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Background/Aims: To investigate a reported outbreak of presumed hepatitis E virus (HEV) infection in a Korean food manufacturing facility and to explore the association between anti-HEV immunoglobulin M (IgM) positivity and coronavirus disease 2019 (COVID-19) infection or vaccination. Methods: Twenty-four cases of anti-HEV IgM positivity were reported among 646 workers at the facility in 2022. An epidemiological investigation was conducted, comprising HEV-RNA testing of blood and environmental samples, analysis of group meal records, and an association between anti-HEV IgM positivity and confirmed COVID-19 infection or vaccination. Results: All 24 patients were asymptomatic, with cases spread sporadically across the facility. HEV RNA was not detected in the serum or environmental samples. Four out of 340 meals (1.2%) showed a significantly higher proportion of anti-HEV positivity in each meal intake group than in the non-intake group on certain days. Although the cumulative rate of COVID-19 infection showed no difference, the anti-HEV IgM positive group showed significantly higher proportions of >2 doses of COVID-19 vaccination (83.3% vs 48.7%, p=0.021), vaccination within 90 days (45.8% vs 19.7%, p=0.008), and having the Moderna vaccine administered as the last vaccine (75.0% vs 14.5%, p<0.001) than those of the anti-HEV negative group. In four multivariable models, three or more COVID-19 vaccinations and the Moderna vaccine as the last vaccine were consistently associated with anti-HEV IgM positivity, while the specific day group meal intake was also a significant factor. Conclusions: This epidemiological investigation showed that anti-HEV IgM positivity may occur as a false-positive result related to COVID-vaccination over three times and use of the Moderna vaccine, although a portion of true HEV infection may not be excluded. [ABSTRACT FROM AUTHOR]

Introduction: We analyzed daily pre-treatment- (PRE) and real-time motion monitoring- (MM) MRI scans of patients receiving definitive prostate radiotherapy (RT) with 1.5 T MRI guidance to assess interfractional and intrafractional variability of the prostate and suggest optimal planning target volume (PTV) margin. Materials and methods: Rigid registration between PRE-MRI and planning CT images based on the pelvic bone and prostate anatomy were performed. Interfractional setup margin (SM) and interobserver variability (IO) were assessed by comparing the centroid values of prostate contours delineated on PRE-MRIs. MM-MRIs were used for internal margin (IM) assessment, and PTV margin was calculated using the van Herk formula. Results: We delineated 400 prostate contours on PRE-MRI images. SM was 0.57 ± 0.42, 2.45 ± 1.98, and 2.28 ± 2.08 mm in the left-right (LR), anteriorposterior (AP), and superior-inferior (SI) directions, respectively, after bone localization and 0.76 ± 0.57, 1.89 ± 1.60, and 2.02 ± 1.79 mm in the LR, AP, and SI directions, respectively, after prostate localization. IO was 1.06 ± 0.58, 2.32 ± 1.08, and 3.30 ± 1.85 mm in the LR, AP, and SI directions, respectively, after bone localization and 1.11 ± 0.55, 2.13 ± 1.07, and 3.53 ± 1.65 mm in the LR, AP, and SI directions, respectively, after prostate localization. Average IM was 2.12 ± 0.86, 2.24 ± 1.07, and 2.84 ± 0.88 mm in the LR, AP, and SI directions, respectively. Calculated PTV margin was 2.21, 5.16, and 5.40 mm in the LR, AP, and SI directions, respectively. Conclusions: Movements in the SI direction were the largest source of variability in definitive prostate RT, and interobserver variability was a non-negligible source of margin. The optimal PTV margin should also consider the internal margin. [ABSTRACT FROM AUTHOR]

