Visualizing the chaperone-mediated folding trajectory of the G protein ß5 ß-propeller.

The Chaperonin Containing Tailless polypeptide 1 (CCT) complex is an essential protein folding machine with a diverse clientele of substrates, including many proteins with ß-propeller domains. Here, we determine the structures of human CCT in complex with its accessory co-chaperone, phosducin-like protein 1 (PhLP1), in the process of folding Gß5, a component of Regulator of G protein Signaling (RGS) complexes. Cryoelectron microscopy (cryo-EM) and image processing reveal an ensemble of distinct snapshots that represent the folding trajectory of Gß5 from an unfolded molten globule to a fully folded ß-propeller. These structures reveal the mechanism by which CCT directs Gß5 folding through initiating specific intermolecular contacts that facilitate the sequential folding of individual ß sheets until the propeller closes into its native structure. This work directly visualizes chaperone-mediated protein folding and establishes that CCT orchestrates folding by stabilizing intermediates through interactions with surface residues that permit the hydrophobic core to coalesce into its folded state.

Interplay of Mediterranean-diet adherence, genetic factors, and metabolic dysfunction-associated steatotic liver disease risk in Korea.

BACKGROUNDS: Metabolic dysfunction-associated steatotic liver disease (MASLD) has gained attention owing to its severe complications. This study aimed to explore the interaction between Mediterranean-diet (MD) adherence, genetic factors, and MASLD risk in a Korean population. METHODS: In total, 33,133 individuals aged 40 years and older from the Korean Genome and Epidemiology Study (KoGES) were analyzed. Participants were assessed for MASLD based on criteria and MD adherence measured by the Korean version of the Mediterranean-Diet Adherence Screener (K-MEDAS). Individuals were categorized into two groups based on their MD adherence: high adherence (K-MEDAS > 6) and low adherence (K-MEDAS < 5). Single nucleotide polymorphism (SNP) genotypes were obtained using the Korea Biobank array. Logistic regression was used to examine the single-marker variants for genetic associations with MASLD prevalence. RESULTS: Individuals were categorized into MASLD (10,018 [30.2%]) and non-MASLD (23,115 [69.8%]) groups. A significant interaction was observed between the rs780094 glucokinase regulatory protein (GCKR) gene and K-MEDAS on MASLD (p < 10 - 2 ). Of individuals with K-MEDAS > 6, those carrying the minor allele (C) of the GCKR gene rs780094 exhibited a lower risk of MASLD compared to those without the allele (odds ratio [OR] = 0.88 [0.85-0.91], p-value = 5.54e-13). CONCLUSION: The study identified a significant interaction involving the rs780094 variant near the GCKR gene, with carriers of the minor allele exhibiting a lower MASLD risk among those adhering well to the MD. Dietary habits influence the MASLD risk associated with the rs780094 allele, emphasizing the need for personalized nutrition recommendations.

Associations of Homeostatic Model Assessment for Insulin Resistance Trajectories With Cardiovascular Disease Incidence and Mortality.

BACKGROUND: Whether trends in insulin resistance changes are related to the risk of cardiovascular disease (CVD) incidence and mortality remains unclear. We aimed to examine the association of homeostatic model assessment for insulin resistance (HOMA-IR) trajectories with CVD incidence and mortality. METHODS: Data from 6755 adults aged 40 to 69 years in the Korea Epidemiology and Genome Study were analyzed. During the exposure period (2001-2006), participants were classified into the increasing HOMA-IR trajectory group and the stable HOMA-IR trajectory group using a latent class mixture model. During the event accrual period (2007-2018), information about CVD and mortality were collected. RESULTS: During the median 9.83-year event accrual period, there were 379 (5.6%) new-onset CVD, 535 (7.9%) all-cause mortality, 102 (1.5%) CVD mortality, and 47 (0.7%) major adverse cardiovascular event mortality cases. Compared with the stable HOMA-IR trajectory group, the fully adjusted hazard ratios (95% CIs) for the increasing HOMA-IR trajectory group were 1.59 (1.04-2.44) for incident CVD, 1.87 (1.30-2.69) for all-cause mortality, 2.33 (1.11-4.89) for CVD mortality, and 3.67 (1.38-9.76) for major adverse cardiovascular event mortality. CONCLUSIONS: An increasing HOMA-IR appears to be independently and positively related to incident CVD, all-cause mortality, CVD mortality, and major adverse cardiovascular event mortality. Early lifestyle interventions for individuals with increasing HOMA-IR trend could be a practical strategy to prevent CVD and CVD mortality.

