Predicting the risk of cardiovascular disease is the key to primary prevention. Machine learning has attracted attention in analyzing increasingly large, complex healthcare data. We assessed ...discrimination and calibration of pre-existing cardiovascular risk prediction models and developed machine learning-based prediction algorithms. This study included 222,998 Korean adults aged 40-79 years, naïve to lipid-lowering therapy, had no history of cardiovascular disease. Pre-existing models showed moderate to good discrimination in predicting future cardiovascular events (C-statistics 0.70-0.80). Pooled cohort equation (PCE) specifically showed C-statistics of 0.738. Among other machine learning models such as logistic regression, treebag, random forest, and adaboost, the neural network model showed the greatest C-statistic (0.751), which was significantly higher than that for PCE. It also showed improved agreement between the predicted risk and observed outcomes (Hosmer-Lemeshow χ
= 86.1, P < 0.001) than PCE for whites did (Hosmer-Lemeshow χ
= 171.1, P < 0.001). Similar improvements were observed for Framingham risk score, systematic coronary risk evaluation, and QRISK3. This study demonstrated that machine learning-based algorithms could improve performance in cardiovascular risk prediction over contemporary cardiovascular risk models in statin-naïve healthy Korean adults without cardiovascular disease. The model can be easily adopted for risk assessment and clinical decision making.
Necroptosis is emerging as a new target for cancer immunotherapy as it is now recognized as a form of cell death that increases tumor immunogenicity, which would be especially helpful in treating ...immune-desert tumors. De novo synthesis of inflammatory proteins during necroptosis appears especially important in facilitating increased anti-tumor immune responses. While late-stage transcription mediated by NF-κB during cell death is believed to play a role in this process, it is otherwise unclear what cell signaling events initiate this transactivation of inflammatory genes.
We employed tandem-affinity purification linked to mass spectrometry (TAP-MS), in combination with the analysis of RNA-sequencing (RNA-Seq) datasets to identify the Tripartite Motif Protein 28 (TRIM28) as a candidate co-repressor. Comprehensive biochemical and molecular biology techniques were used to characterize the role of TRIM28 in RIPK3 activation-induced transcriptional and immunomodulatory events. The cell composition estimation module was used to evaluate the correlation between RIPK3/TRIM28 levels and CD8
T cells or dendritic cells (DC) in all TCGA tumors.
We identified TRIM28 as a co-repressor that regulates transcriptional activity during necroptosis. Activated RIPK3 phosphorylates TRIM28 on serine 473, inhibiting its chromatin binding activity, thereby contributing to the transactivation of NF-κB and other transcription factors, such as SOX9. This leads to elevated cytokine expression, which then potentiates immunoregulatory processes, such as DC maturation. The expression of RIPK3 has a significant positive association with the tumor-infiltrating immune cells populations in various tumor type, thereby activating anti-cancer responses.
Our data suggest that RIPK3 activation-dependent derepression of TRIM28 in cancer cells leads to increased immunostimulatory cytokine production in the tumor microenvironment, which then contributes to robust cytotoxic anti-tumor immunity.
The demand for wheelchairs has increased recently as the population of the elderly and patients with disorders increases. However, society still pays less attention to infrastructure that can ...threaten the wheelchair user, such as sidewalks with cracks/potholes. Although various studies have been proposed to recognize such challenges, they mainly depend on RGB images or IMU sensors, which are sensitive to outdoor conditions such as low illumination, bad weather, and unavoidable vibrations, resulting in unsatisfactory and unstable performance. In this paper, we introduce a novel system based on various convolutional neural networks (CNNs) to automatically classify the condition of sidewalks using images captured with depth and infrared modalities. Moreover, we compare the performance of training CNNs from scratch and the transfer learning approach, where the weights learned from the natural image domain (e.g., ImageNet) are fine-tuned to the depth and infrared image domain. In particular, we propose applying the ResNet-152 model pre-trained with self-supervised learning during transfer learning to leverage better image representations. Performance evaluation on the classification of the sidewalk condition was conducted with 100% and 10% of training data. The experimental results validate the effectiveness and feasibility of the proposed approach and bring future research directions.
Surface‐enhanced Raman scattering (SERS) is one of the most promising methods to detect small molecules for point‐of‐care analysis as it is rapid, nondestructive, label‐free, and applicable for ...aqueous samples. Here, microgels containing highly concentrated yet evenly dispersed gold nanoparticles are designed to provide SERS substrates that simultaneously achieve contamination‐free metal surfaces and high signal enhancement and reproducibility. With capillary microfluidic devices, water‐in‐oil‐in‐water (W/O/W) double‐emulsion drops are prepared to contain gold nanoparticles and hydrogel precursors in innermost drop. Under hypertonic condition, water is selectively pumped out from the innermost drops. Therefore, gold nanoparticles are gently concentrated without forming aggregates, which are then captured by hydrogel matrix. The resulting microgels have a concentration of gold nanoparticles ≈30 times higher and show Raman intensity two orders of magnitude higher than those with no enrichment. In addition, even distribution of gold nanoparticles results in uniform Raman intensity, providing high signal reproducibility. Moreover, as the matrix of the microgel serves as a molecular filter, large adhesive proteins are rejected, which enables the direct detection of small molecules dissolved in the protein solution. It is believed that this advanced SERS platform is useful for in situ detection of toxic molecules in complex mixtures such as biological fluids, foods, and cosmetics.
Surface‐enhanced Raman scattering (SERS)‐active microgels are designed by uniformly loading highly concentrated gold nanoparticles in microgel using microfluidic technology. High density and uniform distribution of gold nanoparticles enhance SERS activity and secure signal reproducibility. Moreover, the hydrogel matrix enables the direct detection of small target molecules without interruption from large adhesives. This class of SERS substrates is promising for point‐of‐care analysis of complex samples.
