This study aimed to identify the candidate miRNAs in the carcinogenesis of endometrial carcinoma, and to explore whether FFPE material would be suitable for miRNA profiling. We identified the ...differences between miRNA expression profiles using human miRNA microarray in endometrioid endometrial adenocarcinomas (EECs) and normal endometria. Of those tested, miR-200a*, miR-200b*, miR-141, miR-182, and miR-205 were greatly enriched. The expressions of these five miRNAs were validated using quantitative real-time reverse transcription-PCR (qRT-PCR). We then performed qRT-PCR miR expression profiling in 30 FFPE specimens (20 EECs, 10 normal endometria) and re-confirmed the results of differential expression between cancer and normal tissue. Following this, we tested whether the specific inhibition of overexpressed miRNAs would alter chemosensitivity. In the in vitro cell viability assay, anti-miR200b* showed a trend toward enhanced cytotoxicity slightly in cisplatin compared to the negative control (p = 0.07). This information provided the candidate miRNAs for further confirmation of the role of miRNAs in the carcinogenesis of EECs, potentially serving as a diagnostic or therapeutic tool. FFPE specimens of endometrial tissues are suitable as a source for miRNA microarray profiling.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by ...massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT, AKT1, PIK3CA, and EIF1AX were frequently co-mutated with driver genes (BRAF
and RAS) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A) were predominantly altered in ATC. CDKN2A loss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation of CD274 (PD-L1) and PDCD1LG2 (PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target in RAS-positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.
•Measles-specific antibodies wane in the absence of boosting by the wild-type virus.•The number of potential measles-susceptible individuals progressively accumulates.•Vaccine-induced immunity is ...less effective than naturally acquired immunity.
In Korea, measles occurs mainly in infants <12months of age, who are unvaccinated. In addition, vaccine populations, including adolescents and young adults, can become infected though importation. Thus, the question arises whether the current level of herd immunity in Korea is now insufficient for protecting against measles infection.
Age-specific measles seroprevalence was evaluated by performing enzyme immunoassays and plaque reduction-neutralization tests on 3050 subjects aged 0–50years (birth cohort 1964–2014) and 480 subjects aged 2–30years (birth cohort 1984–2012).
The overall seropositivity and measles antibody concentrations were 71.5% and 1366mIU/mL, respectively. Progressive decline in antibody levels and seropositivity were observed over time after vaccination in infants, adolescents, and young adults. The accumulation of potentially susceptible individuals in the population was confirmed by comparing data from 2010 and 2014 seroprevalence surveys. The statistical correlation between measles incidence and measles seronegativity was determined.
Waning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea. This trend may be related to limitations of vaccine-induced immunity in the absence of natural boosting by the wild virus, compared to naturally acquired immunity triggered by measles infection. This study provides an important view into the current measles herd immunity in Korea.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Qualitative researchers face unique opportunities and challenges as a result of the disruption of COVID-19. Although the pandemic represents a unique opportunity to study the crisis itself, social ...distancing mandates are restricting traditional face-to-face investigations of all kinds. In this article, we describe options and resources for researchers who find themselves needing to alter their study designs from face-to-face qualitative data collection to a “socially distant” method. Although technologies are constantly changing, we review the latest videoconferencing services available to researchers and provide guidance on what services might best suit a project’s needs. We describe options for various platforms and applications including information about enhanced security applications for researchers collecting sensitive patient health information. Concerns about these technologies including security of the platform and logistical needs such as computer equipment are also discussed. Special attention is given to ethical issues when transitioning research efforts to online venues.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This paper provides a modern overview of corporate governance in China and in doing so highlights many corporate governance features and issues that are, for the most part, unique to China. We also ...describe how papers in this special issue advance our understanding of corporate governance in China and in general.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
It remains controversial whether targeting tumour vasculature can improve radiotherapeutic efficacy. We report that radiation-induced endothelial-to-mesenchymal transition (EndMT) leads to tumour ...vasculature with abnormal SMA
NG2
pericyte recruitment during tumour regrowth after radiotherapy. Trp53 (but not Tgfbr2) deletion in endothelial cells (ECs) inhibited radiation-induced EndMT, reducing tumour regrowth and metastases with a high CD44v6
cancer-stem-cell (CSC) content after radiotherapy. Osteopontin, an EndMT-related angiocrine factor suppressed by EC-Trp53 deletion, stimulated proliferation in dormant CD44v6
cells in severely hypoxic regions after radiation. Radiation-induced EndMT significantly regulated tumour-associated macrophage (TAM) polarization. CXCR4 upregulation in radioresistant tumour ECs was highly associated with SDF-1
TAM recruitment and M2 polarization of TAMs, which was suppressed by Trp53 deletion. These EndMT-related phenomena were also observed in irradiated human lung cancer tissues. Our findings suggest that targeting tumour EndMT might enhance radiotherapy efficacy by inhibiting the re-activation of dormant hypoxic CSCs and promoting anti-tumour immune responses.
