Current Health Data Standardization Project and Future Directions to Ensure Interoperability in Korea.

OBJECTIVES: The need for interoperability at the national level was highlighted in Korea, leading to a consensus on the importance of establishing national standards that align with international technological standards and reflect contemporary needs. This article aims to share insights into the background of the recent national health data standardization policy, the activities of the Health Data Standardization Taskforce, and the future direction of health data standardization in Korea. METHODS: To ensure health data interoperability, the Health Data Standardization Taskforce was jointly organized by the public and private sectors in December 2022. The taskforce operated three working groups. It reviewed international trends in interoperability standardization, assessed the current status of health data standardization, discussed its vision, mission, and strategies, engaged in short-term standardization activities, and established a governance system for standardization. RESULTS: On September 15, 2023, the notice of "Health Data Terminology and Transmission Standards" in Korea was thoroughly revised to improve the exchange of health information between information systems and ensure interoperability. This notice includes the Korea Core Data for Interoperability (KR CDI) and the Korea Core Data Transmission Standard (HL7 FHIR KR Core), which are outcomes of the taskforce's efforts. Additionally, to reinforce the standardized governance system, the Health-Data Standardization Promotion Committee was established. CONCLUSIONS: Active interest and support from medical informatics experts are needed for the development and widespread adoption of health data standards in Korea.

Targeting Heme Oxygenase 2 (HO2) with TiNIR, a Theragnostic Approach for Managing Metastatic Non-Small Cell Lung Cancer.

Despite notable advancements in cancer therapeutics, metastasis remains a primary obstacle impeding a successful prognosis. Our prior study has identified heme oxygenase 2 (HO2) as a promising therapeutic biomarker for the aggressive subsets within tumor. This study aims to systematically evaluate HO2 as a therapeutic target of cancer, with a specific emphasis on its efficacy in addressing cancer metastasis. Through targeted inhibition of HO2 by TiNIR (tumor-initiating cell probe with near infrared), we observed a marked increase in reactive oxygen species. This, in turn, orchestrated the modulation of AKT and cJUN activation, culminating in a substantial attenuation of both proliferation and migration within a metastatic cancer cell model. Furthermore, in a mouse model, clear inhibition of cancer metastasis was unequivocally demonstrated with an HO2 inhibitor administration. These findings underscore the therapeutic promise of targeting HO2 as a strategic intervention to impede cancer metastasis, enhancing the effectiveness of cancer treatments.

Poly-L-Lactic Acid Fillers Improved Dermal Collagen Synthesis by Modulating M2 Macrophage Polarization in Aged Animal Skin.

Poly-L-lactic acid (PLLA) fillers correct cutaneous volume loss by stimulating fibroblasts to synthesize collagen and by augmenting the volume. PLLA triggers the macrophage-induced activation of fibroblasts that secrete transforming growth factor-ß (TGF-ß). However, whether M2 macrophage polarization is involved in PLLA-induced collagen synthesis via fibroblast activation in aged skin is not known. Therefore, we evaluated the effect of PLLA on dermal collagen synthesis via M2 polarization in an H2O2-induced cellular senescence model and aged animal skin. H2O2-treated macrophages had increased expression levels of the M1 marker CD80 and decreased expression levels of the M2 marker CD163, which were reversed by PLLA. The expression levels of interleukin (IL)-4 and IL-13, which mediate M2 polarization, were decreased in H2O2-treated macrophages and increased upon the PLLA treatment. CD163, IL-4, and IL-13 expression levels were decreased in aged skin, but increased after the PLLA treatment. The expression levels of TGF-ß, pSMAD2/SMAD2, connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), collagen type 1A1 (COL1A1), and COL3A1 were also decreased in aged skin, but increased after the PLLA treatment. Moreover, PLLA upregulated phosphatidylinositol 3-kinase p85α (PI3-kinase p85α)/protein kinase B (AKT) signaling, leading to fibroblast proliferation. PLLA decreased the expression of matrix metalloproteinase (MMP) 2 and MMP3, which destroy collagen and elastin fibers in aged skin. The amount of collagen and elastin fibers in aged skin increased following the PLLA treatment. In conclusion, PLLA causes M2 polarization by increasing IL-4 and IL-13 levels and upregulating TGF-ß expression and collagen synthesis in aged skin.

