGA was staged Norwood-Hamilton stages III to VII or Ludwig stages I to III were enrolled in the study from February of 2019 to September of 2019. Patients were divided randomly into two groups of 40 patients each and were given the following treatment: group 1, PRPF was injected in the right half and the left half with placebo; group 2, PRPF was injected in the right half and the left half with PRP. The treatment was processed three times, 1 month apart. Hair growth parameters were evaluated by trichoscope monthly until the sixth month of the study. Patient satisfaction, hair pull test, and side effects were recorded during follow-up., Results: Of the 80 patients included in the study, 47 were men and 33 were women with a mean age of 28.96 ± 4.82 years (range, 21 to 46 years). Both PRP and PRPF showed positive improvement ( P < 0.05) on hair count, terminal hair, and anagen hair after the treatment. Efficacy of PRPF revealed a significant improvement ( P < 0.05) in hair count, terminal hair, vellus hair, and anagen hair versus PRP. There was no statistical difference among any of the parameters in the placebo group., Conclusion: PRPF can be a safe and valuable form of AGA treatment, and has proven to be more effective than PRP., Clinical Relevance Statement: Hybrid therapy of PRP with relative growth factors, such as basic fibroblast growth factor, have prominent efficacy on treatment of AGA., Clinical Question/level of Evidence: Therapeutic, II., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Osteoarthritis (OA) is an inflammatory disease accompanied by synovial joint inflammation, and IL-36 plays an important role in this process. Local application of IL-36 receptor antagonist (IL-36Ra) can effectively control the inflammatory response, thereby protecting cartilage and slowing down the development of OA. However, its application is limited by the fact that it is rapidly metabolized locally. We designed and prepared a temperature-sensitive poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA) hydrogel (IL-36Ra@Gel) system carrying IL-36Ra and evaluated its basic physicochemical characteristics. The drug release curve of IL-36Ra@Gel indicated that this system could slowly release the drug over a longer period. Furthermore, degradation experiments showed that it could be largely degraded from the body within 1 month. The biocompatibility-related results showed that it had no significant effect on cell proliferation compared to the control group. In addition, the expression of MMP-13 and ADAMTS-5 was lower in IL-36Ra@Gel-treated chondrocytes than in the control group, and the opposite results appeared in aggrecan and collagen X. After 8 weeks of treatment with IL-36Ra@Gel by joint cavity injection, HE and Safranin O/Fast green staining showed that the degree of cartilage tissue destruction in the IL-36Ra@Gel-treated group was less than those in other groups. Meanwhile, the joints of mice in the IL-36Ra@Gel group had the most intact cartilage surface, the smallest thickness of cartilage erosion, and the lowest OARSI and Mankins score among all groups. Consequently, the combination of IL-36Ra and PLGA-PLEG-PLGA temperature-sensitive hydrogels can greatly improve the therapeutic effect and prolong the drug duration time, thus effectively delaying the progression of degenerative changes in OA, providing a new feasible nonsurgical treatment for OA.

Background: Sleep duration is associated with hearing loss, especially presbycusis, which is the most common type of hearing loss; however, there is limited evidence regarding this association among the Korean population. We aimed to determine the relationship between sleep duration and high-frequency hearing loss in Korean adults aged ≥40 years., Methods: We examined 5,547 Korean adults aged ≥40 years who completed audiometric tests and questionnaires regarding sleep duration during the 2010-2012 cycle of the Korea National Health and Nutrition Examination Survey. Mild presbycusis was defined as >25 decibels (dB) and <40 dB, whereas moderate-to-severe presbycusis was defined as >40 dB pure tone averages at high frequencies (3,000, 4,000, and 6,000 Hz) for both ears. Additionally, the sleep duration was divided into quartiles. Odds ratios and 95% confidence intervals were estimated using multivariable logistic regression after adjusting for covariates., Results: The prevalence of presbycusis in South Korean adults was 62.1%, of which 61.4% showed moderate to severe presbycusis. The incidence of moderate-to-severe, but not mild, presbycusis showed a significant positive correlation with sleep duration., Conclusion: Our findings suggest that sleep duration is associated with the prevalence of presbycusis.