How to walk to reduce footstep noise in multi-story residential buildings.

Loud footsteps from upstairs cause disturbance to downstairs neighbours in multi-story residential buildings. In this experiment, we examined how participants walk when asked to walk quietly and evaluated the efficiency of their quiet walking patterns. Changes in vertical impact loading rates during the early stance phase, walking speed, and lower limb muscle activity when asked to walk quietly were evaluated from twenty-six young participants. Study data show that participants who struck the ground with the rearfoot reduced the impact loading rate by 44.6% with 29.3% slower walking speed than normal walking. Those who struck with the fore- or mid-foot reduced the impact loading by 69.2% with a 23.4% decrease in speed. Quiet walking with the non-rearfoot strike pattern reduced the impact loading by 48.7%, even when asked to walk as fast as normal walking. The results support the non-rearfoot strike pattern as an efficient walking strategy for lowering footstep impact.Practitioner summary: Data of this study show that voluntary gait alteration, such as adopting a non-rearfoot strike pattern, can reduce footstep impact. The study results propose that implementing such changes could be beneficial in addressing floor noise issues of multi-story residential buildings.Abbreviations: RFS: Rearfoot strike; NRFS: non-rearfoot strike; COP: Center of pressure; NW: Normal walking; QWs: Quiet walking at a preferred slower speed; QWn: Quiet walking at the speed of normal walking; EMG: Electromyography; BW: Body weight; iNEMG: integrated normalized EMG.

Assessing the Feasibility and Efficacy of Pre-Sleep Dim Light Therapy for Adults with Insomnia: A Pilot Study.

Background: Insomnia is increasingly recognized for its marked impact on public health and is often associated with various adverse health outcomes, including cardiovascular diseases and mental health disorders. The aim of this study was to investigate the efficacy of pre-sleep dim light therapy (LT) as a non-pharmacological intervention for insomnia in adults, assessing its influence on sleep parameters and circadian rhythms. Methods: A randomized, open-label, two-arm clinical trial was conducted over two weeks with 40 participants aged 20-60 years, all of whom had sleep disorders (CRIS, KCT0008501). They were allocated into control and LT groups. The LT group received exposure to warm-colored light, minimizing the blue spectrum, before bedtime. The study combined subjective evaluation via validated, sleep-related questionnaires, objective sleep assessments via actigraphy, and molecular analyses of circadian clock gene expression in peripheral blood mononuclear cells. Baseline characteristics between the two groups were compared using an independent t-test for continuous variables and the chi-squared test for categorical variables. Within-group differences were assessed using the paired t-test. Changes between groups were analyzed using linear regression, adjusting for each baseline value and body mass index. The patterns of changes in sleep parameters were calculated using a linear mixed model. Results: The LT group exhibited significant improvements in sleep quality (difference in difference [95% CI]; -2.00 [-3.58, -0.43], and sleep efficiency (LT: 84.98 vs. control: 82.11, p = 0.032), and an advanced Dim Light Melatonin Onset compared to the control group (approximately 30 min). Molecular analysis indicated a significant reduction in CRY1 gene expression after LT, suggesting an influence on circadian signals for sleep regulation. Conclusions: This study provides evidence for the efficacy of LT in improving sleep quality and circadian rhythm alignment in adults with insomnia. Despite limitations, such as a small sample size and short study duration, the results underscore the potential of LT as a viable non-pharmacological approach for insomnia. Future research should expand on these results with larger and more diverse cohorts followed over a longer period to validate and further elucidate the value of LT in sleep medicine. Trial registration: The trial was registered with the Clinical Research Information Service (KCT0008501).