Fatigue Life Improvement of Weld Beads with Overlap Defects Using Ultrasonic Peening.

Welding defects are common during the production of large welded structures. However, few studies have explored methods of compensating for clear welding defects without resorting to re-welding. Here, an ultrasonic peening method to compensate for the deteriorated mechanical properties of overlap weld defects without repair welding was studied. We experimentally investigated changes in the mechanical properties of defective welds before and after ultrasonic peening. The weld specimen with an overlap defect contained a large cavity-type defect inside the weld bead, which significantly reduced the fatigue life. When the surface of the defective test piece was peened, the fatigue life of the weld plate was restored, resulting in an equivalent or higher number of cycles to failure, compared to a specimen with a normal weld. The recovery of mechanical properties was attributed to the effect of surface work hardening by ultrasonic peening and the change in stress distribution. Thus, ultrasonic peening could compensate for the deterioration of mechanical properties such as tensile strength, fatigue life, and elongation due to overlap defects, without resorting to repair welding.

A Fluorogenic Assay: Analysis of Chemical Modification of Lysine and Arginine to Control Proteolytic Activity of Trypsin.

The chemical modification of amino acids plays an important role in the modulation of proteins or peptides and has useful applications in the activation and stabilization of enzymes, chemical biology, shotgun proteomics, and the production of peptide-based drugs. Although chemoselective modification of amino acids such as lysine and arginine via the insertion of respective chemical moieties as citraconic anhydride and phenyl glyoxal is important for achieving desired application objectives and has been extensively reported, the extent and chemoselectivity of the chemical modification of specific amino acids using specific chemical agents (blocking or modifying agents) has yet to be sufficiently clarified owing to a lack of suitable assay methodologies. In this study, we examined the utility of a fluorogenic assay method, based on a fluorogenic tripeptide substrate (FP-AA1-AA2-AA3) and the proteolytic enzyme trypsin, in determinations of the extent and chemoselectivity of the chemical modification of lysine or arginine. As substrates, we used two fluorogenic tripeptide probes, MeRho-Lys-Gly-Leu(Ac) (lysine-specific substrate) and MeRho-Arg-Gly-Leu(Ac) (arginine-specific substrate), which were designed, synthesized, and evaluated for chemoselective modification of specific amino acids (lysine and arginine) using the fluorogenic assay. The results are summarized in terms of half-maximal inhibitory concentrations (IC50) for the extent of modification and ratios of IC50 values (IC50arginine/IC50lysine and IC50lysine/IC50arginine) as a measure of the chemoselectivity of chemical modification for amino acids lysine and arginine. This novel fluorogenic assay was found to be rapid, precise, and reproducible for determinations of the extent and chemoselectivity of chemical modification.

Association of gamma-glutamyl transferase with subclinical coronary atherosclerosis and cardiac outcomes in non-alcoholics.

In an asymptomatic population, we determined the relationship between serum gamma-glutamyl transferase (GGT) and subclinical atherosclerosis, using coronary computed tomography angiography (CCTA). This was a retrospective observational cohort study which analyzed 5120 consecutive asymptomatic individuals with no prior history of coronary artery disease or significant alcohol intake who voluntarily underwent CCTA as part of a general health examination. All subjects were stratified into tertiles based on GGT levels. Degree and extent of subclinical coronary atherosclerosis were evaluated using CCTA. Cardiac events were a composite of all-cause death, myocardial infarction, unstable angina, and coronary revascularization. After adjustment for cardiovascular risk factors, there were no significant differences among GGT tertiles in terms of adjusted odds ratios for non-calcified and mixed plaques. The risk of any atherosclerotic and calcified plaques, significant stenosis, multi-vessel disease, and significant stenosis in the left main or proximal left anterior descending artery was higher in the third GGT tertile than in the first tertile (all p < 0.05). Over a median 5.4-year follow-up, the third GGT tertile had significant adjusted hazards ratios for cardiac events than did the first GGT tertile, even after stepwise adjustment for cardiovascular risk factors (all p < 0.01). In asymptomatic individuals, elevated GGT was independently associated with high-risk feature atherosclerosis and poorer cardiac outcomes.

