Association of hypertension with noodle consumption among Korean adults based on the Health Examinees (HEXA) study.

BACKGROUND/OBJECTIVES: The prevalence of hypertension is increasing, and noodles have a high sodium content, so noodle consumption might be associated with a higher prevalence of hypertension. This study aimed to analyze the association between total and types of noodle intake and the risk of hypertension among Korean adults. Subjects aged 40-69 years were selected for this study. SUBJECTS/METHODS: This study included 56,580 participants (18,246 men and 38,334 women) aged 40-69 years old from the Health Examinees study. Noodle and nutrient intakes were assessed using the food frequency questionnaire. Hypertension was diagnosed as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or antihypertensive medication use. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for hypertension. RESULTS: Higher noodle consumption was associated with increased hypertension among men (HR, 1.273; 95% CI, 1.166-1.390) and women (HR, 1.116; 95% CI, 1.038-1.199). CONCLUSION: We recommended reducing noodle intake and consuming vegetables and fruits to increase potassium intake, which can prevent vascular diseases.

HDAC11 Regulates Palmitate-induced NLRP3 Inflammasome Activation by Inducing YAP Expression in THP-1 Cells and PBMCs.

Histone deacetylase 11 (HDAC11) has been implicated in the pathogenesis of metabolic diseases characterized by chronic low-grade inflammation, such as obesity. However, the influence of HDAC11 on inflammation and the specific effect of HDAC11 on the palmitic acid (PA)-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation are poorly understood. The effect of PA treatment on HDAC11 activity and the NLRP3 inflammasome was investigated in human peripheral blood mononuclear cells and THP-1 cells. The PA-induced responses of key markers of NLRP3 inflammasome activation, including NLRP3 gene expression, caspase-1 p10 activation, cleaved IL-1ß production, and extracellular IL-1ß release, were assessed as well. The role of HDAC11 was explored using a specific inhibitor of HDAC11 and by knockdown using small interfering (si)HDAC11 RNA. The relationship between HDAC11 and yes-associated protein (YAP) in the PA-induced NLRP3 inflammasome was investigated in THP-1 cells with HDAC11 or YAP knockdown. Following PA treatment, HDAC11 activity and protein levels increased significantly, concomitant with activation of the NLRP3 inflammasome. Notably, PA-induced the upregulation of NLRP3, caspase-1 p10 activation, the production of cleaved IL-1ß, and the release of IL-1ß into the extracellular space, all of which were attenuated by FT895 treatment and by HDAC11 knockdown. In THP-1 cells, PA induced the expression of YAP and its interaction with NLRP3, resulting in NLRP3 inflammasome activation, whereas both were inhibited by FT895 and siHDAC11 RNA. These findings demonstrate a pivotal role for HDAC11 in the PA-induced activation of the NLRP3 inflammasome. HDAC11 inhibition thus represents a promising therapeutic strategy for mitigating NLRP3 inflammasome-related inflammation in the context of obesity.

Utilization of traditional herbal medicine formulas for unexplained female infertility in Korea: a retrospective study.

BACKGROUND: This study aimed to investigate the prescription of traditional herbal medicines for the treatment of unexplained female infertility in Korea. By analyzing the relationships among the prescriptions and between the prescriptions and treatment outcomes, we aimed to confirm the utilization of standardized prescriptions and the effectiveness of this standardization. METHODS: The data were derived from the "support projects" of the local government for infertile women to receive Korean medical treatments. The presciption data of 453 participants from 2017 to 2018 were analyzed. Data preprocessing, frequency analysis, and network analysis were conducted. For network analysis, the characteristics of the herbal medicine prescriptions were used to calculate the degree centrality, closeness centrality and eigenvector centrality. Modularity clustering was also performed for cluster analysis. RESULTS: Fifty different prescriptions were used, among which only 22 were used for participants who became pregnant. The recommended standard prescriptions for support projects were used frequently. "BaeranChacksangBang" showed the highest level of in-degree centrality. Among the prescriptions for participants who became pregnant, "JogyeongJongokTang" and "BaeranChacksangBang" were the most influential nodes. "BaeranChacksangBang", "AnjeonYicheonTang", "YukLinZu" and "JogyeongJongokTang" had high closeness centrality among the prescriptions for participants who became pregnant. Clustering analysis of the prescriptions for participants who became pregnant revealed that the prescriptions showed the best modularity when divided into five groups. CONCLUSIONS: These findings depict the utilization of Korean herbal medicine in the real world and the dynamics underlying the herbal medicine prescription patterns for infertile women.