Aims: Etiology of the majority patients with idiopathic partial epilepsy (IPE) remains elusive. We thus screened the potential disease-associated variants in the patients with IPE., Methods: Trios-based whole exome sequencing was performed in a cohort of 320 patients with IPE. Frequency and molecular effects of variants were predicted., Results: Three novel BRWD3 variants were identified in five unrelated cases with IPE, which were four male cases and one female case. The variants included two recurrent missense variants (c.836C>T/p.Thr279Ile and c.4234A>C/p.Ile1412Leu) and one intronic variant close to splice site (c.2475 + 6A>G). The two missense variants were located in WD40 repeat domain and bromodomain, respectively. They were predicted to be damaging by silico tools and change hydrogen bonds with surrounding amino acids. The frequency of mutant alleles in this cohort was significantly higher than that in the controls of East Asian and all population of gnomAD. All these variants were inherited from the asymptomatic mothers. Four male cases presented frequent seizures at onset, while the female case only had two fever-triggered seizures. They showed good responses to valproate and lamotrigine, then finally became seizure free. All the cases had no intellectual disability. Further analysis demonstrated that all previously reported destructive variants of BRWD3 caused intellectual disability, while missense variants located in WD40 repeat domains and bromodomains of BRWD3 were associated with epilepsy., Conclusion: BRWD3 gene is potentially associated with X-linked partial epilepsy without intellectual disability. The genotypes and locations of BRWD3 variants may explain for their phenotypic variation., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objective: BCOR gene, encoding a corepressor of BCL6, plays an important role in fetal development. BCOR mutations were previously associated with oculofaciocardiodental syndrome (OFCD or MCOPS2, OMIM# 300166). The BCOR protein is ubiquitously expressed in multiple areas, including the brain. However, the role of BCOR in neurological disorder remains elusive., Methods: Trios-based whole-exome sequencing was performed in a cohort of 323 cases with partial epilepsy without acquired causes., Results: Seven hemizygous missense BCOR variants, including c 0.103 G>C/p.Asp35His, c.1079 A>G/p.His360Arg, c 0.1097 C>T/p.Thr366Ile, c 0.3301 C>T/p.Pro1101Ser, c 0.3391 C>T/p.Arg1131Trp, c 0.4199 G>A/p.Arg1400Gln, and c 0.5254 G>A/p.Asp1752Asn, were identified in seven cases with partial epilepsy. Two patients presented partial seizures with generalized seizures and/or generalized discharges. One case showed cortical dysplasia in the right temporal-occipital area on MRI. Two cases presented mild developmental delay. However, all patients achieved seizure-free. The frequency of BCOR variants in the present cohort was significantly higher than that in the controls of healthy Chinese volunteers and all populations of Genome Aggregation Database (gnomAD). Computational modeling, including hydrogen bond and prediction of protein stability, implied that the variants lead to structural impairment. Previously, OFCD associated BCOR mutations were mostly destructive mutations in an X-linked dominant (XLD) pattern; in contrast, the BCOR variants identified in this study were all missense variants, which were associated with partial epilepsy in an X-linked recessive (XLR) pattern. The proportion of missense mutations in epilepsy was significantly higher than that in OFCD., Conclusions: BCOR was potentially a candidate pathogenic gene of partial epilepsy with or without developmental delay. The genotype-phenotype correlation helps understanding the mechanism underlying phenotypic variation., Competing Interests: Conflict of interests All authors claim that there are no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

CELSR1 gene, encoding cadherin EGF LAG seven-pass G-type receptor 1, is mainly expressed in neural stem cells during the embryonic period. It plays an important role in neurodevelopment. However, the relationship between CELSR1 and disease of the central nervous system has not been defined. In this study, we performed trios-based whole-exome sequencing in a cohort of 356 unrelated cases with partial epilepsy without acquired causes and identified CELSR1 variants in six unrelated cases. The variants included one de novo heterozygous nonsense variant, one de novo heterozygous missense variant, and four compound heterozygous missense variants that had one variant was located in the extracellular region and the other in the cytoplasm. The patients with biallelic variants presented severe epileptic phenotypes, whereas those with heterozygous variants were associated with a mild epileptic phenotype of benign epilepsy with centrotemporal spikes (BECTS). These variants had no or low allele frequency in the gnomAD database. The frequencies of the CELSR1 variants in this cohort were significantly higher than those in the control populations. The evidence from ClinGen Clinical-Validity Framework suggested a strong association between CELSR1 variants and epilepsy. These findings provide evidence that CELSR1 is potentially a candidate pathogenic gene of partial epilepsy of childhood., (© 2022 Wiley Periodicals LLC.)