Better Surface Integrity and Tribological Properties of Steel Sintered by Powder Metallurgy.

The current research reports the improvement in surface integrity and tribological characteristics of steel prepared using a powder metallurgy (PM) by ultrasonic nanocrystal surface modification (UNSM) at 25 and 300 °C. The surface integrity and tribological properties of three samples, namely, as-PM, UNSM-25 and UNSM-300 were investigated. The average surface roughness (Ra) of the as-PM, UNSM-25 and UNSM-300 samples was measured using a non-contact 3D scanner, where it was found to be 3.21, 1.14 and 0.74 µm, respectively. The top surface hardness was also measured in order to investigate the influence of UNSM treatment temperature on the hardness. The results revealed that the as-PM sample with a hardness of 109 HV was increased up to 165 and 237 HV, corresponding to a 32.1% and 57.2% after both the UNSM treatment at 25 and 300 °C, respectively. XRD analysis was also performed to confirm if any changes in chemistry and crystal size were took place after the UNSM treatment at 25 and 300 °C. In addition, dry tribological properties of the samples were investigated. The friction coefficient of the as-PM sample was 0.284, which was reduced up to 0.225 and 0.068 after UNSM treatment at 25 and 300 °C, respectively. The wear resistance was also enhanced by 33.2 and 52.9% after UNSM treatment at both 25 and 300 °C. Improvements in surface roughness, hardness and tribological properties was attributed to the elimination of big and deep porosities after UNSM treatment. Wear track of the samples and wear scar of the counter surface balls were investigated by SEM to reach a comprehensive discussion on wear mechanisms. Overall, it was confirmed that UNSM treatment at 25 and 300 °C had a beneficial effect on the surface integrity and tribological characteristics of sintered steel by the PM that is used in a shock absorber for a car engine.

Association between serum phosphorus and subclinical coronary atherosclerosis in asymptomatic Korean individuals without kidney dysfunction.

BACKGROUND: There are limited data regarding the relation between serum phosphorus concentration (SPC) and subclinical coronary atherosclerosis in the asymptomatic healthy population without kidney dysfunction. OBJECTIVES: We aimed to investigate the relation between SPC and characteristics of atherosclerotic plaques and cardiac events according to SPCs using a large cohort of asymptomatic Korean individuals. METHODS: We evaluated 6329 asymptomatic Korean individuals [mean age: 53.6 ± 7.6 y, 4611 men (72.9%)] without kidney dysfunction and coronary artery disease who voluntarily underwent coronary computed tomography angiography (CCTA) as part of a general health examination. Study participants were stratified into quartiles according to their SPCs (≤3.0, 3.1-3.3, 3.4-3.7, ≥3.8 mg/dL). The degree and extent of subclinical coronary atherosclerosis were evaluated with CCTA. Stenosis of diameter ≥50% was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, and coronary revascularization. RESULTS: After adjustment for cardiovascular disease risk factors, the risk of any atherosclerotic plaque was significantly higher with increasing SPC quartiles (P = 0.001). In particular, the risk of calcified plaque increased in the second (OR: 1.27; 95% CI: 1.07, 1.51; P = 0.006), third (OR: 1.39; 95% CI: 1.17, 1.64; P < 0.001), and fourth SPC quartiles (OR: 1.50; 95% CI: 1.24, 1.82; P < 0.001) compared with that in the first quartile. However, there were no significant differences in the adjusted ORs for noncalcified plaque, mixed plaque, or significant stenosis. During a follow-up of median 5.4 y, there was no significant difference in cardiac events between the SPC quartiles. CONCLUSIONS: In asymptomatic Korean individuals without kidney dysfunction, a high SPC was an independent predictor of calcified plaques without any difference in cardiac events. Further long-term prospective studies are required to validate these results.

