Association of Delta Neutrophil Index with the 30-day Mortality in Adult Cardiac Surgical Patients.

Purpose: This study aimed to assess the predictive accuracy of 30-day mortality with delta neutrophil index (DNI) in adult cardiac surgical patients. Methods: This study enrolled patients who underwent cardiac surgery under general anesthesia between March 2016 and May 2022 at a tertiary hospital in the Republic of Korea. DNI was measured preoperatively, on postoperative arrival to the surgical intensive care unit (ICU), and 12, 24, 48, and 72 h postoperatively. Receiver operating characteristic (ROC) analysis was employed to identify the prediction accuracy of DNI. An area under ROC curve (AUROC) ≥0.700 was defined as satisfactory predictive accuracy. An optimal cutoff point for the DNI value to maximize predictive accuracy was revealed in the ROC curve, where [sensitivity + specificity] was maximum. Results: This study included a total of 843 patients in the final analyses. The mean age of the study population was 66.9±12.2 years and 38.4% of them were female patients. The overall 30-day mortality rate was 5.2%. Surgery involving the thoracic aorta, history of prior cardiac surgery, or emergency surgery were associated with a higher mortality rate. The DNI showed satisfactory predictive accuracy at 24 h, 48 h, and 72 h postoperatively, with AUROC of 0.729, 0.711, and 0.755, respectively. The optimal cutoff points of DNI at each time point were 3.2, 3.8, and 2.3, respectively. Conclusions: Postoperative DNI is a good predictor of 30-day mortality after cardiac surgery and has the benefit of no additional financial costs or time.

Applicability of Titanium-Based Catalysts in the Photocatalytic Degradation of 2,3,7,8-Tetrachlorodibenzofuran.

Polychlorinated dibenzofurans (PCDFs) are persistent toxic compounds that are ubiquitous in the environment. Nanocomposites of titanium(IV) oxide-vanadium(III) oxide (Ti3V2O7) and titanium(IV) oxide-silicon dioxide (Ti2Si7O30) were prepared and spectroscopically analyzed as potential decontaminants for dioxin-like materials. The analysis confirmed a homogeneous morphology with nanoscale particle size. The Ti-Si sample was found to have a high surface area compared to the Ti-V composite. Vanadium(III) oxide (V2O5) and silicon dioxide (SiO2) were chosen as materials for the formation of heterogeneous compounds with titanium(IV) oxide (TiO2) because they possess a suitable band alignment with TiO2, thus forming effective photocatalysts. This study evaluated the photodegradation of 2,3,7,8-tetrachlorodibenzo-furan (TCDF) in the presence of Ti-Si and Ti-V oxide composites, which was tested using high- (254 nm) and midenergy (302 nm) UV irradiation sources. While Ti-Si showed success in the photodegradation of 2,3,7,8-TCDF dissolved in a (1:1) methanol-tetrahydrofuran (MeOH-THF) solution, the Ti-V composite proved to be a powerful material in adsorbing TCDF with a high capacity immediately upon mixing. Ti-Si oxide was found to decompose TCDF under the two irradiation sources with 98-99% degradation occurring after 70 min. The use of 254 nm as an irradiation source in the presence of Ti-Si was 4.3 times faster than the analogue reaction irradiated without a catalyst. Byproducts of the degradation were evaluated using gas chromatography-mass spectrometry (GC-MS), resulting in a lower chlorinated congener and less toxicity, as the main degradation product.

Casein kinase I inhibitor D4476 influences autophagy and apoptosis in chloroquine-induced adult retinal pigment epithelial-19 cells.