It is known that approximately 10% of successful quitters relapse annually. This study aimed to investigate the factors related to long-term smoking relapse in individuals who succeeded in maintaining smoking cessation for 6 months after attending a regional smoking cessation program. This study enrolled 943 individuals registered for the regional smoking cessation program at the Busan Smoking Cessation Center in 2018-2019 who maintained smoking cessation for 6 months. A survey was conducted using a smartphone link or through phone calls, and the data for 305 participants who finally completed the survey were analyzed. The questionnaire addressed individual, inter-individual, organizational, and community-level factors related to smoking relapse. Multivariate logistic regression analysis was performed to evaluate the factors associated with smoking relapse by period. The Cox proportional hazard regression model was used for the factors associated with smoking relapse for the entire period. The smoking relapse rate at the time of the survey was 25.4%. In the analysis of smoking relapse by period, relapse was associated with the belief that smoking relieves stress, the number of single-person households, and poor subjective health status. In the analysis of smoking relapse during the entire period, we observed a significant association with the belief that smoking relieves stress (hazard ratio [HR]: 2.65, 95% confidence interval [CI]: 1.52-4.61), single-person households (HR: 1.95, 95% CI: 1.16-3.26), and high levels of emotional stress (HR: 1.72, 95% CI: 1.04-2.85). Long-term follow-up is necessary to prevent smoking relapse in single-person households, individuals who believe that smoking relieves stress, and those experiencing high levels of subjective emotional stress. Interventional therapies for stress relief and awareness improvement in smokers need to be developed., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: PRRT2 is a major causative gene for self-limited familial neonatal-infantile epilepsy, paroxysmal kinesigenic dyskinesia, and paroxysmal kinesigenic dyskinesia with infantile convulsions. Voluntary movement trigger is prominent in adolescence and adulthood, but the triggers are unknown in infants., Methods: A gene panel designed for targeted next-generation sequencing (NGS) was used to screen genetic abnormalities in a cohort of 45 cases with infantile convulsions. The copy number variation was detected by a computational method based on the normalized depth of coverage and validated by a quantitative real-time polymerase chain reaction (RT-qPCR) method. The genotype-phenotype correlation of the PRRT2 mutation gene was analyzed., Results: A de novo heterozygous PRRT2 deletion was identified in a child who had infantile convulsions induced by vigorous sucking. Seizures happened during the change of feeding behavior from breast to formula, which led to hungry and vigorous sucking. Ictal electroencephalograms recorded seizures with focal origination, which provided direct evidence of epileptic seizures in infants with PRRT2 mutations. Seizures stopped soon after the feeding behavior was changed by reducing feeding interval time and extending feeding duration. Data reanalysis on our previously reported cases with PRRT2 mutations showed that six of 18 (33.3%) patients had infantile convulsions or infantile non-convulsion seizures during feeding. The mutations included two truncating mutations (c.579dupA/p.Glu194Argfs * 6, and c.649dupC/p.Arg217Profs * 8) that were identified in each of the three affected individuals., Conclusions: This study suggests that feeding, especially vigorous sucking, is potentially a trigger and highlights the significance of feeding behavior in preventing seizures in infants with PRRT2 mutations. Identification of PRRT2 haploinsufficiency mutations in the patients with infantile convulsions induced by sucking suggested a potential genotype-phenotype correlation., 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 © 2022 Liu, Tang, Wan, Luo, Guan, Li, Liu, Li, Liu, Xie and Yi.)

Background: Folic acid is involved in inflammatory reactions; however, the association between folic acid and allergic diseases, particularly asthma, remains unclear. Thus, this study aimed to evaluate the association between serum folic acid levels and asthma in Koreans., Methods: This study analyzed the serum folic acid levels of 6,615 individuals included in the 2016-2018 Korea National Health and Nutrition Examination Survey. The prevalence of asthma was determined using a questionnaire that identified cases of physician-diagnosed asthma. The relationship between serum folic acid levels and asthma was analyzed using logistic regression analysis., Results: Multiple logistic regression analysis showed that a 1 ng/mL increase in serum folic acid level significantly reduced the risk of asthma after adjusting for confounding factors including sex, age, household income, current smoking, current alcohol use, and body mass index (odds ratio [OR], 0.930; 95% confidence interval [CI], 0.876- 0.987; P=0.017). The relationship between the adjusted odds of asthma and serum folic acid levels were consistently inverse (OR, 2.266; 95% CI, 1.126-4.420; P for trend=0.038)., Conclusion: Serum folic acid levels are inversely associated with physician-diagnosed asthma in the Korean population.