Homocysteine is not a risk factor for subclinical coronary atherosclerosis in asymptomatic individuals.

BACKGROUND: Homocysteine has been known as a risk factor for cardiovascular disease. This study sought to evaluate the influence of homocysteine on the risk of subclinical coronary atherosclerosis in asymptomatic individuals. METHODS: We reviewed 3,186 asymptomatic individuals (mean age 53.8 ± 8.0 years, 2,202 men [69.1%]) with no prior history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography (CCTA) and laboratory tests as part of a general health examination. The subjects were stratified into tertiles according to their homocysteine levels. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA. Logistic regression analysis was used to determine the association between homocysteine levels and subclinical coronary atherosclerosis. RESULTS: The prevalence of significant coronary artery stenosis, any atherosclerotic, calcified, mixed, and non-calcified plaques increased with homocysteine tertiles (all p < 0.05). However, after adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios (ORs) for any atherosclerotic plaque (OR 1.06; 95% CI [confidence interval] 0.85-1.32; p = 0.610), calcified plaques (OR 1.17; 95% CI 0.92-1.48; p = 0.199), non-calcified plaques (OR 0.80; 95% CI 0.61-1.04; p = 0.089), and mixed plaques (OR 1.42; 95% CI 0.96-2.11; p = 0.077) between the third and first homocysteine tertiles. In addition, the adjusted OR for significant coronary artery stenosis (OR 0.92; 95% CI 0.63-1.36; p = 0.687) did not differ between the first and third tertiles. CONCLUSIONS: In asymptomatic individuals, homocysteine is not associated with an increased risk of subclinical coronary atherosclerosis.

Triglyceride glucose index is a useful marker for predicting subclinical coronary artery disease in the absence of traditional risk factors.

BACKGROUND: Atherosclerotic cardiovascular (CV) events commonly occur in individuals with a low CV risk burden. This study evaluated the ability of the triglyceride glucose (TyG) index to predict subclinical coronary artery disease (CAD) in asymptomatic subjects without traditional CV risk factors (CVRFs). METHODS: This retrospective, cross-sectional, and observational study evaluated the association of TyG index with CAD in 1250 (52.8 ± 6.5 years, 46.9% male) asymptomatic individuals without traditional CVRFs (defined as systolic/diastolic blood pressure ≥ 140/90 mmHg; fasting glucose ≥126 mg/dL; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol < 40 mg/dL; body mass index ≥25.0 kg/m2; current smoking; and previous medical history of hypertension, diabetes, or dyslipidemia). CAD was defined as the presence of any coronary plaque on coronary computed tomographic angiography. The participants were divided into three groups based on TyG index tertiles. RESULTS: The prevalence of CAD increased with elevating TyG index tertiles (group I: 14.8% vs. group II: 19.3% vs. group III: 27.6%; P < 0.001). Multivariate logistic regression models showed that TyG index was associated with an increased risk of CAD (odds ratio [OR] 1.473, 95% confidence interval [CI] 1.026-2.166); especially non-calcified (OR 1.581, 95% CI 1.002-2.493) and mixed plaques (OR 2.419, 95% CI 1.051-5.569) (all P < 0.05). The optimal TyG index cut-off for predicting CAD was 8.44 (sensitivity 47.9%; specificity 68.5%; area under the curve 0.600; P < 0.001). The predictive value of this cut-off improved after considering the non-modifiable factors of old age and male sex. CONCLUSIONS: TyG index is an independent marker for predicting subclinical CAD in individuals conventionally considered healthy.