Association of non-high-density lipoprotein cholesterol trajectories with the development of non-alcoholic fatty liver disease: an epidemiological and genome-wide association study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) shares common risk factors with cardiovascular diseases. Effects of longitudinal trends in non-high-density lipoprotein (non-HDL) cholesterol on NAFLD development are not understood. This study aimed to assess the relationship between non-HDL cholesterol trajectories and the incidence of NAFLD and to identify genetic differences contributing to NAFLD development between non-HDL cholesterol trajectory groups. METHODS: We analyzed data from 2203 adults (aged 40-69 years) who participated in the Korean Genome and Epidemiology Study. During the 6-year exposure periods, participants were classified into an increasing non-HDL cholesterol trajectory group (n = 934) or a stable group (n = 1269). NAFLD was defined using a NAFLD-liver fat score > -0.640. Multiple Cox proportional hazard regression analysis estimated the hazard ratio (HR) and the 95% confidence interval (CI) for the incidence of NAFLD in the increasing group compared with the stable group. RESULTS: A genome-wide association study identified significant single-nucleotide polymorphisms (SNPs) associated with NAFLD. During the median 7.8-year of event accrual period, 666 (30.2%) newly developed NAFLD cases were collected. Compared with the stable non-HDL group, the adjusted HR (95% CI) for the incidence of NAFLD in the increasing non-HDL cholesterol group was 1.46 (1.25-1.71). Although there were no significant SNPs, the polygenic risk score was highest in the increasing group, followed by the stable and control groups. CONCLUSION: Our study indicates that lifestyle or environmental factors have a greater effect size than genetic factors in NAFLD progression risk. Lifestyle modification could be an effective prevention strategy for NAFLD for people with elevated non-HDL cholesterol.

Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation.

BACKGROUND: Atopic dermatitis (AD) is a complex condition characterized by impaired epithelial barriers and dysregulated immune cells. In this study, we demonstrated Forsythia velutina Nakai extract (FVE) simultaneously inhibits basophils, macrophages, keratinocytes, and T cells that are closely interrelated in AD development. METHODS: We analyzed the effect of FVE on nitric oxide and reactive oxygen species (ROS) production in macrophages, basophil degranulation, T cell activation, and tight junctions in damaged keratinocytes. Expression of cell-type-specific inflammatory mediators was analyzed, and the underlying signaling pathways for anti-inflammatory effects of FVE were investigated. The anti-inflammatory effects of FVE were validated using a DNCB-induced mouse model of AD. Anti-inflammatory activity of compounds isolated from FVE was validated in each immune cell type. RESULTS: FVE downregulated the expression of inflammatory mediators and ROS production in macrophages through TLR4 and NRF2 pathways modulation. It significantly reduced basophil degranulation and expression of type 2 (T2) and pro-inflammatory cytokines by perturbing FcεRI signaling. Forsythia velutina Nakai extract also robustly inhibited the expression of T2 cytokines in activated T cells. Furthermore, FVE upregulated the expression of tight junction molecules in damaged keratinocytes and downregulated leukocyte attractants, as well as IL-33, an inducer of T2 inflammation. In the AD mouse model, FVE showed superior improvement in inflammatory cell infiltration and skin structure integrity compared to dexamethasone. Dimatairesinol, a lignan dimer, was identified as the most potent anti-inflammatory FVE compound. CONCLUSION: Forsythia velutina Nakai extract and its constituent compounds demonstrate promising efficacy as a therapeutic option for prolonged AD treatment by independently inhibiting various cell types associated with AD and disrupting the deleterious link between them.

Comparison of the triglyceride glucose index and modified triglyceride glucose indices in assessing periodontitis in Korean adults.

BACKGROUND: Periodontal diseases are closely connected with insulin resistance (IR) and metabolic syndrome. The Triglyceride Glucose Index (TyG) assesses IR, and recently, a few indices combining TyG and body composition have emerged with higher IR predictive performance than TyG alone. We aimed to examine which TyG-related parameters are most helpful in predicting the risk of periodontal disease. METHODS: From 2013 to 2015, data were collected through the Korean National Health and Nutrition Examination Survey. Periodontitis was defined using the Community Periodontal Index. TyG-body mass index (BMI), TyG-waist circumference (WC), and TyG-waist-to-height ratio (WHtR) were calculated by multiplying TyG index score by BMI, WC, and WHtR, respectively. Multiple logistic regression analysis was used to calculate odds ratio (OR) and 95% confidence intervals (CI). Receiver operating characteristic curves were used to estimate areas under the curve (AUC). RESULTS: Compared to each reference quartile (Q)1, Q4 of the TyG index, TyG-BMI, TyG-WC, and TyG-WHtR were significantly associated with a higher risk of periodontitis after adjusting for confounders (OR, 95% CI; 1.23, 1.01-1.49 for TyG; 1.63, 1.22-2.17 for TyG-BMI; 1.37, 1.04-1.81 for TyG-WC; and 1.53, 1.16-2.02 for TyG-WHtR). The AUC and 95% CIs of TyG, TyG-BMI, TyG-WC, and TyG-WHtR in predicting periodontitis were 0.609 (0.600-0.617), 0.605 (0.596-0.617), 0.629 (0.621-0.637), and 0.636 (0.628-0.644), respectively (all p < .001). CONCLUSIONS: TyG, TyG-BMI, TyG-WC, and TyG-WHtR appear to be significantly associated with the prevalence of periodontitis. Among the TyG and modified TyG indices, TyG-WHtR exhibited the highest predictive performance for periodontitis.