Objective: This study aimed to investigate the correlation between the surface area ratio of medial tibial plateau (MTP) to lateral tibial plateau (LTP) and the mechanical tibiofemoral angle (mTFA)., Methods: Lower limb computed tomography (CT) images were collected at our hospital. Then, the original CT data were analyzed and reconstructed using medical image processing software. The proximal and distal centres of the femur and tibia were marked. The surface areas of MTP and LTP were identified using image processing software. GraphPad Prism 8.0.2 was used to perform the statistical analysis., Results: The surface area ratio of MTP to LTP was significantly correlated with the mTFA in all patients (P<0.0001), male group (P<0.0001), female group (P<0.0001), varus group (P<0.0001), and valgus group (P=0.002). Furthermore, the surface area of MTP and LTP was significantly greater in the male group than in the female group (P<0.0001). There was significant difference in the surface area of the MTP between the varus and valgus groups (P<0.0001). Significant difference was also observed in the surface area ratio of MTP to LTP between the varus and valgus groups (P<0.0001)., Conclusion: The surface area ratio of MTP to LTP was correlated with the mTFA. Within a certain range, the smaller the mTFA, the greater the surface area ratio of MTP to LTP. For patients undergoing total knee arthroplasty, of whom the surface area of the MTP was basically equal to that of the LTP, it is recommended that the osteotomy should be performed in accordance with mechanical alignment standards, and that a symmetrical tibial plateau prosthesis should be used. For patients whose surface area of MTP is significantly greater than that of the LTP, it is recommended that the osteotomy should be performed in accordance with kinematic alignment standards, and that an anatomical tibial plateau prosthesis should be used., (© 2022. Huazhong University of Science and Technology.)

Objective: The LAMA5 gene encodes the laminin subunit α5, the most abundant laminin α subunit in the human brain. It forms heterotrimers with the subunit β1/β2 and γ1/γ3 and regulates neurodevelopmental processes. Genes encoding subunits of the laminin heterotrimers containing subunit α5 have been reported to be associated with human diseases. Among LAMAs encoding the laminin α subunit, LAMA1-4 have also been reported to be associated with human disease. In this study, we investigated the association between LAMA5 and epilepsy., Methods: Trios-based whole-exome sequencing was performed in a cohort of 118 infants suffering from focal seizures with or without spasms. Protein modeling was used to assess the damaging effects of variations. The LAMAs expression was analyzed with data from the GTEX and VarCards databases., Results: Six pairs of compound heterozygous missense variants in LAMA5 were identified in six unrelated patients. All affected individuals suffered from focal seizures with mild developmental delay, and three patients presented also spasms. These variants had no or low allele frequencies in controls and presented statistically higher frequency in the case cohort than in controls. The recessive burden analysis showed that recessive LAMA5 variants identified in this cohort were significantly more than the expected number in the East Asian population. Protein modeling showed that at least one variant in each pair of biallelic variants affected hydrogen bonds with surrounding amino acids. Among the biallelic variants in cases with only focal seizures, two variants of each pair were located in different structural domains or domains/links, whereas in the cases with spasms, the biallelic variants were constituted by two variants in the identical functional domains or both with hydrogen bond changes., Conclusion: Recessive LAMA5 variants were potentially associated with infant epilepsy. The establishment of the association between LAMA5 and epilepsy will facilitate the genetic diagnosis and management in patients with infant epilepsy., 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 © 2022 Luo, Liu, Wang, Luo, Ye, Li, Zhai, Liu, Wang, Gao, Liu, Ye, Li, Gao, Guo, Li, Yi and Liao.)