The antimalarial drug chloroquine (CQ) induces retinopathy, a disorder characterized by lysosomotropic alteration. In this study, we examined whether D4476 (4-(4-(2,3-dihydrobenzo [1,4] dioxin-6-yl)-5-pyridin-2-yl-1H-imidazole-2-yl) benzamide), a specific casein kinase 1 inhibitor, alleviate CQ-induced retinopathy in adult retinal pigment epithelial (ARPE-19) cells. Cultured ARPE-19 cells were exposed to CQ with or without D4476 and cell death was quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To examine autophagy flux, ARPE-19 cells were transfected with green fluorescence protein light chain 3 (GFP-LC3)-red fluorescence protein (RFP)-LC3ΔG plasmid DNA and co-stained with the lysosomal-associated membrane protein (LAMP)-1 antibody. Western blotting and fluorescence-activated cell sorting (FACS) showed apoptosis, whereas the fluorescence intensity of 2'-7'-dichlorofluorescein diacetate revealed levels of cellular oxidative stress. We then confirmed the effect of D4476 on the interaction between Beclin 1 and B-cell lymphoma-2 (Bcl-2) through immunoprecipitation with an anti-Bcl-2 antibody. Following CQ exposure, ARPE-19 cells accumulated autophagosomes because of defective lysosomal degradation. Furthermore, CQ trapped Beclin 1 with Bcl-2, disturbing autophagy initiation and autolysosome formation. However, D4476 alleviated CQ-induced effects by rescuing ARPE-19 cells from CQ-induced toxicity by modulating the association between Beclin 1 and Bcl-2. Therefore, D4476 controls autophagy and apoptosis simultaneously by upregulating autophagy flux, decreasing ROS formation, and triggering the expression of anti-apoptotic proteins through inhibition of mTOR, JNK, and p38 MAPK signals. We conclude that D4476 is a promising treatment strategy for CQ-mediated retinopathy.

Material-Independent Surface Chemistry beyond Polydopamine Coating.

Various methods have been developed in surface chemistry to control interface properties of a solid material. A selection rule among surface chemistries is compatibility between a surface functionalization tool and a target material. For example, alkanethiol deposition on noble metal surfaces, widely known as the formation of a self-assembled monolayer (SAM), cannot be performed on oxide material surfaces. One must choose organosilane molecules to functionalize oxide surfaces. Thus, the surface chemistry strictly depends on the properties of the surface. Polydopamine coating is now generally accepted as the first toolbox for functionalization of virtually any material surface. Layer-by-layer (LbL) assembly is a widely used method to modify properties of versatile surfaces, including organic materials, metal oxides, and noble metals, along with polydopamine coating. On flat solid substrates, the two chemistries of polydopamine coating and LbL assembly provide similar levels of surface modifications. However, there are additional distinct features in polydopamine. First, polydopamine coating is effective for two- or three-dimensional porous materials such as metal-organic frameworks (MOFs), synthetic polyolefin membranes, and others because small-sized dopamine (MW = 153.18 u) and its oxidized oligomers are readily attached onto narrow-spaced surfaces without exhibiting steric hindrance. In contrast, polymers used in LbL assembly are slow in diffusion because of steric hindrance due to their high molecular weight. Second, it is applicable to structurally nonflat surfaces showing special wettability such as superhydrophobicity or superoleophobicity. Third, a nonconducting, insulating polydopamine layer can be converted to be a conducting layer by pyrolysis. The product after pyrolysis is a N-doped graphene-like material that is useful for graphene or carbon nanotube-containing composites. Fourth, it is a suitable method for engineering the surface properties of various composite materials. The surface properties of participating components in composite materials can be unified by polydopamine coating with a simple one-step process. Fifth, a polydopamine layer exhibits intrinsic chemical reactivity by the presence of catecholquinone moieties and catechol radical species on surfaces. Nucleophiles such as amine and thiolate spontaneously react with the functionalized layer. Applications of polydopamine coating are exponentially growing and include cell culture/patterning, microfluidics, antimicrobial surfaces, tissue engineering, drug delivery systems, photothermal therapy, immobilization of photocatalysts, Li-ion battery membranes, Li-sulfur battery cathode materials, oil/water separation, water detoxification, organocatalysts, membrane separation technologies, carbonization, and others. In this Account, we describe various polydopamine coating methods and then introduce a number of chemical derivatives of dopamine that will open further development of material-independent surface chemistry.

The Development of a State-Aware Equipment Maintenance Application Using Sensor Data Ranking Techniques.

Billions of electric equipment are connected to Internet of Things (IoT)-based sensor networks, where they continuously generate a large volume of status information of assets. So, there is a need for state-aware information retrieval technology that can automatically recognize the status of each electric asset and provide the user with timely information suitable for the asset management of electric equipment. In this paper, we investigate state-aware information modeling that specializes in the asset management of electric equipment. With this state-aware information model, we invent a new asset state-aware ranking technique for effective information retrieval for electric power and energy systems. We also derive an information retrieval scenario for IoT in power and energy systems and develop a mobile application prototype. A comparative performance evaluation proves that the proposed technique outperforms the existing information retrieval technique.

