New Graduate Nurses' Competencies, Organizational Socialization, and Turnover Intention.

OBJECTIVE: This study aimed to identify core competencies in new-graduate nurses (NGNs) by determining which competencies affected their organizational socialization (OS) and turnover intention (TI) in their 1st year of employment. BACKGROUND: NGNs face stressful transitions with expanded nursing responsibilities that motivate them to leave their jobs. Therefore, NGN turnover in the 1st year of practice is higher than the overall nurse turnover rate. Previous research suggested that NGNs' competency levels affect their OS and TI. However, little research has been done to determine which competencies affect these variables. METHODS: Multiple linear regression analysis was performed on cross-sectional survey data to determine the effects of NGN work competencies on OS and TI. RESULTS: Health promotion, supervision, interpersonal communication, and direct care competencies significantly predicted NGNs' OS, and computer technology competency significantly predicted NGNs' TI. CONCLUSIONS: NGNs should be given early opportunities for expanded hands-on clinical experiences along with clear awareness of the organization's goals and values. Moreover, they should be offered roles that take advantage of their computer technology skills and that challenge them to contribute to their organization and nursing care in new ways.

Optimal timing for local ablative treatment of bone oligometastases in non-small cell lung cancer.

Oligometastases is a term commonly used to describe a disease state characterized by a limited number of distant metastases, and represents a transient phase between localized and widespread systemic diseases. This subgroup of stage IV cancer has increased in clinical importance due to the possibility of curative rather than palliative treatment. Among advanced lung cancer patients, 30-40% show bone metastases, and can show complications such as pathological fractures. Many prospective studies have shown efficacy of localized treatment in oligometastatic non-small cell lung cancer (NSCLC) in improving progression-free survival and overall survival. Compared to metastases in other organs, bone metastases are unique in terms of tumor microenvironment and clinical outcomes. Radiotherapy is the most frequently used treatment modality for local ablative treatment for both primary and metastatic lesions. Stereotactic body radiation therapy demonstrated more rapid and effective pain control compared to conventional 3D conformal radiotherapy. Radiotherapy improved outcomes in terms of time-to-skeletal related events skeletal-related events (SRE), hospitalization for SRE, pain relief, and overall survival in patients with bone metastases. Decision on timing of local ablative treatment depends on patient's overall clinical status, treatment goals, potential side effects of each approach, and expected initial responses to systemic anti-cancer treatment.

The complete mitochondrial genome of Rana coreana (Anura: Ranidae).

Rana coreana is a brown frog species native to the Korean Peninsula. We characterized the complete mitochondrial genome of the species. The mitochondrial genome sequence of R. coreana is 22,262 bp and comprises 13 protein-coding genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and two control regions (CRs). The CR duplication and gene organization were identical to those observed in Rana kunyuensis and Rana amurensis. A total of 13 protein-coding genes were used to examine the phylogenetic relationships between this species and the genus Rana. R. coreana living on the Korean Peninsula, formed a cluster with R. kunyuensis and R. amurensis, with R. coreana showing the closest phylogenetic affinity for R. kunyuensis.

Identification of a biosynthetic gene cluster for a red pigment cristazarin produced by a lichen-forming fungus Cladonia metacorallifera.

Lichens are known to produce many novel bioactive metabolites. To date, approximately 1,000 secondary metabolites have been discovered, which are predominantly produced by the lichen mycobionts. However, despite the extensive studies on production of lichen secondary metabolites, little is known about the responsible biosynthetic gene clusters (BGCs). Here, we identified a putative BGC that is implicated in production of a red pigment, cristazarin (a naphthazarin derivative), in Cladonia metacorallifera. Previously, cristazarin was shown to be specifically induced in growth media containing fructose as a sole carbon source. Thus, we performed transcriptome analysis of C. metacorallifera growing on different carbon sources including fructose to identify the BGC for cristazarin. Among 39 polyketide synthase (PKS) genes found in the genome of C. metacorallifera, a non-reducing PKS (coined crz7) was highly expressed in growth media containing either fructose or glucose. The borders of a cristazarin gene cluster were delimited by co-expression patterns of neighboring genes of the crz7. BGCs highly conserved to the cristazarin BGC were also found in C. borealis and C. macilenta, indicating that these related species also have metabolic potentials to produce cristazarin. Phylogenetic analysis revealed that the Crz7 is sister to fungal PKSs that biosynthesize an acetylated tetrahydoxynaphthalene as a precursor of melanin pigment. Based on the phylogenetic placement of the Crz7 and putative functions of its neighboring genes, we proposed a plausible biosynthetic route for cristazarin. In this study, we identified a lichen-specific BGC that is likely involved in the biosynthesis of a naphthazarin derivative, cristazarin, and confirmed that transcriptome profiling under inducing and non-inducing conditions is an effective strategy for linking metabolites of interest to biosynthetic genes.