Objective: SHROOM4 gene encodes an actin-binding proteins, which plays an important role in cytoskeletal architecture, synaptogenesis, and maintaining gamma-aminobutyric acid receptors-mediated inhibition. SHROOM4 mutations were reported in patients with the Stocco dos Santos type of X-linked syndromic intellectual developmental disorder (SDSX; OMIM# 300434). In this study, we investigated the association between SHROOM4 and epilepsy., Methods: Trios-based whole-exome sequencing was performed in a cohort of 320 cases with idiopathic generalized epilepsy or idiopathic partial epilepsy. Protein modeling was used to assess the damaging effects of variations., Results: Six hemizygous missense SHROOM4 variants, including c.13C > A/p. Pro5Thr, c.3236C > T/p.Glu1079Ala, c.3581C > T/p.Ser1194Leu, c.4288C > T/p.Arg1430Cys, c.4303G > A/p.Val1435Met, c.4331C > T/p.Pro1444Leu, were identified in six cases with idiopathic epilepsy without intellectual disability. All patients presented with features of generalized seizures or generalized discharges. These hemizygous variants had no or extremely low allele frequencies in controls and showed statistically higher frequency in the case cohort than controls. All variants were predicted to alter hydrogen bond with surrounding amino acids or decreased protein stability. The SHROOM4 variants reported in patients with SDSX were mostly destructive or duplicative variants; in contrast, the SHROOM4 variants were all missense variants, suggesting a potential genotype-phenotype correlation. The two missense variants associated with SDSX were located in the middle of SHROOM4 protein, whereas variants associated with idiopathic epilepsy were located around the N-terminal PDZ domain and the C-terminal ASD2 domain., Significance: SHROOM4 was potentially a candidate pathogenic gene of idiopathic epilepsy without intellectual disability. The genotype-phenotype correlation and sub-regional effect helps understanding the mechanism underlying phenotypic variation., 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 © 2022 Bian, Li, Wang, Luo, Li, Gao, He and Yi.)

Purpose: Previously, mutations in the voltage-gated calcium channel subunit alpha1 A ( CACNA1A ) gene have been reported to be associated with paroxysmal disorders, typically as episodic ataxia type 2. To determine the relationship between CACNA1A and epilepsies and the role of molecular sub-regional on the phenotypic heterogeneity., Methods: Trio-based whole-exome sequencing was performed in 318 cases with partial epilepsy and 150 cases with generalized epilepsy. We then reviewed all previously reported CACNA1A mutations and analyzed the genotype-phenotype correlations with molecular sub-regional implications., Results: We identified 12 CACNA1A mutations in ten unrelated cases of epilepsy, including four de novo null mutations (c.2963&#95;2964insG/p.Gly989Argfs*78, c.3089 + 1G > A, c.4755 + 1G > T, and c.6340-1G > A), four de novo missense mutations (c.203G > T/p.Arg68Leu, c.3965G > A/p.Gly1322Glu, c.5032C > T/p.Arg1678Cys, and c.5393C > T/p.Ser1798Leu), and two pairs of compound heterozygous missense mutations (c.4891A > G/p.Ile1631Val& c.5978C > T/p.Pro1993Leu and c.3233C > T/p.Ser1078Leu&c.6061G > A/p.Glu2021Lys). The eight de novo mutations were evaluated as pathogenic or likely pathogenic mutations according to the criteria of American College of Medical Genetics and Genomics (ACMG). The frequencies of the compound heterozygous CACNA1A mutations identified in this cohort were significantly higher than that in the controls of East Asian and all populations ( P = 7.30 × 10 -4 , P = 2.53 × 10 -4 ). All of the ten cases were ultimately seizure-free after antiepileptic treatment, although frequent epileptic seizures were observed in four cases. Further analysis revealed that episodic ataxia type 2 (EA2) had a tendency of higher frequency of null mutations than epilepsies. The missense mutations in severe epileptic phenotypes were more frequently located in the pore region than those in milder epileptic phenotypes ( P = 1.67 × 10 -4 ); de novo mutations in the epilepsy with intellectual disability (ID) had a higher percentage than those in the epilepsy without ID ( P = 1.92 × 10 -3 )., Conclusion: This study suggested that CACNA1A mutations were potentially associated with pure epilepsy and the spectrum of epileptic phenotypes potentially ranged from the mild form of epilepsies such as absence epilepsy or partial epilepsy, to the severe form of developmental epileptic encephalopathy. The clinical phenotypes variability is potentially associated with the molecular sub-regional of the mutations., 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 © 2022 Li, Li, Liang, Liu, Jiang, Gao, Li, Tang, Shi, Li, He, Li, Bian, Yi, Cheng and Wang.)