Spatiotemporal cell junction assembly in human iPSC-CM models of arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disorder that causes life-threatening arrhythmias and myocardial dysfunction. Pathogenic variants in Plakophilin-2 (PKP2), a desmosome component within specialized cardiac cell junctions, cause the majority of ACM cases. However, the molecular mechanisms by which PKP2 variants induce disease phenotypes remain unclear. Here we built bioengineered platforms using genetically modified human induced pluripotent stem cell-derived cardiomyocytes to model the early spatiotemporal process of cardiomyocyte junction assembly in vitro. Heterozygosity for truncating variant PKP2R413X reduced Wnt/ß-catenin signaling, impaired myofibrillogenesis, delayed mechanical coupling, and reduced calcium wave velocity in engineered tissues. These abnormalities were ameliorated by SB216763, which activated Wnt/ß-catenin signaling, improved cytoskeletal organization, restored cell junction integrity in cell pairs, and improved calcium wave velocity in engineered tissues. Together, these findings highlight the therapeutic potential of modulating Wnt/ß-catenin signaling in a human model of ACM.

Fibre-infused gel scaffolds guide cardiomyocyte alignment in 3D-printed ventricles.

Hydrogels are attractive materials for tissue engineering, but efforts to date have shown limited ability to produce the microstructural features necessary to promote cellular self-organization into hierarchical three-dimensional (3D) organ models. Here we develop a hydrogel ink containing prefabricated gelatin fibres to print 3D organ-level scaffolds that recapitulate the intra- and intercellular organization of the heart. The addition of prefabricated gelatin fibres to hydrogels enables the tailoring of the ink rheology, allowing for a controlled sol-gel transition to achieve precise printing of free-standing 3D structures without additional supporting materials. Shear-induced alignment of fibres during ink extrusion provides microscale geometric cues that promote the self-organization of cultured human cardiomyocytes into anisotropic muscular tissues in vitro. The resulting 3D-printed ventricle in vitro model exhibited biomimetic anisotropic electrophysiological and contractile properties.

Stretchable Low-Impedance Conductor with Ag-Au-Pt Core-Shell-Shell Nanowires and in Situ Formed Pt Nanoparticles for Wearable and Implantable Device.

Mechanically soft metallic nanocomposites have gained much attention as a key material for intrinsically stretchable biointegrated devices. However, it has been challenging to develop a stretchable conductive nanocomposite with all the desired material characteristics including high conductivity, high stretchability, low cytotoxicity, and low impedance. Here, we present a material strategy for the stretchable conductive nanocomposite, particularly emphasizing low impedance, by combining silver-gold-platinum core-shell-shell nanowires and homogeneously dispersed in situ synthesized platinum nanoparticles (Pt NPs). The highly embossed structure of the outermost Pt shell, together with the intrinsic electrical property of Pt, contributes to minimizing the impedance. The gold-platinum double-layer sheath prevents leaching of cytotoxic Ag ions, thus improving biocompatibility. Homogeneously dispersed Pt NPs, synthesized in situ during fabrication of the nanocomposite, simultaneously enhance conductivity, reduce impedance, and improve stretchability by supporting the percolation network formation. This intrinsically stretchable nanocomposite conductor can be applied to wearable and implantable bioelectronics for recording biosignals and delivering electrical stimulations in vivo.

Ventricular tachyarrhythmia treatment and prevention by subthreshold stimulation with stretchable epicardial multichannel electrode array.

The implantable cardioverter-defibrillator (ICD) is an effective method to prevent sudden cardiac death in high-risk patients. However, the transvenous lead is incompatible with large-area electrophysiological mapping and cannot accommodate selective multichannel precision stimulations. Moreover, it involves high-energy shocks, resulting in pain, myocardial damage, and recurrences of ventricular tachyarrhythmia (VTA). We present a method for VTA treatment based on subthreshold electrical stimulations using a stretchable epicardial multichannel electrode array, which does not disturb the normal contraction or electrical propagation of the ventricle. In rabbit models with myocardial infarction, the infarction was detected by mapping intracardiac electrograms with the stretchable epicardial multichannel electrode array. Then, VTAs could be terminated by sequential electrical stimuli from the epicardial multichannel electrode array beginning with low-energy subthreshold stimulations. Last, we used these subthreshold stimulations to prevent the occurrence of additional VTAs. The proposed protocol using the stretchable epicardial multichannel electrode array provides opportunities toward the development of innovative methods for painless ICD therapy.