[Primary Neuroendocrine Carcinoma of the Breast: A Case Report and Literature Review]. / ìœ ë°©ì—ì„œ 발생한 원발성 ì‹ ê²½ë‚´ë¶„ë¹„ì•”ì¢ : 증례 ë³´ê³ ì™€ ë¬¸í—Œê³ ì°°.

In general, neuroendocrine cancer develops in the digestive or respiratory tract, and when it is found in other organs, it is often due to metastasis. Primary neuroendocrine carcinoma of the breast occurs very rarely, and the exact clinical picture, radiological findings, treatment and prognosis are not well known. Furthermore, only a small number of literature reports have been published. Here, we report the imaging findings of primary neuroendocrine carcinoma in the breast of a 51-year-old female, along with a literature review.

[Radiologic Manifestations of Pulmonary Nuclear Protein in Testis Midline Carcinoma: A Case Report]. / 폐에 발생한 ê³ í™˜ 핵단백질 ì •ì¤‘ì„ ì•”ì˜ ì˜ìƒì˜í•™ì  소견: 증례 ë³´ê³ .

Nuclear portein in testis (NUT) midline carcinoma is a very rare and low-differentiating malignant epithelial tumor that differentiates very aggressively and has poor prognosis. NUT midline carcinoma occurring in the lungs in particular can be confused with other cancers because few cases have been reported in Korea to date and can show various histological forms. Reports of radiology findings are very rare worldwide. Here we report the imaging findings of pulmonary NUT midline carcinoma in a 25-year-old female along with pathological findings.

Development of InDel markers for interspecific hybridization between hill pigeons and feral pigeons based on whole-genome re-sequencing.

Interspecific hybridization occurs among birds, and closely related sister taxa tend to hybridize at a high rate. Genomic hybridization markers are useful for understanding the patterns and processes of hybridization and for conserving endangered species in captivity and the wild. In this study, we developed genomic hybridization markers for the F1 progeny of the sister taxa feral pigeons (Columba livia var. domestica) and endangered hill pigeons (Columba rupestris) (family Columbidae). Using whole-genome re-sequencing data, we performed genome-wide analysis for insertion/deletion (InDel) polymorphisms and validated using primers. We conducted polymerase chain reaction (PCR) and agarose gel electrophoresis to identify species-specific InDels. We produced eight F1 hybrids of hill and feral pigeons, and their samples were tested by re-performing analyses and sequencing using 11 species-specific InDel polymorphisms. Eight InDel markers simultaneously amplified two DNA fragments from all F1 hybrids, and there was no abnormality in the sequencing results. The application of genomic tools to detect hybrids can play a crucial role in the assessment of hybridization frequency in the wild. Moreover, systematic captive propagation efforts with hybrids can help control the population decline of hill pigeons.

Whole-genome sequencing revealed different demographic histories among the Korean endemic hill pigeon (Columba rupestris), rock pigeon (Columba livia var. domestica) and oriental turtle dove (Streptopelia orientalis).

BACKGROUND: The family Columbidae is known as the pigeon family and contains approximately 351 species and 50 genera. Compared to the wealth of biological and genomic information on these Columba livia var. domesteca, information on Columba rupestris and Streptopelia orientalis has been rather limited. The C. rupestris population size is decreasing in Korea. OBJECTIVES: Whole-genome sequencing and identification of population characterization of each species based genome variation on 9 Korean pigeon and dove samples, namely, six hill pigeon (C. rupestris), one rock pigeon (C. livia var. domestica) and two oriental turtle dove (S. orientalis) samples. RESULTS: The whole genome of 9 genotypes were sequenced and mapped to the C. livia reference genome. Sequence alignment showed over 96% identity in C. rupestris and 94% identity in S. orientalis to the reference genome (GenBank assembly accession: GCA_001887795.1). Sequence variations, including single nucleotide polymorphisms (SNPs), insertions and deletions (InDels), and structural variations, revealed that intergenus (Columba vs. Streptopelia) variations were approximately four times higher than intragenus variations (C. livia vs. C. rupestris). Of the two Columba species, C. livia var. domestica is closer to S. orientalis than C. rupestris. Pairwise sequentially Markovian coalescent (PSMC) demographic history analysis revealed that the three species underwent a common population bottleneck between 105 and 120 Kya; since then, the effective population sizes of the rock pigeon and oriental turtle dove have increased. CONCLUSION: The effective population size of the hill pigeon, an Endangered Species of Grade II in Korea, has increased slowly from the second severe bottleneck that occurred approximately 0.5-1.4 × 104 years ago. Our results showed no relationship between copy number variation in the Norrie disease protein (NDP) regulatory regions and plumage color patterns. We report the first comparative analysis of three pigeon genomes.