Metabolic syndrome (MetS) is a disease with a high prevalence that threatens the health of modern people. Patient education is essential to control MetS. This prospective study aimed to evaluate 6-month changes in health indicators following a two-day education program for patients with MetS aged 45 or older. Education about MetS, lifestyle modification, nutrition, and physical activity was provided. At 3 and 6 months after the program, participants visited for follow-up. Twenty-two patients completed the 6-month study. Waist circumference was reduced, and life quality and depression index improved in 3 and 6 months compared to pre-education. Blood pressure decreased, and anxiety index improved at three months. Nutritional knowledge was well maintained for 3 and 6 months. High-density lipoprotein-cholesterol levels increased at six months. Three out of twenty-two patients did not satisfy MetS criteria at the end of the study due to improved indicators. A two-day multidisciplinary education program positively affected health indicators in MetS patients. Participation in the program also help with life satisfaction and positive emotional condition. However, some indicators improved in 3 months, but the effect disappeared 6 months after the program.

Aims: To identify novel pathogenic gene of febrile seizures (FS)/epilepsy with antecedent FS (EFS+)., Methods: The trio-based whole-exome sequencing was performed in a cohort of 462 cases with FS/EFS+. Silico programs, sequence alignment, and protein modeling were used to predict the damaging of variants. Statistical testing was performed to analyze gene-based burden of variants., Results: Five heterozygous missense variants in CELSR3 were detected in five cases (families) with eight individuals (five females, three males) affected. Two variants were de novo, and three were identified in families with more than one individual affected. All the variants were predicted to be damaging in silico tools. Protein modeling showed that the variants resulted in disappearance of multiple hydrogen bonds and one disulfide bond, which potentially caused functional impairments of protein. The frequency of CELSR3 variants identified in this study was significantly higher than that in controls. All affected individuals were diagnosed with FS/EFS+, including six patients with FS and two patients with EFS+. All cases presented favorable outcomes without neurodevelopmental disorders., Conclusions: CELSR3 variants are potentially associated with FS/EFS+., (© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Background: There is controversy over whether use of new oral anticoagulants (NOACs) associates with increased hemorrhage risk compared with non-NOAC. Meanwhile, determining which NOAC to use remains unclear. We aimed to summarize the evidence about NOACs in venous thromboembolism (VTE) prevention for patients with total hip and knee arthroplasty (THA and TKA). Methods: We searched RCTs assessing NOACs for VTE prophylaxis in adults undergoing THA and TKA in Medline, Embase, and Cochrane up to May 2021. Primary outcomes were VTE [included deep vein thrombosis (DVT) and pulmonary embolism (PE)], major VTE, and major bleeding. The rank probabilities of each treatment were summarized by the surface under the cumulative ranking curve area (SUCRA). Results: 25 RCTs with 42,994 patients were included. Compared with non-NOAC, NOACs were associated with a decreased risk of VTE (RR 0.68; 95% CI 0.55-0.84) and major VTE (RR = 0.52; 95% CI 0.35-0.76). Additionally, rivaroxaban, apixaban, and edoxaban but not dabigatran and betrixaban, did confer a higher efficacy compared with non-NOAC. None of the individual NOACs increased the risk of bleeding, while apixaban and betrixaban were even associated with a decreased risk of bleeding. In the comparison of different NOACs, rivaroxaban was associated with the greatest benefits in VTE (SUCRA = 79.6), DVT (SUCRA = 88.8), and major VTE (SUCRA = 89.9) prevention. Furthermore, subgroup analysis confirmed that NOACs associated with a higher efficacy tendency in patients with follow-up duration <60 days than follow-up duration ≥60 days. Conclusion: Evidence suggests that NOACs exert more benefits on VTE prophylaxis, and none of the individual NOACs increased hemorrhage compared with non-NOAC. Among various NOACs, rivaroxaban is recommended in patients with lower bleeding risk, and apixaban is recommended in patients with higher bleeding risk. Systematic Review Registration : [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021266890]., 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 © 2022 Yi, Gong, Gong, Zhou, Hu and Xu.)