High-density lipoprotein cholesterol and the risk of obstructive coronary artery disease beyond low-density lipoprotein cholesterol in non-diabetic individuals.

AIMS: The relationship between high-density lipoprotein cholesterol and the severity of coronary artery disease beyond low-density lipoprotein cholesterol, the primary target of cholesterol-lowering therapy, remains uncertain. We evaluated the association between high-density lipoprotein cholesterol and obstructive coronary artery disease using parameters of any obstructive plaque, obstructive plaque in the left main coronary artery or proximal left anterior descending artery, and obstructive plaque in multi-vessels, according to low-density lipoprotein cholesterol levels. METHODS AND RESULTS: We analyzed 5130 asymptomatic non-diabetics who underwent coronary computed tomography angiography for general health examination. Obstructive plaque was defined as a plaque with ≥50% luminal diameter stenosis. The participants were divided into three groups based on low-density lipoprotein cholesterol levels of ≤129, 130-159, and ≥160 mg/dl. The prevalence of any obstructive plaque (5.9% vs 6.4% vs 10.6%) and obstructive plaque in the left main coronary artery or proximal left anterior descending artery (2.1% vs 2.1% vs 4.3%) significantly increased with low-density lipoprotein cholesterol category (all p < 0.05). Compared with subjects with high-density lipoprotein cholesterol level ≥40 mg/dl, those with high-density lipoprotein cholesterol level <40 mg/dl had a significantly higher prevalence of any obstructive plaque (10.4% vs 5.1%), obstructive plaque in the left main coronary artery or proximal left anterior descending artery (3.6% vs 1.8%), and obstructive plaque in multi-vessels (4.3% vs 1.1%), only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p < 0.05). Multiple regression analysis showed that increased high-density lipoprotein cholesterol levels were associated with a reduced risk of all obstructive coronary artery disease parameters only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p < 0.05). CONCLUSION: Increased high-density lipoprotein cholesterol levels were independently associated with a lower risk of obstructive coronary artery disease in asymptomatic non-diabetics with low low-density lipoprotein cholesterol levels.

Impact of Diabetes Control on Subclinical Atherosclerosis: Analysis from Coronary Computed Tomographic Angiography Registry.

BACKGROUND: There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis. METHODS: We analyzed 6,434 consecutive asymptomatic individuals without previous history of coronary artery disease who underwent coronary computed tomographic angiography (CCTA) (mean age, 53.7±7.6 years and 4,694 men [73.0%]). The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Study participants were categorized as normal (n=5,319), controlled diabetes (glycosylated hemoglobin [HbA1c] <7%, n=747), or uncontrolled diabetes (HbA1c ≥7%, n=368), respectively. RESULTS: Compared with normal individuals, there were no statistically significant differences in the risk of for any atherosclerotic plaque (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.98 to 1.38; P=0.086) and significant coronary artery stenosis (OR, 1.08; 95% CI, 0.82 to 1.42; P=0.583) in controlled diabetic individuals. In contrast, uncontrolled diabetic individuals had consistently higher risks of any atherosclerotic plaque (OR, 2.16; 95% CI, 1.70 to 2.75; P<0.001) and significant coronary artery stenosis (OR, 3.34; 95% CI, 2.52 to 4.43; P<0.001) than normal individuals. During a follow-up of median 5.4 years, there was no significant difference in cardiac events between normal and controlled diabetic individuals (P=0.365). However, uncontrolled diabetes was associated with an increased risk of cardiac events compared with normal individuals (P<0.001) and controlled diabetic individuals (P=0.023). CONCLUSION: Asymptomatic uncontrolled diabetes was associated with significant subclinical coronary atherosclerosis with subsequent high risk for cardiac events.

Three-Dimensional Computed Tomographic Analysis of Normal and Aneurysmal Aortic Roots: Is There a Specific Geometric Pattern in the Aortic Root?