Trends in serum uric acid levels among Korean children and adolescents between 2016 and 2020: a nationwide study.

The aim of this study was to examine trends in serum uric acid (SUA) levels over a recent 5-year period according to age, sex, obesity, and abdominal obesity among Korean children and adolescents. We conducted a serial cross-sectional analysis using nationally representative data from the Korea National Health and Nutritional Examination Survey from 2016 to 2020. The study outcome was trends in SUA levels. SUA trends were analyzed by survey-weighted linear regression analysis considering the survey year as a continuous variable. SUA trends were also analyzed for subgroups based on age, sex, abdominal obesity, or obesity. This study included 3,554 children and adolescents aged 10-18 years. SUA increased significantly over the study period in boys (p for trend = 0.043), but not in girls (p for trend = 0.300). In age-specific analyses, SUA increased significantly in the 10-12 years group (p for trend = 0.029). After adjusting for age, SUA increased significantly in the obese group of both boys (p for trend = 0.026) and girls (p for trend = 0.023), but not in the overweight, normal, or under-weight groups of either sex. After adjusting for age, SUA increased significantly in the abdominal obesity group of boys (p for trend = 0.017) and girls (p for trend = 0.014), but not in the non-abdominal obesity group of either sex.   Conclusion: In the current study, SUA levels significantly increased in both boys and girls with obesity or abdominal obesity. Further studies of the effect of SUA on health outcomes in boys and girls with obesity or abdominal obesity are needed. What is Known: • High serum uric acid (SUA) is a risk factor for various metabolic diseases, including gout, hypertension, and type 2 diabetes. What is New: • SUA levels increased in boys and the 10-12 years group of Korean children and adolescents. • SUA levels increased significantly in Korean children and adolescents with obesity or central obesity.

Feasibility and Efficacy of Morning Light Therapy for Adults with Insomnia: A Pilot, Randomized, Open-Label, Two-Arm Study.

Background and Objectives: Light therapy (LT) is used as an adjunctive treatment for sleep problems. This study evaluates the impact of LT on sleep quality and sleep-related parameters in patients with sleep disorders. Materials and Methods: We performed a pilot, randomized, open-label clinical trial. Fourteen patients aged 20-60 years with insomnia were randomized into the control and LT groups (1:1 ratio). The LT group was instructed to use a device that provides bright LT (6000 K, 380 lux, wavelength 480 nm) for at least 25 min before 09:00 a.m. for two weeks. A self-reported questionnaire was used to evaluate circadian preference, mood, and sleep-related parameters. We analyzed serum cortisol levels and clock genes' expression. Results: The Epworth Sleepiness Scale (ESS), insomnia severity index(ISI), and Pittsburgh Sleep Quality index(PSQI) were significantly improved within the LT group only after the two-week period. When comparing the two groups, only the change in ESS was significant (mean difference, control: -0.14 vs. LT: -1.43, p = 0.021) after adjusting for the baseline characteristics. There were no significant differences in serum cortisol or clock genes' expression. Conclusions: LT can improve daytime sleepiness in patients with sleep disorders; however, further well-designed studies are warranted to confirm its efficacy.

Protein interactome and cell-type expression analyses reveal that cytoplasmic FMR1-interacting protein 1 (CYFIP1), but not CYFIP2, associates with astrocytic focal adhesion.