Background: The use of helmet treatment for positional plagiocephaly has increased recently; however, its effect is unknown in Korea. Purpose: This study aimed to investigate the effectiveness of helmet therapy and identify its influencing factors. Methods: Ninety pediatric patients diagnosed with moderate to severe positional plagiocephaly received helmet therapy. Severity of moderate to severe positional plagiocephaly was defined as cranial vault asymmetry (CVA) >10 mm or CVA index (CVAI) >6%. Patients were categoriz ed by age, severity, and daily helmet wear. Multiple regression analysis controlled for factors like sex and prematurity. Treatment success was assessed by comparing pre/posthelmet theray CVA and CVAI, considering normalization or decrease to mild plagiocephaly (CVA =10 mm or CVAI =6%). Results: A total of 90 participants were enrolled (mean age, 5.6±1.6 months; male, 53 [58.9%]). The mean helmet therapy duration was 6.4±2.7 months, while the mean daily wear time was 18.4±2.7 hours. Among the 90 patients, 66 (73.3%) had moderate disease and 24 (26.7%) had severe disease. The mean CVA and CVAI decreased by 6.3±2.7 mm and 4.3%±1.8% after versus before treatment (P<0.001). Treatment was successful in 76 infants (84.4%). The most effective changes in CVA and CVAI were noted in those who began treatment before 9 months of age (6.2±2.5 mm and 5.0%±1.9%, P<0.001), had high compliance (6.2±2.4 mm and 4.9%±1.9%, P<0.001), and had high severity (8.0±2.3 mm and 6.6%±1.7%, P<0.001). Conclusion: Starting helmet treatment before 9 months and wearing it over 15 hours daily yielded better outcomes. [ABSTRACT FROM AUTHOR]

Background: Oligometastatic disease (OMD) represents an indolent cancer status characterized by slow tumor growth and limited metastatic potential. The use of local therapy in the management of the condition continues to rise. This study aimed to investigate the advantage of pretreatment tumor growth rate in addition to baseline disease burden in characterizing OMDs, generally defined by the presence of ≤ 5 metastatic lesions. Methods: The study included patients with metastatic melanoma treated with pembrolizumab. Gross tumor volume of all metastases was contoured on imaging before (TP-1) and at the initiation of pembrolizumab (TP0). Pretreatment tumor growth rate was calculated by an exponential ordinary differential equation model using the sum of tumor volumes at TP-1 and TP0 and the time interval between TP-1. and TP0. Patients were divided into interquartile groups based on pretreatment growth rate. Overall survival, progression-free survival, and subsequent progression-free survival were the study outcomes. Results: At baseline, median cumulative volume and number of metastases were 28.4 cc (range, 0.4-1194.8 cc) and 7 (range, 1-73), respectively. The median interval between TP-1 and TP0 was -90 days and pretreatment tumor growth rate (×10-2 days-1) was median 4.71 (range -0.62 to 44.1). The slow-paced group (pretreatment tumor growth rate ≤ 7.6 ×10-2 days-1, the upper quartile) had a significantly higher overall survival rate, progression-free survival, and subsequent progression-free survival compared to those of the fast-paced group (pretreatment tumor growth rate > 7.6 ×10-2 days-1). Notably, these differences were prominent in the subgroup with >5 metastases. Conclusion: Pretreatment tumor growth rate is a novel prognostic metric associated with overall survival, progression-free survival, and subsequent progression-free survival among metastatic melanoma patients, especially patients with >5 metastases. Future prospective studies should validate the advantage of disease growth rate plus disease burden in better defining OMDs. [ABSTRACT FROM AUTHOR]

Background: Misperception of body weight is associated with various psychological and health problems, including obesity, eating disorders, and mental problems. To date, female-specific risk factors, including socioeconomic or health-related lifestyle features, or their indicative performance for the misperception in Asian women according to age groups remain unknown. Objectives: To investigate the prevalence and associated risk factors for the mismatch in self-perceived body weight and evaluated the classification performance of the identified risk factors across age groups in female adults. Methods: We analyzed data of 22,121 women (age 19–97 years) from the 7-year Korea National Health and Nutrition Examination Survey dataset (2010-2016). We evaluated self-perceived body weight of the participants with their actual weight using the body mass index cut-off and grouped them by age: early adulthood (19–45), middle adulthood (46–59), and late adulthood (≥60). Logistic regression was conducted in each age group based on their weight misperception. The classification performance of the identified risk factors was evaluated with a bagging tree ensemble model with 5-fold cross-validation. Results: 22.2% (n=4,916) of the study participants incorrectly perceived their body weight, of which 14.1% (n=3,110) and 8.2% (n=1,806) were in the underestimated and overestimated groups. Among the age groups, the proportion of participants who misperceived their body weight was highest in late adulthood (31.8%) and the rate of overestimation was highest in early adulthood (14.1%). We found that a lower education level, absence of menopause, perception of themselves as unhealthy, and efforts for weight management were significantly associated with the overall misperception (overestimation or underestimation) of body weight across age groups. Based on the identified risk factors, the highest area under the receiver operating curve (AUROC) and accuracy of the best classification model (weight overestimation in all participants) were 0.758 and 0.761, respectively. Adding various associated lifestyle factors to the baseline model resulted in an average increase of 0.159 and 0.135 in AUROC for classifying weight underestimation and overestimation, respectively. Conclusions: Age, education level, marital status, absence of menopause, amount of exercise, efforts for weight management (gain, loss, and maintenance), and self-perceived health status were significantly associated with the mismatch of body weight. [ABSTRACT FROM AUTHOR]