Bone-Adhesive Anisotropic Tough Hydrogel Mimicking Tendon Enthesis.

Tendon consists of soft collagen, yet it is mechanically strong and firmly adhered to the bone owing to its hierarchically anisotropic structure and unique tendon-to-bone integration (enthesis), respectively. Despite the recent advances in biomaterials, hydrogels simultaneously providing tendon-like high mechanical properties and strong adhesion to bone-mimicking enthesis is still challenging. Here, a strong, stiff, and adhesive triple-network (TN) anisotropic hydrogel that mimics a bone-adhering tendon is shown. The tough adhesive TN hydrogel is developed by combining imidazole-containing polyaspartamide (providing multiple hydrogen bonds to the bone surface) and energy-dissipative alginate-polyacrylamide double-network. To mimic the anisotropic structure and high mechanical properties of tendons, the bone-adhered TN hydrogel is linearly stretched and subsequently fixed via secondary cross-linking. The resulting hydrogel exhibits high tensile modulus and strength while maintaining a high bone adhesion without chemical modification of the bone surface. Furthermore, a bone-ligament-bone structure with strong bone adhesion reminiscent of the natural ligament is realized.

Randomized, single-blind, placebo-controlled trial on Hominis placenta extract pharmacopuncture for hot flashes in peri- and post-menopausal women.

Background: Hominis placenta pharmacopuncture is widely used for climacteric symptoms. This study examined the efficacy and safety of pharmacopuncture with PLC (the extract of Hominis placenta) on hot flashes for perimenopausal and postmenopausal women. Methods: This study was a randomized placebo-controlled single-blind trial, which recruited 128 perimenopausal and postmenopausal women, randomly assigned to receive pharmacopuncture with PLC or normal saline (NS) for eight weeks. The primary outcome was the mean changes in the hot flash score (HFS) and the secondary outcomes were the mean changes in the Menopause Rating Scale (MRS), follicle-stimulating hormone (FSH) levels, and estradiol (E2) levels from baseline to eight weeks. Missing values were imputed using the last-observation-carried-forward method. Results: After treatment (week 9), the HFS decreased significantly in both groups (p = 0.000). The residual HFS was 47.09 ± 41.39% and 56.45 ± 44.92 % in the PLC and control groups, respectively (p = 0.262). One month after the treatment (week 13), the score of the PLC group was reduced, but the score increased in the control group (p = 0.077). There were no statistically significant differences in the mean changes in MRS, FSH, and E2 between the two groups. No serious adverse events related to this trial were noted. Conclusion: In this study, Hominis placenta extract pharmacopuncture did not differ significantly from NS in reducing the hot flash score. While this therapy appears safe, the potential for long-term effect of PLC extract needs to be examined in a large randomized controlled trial with appropriate controls.

Rapid and Accurate On-Site Immunodiagnostics of Highly Contagious Severe Acute Respiratory Syndrome Coronavirus 2 Using Portable Surface-Enhanced Raman Scattering-Lateral Flow Assay Reader.

In early 2022, the number of people infected with the highly contagious mutant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), called Omicron, was increasing worldwide. Therefore, several countries approved the lateral flow assay (LFA) strip as a diagnostic method for confirming SARS-CoV-2 instead of reverse transcription-polymerase chain reaction (RT-PCR), which takes a long time to generate the results. However, owing to the limitation of detection sensitivity, commercial LFA strips have high false-negative diagnosis rates for patients with low virus concentrations. Therefore, in this study, we developed a portable surface-enhanced Raman scattering (SERS)-LFA reader based on localized surface plasmon effects to solve the sensitivity problem of the commercial LFA strip. We tested 54 clinical samples using this portable SERS-LFA reader, which generated 49 positive and 5 negative results. Out of the 49 positive results, SERS-LFA classified only 2 as false negative, while the commercial LFA classified 21 as false negative. This confirmed that the false-negative rate had significantly improved compared to that of commercial LFA strips. We believe that the proposed SERS-LFA system can be utilized as a point-of-care diagnostic system to quickly and accurately determine a virus infection that could spread significantly within a short period.