Pretreatment methods for monitoring microplastics in soil and freshwater sediment samples: A comprehensive review.

This paper reviews the currently used pretreatment methods for microplastics (MPs) analysis in soil and freshwater sediments, primarily sample processing, pretreatment, and characterization methods for MPs analysis. In addition, analytical tools (e.g., lab instruments), MPs characteristics, and MPs quantity, are included in this review. Prior to pretreatment, soil and sediment samples are typically processed using sieving and drying methods, and a sample quantity of <50 g was mostly used for the pretreatment. Density separation was commonly performed before organic matter removal. Sodium chloride (NaCl) and zinc chloride (ZnCl2) were most often used for density separation, and hydrogen peroxide (H2O2) oxidation was most frequently used to remove organic matter. Although advantages of each pretreatment method have been investigated, it is still challenging to determine a universal pretreatment method due to sample variability (e.g., sample characteristics). Furthermore, it is highly required to establish standard pretreatment methods that can be used for various environmental matrices, including air, water, and wastes as well as soil and sediment.

Ginsenoside protopanaxadiol protects adult retinal pigment epithelial-19 cells from chloroquine by modulating autophagy and apoptosis.

Chloroquine often causes serious eye and vision problems, which are mainly mediated by lysosomotropic alteration. In this study, we investigated whether the ginsenoside protopanaxadiol relieves chloroquine-induced retinopathy by restoring lysosomotropic abnormalities in human adult retinal pigment epithelial-19 cells. Cytotoxicity was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Morphological alterations in autophagosomes of adult retinal pigment epithelial-19 cells was detected using confocal microscopy. Apoptosis was examined using flow cytometry, whereas cellular reactive oxygen species levels were determined by measuring the fluorescence intensity of 5-(and-6)-carboxy-2'-7'-dichlorohydrofluorescein diacetate. Lysosomal function was assessed by measuring lysosomal pH and enzyme activity. Immunoprecipitation and western blotting analyses were performed. Adult retinal pigment epithelial-19 cells accumulated autophagosomes with fusion defects in lysosomes and reactive oxygen species formation following exposure to chloroquine. This effect trapped Beclin-1 and B-cell lymphoma 2 interfering with autophagy initiation and autophagosome development. Protopanaxadiol alleviated chloroquine-induced toxicity by modulating the interaction between Beclin-1 and Bcl-2, which was mediated by the AMP-activated protein kinase-mammalian target of rapamycin signal axis. Furthermore, autophagy and apoptosis were simultaneously controlled by protopanaxadiol via upregulation of autophagy flux and decreased reactive oxygen species formation and apoptotic protein expression. These findings suggest that protopanaxadiol is a promising treatment strategy for chloroquine-mediated retinopathy.

Addressing the Shortcomings of Polyphenol-Derived Adhesives: Achievement of Long Shelf Life for Effective Hemostasis.

For rapid and effective hemostasis of uncontrollable bleeding, versatile hemostatic agents have been emerging. Among them, polyphenol-derived adhesives have attracted those hemostatic materials due to instantaneous formation of sticky barriers by robust interactions between the material and the serum proteins from wound. However, a critical challenge in such phenolic materials lies in long-term storage due to spontaneous oxidation under humid environments, leading to changes in hemostatic capability and adhesive strength. Here, we report a transparent hemostatic film consisting of gallol-conjugated chitosan (CHI-G) for minimizing the phenolic oxidation even for 3 months and maintaining strong tissue adhesiveness and its hemostatic ability. The film undergoes a phase transition from solid to injectable hydrogels at physiological pH for efficiently stopping internal and external hemorrhage. Interestingly, the hemostatic capability of the CHI-G hydrogels after 3 month storage depends on (i) the folded microstructure of the polymer with optimal gallol modification and (ii) an initial phase of either a solution state or a solid film. When the hydrogels are originated from the dehydrated film, their successful hemostasis is observed in a liver bleeding model. Our finding would provide an insight for design rationale of hemostatic formulations with long shelf-life.

Designing Adaptive Binders for Microenvironment Settings of Silicon Anode Particles.