Current knowledge of the aortic root geometric anatomy and its surgical implications remain limited. We analyzed multiple predefined parameters of the aortic root to increase our understanding of the geometric changes that occur in normal and aneurysmal transformations. Between November 2003 and September 2015, the aortic roots of 107 healthy subjects (control group) and 105 annuloaortic ectasia (AAE) patients (AAE group) were analyzed using multiplanar reformatted computed tomographic images. The intercommissural distance (ICD), sinus width (SW), and sinus volume (SV) of the left (LCS), right (RCS), and noncoronary sinuses (NCS) of Valsalva were adopted as study parameters. In the control group, all study parameters of the LCS were smaller than those of the RCS and the NCS. In the AAE group, all parameters of the LCS were significantly smaller than those of the RCS or NCS, but the RCS and NCS parameters were similar. Proportionately less LCS enlargement relative to either the RCS or NCS was observed in root aneurysm(AAE group) than in the control group. We observed a distinct aortic root geometric pattern which was characterized by the LCS being smaller than either the RCS or NCS, while the latter were similar. This geometric configuration was significantly accentuated in AAE patients due to the greater disproportionate disparity in the LCS relative to either the RCS or NCS than in the roots of normal control subjects. Clin. Anat. 32:117-123, 2019. © 2019 Wiley Periodicals, Inc.

High HDL-C levels reduce the risk of obstructive coronary artery disease in asymptomatic diabetics who achieved optimal glycemic control.

The benefit of a high level of high-density lipoprotein cholesterol (HDL-C) against coronary atherosclerosis risk after achieving optimal glycemic control (OGC) in diabetics remains uncertain. We aimed to evaluate the association between HDL-C and obstructive coronary artery disease (CAD) according to OGC status in diabetics. We analyzed 1,114 asymptomatic diabetics who underwent coronary computed tomographic angiography in a health examination. OGC was defined as hemoglobin A1C <7.0%. Obstructive CAD was defined as the presence of plaques with ≥50% stenosis. Patients with a high HDL-C level (≥40 mg/dL and ≥50 mg/dL in males and females, respectively) showed a lower prevalence of obstructive CAD than those with a low HDL-C level in the OGC group (8.9% vs. 14.4%; p = 0.046), but not in the non-OGC group (22.3% vs. 23.2%, p = 0.850). Multiple logistic regression models showed that the risk for obstructive CAD was lower in patients with a high HDL-C level than in those with a low HDL-C level in the OGC group (odds ratio: 0.584, 95% confidence interval: 0.343-0.995; p = 0.048), but not in the non-OGC group. In conclusion, it may be necessary to maintain a high HDL-C level to reduce the risk of obstructive CAD in asymptomatic diabetics after OGC is achieved.

Association between insulin resistance, hyperglycemia, and coronary artery disease according to the presence of diabetes.

This study evaluated the relationship of insulin resistance (IR) and glycemic control status to the presence and severity of coronary artery disease (CAD) according to diabetes. The relationship of IR parameters including homeostatic model assessment of IR (HOMA-IR), triglyceride-glucose (TyG) index, and triglyceride-to-high density lipoprotein cholesterol ratio (TG/HDL), and hemoglobin A1C (HbA1C) level to CAD and obstructive CAD was evaluated in 5,764 asymptomatic subjects who underwent coronary computed tomographic angiography. Non-diabetics (n = 4768) and diabetics (n = 996) were stratified into four groups based on the quartiles of HOMA-IR and the TyG index and were grouped based on the TG/HDL cut-offs of 3.5, respectively. CAD and obstructive CAD were defined as the presence of any plaques and plaques with ≥50% stenosis, respectively. The prevalence of CAD (59.0% vs. 39.0%) and obstructive CAD (15.0% vs. 6.6%) was higher in diabetic than in non-diabetic patients (p < 0.001, respectively). In non-diabetic patients, the adjusted odds ratio for both CAD and obstructive CAD significantly increased, but only with higher TyG index quartiles. Unlike non-diabetics, the adjusted odds ratio for obstructive CAD significantly increased in diabetic patients with a TG/HDL level ≥ 3.5. The HbA1C, rather than IR parameters, was independently associated with both CAD and obstructive CAD in diabetics. In conclusion, among IR parameters, TyG index was independently associated with the presence of CAD and obstructive CAD in non-diabetic patients. In contrast, the glycemic control status, rather than IR, was importantly related to both CAD and obstructive CAD in established diabetic patients.