Factors influencing posttraumatic growth among nurses caring for COVID-19 patients: A path analysis.

AIMS: Based on Calhoun and Tedeschi's posttraumatic growth model, this study aimed to establish a path model of posttraumatic growth among nurses who provided care for coronavirus disease 2019 (COVID-19) patients and to examine the associations between the relevant variables. BACKGROUND: There are increasingly many studies examining the psychological health status of nurses caring for patients on the front lines of COVID-19. However, research results showing the effects of various variables affecting nurses' posttraumatic growth through positive psychological transformation are insufficient. METHODS: This cross-sectional study was based on a sample of 229 nurses who cared for COVID-19 patients for more than 1 month in South Korea from April to May 2021. RESULTS: The fitness of the modified path model (χ2 = 1.380, p = .502, GFI = 0.99, CFI = 1.00, NFI = 0.99, RMSEA = 0.00 and TLI = 1.01) was higher than that of the hypothesis path model (χ2 = 124.133, p < .001, GFI = 0.85, CFI = 0.66, NFI = 0.65, RMSEA = 0.36 and TLI = 0.15). Deliberate rumination had directly influenced posttraumatic growth and posttraumatic stress disorder and social support had a direct and indirect effect on posttraumatic growth. Self-disclosure indirectly influenced posttraumatic growth through deliberate rumination but was not significant. CONCLUSIONS: In order to improve posttraumatic growth of nurses caring for COVID-19 patients, it is necessary to provide and support opportunities for self-disclosure. IMPLICATION FOR NURSING MANAGEMENT: The results of this study can help institutions and nurse managers comprehensively understand the factors affecting posttraumatic growth of nurses caring for COVID-19 patients in the front lines and determine basic strategies based on the importance of these factors.

Impact of urinary iodine concentration on blood glucose levels and blood pressure: a nationwide population-based study.

PURPOSE: Iodine is a vital trace element for systemic metabolic control as well as thyroid hormone synthesis. Though iodine has significant antioxidant and anti-inflammatory effects, reports on its effects on metabolic disorders are limited and inconsistent. METHODS: Impact of urinary iodine concentrations (UICs) on fasting blood glucose (FBG) levels and blood pressure (BP) in the general Korean population was evaluated adjusting for covariates including thyrotropin level and presence of thyroid diseases. RESULTS: The median UIC was 302.3 µg/L in all participants and was significantly lower in those with dysglycemia (303.6 µg/L in normal participants, 285.1 µg/L in participants with FBG levels of 100-125 mg/dL, and 261.8 µg/L in participants with FBG levels ≥ 126 mg/dL; p = 0.002). Similarly, the UIC was lower in participants with higher BP (311.6 µg/L in normal participants, 288.7 µg/L in prehypertensive participants, and 265.8 µg/L in hypertensive participants; p < 0.001). The multiple linear regression model showed a negative correlation between the UIC and FBG levels (p = 0.002), and the UIC and systolic BP (p < 0.001). One standard deviation increase in the UIC showed odds ratios of 0.84 (95% confidence interval [CI] = 0.73-0.98) for elevated FBG levels (≥ 100 mg/dL) and 0.94 (95% CI = 0.88-0.99) for elevated SBP (≥ 120 mm Hg) after full adjustment. CONCLUSION: Higher UICs were associated with lower FBG and BP levels, independent of thyroid function and other confounding factors in Korea, an iodine-replete country.

Comparison of Laser and Conventional Lancing Devices for Blood Glucose Measurement Conformance and Patient Satisfaction in Diabetes Mellitus.