The two members of the cytoplasmic FMR1-interacting protein family, CYFIP1 and CYFIP2, are evolutionarily conserved multifunctional proteins whose defects are associated with distinct types of brain disorders. Even with high sequence homology between CYFIP1 and CYFIP2, several lines of evidence indicate their different functions in the brain; however, the underlying mechanisms remain largely unknown. Here, we performed reciprocal immunoprecipitation experiments using CYFIP1-2 × Myc and CYFIP2-3 × Flag knock-in mice and found that CYFIP1 and CYFIP2 are not significantly co-immunoprecipitated with each other in the knock-in brains compared with negative control wild-type (WT) brains. Moreover, CYFIP1 and CYFIP2 showed different size distributions by size-exclusion chromatography of WT mouse brains. Specifically, mass spectrometry-based analysis of CYFIP1-2 × Myc knock-in brains identified 131 proteins in the CYFIP1 interactome. Comparison of the CYFIP1 interactome with the previously identified brain region- and age-matched CYFIP2 interactome, consisting of 140 proteins, revealed only eight common proteins. Investigations using single-cell RNA-sequencing databases suggested non-neuronal cell- and neuron-enriched expression of Cyfip1 and Cyfip2, respectively. At the protein level, CYFIP1 was detected in both neurons and astrocytes, while CYFIP2 was detected only in neurons, suggesting the predominant expression of CYFIP1 in astrocytes. Bioinformatic characterization of the CYFIP1 interactome, and co-expression analysis of Cyfip1 with astrocytic genes, commonly linked CYFIP1 with focal adhesion proteins. Immunocytochemical analysis and proximity ligation assay suggested partial co-localization of CYFIP1 and focal adhesion proteins in cultured astrocytes. Together, these results suggest a CYFIP1-specific association with astrocytic focal adhesion, which may contribute to the different brain functions and dysfunctions of CYFIP1 and CYFIP2. Cover Image for this issue: https://doi.org/10.1111/jnc.15410.

Machine learning-based survival rate prediction of Korean hepatocellular carcinoma patients using multi-center data.

AIM: To predict survival time of Korean hepatocellular carcinoma (HCC) patients using multi-center data as a foundation for the development of a predictive artificial intelligence model according to treatment methods based on machine learning. METHODS: Data of patients who underwent treatment for HCC from 2008 to 2015 was provided by Korean Liver Cancer Study Group and Korea Central Cancer Registry. A total of 10,742 patients with HCC were divided into two groups, with Group I (2920 patients) confirmed on biopsy and Group II (5562 patients) diagnosed as HCC according to HCC diagnostic criteria as outlined in Korean Liver Cancer Association guidelines. The data were modeled according to features of patient clinical characteristics. Features effective in predicting survival rate were analyzed retrospectively. Various machine learning methods were used. RESULTS: Target was overall survival time, which divided into approximately 60 months (= /< 60 m, > 60 m). Target distribution in Group I (total 514 samples) was 28.8%: (148 samples) less than 60 months, 71.2% (366 samples) greater than 60 months, and in Group II (total 757 samples) was 66.6% (504 samples) less than 60 months, 33.4% (253 samples) greater than 60 months. Using NG Boost method, its accuracy was 83%, precision 84%, sensitivity 95%, and F1 score 89% for more than 60 months survival time in Group I with surgical resection. Moreover, its accuracy was 79%, precision 82%, sensitivity 87%, and F1 score 84% for less than 60 months survival time in Group II with TACE. The feature importance with gain criterion indicated that pathology, portal vein invasion, surgery, metastasis, and needle biopsy features could be explained as important factors for prediction in case of biopsy (Group I). CONCLUSION: By developing a predictive model using machine learning algorithms to predict prognosis of HCC patients, it is possible to project optimized treatment by case according to liver function and tumor status.

Low-protein diet is inversely related to the incidence of chronic kidney disease in middle-aged and older adults: results from a community-based prospective cohort study.

PURPOSE: Dietary protein intake can modulate renal health. However, the effect of dietary protein restriction on kidney function in the general population remains unclear. This study aimed to examine the association between total protein intake and new-onset chronic kidney disease (CKD) in Korean adults. METHODS: We included 7339 participants from the Korean Genome and Epidemiology Study. Participants were divided into low-protein diet (LPD, < 0.8 g/kg/day), normal-protein diet (NPD, 0.8-1.3 g/kg/day), and high-protein diet (HPD, > 1.3 g/kg/day) groups. New-onset CKD was defined as two consecutive events of estimated glomerular filtration rate < 60 mL/min/1.73 m2. Multivariable Cox hazard regression analysis was conducted to examine the association of total protein intake with new-onset CKD. Subgroup analyses according to diabetes mellitus (DM) status were performed. We performed the same analyses by dividing participants into total protein, plant protein, and animal protein intake tertiles. RESULTS: During a median follow-up of 13.7 years, 633 (8.7%) participants newly developed CKD. The fully adjusted hazard ratios (HR) with 95% confidence interval (CI) for incident CKD of the LPD and HPD groups compared with the NPD group were 1.49 (1.18-1.87) and 0.63 (0.45-0.87), respectively. The HR (95% CI) of the highest tertile group of plant protein intake for incident CKD was 0.72 (0.54-0.93), compared with that of the lowest tertile group. Similar trends were observed only in the non-DM subgroup, not in the DM subgroup. CONCLUSION: Protein intake, especially plant proteins, was negatively associated with the incidence of new-onset CKD in middle-aged and older Korean adults.