This study reports the concept of an "adaptive binder" to address the silicon anode challenge in Li-ion batteries. Binders exhibit adaptable capabilities upon gradual changes in the microenvironments surrounding silicon particles during anodic expansion-shrinkage cycles. Long, flexible binder chains are repositioned and reoriented upon the gradual formation of Si-micro-environments (Si-µ-env) during the early battery cycles. At this stage, the chemical interactions between the polymeric binders are reversible hydrogen bonds. As the Si-µ-env become stably set by repeated battery cycles, the chemical interactions exhibit reversible-to-irreversible transitions by the formation of covalent linkages between the binder polymers at the later stage of cycles. The binder polymer showing the aforementioned adaptive properties is hyaluronic acid, which has never been explored as a silicon-anode binder material, onto which the plant-inspired adhesive phenolic moiety, gallol (1,2,3-trihydroxybenzene), is conjugated (HA-GA) for stable adhesion to the surfaces of silicon particles. It is confirmed that the HA-GA binder can maintain a charge capacity that is approximately 3.3 times higher (1153 mAh g-1 ) than that of the nonconjugated HA binder (347 mAh g-1 ) after 600 cycles even at a rapid charge/discharge rate of 1 C (3500 mA g-1 ), indicating that adaptive properties are an important factor to consider in designing silicon-anode binders.

Pastable, Adhesive, Injectable, Nanofibrous, and Tunable (PAINT) Biphasic Hybrid Matrices as Versatile Therapeutic Carriers.

A critical challenge in many pharmaceutical fields is developing versatile adjuvant devices that can reduce the off-target delivery of therapeutic materials to target lesions. Herein, a biphasic hybrid fibrous system that can manipulate the spatial and temporal delivery of various therapeutic agents to target lesions by integrating multiple distinct systems and technologies such as fluffy coaxial electrospun polycaprolactone (PCL)/polystyrene (PS) fibers, cyclohexane-mediated leaching to remove PS layers selectively, amine display on PCL fibers, conjugation of naturally occurring adhesive gallol molecules onto hyaluronic acid (HA-g), and electrostatically complexing the aminated PCL fibers with the gallol-conjugated HA. In the context of "paintable" systems on target lesions, the resulting system is called a PAINT matrix (abbreviated according to the initial letter of its features: pastable, adhesive, injectable, nanofibrous, and tunable). Its viscoelastic property, which was attributed by coalescing aminated PCL fibers with viscous HA-g, enabled it to be noninvasively injected and fit into any cavity in the body with various morphologies, manually pasted on tissue surfaces, and adhered onto moisture-rich surfaces to ensure the secure delivery of therapeutics toward the target lesions. The PAINT matrix efficiently supplied immunomodulatory human neural stem cells (hNSCs) at rat hemisectioned spinal cord injury (SCI) sites and promoted both locomotive and sensory recovery in SCI models, presumably by protecting hNSCs against host immunosurveillance. The PAINT matrix will be broadly utilized for efficiently delivering therapeutics to difficult-to-reach target lesions by direct infusion or conventional biomaterial-mediated approaches due to their locations, wet surfaces, or complicated ambient environments.

Polydopamine and Its Derivative Surface Chemistry in Material Science: A Focused Review for Studies at KAIST.

Polydopamine coating, the first material-independent surface chemistry, and its related methods significantly influence virtually all areas of material science and engineering. Functionalized surfaces of metal oxides, synthetic polymers, noble metals, and carbon materials by polydopamine and its related derivatives exhibit a variety of properties for cell culture, microfluidics, energy storage devices, superwettability, artificial photosynthesis, encapsulation, drug delivery, and numerous others. Unlike other articles, this review particularly focuses on the development of material science utilizing polydopamine and its derivatives coatings at the Korea Advanced Institute of Science and Technology for a decade. Herein, it is demonstrated how material-independent coating methods provide solutions for challenging problems existed in many interdisciplinary areas in bio-, energy-, and nanomaterial science by collaborations and independent research.

Diatom Frustule Silica Exhibits Superhydrophilicity and Superhemophilicity.