Background: Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which contributes to the development of occlusive vascular diseases, requires elevated mitochondrial oxidative phosphorylation to meet the increased requirements for energy and anabolic precursors. Therefore, therapeutic strategies based on blockade of mitochondrial oxidative phosphorylation are considered promising for treatment of occlusive vascular diseases. Here, we investigated whether DN200434, an orally available estrogen receptor-related gamma inverse agonist, inhibits proliferation and migration of VSMCs and neointima formation by suppressing mitochondrial oxidative phosphorylation. Methods: VSMCs were isolated from the thoracic aortas of 4-week-old Sprague-Dawley rats. Oxidative phosphorylation and the cell cycle were analyzed in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using a Seahorse XF-24 analyzer and flow cytometry, respectively. A model of neointimal hyperplasia was generated by ligating the left common carotid artery in male C57BL/6J mice. Results: DN200434 inhibited mitochondrial respiration and mammalian target of rapamycin complex 1 activity and consequently suppressed FBS- or PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Furthermore, DN200434 reduced carotid artery ligation-induced neointima formation in mice. Conclusion: Our data suggest that DN200434 is a therapeutic option to prevent the progression of atherosclerosis. [ABSTRACT FROM AUTHOR]

Cracks affect the robustness and adaptability of various infrastructures, including buildings, bridge piers, pavement, and pipelines. Therefore, the robustness and the reliability of automated crack detection are essential. In this study, we conducted image segmentation using various crack datasets by applying the advanced architecture of U-Net. First, we collected and integrated crack datasets from prior studies, including the cracks in buildings and pavements. For effective localization and detection of cracks, we used U-Net-based neural networks, ResUNet, VGGU-Net, and EfficientU-Net. The models were evaluated by the five-fold cross-validation using several evaluation metrics including mean pixel accuracy (MPA), mean intersection over union (MIoU), and confusion matrix. The results of the integrated dataset showed that ResU-Net (68.47%) achieves the highest MIoU with a relatively low number of parameters compared to VGGU-Net (67.71%) and EfficientU-Net (68.07%). In addition to the performance, ResUNet showed the lowest test runtime, 40 milliseconds per single image, and the highest true positive rate of 45.00% in the pixel-wise recognition test. As the models were trained and validated with diverse surfaces, the proposed approach can be used as a pre-trained model in the task with relatively few data sources. Furthermore, both practical and managerial implications are discussed herein. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 23 (FGF23), a hormone generally derived from bone, is important in phosphate and vitamin D homeostasis. In acute kidney injury (AKI) patients, high-circulating FGF23 levels are associated with disease progression and mortality. However, the organ and cell type of FGF23 production in AKI and the molecular mechanism of its excessive production are still unidentified. For insight, we investigated folic acid (FA)-induced AKI in mice. Interestingly, simultaneous with FGF23, orphan nuclear receptor ERR-γ expression is increased in the liver of FA-treated mice, and ectopic overexpression of ERR-γ was sufficient to induce hepatic FGF23 production. In patients and in mice, AKI is accompanied by up-regulated systemic IL-6, which was previously identified as an upstream regulator of ERR-γ expression in the liver. Administration of IL-6 neutralizing antibody to FAtreated mice or of recombinant IL-6 to healthy mice confirms IL-6 as an upstream regulator of hepatic ERR-γ-mediated FGF23 production. A significant (P < 0.001) interconnection between high IL-6 and FGF23 levels as a predictor of AKI in patients that underwent cardiac surgery was also found, suggesting the clinical relevance of the finding. Finally, liver-specific depletion of ERR-γ or treatment with an inverse ERR-γ agonist decreased hepatic FGF23 expression and plasma FGF23 levels in mice with FA-induced AKI. Thus, inverse agonist of ERR-γ may represent a therapeutic strategy to reduce adverse plasma FGF23 levels in AKI. [ABSTRACT FROM AUTHOR]