Asymmetric and Reduced Xanthene Fluorophores: Synthesis, Photochemical Properties, and Application to Activatable Fluorescent Probes for Detection of Nitroreductase.

Xanthene fluorophores, including fluorescein, rhodol, and rhodamines, are representative classes of fluorescent probes that have been applied in the detection and visualization of biomolecules. "Turn on" activatable fluorescent probes, that can be turned on in response to enzymatic reactions, have been developed and prepared to reduce the high background signal of "always-on" fluorescent probes. However, the development of activity-based fluorescent probes for biological applications, using simple xanthene dyes, is hampered by their inefficient synthetic methods and the difficulty of chemical modifications. We have, thus, developed a highly efficient, versatile synthetic route to developing chemically more stable reduced xanthene fluorophores, based on fluorescein, rhodol, and rhodamine via continuous Pd-catalyzed cross-coupling. Their fluorescent nature was evaluated by monitoring fluorescence with variation in the concentration, pH, and solvent. As an application to activatable fluorescent probe, nitroreductase (NTR)-responsive fluorescent probes were also developed using the reduced xanthene fluorophores, and their fluorogenic properties were evaluated.

Serum uric acid level and subclinical coronary atherosclerosis in asymptomatic individuals: An observational cohort study.

BACKGROUND AND AIMS: There are limited data on the association between serum uric acid (SUA) level and subclinical coronary atherosclerosis. This study investigated the influence of SUA level on subclinical coronary atherosclerosis, as detected by coronary computed tomography angiography (CCTA), in an asymptomatic population. METHODS: We evaluated 6431 asymptomatic individuals (mean age 53.6 ±â€¯7.6 years, 4691 men [72.9%]) with no prior history of coronary artery disease, who voluntarily underwent laboratory tests and CCTA as part of a general health examination. The participants were stratified into quartiles according to their SUA levels. Coronary atherosclerotic plaques (calcified, mixed, and non-calcified plaques) were assessed using CCTA. Logistic regression analysis was used to determine the association between SUA levels and subclinical coronary atherosclerosis. RESULTS: The prevalence of any atherosclerotic, calcified, mixed, and non-calcified plaques increased with SUA quartiles (all p < 0.001). After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios for calcified plaque (1.19; 95% CI 0.98-1.46; p = 0.080) and mixed plaque (1.25; 95% CI 0.94-1.67; p = 0.132) in the fourth SUA quartile compared to the first quartile. However, the adjusted odds ratios for any atherosclerotic plaque (1.39; 95% CI 1.16-1.68; p < 0.001) and non-calcified plaque (1.38; 95% CI 1.11-1.72; p = 0.004) were significantly higher in the fourth SUA quartile. CONCLUSIONS: In asymptomatic individuals, high SUA level was an independent predictor of non-calcified plaques, suggesting an increased cardiovascular risk.

Independent role of low-density lipoprotein cholesterol in subclinical coronary atherosclerosis in the absence of traditional cardiovascular risk factors.