Feasibility and efficacy of TouchCare system using application for older adults living alone: a pilot pre-experimental study.

BACKGROUND: With the number of older people living alone continuously rising, health-monitoring systems using information and communication technology (ICT) have been developed to manage their health issues. Life logging and human body communication sensor, types of ICT, have been adapted to manage and monitor health status of the elderly. However, its feasibility and efficacy remain unclear. This study aimed to examine the feasibility of TouchCare system which combined life logging with human body communication technology and its effect on the physical and psychological status of older adults living alone. METHODS: The TouchCare system, which consisted of a wearable watch, touchpad sensors, TouchCare application, and context-aware artificial intelligence, was developed by DNX Co. Ltd and used by the participants for 5 months. Out of the 111 selected participants, 91 replied to the satisfaction survey, and 22 participated in further investigation regarding their physical and psychological status. Finally, health assessment from 14 participants and sensor data from 13 participants (mean age = 77.4; SD = 3.8) were analyzed to compare their health status and health-related behaviors before and after use of the system. RESULTS: Out of the 91 participants who took the survey, 51.6% were satisfied with the system. Nutritional status (pre-intervention (10.6 ± 2.0) vs. post-intervention (11.8 ± 1.9), P = 0.04) and fall efficacy (pre-intervention (89.2 ± 15.3) vs. post-intervention (99.9 ± 0.5), P = 0.001) significantly improved after use of the system. Chronic pain (pre-intervention (4.8 ± 2.5) vs. post-intervention (4.4 ± 3.7), P = 0.78) and depressive symptoms (pre-intervention (5.7 ± 3.9) vs. post-intervention (5.4 ± 3.1), P = 0.60) reduced, while cognitive function (pre-intervention (4.1 ± 1.4) vs. post-intervention (4.6 ± 1.1), P = 0.15) and physical performance related to walking improved (pre-intervention (3.9 ± 0.2) vs. post-intervention (4.0 ± 0), P = 0.35), but were not significant. Behaviors related to physical activity and gait improved after use of the system; touch counts of refrigerator and microwave also increased with a decrease in night touch counts. CONCLUSIONS: The TouchCare system was acceptable to older people living alone, and it efficiently managed their daily living while promoting their health-related behaviors. Further experimental studies are required to verify the effectiveness of the system, and to develop the system which meet the individualized needs of older people living alone.

Multitask Siamese Network for Remote Photoplethysmography and Respiration Estimation.

Heart and respiration rates represent important vital signs for the assessment of a person's health condition. To estimate these vital signs accurately, we propose a multitask Siamese network model (MTS) that combines the advantages of the Siamese network and the multitask learning architecture. The MTS model was trained by the images of the cheek including nose and mouth and forehead areas while sharing the same parameters between the Siamese networks, in order to extract the features about the heart and respiratory information. The proposed model was constructed with a small number of parameters and was able to yield a high vital-sign-prediction accuracy, comparable to that obtained from the single-task learning model; furthermore, the proposed model outperformed the conventional multitask learning model. As a result, we can simultaneously predict the heart and respiratory signals with the MTS model, while the number of parameters was reduced by 16 times with the mean average errors of heart and respiration rates being 2.84 and 4.21. Owing to its light weight, it would be advantageous to implement the vital-sign-monitoring model in an edge device such as a mobile phone or small-sized portable devices.

A Case-Matched Analysis of Laparoscopic Liver Resection for Hepatocellular Carcinoma Located in Posterosuperior Segments of the Liver According to Adaption of Developed Techniques.