Purpose: Intensity-modulated radiotherapy (IMRT) allows for more precise treatment, reducing unwanted radiation to nearby structures. We investigated the safety and feasibility of IMRT for anaplastic ependymoma patients below 3 years of age. Materials and Methods: A total of 9 anaplastic ependymoma patients below 3 years of age, who received IMRT between October 2011 and December 2017 were retrospectively reviewed. The median equivalent dose in 2 Gy fractions was 52.0 Gy (range, 48.0 to 60.0 Gy). Treatment outcomes and neurologic morbidities were reviewed in detail. Results: The median patient age was 20.9 months (range, 12.1 to 31.2 months). All patients underwent surgery. The rates of 5-year overall survival, freedom from local recurrence, and progression-free survival were 40.6%, 53.3%, and 26.7%, respectively. Of the 9 patients, 5 experienced recurrences (3 had local recurrence, 1 had both local recurrence and cerebrospinal fluid [CSF] seeding, and 1 had CSF seeding alone). Five patients died because of disease progression. Assessment of neurologic morbidity revealed motor dysfunction in 3 patients, all of whom presented with hydrocephalus at initial diagnosis because of the location of the tumor and already had neurologic deficits before radiotherapy (RT). Conclusion: Neurologic morbidity is not caused by RT alone but may result from mass effects of the tumor and surgical sequelae. Administration of IMRT to anaplastic ependymoma patients below 3 years of age yielded encouraging local control and tolerable morbidities. High-precision modern RT such as IMRT can be considered for very young patients with anaplastic ependymoma. [ABSTRACT FROM AUTHOR]

Phosphoserine phosphatase (PSPH) is one of the key enzymes of the L-serine synthesis pathway. PSPH is reported to affect the progression and survival of several cancers in an L-serine synthesis-independent manner, but the mechanism remains elusive. We demonstrate that PSPH promotes lung cancer progression through a noncanonical L-serine-independent pathway. PSPH was significantly associated with the prognosis of lung cancer patients and regulated the invasion and colony formation of lung cancer cells. Interestingly, L-serine had no effect on the altered invasion and colony formation by PSPH. Upon measuring the phosphatase activity of PSPH on a serine-phosphorylated peptide, we found that PSPH dephosphorylated phospho-serine in peptide sequences. To identify the target proteins of PSPH, we analyzed the protein phosphorylation profile and the PSPH-interacting protein profile using proteomic analyses and found one putative target protein, IRS-1. Immunoprecipitation and immunoblot assays validated a specific interaction between PSPH and IRS-1 and the dephosphorylation of phospho-IRS-1 by PSPH in lung cancer cells. We suggest that the specific interaction and dephosphorylation activity of PSPH have novel therapeutic potential for lung cancer treatment, while the metabolic activity of PSPH, as a therapeutic target, is controversial. [ABSTRACT FROM AUTHOR]