Comparative effectiveness of different acupuncture therapies for neck pain.

BACKGROUND: Neck pain is a common musculoskeletal symptom that has negative effects on quality of life and work productivity. Acupuncture has been widely used for neck pain, and a number of randomized controlled trials (RCTs) and systematic reviews (SRs) have evaluated its effectiveness. However, previous studies have obtained inconsistent results regarding the effects of acupuncture for neck pain, and there is no SR for the comparative efficacy and safety of various types of acupuncture. Therefore, we herein conducted a SR and network meta-analysis to compare and rank different types of acupuncture with respect to their effectiveness in treating neck pain. METHODS: We searched 9 electronic databases for relevant RCTs published from their inception to July 1, 2021. Pairwise meta-analyses and network meta-analysis were performed with R software using the frequentist framework. Change of pain intensity was assessed as the primary outcome, and change of pain-related disability and efficacy rate were assessed as secondary outcomes. The Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument were used to evaluate the quality of the included RCTs and the certainty of the evidence. RESULTS: A total of 65 RCTs involving 5266 participants and 9 interventions were included. Three network meta-analyses were constructed for the following: pain intensity (42 RCTs, 3158 participants), pain-related disability (21 RCTs, 1581 participants), and efficacy rate (40 RCTs, 3512 participants). The results indicated that fire acupuncture, electroacupuncture, and warm acupuncture were more effective than manual acupuncture in terms of pain intensity reduction and efficacy rate, and that electroacupuncture decreased pain-related disability more effectively than manual acupuncture. Fire acupuncture ranked first among the 9 interventions. The overall q of evidence was very low according to the GRADE assessment. The reported adverse events were not serious. CONCLUSION: Fire acupuncture, warm acupuncture, acupoint catgut embedding, and electroacupuncture ranked higher than other interventions (usual care, sham acupuncture, no treatment) in reducing the pain and disability index scores and the efficacy rate. However, the included trials were evaluated as being of low quality; thus, we recommend additional well-designed RCTs with larger sample sizes to confirm these findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021235274.

Recreating the heart's helical structure-function relationship with focused rotary jet spinning.

Helical alignments within the heart's musculature have been speculated to be important in achieving physiological pumping efficiencies. Testing this possibility is difficult, however, because it is challenging to reproduce the fine spatial features and complex structures of the heart's musculature using current techniques. Here we report focused rotary jet spinning (FRJS), an additive manufacturing approach that enables rapid fabrication of micro/nanofiber scaffolds with programmable alignments in three-dimensional geometries. Seeding these scaffolds with cardiomyocytes enabled the biofabrication of tissue-engineered ventricles, with helically aligned models displaying more uniform deformations, greater apical shortening, and increased ejection fractions compared with circumferential alignments. The ability of FRJS to control fiber arrangements in three dimensions offers a streamlined approach to fabricating tissues and organs, with this work demonstrating how helical architectures contribute to cardiac performance.

Cellular and Engineered Organoids for Cardiovascular Models.

An ensemble of in vitro cardiac tissue models has been developed over the past several decades to aid our understanding of complex cardiovascular disorders using a reductionist approach. These approaches often rely on recapitulating single or multiple clinically relevant end points in a dish indicative of the cardiac pathophysiology. The possibility to generate disease-relevant and patient-specific human induced pluripotent stem cells has further leveraged the utility of the cardiac models as screening tools at a large scale. To elucidate biological mechanisms in the cardiac models, it is critical to integrate physiological cues in form of biochemical, biophysical, and electromechanical stimuli to achieve desired tissue-like maturity for a robust phenotyping. Here, we review the latest advances in the directed stem cell differentiation approaches to derive a wide gamut of cardiovascular cell types, to allow customization in cardiac model systems, and to study diseased states in multiple cell types. We also highlight the recent progress in the development of several cardiovascular models, such as cardiac organoids, microtissues, engineered heart tissues, and microphysiological systems. We further expand our discussion on defining the context of use for the selection of currently available cardiac tissue models. Last, we discuss the limitations and challenges with the current state-of-the-art cardiac models and highlight future directions.

Would You Trust Driverless Service? Formation of Pedestrian's Trust and Attitude Using Non-Verbal Social Cues.