To explore the correlation between the changes of the intestinal flora of newly treated pulmonary tuberculosis patients and the immune indicators of the body, and to provide a reference for the prevention and treatment of pulmonary tuberculosis. A single-center and case-control study was adopted. From October 2020 to April 2021, 43 patients with newly diagnosed tuberculosis in the Department of Tuberculosis, Affiliated Changsha Central Hospital,University of South China were selected as the control group. 43 cases of newly treated pulmonary tuberculosis (PTB), 43 healthy control (HC) during the same period, collected fresh feces and whole blood of subjects, and used Illumina Hiseq high-throughput sequencing technology to analyze 16S of all microorganisms in feces The V4 region of rRNA was amplified and sequenced, and the structure of the intestinal flora was analyzed by QIIME software. Use flow cytometry to determine the subject's immune indicators (CD3 + , CD4 + , CD8 + , CD4 + CD25 + CD127 - Treg, CD14 + CD16 + , CD14 + CD16 - ), and analyze the changes in intestinal flora and immune function in newly treated pulmonary tuberculosis patients Inherent connection. The χ² test, t test, and Wilcox rank sum test were used to analyze the differences in age, gender, α diversity, and relative abundance of the two groups of people. Compared with the HC group, the alpha diversity of the intestinal flora in the PTB group decreased (shannon index: t =3.906, P =0.000 2; simpson index: Z =553, P =0.004 7; chao1 index: t =5.395, P =0.000 0). β diversity analysis showed that there were significant differences in the structure of the intestinal flora between the two groups ( P =0.000). Species difference analysis showed that at the phylum level, the relative abundance of Firmicutes in the PTB group was significantly lower than that in the HC group ( Z =486.0, P =0.000 5). At the genus level, there are 15 different bacterial genera between the two groups. In the PTB group, bifidobacterium, enterococcus, lactobacillus, anaerostipes, the relative abundance of the above 5 genera of veillonella is higher than that of the HC group ( P <0.05); Butyricimonas, clostridium, and broutella (blautia), coprococcus, dorea, lachnospira, roseburia, faecalibacterium, ruminococcus, the relative abundance of 10 bacterial genera including dialister was lower than that of the HC group ( P <0.05). Comparison of immune indexes between groups showed that CD14 + CD16 + monocytes (%) in the PTB group were higher than those in the HC group ( t =2.456, P =0.001 6<0.05), while CD14 + CD16 - monocytes (%) were lower than HC ( t =-4.368, P =0.000<0.05), while the differences in CD3 + , CD4 + , CD8 + , CD4 + /CD8 + and Treg (CD4 + CD25 + CD127 - ) were not statistically significant ( P >0.05). Spearman correlation analysis showed that Firmicutes in the PTB group was negatively correlated with CD4 + /CD8 + , CD14 + CD16 + ( r =-0.218, P =0.048; r =-0.245, P =0.025), and positively correlated with CD14 + CD16 - Correlation ( r =0.250, P =0.022); At the genus level, Faecalis is positively correlated with CD4 + /CD8 + and CD4 + ( r =0.250, P =0.023; r =0.258, P =0.019); Rosella and CD3 + , CD8 + and CD14 + CD16 - are positively correlated ( r =0.27, P =0.024; r =0.219, P =0.046; r =0.027, P =0.039), and negatively correlated with CD14 + CD16 + ( r =-0.280, P = 0.01). Changes in the structure of the intestinal flora of newly treated pulmonary tuberculosis patients may be one of the influencing factors of the immune function of the body. Targeted optimization of the structure of the intestinal flora and improvement of the body's immunity may be used as an effective auxiliary treatment for pulmonary tuberculosis.

The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2), which is highly expressed in the brain-predominantly in the cerebral cortex-and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability. However, the functional significance of the UNC13B mutation in human disease is not known. In this study, we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy without acquired causes by trio-based whole-exome sequencing. UNC13B variants were identified in 12 individuals affected by partial epilepsy and/or febrile seizures from eight unrelated families. The eight probands all had focal seizures and focal discharges in EEG recordings, including two patients who experienced frequent daily seizures and one who showed abnormalities in the hippocampus by brain MRI; however, all of the patients showed a favourable outcome without intellectual or developmental abnormalities. The identified UNC13B variants included one nonsense variant, two variants at or around a splice site, one compound heterozygous missense variant and four missense variants that cosegregated in the families. The frequency of UNC13B variants identified in the present study was significantly higher than that in a control cohort of Han Chinese and controls of the East Asian and all populations in the Genome Aggregation Database (gnomAD). Computational modelling, including hydrogen bond and docking analyses, suggested that the variants lead to functional impairment. In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila. Electrophysiological recordings showed that excitatory neurons in Unc13b-deficient flies exhibited increased excitability. These results indicate that UNC13B is potentially associated with epilepsy. The frequent daily seizures and hippocampal abnormalities but ultimately favourable outcome under anti-epileptic therapy in our patients indicate that partial epilepsy caused by UNC13B variant is a clinically manageable condition., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)