Purpose: Internal mammary lymph node (IMN) involvement is associated with poor prognosis in breast cancer. This study investigated the treatment outcomes of initial clinically IMN-positive breast cancer patients who received adjuvant radiotherapy (RT), including IMN irradiation, following primary breast surgery. Materials and Methods: We retrospectively reviewed data of 95 breast cancer patients with clinically detected IMNs at diagnosis treated with surgery and RT between June 2009 and December 2015. Patients received adjuvant RT to the whole breast/chest wall and regional lymph node (axillary, internal mammary, and supraclavicular) areas. Twelve patients received an additional boost to the IMN area. Results: The median follow-up was 43.2 months (range, 4.5 to 100.5 months). Among 77 patients who received neoadjuvant chemotherapy, 52 (67.5%) showed IMN normalization and 19 (24.6%) showed a partial response to IMN. There were 3 and 24 cases of IMN failure and any recurrence, respectively. The 5-year IMN failure-free survival, disease-free survival (DFS), and overall survival (OS) were 96%, 70%, and 84%, respectively. IMN failure-free survival was significantly affected by resection margin status (97.7% if negative, 87.5% for close or positive margins; p = 0.009). All three patients with IMN failure had initial IMN size =1 cm and did not receive IMN boost irradiation. The median age of the three patients was 31 years, and all had hormone receptor-negative tumors. Conclusion: RT provides excellent IMN control without the support of IMN surgery. Intensity-modulated radiotherapy, including IMN boost for breast cancer patients, is a safe and effective technique for regional lymph node irradiation. [ABSTRACT FROM AUTHOR]

The stepwise development of T cells from a multipotent precursor is guided by diverse mechanisms, including interactions among lineage-specific transcription factors (TFs) and epigenetic changes, such as DNA methylation and hydroxymethylation, which play crucial roles in mammalian development and lineage commitment. To elucidate the transcriptional networks and epigenetic mechanisms underlying T-cell lineage commitment, we investigated genome-wide changes in gene expression, DNA methylation and hydroxymethylation among populations representing five successive stages of T-cell development (DN3, DN4, DP, CD4+, and CD8+) by performing RNA-seq, MBD-seq and hMeDIP-seq, respectively. The most significant changes in the transcriptomes and epigenomes occurred during the DN4 to DP transition. During the DP stage, many genes involved in chromatin modification were up-regulated and exhibited dramatic changes in DNA hydroxymethylation. We also observed 436 alternative splicing events, and approximately 57% (252) of these events occurred during the DP stage. Many stage-specific, differentially methylated regions were observed near the stage-specific, differentially expressed genes. The dynamic changes in DNA methylation and hydroxymethylation were associated with the recruitment of stage-specific TFs. We elucidated interactive networks comprising TFs, chromatin modifiers, and DNA methylation and hope that this study provides a framework for the understanding of the molecular networks underlying T-cell lineage commitment. [ABSTRACT FROM AUTHOR]

Recently, the international audience is interested in finding cases of denuclearization in the past to draw out lessons that can be applied to North Korea. In order to find the optimal reference point, it is crucial to carefully examine the background of North Korea's decision to begin denuclearization talks. Thus, this paper will begin by discussing the overall context of the talks and highlight core issues that may occur during the process of denuclearization. Next, it will examine which case is most relevant to the negotiations with North Korea, and will analyze key implications of Iran's nuclear deal, which is the most recent and similar to the case of North Korea. And by focusing on the core issues identified, it will suggest policy considerations for preparing strategies to continue negotiations with North Korea. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to compare dosimetric characteristics of three-dimensional conformal radiotherapy (3D-CRT) and two types of intensity-modulated radiotherapy (IMRT) which are step-and-shoot intensity modulated radiotherapy (s-IMRT) and modulated arc therapy (mARC) for thoracic esophageal cancer and analyze whether IMRT could reduce organ-at-risk (OAR) dose. Materials and Methods: We performed 3D-CRT, s-IMRT, and mARC planning for ten patients with thoracic esophageal cancer. The dose-volume histogram for each plan was extracted and the mean dose and clinically significant parameters were analyzed. Results: Analysis of target coverage showed that the conformity index (CI) and conformation number (CN) in mARC were superior to the other two plans (CI, p = 0.050; CN, p = 0.042). For the comparison of OAR, lung V5 was lowest in s-IMRT, followed by 3D-CRT, and mARC (p = 0.033). s-IMRT and mARC had lower values than 3D-CRT for heart V30 (p = 0.039), V40 (p = 0.040), and V50 (p = 0.032). Conclusion: Effective conservation of the lung and heart in thoracic esophageal cancer could be expected when using s-IMRT. The mARC was lower in lung V10, V20, and V30 than in 3D-CRT, but could not be proven superior in lung V5. In conclusion, low-dose exposure to the lung and heart were expected to be lower in s-IMRT, reducing complications such as radiation pneumonitis or heart-related toxicities. [ABSTRACT FROM AUTHOR]