Self-monitoring of capillary blood glucose is important for controlling diabetes. Recently, a laser lancing device (LMT-1000) that can collect capillary blood without skin puncture was developed. We enrolled 150 patients with type 1 or 2 diabetes mellitus. Blood sampling was performed on the same finger on each hand using the LMT-1000 or a conventional lancet. The primary outcome was correlation between glucose values using the LMT-1000 and that using a lancet. And we compared the pain and satisfaction of the procedures. The capillary blood sampling success rates with the LMT-1000 and lancet were 99.3% and 100%, respectively. There was a positive correlation (r=0.974, P<0.001) between mean blood glucose levels in the LMT-1000 (175.8±63.0 mg/dL) and conventional lancet samples (172.5±63.6 mg/dL). LMT-1000 reduced puncture pain by 75.0% and increased satisfaction by 80.0% compared to a lancet. We demonstrated considerable consistency in blood glucose measurements between samples from the LMT-1000 and a lancet, but improved satisfaction and clinically significant pain reduction were observed with the LMT-1000 compared to those with a lancet.

Myocardial Infarction, Stroke, and All-Cause Mortality according to Low-Density Lipoprotein Cholesterol Level in the Elderly, a Nationwide Study.

BACKGROUND: We assessed the myocardial infarction (MI), stroke, and all-cause death risks during follow-up according to the low-density lipoprotein cholesterol (LDL-C) levels among older adults. METHODS: The Korean National Health Insurance Service datasets (2002 to 2020) were used for this population-based cohort study. The hazards of MI, stroke, and all-cause mortality during follow-up were analyzed according to LDL-C level in individuals aged ≥65 years without baseline cardiovascular diseases (n=1,391,616). RESULTS: During a mean 7.55 years, 52,753 MIs developed; 84,224 strokes occurred over a mean 7.47 years. After a mean 8.50 years, 233,963 died. A decrease in LDL-C was associated with lower hazards of MI and stroke. The decreased hazard of stroke in lower LDL-C was more pronounced in statin users, and individuals with diabetes or obesity. The hazard of all-cause death during follow-up showed an inverted J-shaped pattern according to the LDL-C levels. However, the paradoxically increased hazard of mortality during follow-up in lower LDL-C was attenuated in statin users and individuals with diabetes, hypertension, or obesity. In statin users, lower LDL-C was associated with a decreased hazard of mortality during follow-up. CONCLUSION: Among the elderly, lower LDL-C was associated with decreased risks of MI and stroke. Lower LDL-C achieved by statins in the elderly was associated with a decreased risk of all-cause death during follow-up, suggesting that LDL-C paradox for the premature death risk in the elderly should not be applied to statin users. Intensive statin therapy should not be hesitated for older adults with cardiovascular risk factors including diabetes.

Implications of fasting plasma glucose variability on the risk of incident peripheral artery disease in a population without diabetes: a nationwide population-based cohort study.

BACKGROUND: Diabetes have been known as a traditional risk factor of developing peripheral artery disease (PAD). However, the study evaluating the impact of long-term glycemic variability on the risk of developing PAD is limited, especially in a general population without diabetes. METHODS: We included 152,931 individuals without diabetes from the Korean National Health Insurance Service-Health Screening Cohort. Fasting plasma glucose (FPG) variability was measured using coefficient variance (FPG-CV), standard deviation (FPG-SD), and variability independent of the mean (FPG-VIM). RESULTS: A total of 16,863 (11.0%) incident cases of PAD were identified during a median follow-up of 8.3 years. Kaplan-Meier curves showed a progressively increasing risk of PAD in the higher quartile group of FPG variability than in the lowest quartile group (log rank P < 0.001). Multivariable Cox proportional hazard analysis showed the hazard ratio for PAD prevalence as 1.11 (95% CI 1.07-1.16, P < 0.001) in the highest FPG-CV quartile than in the lowest FPG-CV quartile after adjusting for confounding variables, including mean FPG. Similar degree of association was shown in the FPG-SD and FPG-VIM. In sensitivity analysis, the association between FPG variability and the risk of developing PAD persisted even after the participants were excluded based on previously diagnosed diseases, including stroke, coronary artery disease, congestive heart failure, chronic kidney disease, or current smokers or drinkers. Subgroup analysis demonstrated that the effects of FPG variability on the risk of PAD were more powerful in subgroups of younger age, regular exercisers, and those with higher income. CONCLUSIONS: Increased long-term glycemic variability may have a significant prognostic effect for incident PAD in individuals without diabetes.

Restoration of Immune Privilege in Human Dermal Papillae Controlling Epithelial-Mesenchymal Interactions in Hair Formation.