Despite the widespread application of Autonomous Vehicles (AV) to various services, there has been relatively little research carried out on pedestrian-AV interaction and trust within the context of service provided by AV. This study explores the communication design strategy promoting a pedestrian's trust and positive attitude to driverless services within the context of pedestrian-AV interaction using non-verbal social cues. An empirical study was conducted with an experimental VR environment to measure participants' intimacy, trust, and brand attitude toward AV. Further understanding of their social interaction experiences was explored through semi-structured interviews. As a result of the study, the interaction effect of social cues was found, and it was revealed that brand attitude was formed by the direct effects of intimacy and trust as well as the indirect effects of intimacy through trust's mediation. Furthermore, 'Conceptual Definition of Space' was identified to generate differences in the interplay among intimacy, trust, and brand attitude according to social cues. Quantitative and qualitative results were synthesized to discuss implications considering the service context. Practical implications were also addressed suggesting specific design strategies for utilizing the sociality of AV.

Thermodynamic patterns duringin-situheating of InAs nanowires encapsulated in Al2O3shells.

Understanding the dynamic thermal behavior of nanomaterials based on their unique physical and chemical properties is critical for their applications. In this study, the thermal behavior of single-crystalline InAs nanowires in an amorphous Al2O3shell was investigated by conductingin situheating experiments in a transmission electron microscope. Two different thermodynamic patterns were observed during thein situheating experiments: (1) continuous vaporization and condensation simultaneously at temperatures lower than 838.15 K, and (2) pure evaporation at temperatures higher than 878.15 K. During the simultaneous condensation and vaporization in closer areas in a single InAs nanowire, the front edge of the vaporization was flat, while that of the condensation actively changed with time and temperature. Pure vaporization was conducted via layer-by-layer evaporation followed by three-dimensional vaporization at the final stage. The thermal behaviors of the InAs nanowires were demonstrated from a thermodynamic point of view.

Effectiveness and safety of Korean medicine for treating women with unexplained infertility: A multi-center observational study.

BACKGROUND: This study was conducted to demonstrate the effectiveness and safety of herbal medicine and acupuncture treatment in unexplained infertile females. METHODS: One hundred patients were recruited from 3 Korean Medicine hospitals in Korea and they voluntarily signed informed consent agreements. Participants took the Onkyeong-tang (120cc) twice daily between menstrual cycle day (MCD) 3 and 12, and herbal medicine for ovulation and implantation (120cc) twice daily between MCD 13 and 28. They also received acupuncture and moxibustion treatment during 4 menstrual cycles. After the 4 menstrual cycle treatment period, there were 3 menstrual cycle observation periods. The primary outcome is signified by clinical pregnancy rates (CPR) and the secondary outcomes were implantation rates (IR), ongoing pregnancy rates (OPR), and live birth rates. RESULTS: 90 patients completed the study. 13 of the 90 subjects became pregnant. The CPR and IR was 14.44%. 7 of 13 pregnant subjects had continuing pregnancy for over 12 weeks, so that the OPR was 53.85%. The birth rate was 7.78%. All 7 pregnant patients gave birth to their babies and all the babies were live singletons and healthy. There were no serious adverse events. CONCLUSIONS: The findings of this study may provide the possibility of effectiveness and safety of Korea medicine treatment for unexplained infertile women. Further study is required due to lack of control and small sample size in this study.

The effectiveness of different acupuncture therapies for neck pain: A protocol for systematic review and/or network meta-analysis.

BACKGROUND: Neck pain is common musculoskeletal disorders in adult population. Acupuncture treatment has been widely used for treating neck pain. Nevertheless, previous systematic reviews (SRs) on acupuncture for neck pain remain controversial, and there is no SR for the comparative efficacy and safety of various types of acupuncture. Therefore, this study aims to evaluate and rank the effectiveness and safety of different types of acupuncture for neck pain by SR and network meta-analysis. METHODS: Nine databases will be searched, including Ovid-MEDLINE, EMBASE, Cochrane library, China National Knowledge Infrastructure (CNKI), KoreaMed, Korean medical database (KMBASE), Korean Studies Information Service System (KISS), ScienceON, and Oriental Medicine Advanced Searching Integrated System (OASIS) from their inception to July 2021. The primary outcome is the change of pain intensity. A frequentist network meta-analysis will be performed to compare all relative outcomes of different acupuncture methods, using R software. The quality of included randomized controlled trials will be assessed by Cochrane Collaboration "risk of bias" tools and the evidence will be evaluated by the Grading of Recommendations Assessment, Development and Evaluation instrument. RESULTS: The final findings of this network meta-analysis will be published in a recognized journal. CONCLUSIONS: Our study will evaluate and compare the effectiveness of various types of acupuncture for neck pain and provide clinicians with best option for what types of acupuncture treatments are effective. TRIAL REGISTRATION NUMBER: INPLASY202120041.