This paper aims to show trading patterns of certain items highly likely to be used to develop nuclear and missile programs in North Korea. It analyzed North Korea's trade of nuclear--and missile--related items for ten years from 2006 to 2015 to identify items in large volume as well as in increased demand and key suppliers that contribute to sanctions--busting. This paper found that UN sanctions against North Korea were not effective in controlling the flow of strategic items to North Korea. Rather, a small number of states are responsible for a large share of trade with North Korea that has continued to seek alternative suppliers. It also found that China is a single supplier for multiple items and plays a major role along with several others that either specialize in exports of specific items or gradually expand the scope of supplies. Because the presence of a third country that provides North Korea's resilience and diversion of sanctions is crucial, this paper recommends policy suggestions to enhance effectiveness of the existing sanctions regime. [ABSTRACT FROM AUTHOR]

The article focuses on Onychocryptosis, also known as an ingrown toenail or unguis incarnatus, which is a common form of nail disease in the pediatric population. Topics discussed include the pathology of the disease which occurs when the lateral nail groove no longer facilitates unopposed distal growth of the toenail; medical management of the disease including serial treatments of soaking the foot in warm, soapy water, followed by application of antibiotic ointment until symptoms resolve.

GSK5182 (4) is currently one of the lead compounds for the development of estrogen-related receptor gamma (ERRγ) inverse agonists. Here, we report the design, synthesis, pharmacological and in vitro absorption, distribution, metabolism, excretion, toxicity (ADMET) properties of a series of compounds related to 4. Starting from 4, a series of analogs were structurally modified and their ERRγ inverse agonist activity was measured. A key pharmacophore feature of this novel class of ligands is the introduction of a heterocyclic group for A-ring substitution in the core scaffold. Among the tested compounds, several of them are potent ERRγ inverse agonists as determined by binding and functional assays. The most promising compound, 15g, had excellent binding selectivity over related subtypes (IC50 = 0.44, >10, >10, and 10 μM at the ERRγ, ERRα, ERRβ, and ERα subtypes, respectively). Compound 15g also resulted in 95% transcriptional repression at a concentration of 10 μM, while still maintaining an acceptable in vitro ADMET profile. This novel class of ERRγ inverse agonists shows promise in the development of drugs targeting ERRγ-related diseases. [ABSTRACT FROM AUTHOR]

Hair loss is a major dermatological disease in veterinary and human medicine. Active studies on hair regeneration with mesenchymal stem cells have been performed in an effort to solve the limitations of conservative treatments in human medicine. Our understanding of the canine hair follicle (HF), considering a useful model for the study of the human alopecia, is limited. This study was designed to broaden our understanding of canine dermal papilla (DP), and to reconstruct dermal papilla-like tissue (DPLT) using canine adipose-derived mesenchymal stem cells (AD-MSCs), as an alternative to actual DP. We cultured canine DPs, observed their culture patterns and compared their expression level of DP-related genes and proteins with those of DPLTs by performing RT-PCR analysis and Western blotting. Canine dermal papilla cells (DPCs) showed multilayer culture patterns with pseudo-papillae. Reconstruction of DPLTs was performed successfully. Not only were they morphologically similar to actual DPs, but we also observed similarities between DPCs and DPLTs in molecular characteristics. These findings suggested that DPLT was a viable substitute for DP. This study will not only be helpful for understanding the morphological and molecular characteristics of canine DPCs, but may also serve as a basis for understanding human hair follicle biology and potential therapeutic strategies for alopecia. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell carcinoma (HNSCC) is the 11th leading cancer by incidence worldwide. Surgery and radiotherapy have been the major treatment for patients with HNSCC while chemotherapy has become an important treatment option for locally advanced HNSCC. Understanding of the molecular mechanisms underlying HNSCC impelled the development of targeted therapeutic agents. The development and combinations of targeted therapies in different cellular pathways may be needed to fulfill the unmet needs of current HNSCC chemotherapy. Results: A series of N3-acyl-N5-aryl-3,5-diaminoindazoles were synthesized and their anti-proliferative activities were evaluated against human cancer cell lines, Caki, A549, AMC-HN1, AMC-HN3, AMC-HN4, AMC-HN6, and SNU449. The cellular selectivity of compound was obtained by the modification of substituent at N5-aryl group of 3,5-diaminoindazole. Compound 9a and 9b showed more than 7-fold selectivity for AMC-HN4 and AMC-HN3, respectively. Conclusions: N3-acyl-N5-aryl-3,5-diaminoindazole analogues can be used as hits in the development of anticancer drug for HNSCC. [ABSTRACT FROM AUTHOR]