BACKGROUND: Hair follicles are among a handful of organs that exhibit immune privilege. Dysfunction of the hair follicle immune system underlies the development of inflammatory diseases, such as alopecia areata. METHODS: Quantitative reverse transcription PCR and immunostaining was used to confirm the expression of major histocompatibility complex class I in human dermal papilla cells. Through transcriptomic analyses of human keratinocyte stem cells, major histocompatibility complex class I was identified as differentially expressed genes. Organ culture and patch assay were performed to assess the ability of WNT3a conditioned media to rescue immune privilege. Lastly, CD8+ T cells were detected near the hair bulb in alopecia areata patients through immunohistochemistry. RESULTS: Inflammatory factors such as tumor necrosis factor alpha and interferon gamma were verified to induce the expression of major histocompatibility complex class I proteins in dermal papilla cells. Additionally, loss of immune privilege of hair follicles was rescued following treatment with conditioned media from outer root sheath cells. Transcriptomic analyses found 58 up-regulated genes and 183 down-regulated genes related in MHC class I+ cells. Using newborn hair patch assay, we demonstrated that WNT3a conditioned media with epidermal growth factor can restore hair growth. In alopecia areata patients, CD8+ T cells were increased during the transition from mid-anagen to late catagen. CONCLUSION: Identification of mechanisms governing epithelial and mesenchymal interactions of the hair follicle facilitates an improved understanding of the regulation of hair follicle immune privilege.

Increased Risk of Type 2 Diabetes in Patients With Thyroid Cancer After Thyroidectomy: A Nationwide Cohort Study.

CONTEXT: Abnormal thyroid function after thyroidectomy and subsequent thyroid-stimulating hormone suppression can have detrimental effects on glucose homeostasis in patients with thyroid cancer. OBJECTIVE: To investigate whether thyroidectomy increases the risk of type 2 diabetes in patients with thyroid cancer and to explore the association between levothyroxine dosage and type 2 diabetes risk. METHODS: A retrospective population-based cohort study using the Korean National Health Insurance database. We included 36 377 thyroid cancer patients without known diabetes who underwent thyroidectomy between 2004 and 2013. Matched subjects with nonthyroid cancer were selected using 1:1 propensity score matching. The main outcome measure was newly developed type 2 diabetes mellitus. RESULTS: Patients with thyroid cancer who underwent thyroidectomy had a higher risk of developing type 2 diabetes mellitus than the matched controls (hazard ratio [HR] 1.43, 95% CI 1.39-1.47). Among patients with thyroid cancer, when the second quartile group (in terms of the mean levothyroxine dosage; 101-127 µg/day) was considered the reference group, the risk of type 2 diabetes mellitus increased in the first quartile (<101 µg/day; HR 1.45, 95% CI 1.36-1.54) and fourth quartile groups (≥150 µg/day; HR 1.37, 95% CI 1.29-1.45); meanwhile, the risk decreased in the third quartile group (128-149 µg/day; HR 0.91, 95% CI 0.85-0.97). CONCLUSION: Patients with thyroid cancer who underwent thyroidectomy were more likely to develop type 2 diabetes mellitus than the matched controls. There was a U-shaped dose-dependent relationship between the levothyroxine dosage and type 2 diabetes mellitus risk.

Risk of Diabetes in Patients with Long-Standing Graves' Disease: A Longitudinal Study.

BACKGROUND: The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies. METHODS: The risk of diabetes in patients with Graves' disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group. RESULTS: A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019). CONCLUSION: The risk of diabetes was significantly higher in patients with long-standing Graves' disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.

Optimization of Agrobacterium tumefaciens-Mediated Transformation of Xylaria grammica EL000614, an Endolichenic Fungus Producing Grammicin.

An endolichenic fungus Xylaria grammica EL000614 produces grammicin, a potent nematicidal pyrone derivative that can serve as a new control option for root-knot nematodes. We optimized an Agrobacterium tumefaciens-mediated transformation (ATMT) protocol for X. grammica to support genetic studies. Transformants were successfully generated after co-cultivation of homogenized young mycelia of X. grammica with A. tumefaciens strain AGL-1 carrying a binary vector that contains the bacterial hygromycin B phosphotransferase (hph) gene and the eGFP gene in T-DNA. The resulting transformants were mitotically stable, and PCR analysis showed the integratin of both genes in the genome of transformants. Expression of eGFP was confirmed via fluorescence microscopy. Southern analysis showed that 131 (78.9%) out of 166 transformants contained a single T-DNA insertion. Crucial factors for producing predominantly single T-DNA transformants include 48 h of co-cultivation, pre-treatment of A. tumefaciens cells with acetosyringone before co-cultivation, and using freshly prepared mycelia. The established ATMT protocol offers an efficient tool for random insertional mutagenesis and gene transfer in studying the biology and ecology of X. grammica.