Background and Objectives: Laparoscopic liver resection (LLR) for the hepatocellular carcinoma (HCC) located in posterosuperior (PS) segment is technically demanding, but has been overcome by accumulated experiences and technological improvements. We analyzed peri-and post-operative results before and after the adaptation of the enhanced techniques. Materials and Methods: We retrospectively reviewed 246 patients who underwent LLR for HCC in PS segments from September 2003 to December 2019. According to the introduction of advanced techniques including intercostal trocars, Pringle maneuver, and semi-lateral French position, the patients were divided into Group 1 (n = 43), who underwent LLR from September 2003 to December 2011, and Group 2 (n = 203), who underwent LLR from January 2012 to December 2019. Among these cases, 136 patients (Group 1 = 34, Group 2 = 102) were selected by case-matched analysis using perioperative variables. Results: Mean operation time (362 min vs. 291 min) and hospital stay (11 days vs. 8 days, p = 0.023) were significantly longer in Group 1 than Group 2. Otherwise, disease-free survival (DFS) rate was shorter and resection margin (1.3 mm vs. 0.7 mm, p = 0.034) were smaller in Group 2 than Group 1. However, there was no difference in type of complication (p = 0.084), severity of complication graded by the Clavien-Dindo grade system (p = 0.394), and 5-year overall survival (OS) rates (p = 0.986). In case-matched analysis, operation time (359 min vs. 266 min p = 0.002) and hospital stay (11.5 days vs. 8.0 days, p = 0.032) were significantly different, but there was no significant difference in resection margin, DFS, and OS. Conclusions: The adaptation of improved techniques has reduced the complexity of LLR in PS segments.

Differential relationship between dietary fat and cholesterol on total mortality in Korean population cohorts.

BACKGROUND: Associations among dietary fat, cholesterol intake and total mortality remain controversial, and most available data cover Western populations. The aim of this study was to assess associations for dietary fat and cholesterol in relation to total mortality in Koreans. METHODS: This study used data from three prospective Korean Genome and Epidemiology studies (conducted between June 2001 and December 2013). A total of 194,295 middle-aged and older Korean adults were included. Dietary fat intake was classified into quintiles. Dietary cholesterol intake was categorized into three groups based on cholesterol intake as follows: <200 mg, 200-299 mg and ≥300 mg. A multivariable Cox frailty model with random effects was applied to calculate hazard ratios (HR) and 95% confidence intervals (CIs) after adjusting for confounders. RESULTS: We documented 3866 deaths across a mean (min-max) follow-up period of 8.15 years (3-13 years). Higher fat intake was associated with lower total mortality (Q5 vs. Q1, HR 0.82 [95% CI 0.69, 0.98]; p trend < 0.01) after adjusting for age, sex, body mass index, alcohol, smoking, exercise and total calorie and protein (%) intake. Higher dietary cholesterol intake (≥300 mg/day) was associated with a higher risk of total mortality (HR 1.19 [95% CI 1.04, 1.37]) than lower cholesterol intake (<200 mg/day) in the multivariate model. CONCLUSIONS: In Koreans, high dietary fat intake is associated with a lower risk of total mortality, while dietary cholesterol intake above 300 mg/day is associated with a higher risk of total mortality.

Identification of susceptibility loci for cardiovascular disease in adults with hypertension, diabetes, and dyslipidemia.

BACKGROUND: Hypertension (HTN), diabetes mellitus (DM), and dyslipidemia (DL) are well-known risk factors of cardiovascular disease (CVD), but not all patients develop CVDs. Studies have been limited investigating genetic risk of CVDs specific to individuals with metabolic diseases. This study aimed to identify disease-specific and/or common genetic loci associated with CVD susceptibility in chronic metabolic disease patients. METHODS: We conducted a genome-wide association study (GWAS) of a multiple case-control design with data from the City Cohort within Health EXAminees subcohort of the Korean Genome and Epidemiology Study (KoGES_HEXA). KoGES_HEXA is a population-based prospective cohort of 173,357 urban Korean adults that had health examinations at medical centers. 42,393 participants (16,309 HTN; 5,314 DM; 20,770 DL) were analyzed, and each metabolic disease group was divided into three CVD case-controls: coronary artery disease (CAD), ischemic stroke (IS), and cardio-cerebrovascular disease (CCD). GWASs were conducted for each case-control group with 7,975,321 imputed single nucleotide polymorphisms using the Phase 3 Asian panel from 1000 Genomes Project, by logistic regression and controlled for confounding variables. Genome-wide significant levels were implemented to identify important susceptibility loci. RESULTS: Totaling 42,393 individuals, this study included 16,309 HTN (mean age [SD], 57.28 [7.45]; 816 CAD, 398 IS, and 1,185 CCD cases), 5,314 DM (57.79 [7.39]; 361 CAD, 153 IS, and 497 CCD cases), and 20,770 DL patients (55.34 [7.63]; 768 CAD, 295 IS, and 1,039 CCD cases). Six genome-wide significant CVD risk loci were identified, with relatively large effect sizes: 1 locus in HTN (HTN-CAD: 17q25.3/CBX8-CBX4 [OR, 2.607; P = 6.37 × 10-9]), 2 in DM (DM-IS: 4q32.3/MARCH1-LINC01207 [OR, 5.587; P = 1.34 × 10-8], and DM-CCD: 17q25.3/RPTOR [OR, 3.511; P = 1.99 × 10-8]), and 3 in DL (DL-CAD: 9q22.2/UNQ6494-LOC101927847 [OR, 2.282; P = 7.78 × 10-9], DL-IS: 3p22.1/ULK4 [OR, 2.162; P = 2.97 × 10-8], and DL-CCD: 2p22.2/CYP1B1-CYP1B1-AS1 [OR, 2.027; P = 4.24 × 10-8]). CONCLUSIONS: This study identified 6 susceptibility loci and positional candidate genes for CVDs in HTN, DM, and DL patients using an unprecedented study design. 1 locus (17q25.3) was commonly associated with CAD. These associations warrant validation in additional studies for potential therapeutic applications.