This study explores answers to such questions as "Why has North Korea been so immune to regime change?" and "What are the leading causes of North Korea's regime fragility?" It acknowledges that indicators of macroeconomic performance, although they are primary indicators of a successful state, are neither available nor reliable for the study of North Korea's regime stability. Therefore, this study tries to specify factors affecting the leadership rather than looking at a broad matrix of indicators. This study assumes that it becomes increasingly important for the North Korean leadership to provide privileged benefits to rent-seeking elites for the regime maintenance and hence tries to analyze variables related to change of identity and interests of the North Korean power elites. First, it identifies key variables of North Korea's stability by reclassifying indicators from the indicator clusters examined in the previous studies. Next, it analyzes factors directly related to the leader-follower relationship in North Korea such as ruling ideology, elite composition, rent-seeking behaviors and opportunity cost of choosing alternative options. Findings of this study reveal many paradoxes in North Korea and suggest that North Korean elites' support for the Kim Jong Un regime depends on the young new leader's ability to retain the mechanism of providing benefits to the elites and increasing the opportunity cost of elites' defection. [ABSTRACT FROM AUTHOR]

The article cites a research study that examines the efficacy of Rubus coreanus Miquel (RCM) in inhibiting the growth of prostate cancer cells differing in androgen dependency. Cell viability is more effectively reduced by ethanol extracts of unripe RCM (EUR) than water extracts or ripe RCM. It was found that in the androgen-dependent LNCaP cells, EUR-induced growth inhibition was greater.

The bromodomain protein Brd4 plays critical roles in cellular proliferation and cell cycle progression. In this study, we investigated the involvement of Brd4 in cell cycle regulation and observed aberrant chromosome segregation and failures in cytokinesis in cancer cells as well as in primary keratinocytes in which Brd4 has been knocked down by RNA interference. Suppression of Brd4 protein levels in proliferating cells decreased Aurora B protein and transcript levels and abolished its chromosomal distribution. In contrast, exogenous Brd4 expression stimulated Aurora B promoter reporter activity and upregulated endogenous Aurora B expression. Aurora B kinase is a chromosomal passenger protein that is essential for chromosome segregation and cytokinesis. Either overexpression of Aurora B or its inactivation can induce defects in centrosome function, spindle assembly, chromosome alignment, and cytokinesis in various cancer cells. The impaired regulation of Aurora B expression in human cells by Brd4 knockdown or overexpression coincided with mitotic catastrophe and multinucleation that are typically observed when Aurora B is inactivated or overexpressed. Overall, our data suggest that Brd4 is essential for the maintenance of the cell cycle progression mediated at least in part through the control of transcription of the Aurora B kinase cell cycle regulatory gene. [ABSTRACT FROM AUTHOR]

In the past decade, several functional extensions of optical coherence tomography (OCT) have emerged, and this review highlights key advances in instrumentation, theoretical analysis, signal processing and clinical application of these extensions. We review five principal extensions: Doppler OCT (DOCT), polarization-sensitive OCT (PS-OCT), optical coherence elastography (OCE), spectroscopic OCT (SOCT), and molecular imaging OCT. The former three have been further developed with studies in both ex vivo and in vivo human tissues. This review emphasizes the newer techniques of SOCT and molecular imaging OCT, which show excellent potential for clinical application but have yet to be well reviewed in the literature. SOCT elucidates tissue characteristics, such as oxygenation and carcinogenesis, by detecting wavelength-dependent absorption and scattering of light in tissues. While SOCT measures endogenous biochemical distributions, molecular imaging OCT detects exogenous molecular contrast agents. These newer advances in functional OCT broaden the potential clinical application of OCT by providing novel ways to understand tissue activity that cannot be accomplished by other current imaging methodologies. [ABSTRACT FROM AUTHOR]