Special surface wettability attracts significant attention. In this study, dramatic differences in wettability are demonstrated for microparticles with the same chemical composition, SiO2. One is natural silica prepared from the diatom, Melosira nummuloides, and the other is synthetic silica. We found that surface properties of synthetic silica are hydro- and hemophobic. However, diatom frustule silica exhibits superhydrophilicity and even superhemophilicity. Interestingly, such superhydrophilicity of natural silica is not solely originated from nanoporous structures of diatoms but from the synergy of high-density silanol anions and the nanoarchitecture. Furthermore, the observation of superhemophilicity of natural silica is also an interesting finding, because not all superhydrophilic surfaces show superhemophilicity. We demonstrate that superhemowettability is a fundamental principle for developing micropowder-based hemostatic materials despite existing hemorrhaging studies using diatoms.

The area of ground glass opacities of the lungs as a predictive factor in acute paraquat intoxication.

Even though plasma paraquat (PQ) levels have known to be an informative predictor, many patients succumb at low PQ levels in acute PQ intoxication. This study was designed to see whether the high resolution computerized tomography (HRCT) of the lungs would be a predictive measure in acute PQ intoxication. HRCT of the lungs was obtained from 119 patients with acute PQ intoxication on 7 days after PQ ingestion. The areas with ground glass opacities (GGOs) were evaluated at five levels with the area measurement tool of the picture archiving and communication systems. Among 119 patients, 102 survived and 17 died. The plasma PQ levels were significantly higher in the non-survivors than in the survivors (2.6+/-4.0 microg/mL vs. 0.2+/-0.4 microg/mL, P=0.02). The area with GGOs was 2.0+/-6.4% in the survivors and 73.0+/- 29.9% in the non-survivors (P<0.001). No patients survived when the area with GGOs was more than 40% but all of the patients survived when the area affected by GGOs was less than 20%. In conclusion, the area of GGOs is a useful predictor of survival in acute PQ intoxication, especially in patients with low plasma PQ levels.

Targeting the MYC Oncogene in Burkitt Lymphoma through HSP90 Inhibition.

Overexpression of the MYC oncogene is a key feature of many human malignancies including Burkitt lymphoma. While MYC is widely regarded to be a promising therapeutic target, a clinically effective MYC inhibitor is still elusive. Here, we report an alternative strategy, targeting MYC indirectly through inhibition of the HSP90 machinery. We found that inhibition of HSP90 function reduces MYC expression in human Burkitt lymphoma through suppression of MYC transcription and destabilization of MYC protein, thereby diminishing the proliferation of tumor cells. Consistently, treatment of Burkitt lymphoma cell lines with HSP90 inhibitors (17-AAG or 17-DMAG) was accompanied by downregulation of canonical MYC target genes. Combination treatment with 17-DMAG and the proteasome inhibitor, MG-132, led to accumulation of MYC protein, indicating that upon HSP90 inhibition, MYC is degraded by the proteasome. Using co-immunoprecipitation, we furthermore demonstrated a direct interaction between MYC and HSP90, indicating that MYC is an HSP90 client protein in Burkitt lymphoma. Together, we report here the use of HSP90 inhibitors as an alternative approach to target the MYC oncogene and its network in Burkitt lymphoma.

Pesticide-initiated idiopathic environmental intolerance in South Korean farmers.

This study was designed to study patients with intolerance to pesticide smells. Ten subjects chosen were complaining of vague symptoms such as headache, dizziness, fatigue, nausea, vomiting, abdominal pain, myalgia, flu-like symptoms, etc., whenever exposed to the pesticide smells even at low intensity. To determine whether the etiology of this kind of pesticide hypersensitivity was of organic or psychiatric nature, all the subjects underwent tests as follows: complete blood cell count, urinalysis, and blood chemistry as routine tests; esophogastroduodenoscopy and abdomen ultrasonography for the gastrointestinal symptoms; chest x-ray, pulmonary function tests, and electrocardiography for the respiratory and/or cardiac symptoms; nerve conduction velocity and brain magnetic resonance imaging (MRI) for peripheral and central nerve system symptoms; and K-WAIS, Rey-Kim memory test, Rorschach, Mini Mental State Examination (MMSE), and Minnesota Multiphasic Personality Inventory (MMPI) for psychoanalysis. Of the 10 cases in which the chief complaint was headache, symptoms of two cases were caused by maxillary sinusitis. Another two showed typical multiple chemical sensitivity (MCS) or idiopathic environmental intolerance (IEI). Six out of the 10 cases, whose symptoms closely resembled the others, did not conclusively meet the criteria of classic MCS or IEI. The subjects of this case shared vague fears, both fear of pesticides and hypochondriasis. Some subjects faced financial insecurity and social uncertainty; others felt uneasy about the future of their farming life. Thus, to help verify the causes of MCS or IEI, which is strongly suggestive of pesticide smells, diagnosis needs a dual approach: on the anima and soma. Psychoanalysis can delve into the mental status of the patients to see whether the patients are aware of their symptoms. Clinical tests can see through the physical structure and functions of the organs on which patients' complaints are centered.