Niche-based distribution models are often used to predict the spread of invasive species. These models assume niche conservation during invasion, but invasive species can have different requirements ...from populations in their native range for many reasons, including niche evolution. I used distribution modelling to investigate niche conservatism for the Asian tiger mosquito (Aedes albopictus Skuse) during its invasion of three continents. I also used this approach to predict areas at risk of invasion from propagules originating from invasive populations. Models were created for Southeast Asia, North and South America, and Europe. I used maximum entropy (M axent) to create distribution models using occurrence data and 18 environmental datasets. One native model was created for Southeast Asia; this model was projected onto North America, South America and Europe. Three models were created independently for the non-native ranges and projected onto the native range. Niche overlap between native and non-native predictions was evaluated by comparing probability surfaces between models using real data and random models generated using a permutation approach. The native model failed to predict an entire region of occurrences in South America, approximately 20% of occurrences in North America and nearly all Italian occurrences of A. albopictus. Non-native models poorly predict the native range, but predict additional areas at risk for invasion globally. Niche overlap metrics indicate that non-native distributions are more similar to the native niche than a random prediction, but they are not equivalent. Multivariate analyses support modelled differences in niche characteristics among continents, and reveal important variables explaining these differences. The niche of A. albopictus has shifted on invaded continents relative to its native range (Southeast Asia). Statistical comparisons reveal that the niche for introduced distributions is not equivalent to the native niche. Furthermore, reciprocal models highlight the importance of controlling bi-directional dispersal between native and non-native distributions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Aims
Canagliflozin is a sodium glucose co‐transporter 2 inhibitor in development for type 2 diabetes mellitus (T2DM). The efficacy and safety of canagliflozin were evaluated in subjects with T2DM ...inadequately controlled with diet and exercise.
Methods
In this 26‐week, randomized, double‐blind, placebo‐controlled, phase 3 trial, subjects (N = 584) received canagliflozin 100 or 300 mg or placebo once daily. Primary endpoint was the change from baseline in haemoglobin A1c (HbA1c) at week 26. Secondary endpoints included the proportion of subjects achieving HbA1c < 7.0%; change from baseline in fasting plasma glucose (FPG), 2‐h postprandial glucose (PPG) and systolic blood pressure (BP); and percent change in body weight, high‐density lipoprotein cholesterol (HDL‐C) and triglycerides. Adverse events (AEs) were recorded throughout the study.
Results
At week 26, HbA1c was significantly reduced from baseline with canagliflozin 100 and 300 mg compared with placebo (−0.77, −1.03 and 0.14%, respectively; p < 0.001 for both). Both canagliflozin doses significantly decreased FPG, 2‐h PPG, body weight and systolic BP (p < 0.001 for all), and increased HDL‐C compared with placebo (p < 0.01 for both). Overall incidences of AEs were modestly higher with canagliflozin versus placebo; rates of serious AEs and AE‐related discontinuations were low and similar across groups. Incidences of genital mycotic infections, urinary tract infections and osmotic diuresis‐related AEs were higher with canagliflozin; these led to few discontinuations. The incidence of hypoglycaemia was low across groups.
Conclusion
Canagliflozin treatment improved glycaemic control, reduced body weight and was generally well tolerated in subjects with T2DM inadequately controlled with diet and exercise.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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