AIMS: Individuals without traditional cardiovascular risk factors (CVRFs) still experience adverse events in clinical practice. This study evaluated the predictors of subclinical coronary atherosclerosis in individuals without traditional CVRFs. METHODS AND RESULTS: A total of 1250 (52.8 ± 6.5 years, 46.9% male) asymptomatic individuals without CVRFs who underwent coronary computed tomographic angiography for a general health examination were analysed. The following were considered as traditional CVRFs: systolic/diastolic blood pressure ≥140/90 mmHg; fasting glucose ≥126 mg/dL; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol (LDL-C) ≥160 mg/dL; high-density lipoprotein cholesterol <40 mg/dL; body mass index ≥25.0 kg/m2; current smoking status; and previous medical history of hypertension, diabetes, and dyslipidaemia. Subclinical atherosclerosis, defined as the presence of any coronary plaque, was present in 20.6% cases; the incidences of non-calcified, calcified, and mixed plaque were 9.6%, 12.6%, and 2.6%, respectively. Multivariate regression analysis showed that LDL-C level [odds ratio (OR): 1.008; 95% confidence interval (CI): 1.001-1.015], together with age (OR: 1.101; 95% CI: 1.075-1.128) and male sex (OR: 5.574; 95% CI: 3.310-9.388), was associated with the presence of subclinical atherosclerosis (All P < 0.05). LDL-C level was significantly associated with an increased risk of calcified plaques rather than non-calcified or mixed plaques. CONCLUSION: LDL-C, even at levels currently considered within normal range, is independently associated with the presence of subclinical coronary atherosclerosis in individuals without traditional CVRFs. Our results suggest that a stricter control of LDL-C levels may be necessary for primary prevention in individuals who are conventionally considered healthy.

Incremental Value of Subtended Myocardial Mass for Identifying FFR-Verified Ischemia Using Quantitative CT Angiography: Comparison With Quantitative Coronary Angiography and CT-FFR.

OBJECTIVES: This study examined the incremental value of subtended myocardial mass (Vsub) as assessed by coronary computed tomography angiography (CTA) for identifying lesion-specific ischemia verified by invasive fractional flow reserve (FFR) in quantitative coronary CTA. BACKGROUND: FFR is determined not only by coronary stenosis severity, but also by Vsub. One-step evaluation of combined Vsub and coronary lesion morphology may improve the accuracy of coronary CTA for identifying ischemia-producing lesions. METHODS: A total of 246 intermediate coronary artery lesions (30% to 80% diameter stenosis) in 220 patients (mean age 61.7 years, 168 men) interrogated by FFR were retrospectively studied. Coronary CTA data were used to assess the Vsub by coronary artery stenosis, minimal lumen area (MLA), percentage of aggregated plaque volume (%APV), positive remodeling, and low-attenuation plaque. The ability of Vsub/MLA2 to discriminate lesions with FFR ≤0.80 was examined. Diagnostic performance, odds ratios, and category-less net reclassification improvements of coronary CTA parameters for FFR-verified (≤0.80) ischemia were evaluated. On-site computed tomography (CT) derived-FFR (CT-FFR) and quantitative coronary angiography (QCA) data were also compared. RESULTS: Of 246 lesions, 84 (34.1%) showed an FFR ≤0.80. Vsub was independently associated with an FFR ≤0.80 (odds ratio: 1.04/1 cm3; p = 0.032) and showed incremental value over MLA. Vsub/MLA2 >4.16 was the best single parameter for discriminating an FFR ≤0.80 with 83.3% sensitivity and 67.9% specificity. The area under the curve (AUC) of Vsub/MLA2 >4.16 (0.80 [95% confidence interval: 0.75 to 0.85]) was better than that of MLA (change in [Δ]AUC: 0.069; p < 0.001), %APV (ΔAUC: 0.096; p = 0.017), and diameter stenosis of QCA (ΔAUC: 0.080; p = 0.037) and was comparable to that of CT-FFR (AUC 0.77; ΔAUC: 0.035; p = 0.304). CONCLUSIONS: Vsub is an independent determinant of an FFR ≤0.80. The mathematical index of Vsub/MLA2 >4.16 assessed by coronary CTA shows better diagnostic performance for the detection of ischemia-producing lesions than CT-derived MLA alone or %APV and QCA parameters and was comparable to that of on-site CT-FFR.