A bioinspired and hierarchically structured shape-memory material.

Shape-memory polymeric materials lack long-range molecular order that enables more controlled and efficient actuation mechanisms. Here, we develop a hierarchical structured keratin-based system that has long-range molecular order and shape-memory properties in response to hydration. We explore the metastable reconfiguration of the keratin secondary structure, the transition from α-helix to ß-sheet, as an actuation mechanism to design a high-strength shape-memory material that is biocompatible and processable through fibre spinning and three-dimensional (3D) printing. We extract keratin protofibrils from animal hair and subject them to shear stress to induce their self-organization into a nematic phase, which recapitulates the native hierarchical organization of the protein. This self-assembly process can be tuned to create materials with desired anisotropic structuring and responsiveness. Our combination of bottom-up assembly and top-down manufacturing allows for the scalable fabrication of strong and hierarchically structured shape-memory fibres and 3D-printed scaffolds with potential applications in bioengineering and smart textiles.

Novel Prognostic Factor for Uveal Melanoma: Bioinformatics Analysis of Three Independent Cohorts.

BACKGROUND/AIM: Because 50% of uveal melanoma metastasize within 10 years of diagnosis, there is urgent need for accurate prognostic factors. MATERIALS AND METHODS: To identify genes that can act as prognostic factors in uveal melanoma, we performed survival analyses using three independent cohorts. Using log-rank test and univariate cox regression, genes which could stratify the prognosis in all cohorts simultaneously depending on their expression levels were selected as novel biomarkers. Hub genes were obtained by analyzing the interaction and relationship between the selected genes using String and Cytoscape. Additionally, prognostic power was calculated by using C-indices and AUC. RESULTS: A total of 37 oncogene-like and 14 tumor suppressor-like genes were selected. Protein-protein analysis revealed that NDUFB9, NDUFV2, CYC1 among oncogene-like genes, CTNNB1 among tumor suppressor-like genes were found to be hub genes and core biomarkers in uveal melanoma. CONCLUSION: NDUFB9, NDUFV2, CYC1 and CTNNB1 genes may act as prognostic factors in uveal melanoma.

A User-Friendly, Web-Based Integrative Tool (ESurv) for Survival Analysis: Development and Validation Study.

BACKGROUND: Prognostic genes or gene signatures have been widely used to predict patient survival and aid in making decisions pertaining to therapeutic actions. Although some web-based survival analysis tools have been developed, they have several limitations. OBJECTIVE: Taking these limitations into account, we developed ESurv (Easy, Effective, and Excellent Survival analysis tool), a web-based tool that can perform advanced survival analyses using user-derived data or data from The Cancer Genome Atlas (TCGA). Users can conduct univariate analyses and grouped variable selections using multiomics data from TCGA. METHODS: We used R to code survival analyses based on multiomics data from TCGA. To perform these analyses, we excluded patients and genes that had insufficient information. Clinical variables were classified as 0 and 1 when there were two categories (for example, chemotherapy: no or yes), and dummy variables were used where features had 3 or more outcomes (for example, with respect to laterality: right, left, or bilateral). RESULTS: Through univariate analyses, ESurv can identify the prognostic significance for single genes using the survival curve (median or optimal cutoff), area under the curve (AUC) with C statistics, and receiver operating characteristics (ROC). Users can obtain prognostic variable signatures based on multiomics data from clinical variables or grouped variable selections (lasso, elastic net regularization, and network-regularized high-dimensional Cox-regression) and select the same outputs as above. In addition, users can create custom gene signatures for specific cancers using various genes of interest. One of the most important functions of ESurv is that users can perform all survival analyses using their own data. CONCLUSIONS: Using advanced statistical techniques suitable for high-dimensional data, including genetic data, and integrated survival analysis, ESurv overcomes the limitations of previous web-based tools and will help biomedical researchers easily perform complex survival analyses.