SET contributes to the epithelial-mesenchymal transition of pancreatic cancer.

Pancreatic cancer has a devastating prognosis due to 80-90% of diagnostic cases occurring when metastasis has already presented. Activation of the epithelial-mesenchymal transition (EMT) is a prerequisite for metastasis because it allows for the dissemination of tumor cells to blood stream and secondary organs. Here, we sought to determine the role of SET oncoprotein, an endogenous inhibitor of PP2A, in EMT and pancreatic tumor progression. Among the two major isoforms of SET (isoform 1 and isoform 2), higher protein levels of SET isoform 2 were identified in aggressive pancreatic cancer cell lines. Overexpressing SET isoform 2, and to a lesser extent SET isoform 1, in epithelial cell lines promoted EMT-like features by inducing mesenchymal characteristics and promoting cellular proliferation, migration, invasion, and colony formation. Consistently, knockdown of SET isoforms in the mesenchymal cell line partially resisted these characteristics and promoted epithelial features. SET-induced EMT was likely facilitated by increased N-cadherin overexpression, decreased PP2A activity and/or increased expression of key EMT-driving transcription factors. Additionally, SET overexpression activated the Rac1/JNK/c-Jun signaling pathway that induced transcriptional activation of N-cadherin expression. In vivo, SET isoform 2 overexpression significantly correlated with increased N-cadherin in human PDAC and to tumor burden and metastatic ability in an orthotopic mouse tumor model. These findings identify a new role for SET in cancer and have implications for the design and targeting of SET for intervening pancreatic tumor progression.

Phenolic condensation and facilitation of fluorescent carbon dot formation: a mechanism study.

Fluorescent carbon dots have received considerable attention as a result of their accessibility and potential applications. Although several prior studies have demonstrated that nearly any organic compound can be converted into carbon dots by chemical carbonization processes, mechanisms explaining the formation of carbon dots still remain unclear. Herein, we propose a seed-growth mechanism of carbon dot formation facilitated by ferulic acid, a widespread and naturally occurring phenolic compound in the seeds of Ocimum basilicum (basil). Ferulic acid triggers the local condensation of polysaccharide chains and forms catalytic core regions resulting in nanoscale carbonization. Our study indicates that carbon dots generated from natural sources might share the similar mechanism of phenolic compound mediated nanoscale condensation followed by core carbonization.

Association between parkinsonism and participation in agriculture in Korea.

BACKGROUND AND PURPOSE: Environmental factors might influence the pathogenesis of Parkinson's disease (PD) or multiple-system atrophy (MSA), and previous examinations of pesticide exposure, well-water drinking, and farming have produced inconclusive results. Because agriculture has been of considerable importance to Korean society, and hence the risk of exposure to pesticides was high in Korea, this study investigated whether such exposure is associated with elevated risks of developing PD and MSA. METHODS: Two hundred and thirty-five PD patients, 133 MSA patients, and 77 normal control subjects were examined. Data concerning environmental factors were collected by face-to-face interviews using a structured questionnaire. Odds ratios (ORs) were calculated by binary logistic regression. RESULTS: ORs for environmental risk factors for developing PD were 1.06 [95% confidence interval (CI) = 1.02-1.10] for age and 2.37 (95% CI = 1.32-4.27) for rural well-water drinking for >10 years. Smoking >10 pack-years (OR = 0.31; 95% CI = 0.11-0.64) was a preventable factor for developing PD in this study. However, no significant risk factors were identified for MSA. CONCLUSIONS: These results suggest that exposure to certain environmental risk factors plays a role in the development of PD. However, the development of MSA appears to be independent of environmental risk factors in Korean patients.