Implication of thyroid function in periodontitis: a nationwide population-based study.

Possible links between periodontitis and various cardiometabolic and autoimmune diseases have been advocated on the basis of chronic inflammation or oxidative stress. However, the association between periodontitis and thyroid dysfunction is under-researched. Participants without previous thyroid disease or ongoing thyroid-related medication were included from a nationwide population-level survey. Participants were categorized into tertiles of thyroid stimulating hormone (TSH) levels (first tertile < 1.76 mIU/L; second tertile 1.76-2.83 mIU/L; third tertile > 2.83 mIU/L), and periodontal condition was assessed using the Community Periodontal Index. Of the total of 5468 participants, 1423 had periodontitis (26%). A significant difference in the weighted prevalence of periodontitis according to TSH tertiles was observed, with the highest prevalence in the first tertile (26.5%) and the lowest prevalence in the third tertile (20.9%, p = 0.003). Subjects in the first TSH tertile had higher odds for periodontitis than those in the third tertile (OR 1.36, 95% CI 1.10-1.68; p for trend = 0.005) after adjusting for covariates. This association was consistent across subgroups and within sensitivity analyses among subjects without specific factors affecting thyroid function or diseases reported to be related to periodontitis. The present study demonstrated that low TSH levels were associated with significantly higher odds for periodontitis.

Structural insights into the clustering and activation of Tie2 receptor mediated by Tie2 agonistic antibody.

Angiopoietin (Angpt)-Tie receptor 2 (Tie2) plays key roles in vascular development and homeostasis as well as pathological vascular remodeling. Therefore, Tie2-agonistic antibody and engineered Angpt1 variants have been developed as potential therapeutics for ischemic and inflammatory vascular diseases. However, their underlying mechanisms for Tie2 clustering and activation remain elusive and the poor manufacturability and stability of Angpt1 variants limit their clinical application. Here, we develop a human Tie2-agonistic antibody (hTAAB), which targets the membrane proximal fibronectin type III domain of Tie2 distinct from the Angpt-binding site. Our Tie2/hTAAB complex structures reveal that hTAAB tethers the preformed Tie2 homodimers into polygonal assemblies through specific binding to Tie2 Fn3 domain. Notably, the polygonal Tie2 clustering induced by hTAAB is critical for Tie2 activation and are resistant to antagonism by Angpt2. Our results provide insight into the molecular mechanism of Tie2 clustering and activation mediated by hTAAB, and the structure-based humanization of hTAAB creates a potential clinical application.

Combination of Statin and Ezetimibe versus Statin Monotherapy on Cardiovascular Disease and Type 2 Diabetes Incidence among Adults with Impaired Fasting Glucose: a Propensity-Matched Nationwide Cohort Study.

OBJECTIVE: We investigated the effects of statin-ezetimibe combination therapy compared with statin-only treatment on the hazard of incident type 2 diabetes (T2D), myocardial infarction (MI), and stroke among adults with impaired fasting glucose (IFG) in a real-world setting. METHODS: The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this propensity-matched nationwide cohort study. Among 56,633 IFG patients without baseline cardiovascular disease (CVD) and/or T2D who initiated statin therapy with or without ezetimibe, 1,155 with statin-ezetimibe combination therapy were matched based on a propensity score at a 1:5 ratio with 5,775 patients who received statin monotherapy. The hazards of T2D, MI, and stroke were compared between these treatment groups. RESULTS: The incidence rate per 1,000 person-years was 19.62 (statin monotherapy group) and 21.02 (combined treatment group) for T2D, 1.53 (statin monotherapy group) and 1.70 (combined treatment group) for MI, and 1.99 (statin monotherapy group) and 2.06 (combined treatment group) for stroke. The hazards of T2D, MI, and stroke were not significantly different between the statin monotherapy group and the statin-ezetimibe combination therapy group. CONCLUSION: The combination of ezetimibe in addition to statin treatment was not associated with a significantly different risk of T2D and CVDs compared with statin monotherapy in Korean adults with IFG.