Improved Outcomes of Laparoscopic Liver Resection for Hepatocellular Carcinoma Located in Posterosuperior Segments of the Liver.

BACKGROUND: LLR is widely adapted for HCC, while LLR in PS segments is still challenging. With recent improvement of techniques and accumulation of experiences, LLR in PS segments is feasible, but studies investigating the result after the modifications are lacking. METHODS: In this single-center, retrospective study, 149 patients who underwent LLR for HCC located in PS segments from September 2003 to December 2016 were analyzed. The patients were divided into Group 1 (n=43) and Group 2 (n=106) who underwent LLR before and after 2012, respectively, when advanced techniques including use of intercostal trocars, Pringle maneuver, and semi-lateral position of patient were introduced. Also, these patients were compared with those who underwent open liver resection (OLR; n=124) for HCC in PS segments during the same period. RESULTS: Mean operative time (394.7 minutes vs 331.2 minutes; P=0.013), intraoperative blood loss (1545.8 ml vs 1208.2 ml; P=0.020), and hospital stay (11.6 days vs 9.2, P<0.001) were significantly less in Group 2. Postoperative complication rate (18.6% vs 18.9%; P=0.970), open conversion rate (23% vs 17%; P=0.374), 5-year overall (79% vs 89%; P=0.607) and 5-year disease-free (52% vs 53%; P=0.657) survival rates were not significantly different between the groups. Compared to the OLR group, complication rate (40.3% vs 18.8%; P< 0.001) and hospital stay (17.6 days vs 9.7 days; P< 0.001) were significantly lower in the LLR group. CONCLUSION: The complexity of LLR for HCC in PS segments is being gradually overcome by the introduction of advanced techniques.

Comparison of bacterial community profiles from large intestine specimens, rectal swabs, and stool samples.

The human gastrointestinal tract contains a complex and dynamic population of microorganisms, known as the gut microbiota. Although interest in the role of the gut microbiota in human health has increased in recent years, there remains no standard sampling protocol for analyzing these organisms. Here, we aimed to characterize the microbial composition of distinct segments of the large intestine and to determine whether rectal swabs are suitable for identifying colon microbiota. A total of 100 participants who underwent screening colonoscopy from October 2019 to October 2020 were included in this study. Large intestinal samples (ascending colon, descending colon, sigmoid colon, and rectum) were aspirated by colonoscopy. Rectal swabs were collected before colonoscopy, and stool samples were collected before patients began colonoscopy preparation. All samples were subjected to 16S ribosomal RNA gene sequencing. We identified differences in the number of phylum-level operational taxonomic units among large intestinal samples, rectal swabs, and stool. Five major phyla were detected in all samples (Firmicutes, Bacteroides, Proteobacteria, Actinobacteria, Fusobacteria), although their relative abundances varied. Notably, we found that the microbial compositions of rectal swabs were most similar to those of the sigmoid colon and rectum, whereas the microbiota in stool were relatively different than those from the large intestine and rectal swabs. Our results reveal the existence of microbial heterogeneity within different large intestinal compartments and further suggest that rectal swabs are an acceptable and practical tool for gut microbiota analysis. KEY POINTS: • Our findings highlight local microbiome variations within different regions of the large intestine. • Stool samples do not appear to fully recapitulate the gut microbiome. • Our data from a large population-based cohort indicate that rectal swabs can be used to study the gut microbiome.