Even with increasing awareness of sex-related differences in atherosclerotic cardiovascular disease (ASCVD), it remains unclear whether the progression of coronary atherosclerosis differs between ...women and men. We sought to compare coronary artery calcium (CAC) progression between women and men. From a retrospective, multicentre registry of consecutive asymptomatic individuals who underwent CAC scoring, we identified 9,675 men and 1,709 women with follow-up CAC scoring. At baseline, men were more likely to have a CAC score >0 than were women (47.8% vs. 28.6%). The probability of CAC progression at 5 years, defined as √CAC score (follow-up)-√CAC score (baseline) ≥2.5, was 47.4% in men and 29.7% in women (p<0.001). When we stratified subjects according to the 10-year ASCVD risk (<5%, ≥5% and <7.5%, and ≥7.5%), a sex difference was observed in the low risk group (CAC progression at 5 years, 37.6% versus 17.9%; p<0.001). However, it became weaker as the 10-year ASCVD risk increased (64.2% versus 46.2%; p<0.001, and 74.8% versus 68.7%; p = 0.090). Multivariable analysis demonstrated that male sex was independently associated with CAC progression rate among the entire group (p<0.001). Subgroup analyses showed an independent association between male sex and CAC progression rate only in the low-risk group. The CAC progression rate is higher in men than in women. However, the difference between women and men diminishes as the 10-year ASCVD risk increases.
Beginning in 2006, epidemics of a fatal lung injury of unknown cause in children were observed in Korea every spring. A recent study demonstrated that this type of children's interstitial lung ...disease (chILD) is associated with humidifier disinfectant use.
To determine the clinical characteristics of this type of chILD and to assess whether the nationwide suspension of humidifier disinfectant sales in the autumn of 2011 affected its incidence.
The clinical characteristics of suspected cases between 2006 and 2011 were determined by a nationwide retrospective study. The potential causal relationship with humidifier disinfectants was examined by a prospective surveillance study after humidifier disinfectant sales were suspended.
In total, 138 children were diagnosed with this type of chILD, which was characterized by rapid progression, high mortality, predominance in the spring season, and a familial tendency. The annual incidence increased in 2011 and then dropped to zero in 2012. The children were on average 30.4 months old. The most frequent symptoms at admission were cough and dyspnea. As the disease progressed, the typical complication was spontaneous air leak. Eighty children (58%) died. Two years after humidifier disinfectant-sale suspension, no more new cases were found.
This study suggests that humidifier disinfectant inhalation causes an idiopathic type of chILD that is characterized by spontaneous air leak, rapid progression, lack of response to treatment, and high mortality. Further safety studies must be performed on common environmental compounds, particularly those that enter the human body by an unusual route.
Tuberculosis (TB) caused by Mycobacterium tuberculosis constitutes an ongoing threat to global health. An antigen that can induce dendritic cell (DC) maturation and lead to enhanced cellular immunity ...is crucial to the development of an effective TB vaccine. Here, we investigated the functional roles and the related signaling mechanism of the Rv0577 protein, a M. tuberculosis complex‐restricted secreted protein involved in the methylglyoxal detoxification pathway. Rv0577 recognizes Toll‐like receptor 2 (TLR2) and functionally induces DC maturation by augmenting the expression of cell surface molecules (CD80, CD86, and MHC class I and II) and proinflammatory cytokine production (TNF‐α, IL‐1β, IL‐6, and IL‐12p70) in DCs on MyD88‐dependent signaling, mitogen‐activated protein kinases, and nuclear factor κB signaling pathways. In addition, Rv0577‐treated DCs activated naive T cells, effectively polarized CD4+ and CD8+ T cells to secrete IFN‐γ and IL‐2, and induced T‐cell proliferation, indicating that this protein possibly contributes to Th1‐polarization of the immune response. More important, unlike LPS, Rv0577‐treated DCs specifically induced the proliferation of memory CD4+/CD8+CD44high CD62Llow T cells in the spleen of M. tuberculosis‐infected mice in a TLR2‐dependent manner. Taken together, these findings suggest that Rv0577 may regulate innate and adaptive immunity by interacting with TLR2, a finding that could be helpful in the design of new TB vaccines.—Byun, E.‐H., Kim, W. S., Kim, J.‐S., Jung, I. D., Park, Y.‐M., Kim, H.‐J., Cho, S.‐N., Shin, S. J. Mycobacterium tuberculosis Rv0577, a novel TLR2 agonist, induces maturation of dendritic cells and drives Th1 immune response. FASEB J. 26, 2695‐2711 (2012). www.fasebj.org
Finger-vein, as a secure and convenient biometric characteristic in nature, has been widely studied for authentication in recent years. In this paper, we propose an efficient finger-vein extraction ...algorithm based on random forest training and regression with efficient local binary pattern feature. By integrating with a vein pattern matching method which is robust to finger misalignment, we achieved state-of-the-art finger-vein recognition. Thorough experiments have been conducted on two popular databases to prove the effectiveness and robustness of the proposed method.
This paper presents the design optimization of a linkage-based wheel mechanism with two degrees of freedom, for stable step climbing. The mechanism has seven rotational joints and one prismatic ...joint. Kinematic and dynamic analyses of the mechanism were performed. The design was optimized in terms of linkage length and architecture to better manipulate the mechanism in its workspace, which was defined here by the targeted step size, as well as to ensure stability while climbing stairs. Optimization by genetic algorithm was performed using MATLAB. The optimized mechanism exhibited enhanced torque transmission from the input torque to the exerted for at the lobe of the wheel. Compliance control of the transformation will be addressed in the future.
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