Predictive biomarkers for 5-fluorouracil and oxaliplatin-based chemotherapy in gastric cancers via profiling of patient-derived xenografts.

Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies

An integrative approach for exploring the nature of fibroepithelial neoplasms.

BACKGROUND: Malignant phyllodes tumour (MPT) is a rare breast malignancy with epithelial and mesenchymal features. Currently, there are no appropriate research models or effective targeted therapeutic approaches for MPT. METHODS: We collected fresh frozen tissues from nine patients with MPT and performed whole-exome and RNA sequencing. Additionally, we established patient-derived xenograft (PDX) models from patients with MPT and tested the efficacy of targeting dysregulated pathways in MPT using the PDX model from one MPT. RESULTS: MPT has unique molecular characteristics when compared to breast cancers of epithelial origin and can be classified into two groups. The PDX model derived from one patient with MPT showed that the mouse epithelial component increased during tumour growth. Moreover, targeted inhibition of platelet-derived growth factor receptor (PDGFR) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) by imatinib mesylate and PKI-587 showed in vivo tumour suppression effects. CONCLUSIONS: This study revealed the molecular profiles of MPT that can lead to molecular classification and potential targeted therapy, and suggested that the MPT PDX model can be a useful tool for studying the pathogenesis of fibroepithelial neoplasms and for preclinical drug screening to find new therapeutic strategies for MPT

Opposing Regulation of PROX1 by Interleukin-3 Receptor and NOTCH Directs Differential Host Cell Fate Reprogramming by Kaposi Sarcoma Herpes Virus

Lymphatic endothelial cells (LECs) are differentiated from blood vascular endothelial cells (BECs) during embryogenesis and this physiological cell fate specification is controlled by PROX1, the master regulator for lymphatic development. When Kaposi sarcoma herpes virus (KSHV) infects host cells, it activates the otherwise silenced embryonic endothelial differentiation program and reprograms their cell fates. Interestingly, previous studies demonstrated that KSHV drives BECs to acquire a partial lymphatic phenotype by upregulating PROX1 (forward reprogramming), but stimulates LECs to regain some BEC-signature genes by downregulating PROX1 (reverse reprogramming). Despite the significance of this KSHV-induced bidirectional cell fate reprogramming in KS pathogenesis, its underlying molecular mechanism remains undefined. Here, we report that IL3 receptor alpha (IL3Rα) and NOTCH play integral roles in the host cell type-specific regulation of PROX1 by KSHV. In BECs, KSHV upregulates IL3Rα and phosphorylates STAT5, which binds and activates the PROX1 promoter. In LECs, however, PROX1 was rather downregulated by KSHV-induced NOTCH signal via HEY1, which binds and represses the PROX1 promoter. Moreover, PROX1 was found to be required to maintain HEY1 expression in LECs, establishing a reciprocal regulation between PROX1 and HEY1. Upon co-activation of IL3Rα and NOTCH, PROX1 was upregulated in BECs, but downregulated in LECs. Together, our study provides the molecular mechanism underlying the cell type-specific endothelial fate reprogramming by KSHV

BRAND VISUALIZATION OF A COMPANY SELLING SCANDINAVIAN DESIGN

There is a strong Scandinavian design trend in South Korea. Together with the growing economy it makes South Korea a very potential market for Scandinavian design products. However, to be successful in that market, a proper branding is required. The goal of this study was to create a solid branding for a starting company “Aamutulee” selling Scandinavian design in South Korea via an online store. The brand needed to be specifically targeted to South Korean consumers and create a strong positive association with Scandinavia and Scandinavian design. The brand creation was done by first conducting a research survey to study the target market and the local preferences. Then the gained information was used together with the related knowledge of branding throughout the design process of the different elements of the brand. The outcome of the work was a well thought brand platform for the company, and a matching design guide and visual identity including brand mark, logotype and typeface. The survey research was found to be very useful for the work and the gathered information influenced all the parts of the brand. Together the brand platform, design guide and the visual identity form a solid branding for the company and provide a clear track for the future expansions of the brand

An infinite family of Griesmer quasi-cyclic self-orthogonal codes

Our aim for this paper is to find the construction method for quasi-cyclic self-orthogonal codes over the finite field F-pm. We first explicitly determine the generators of alpha-constacyclic codes over the finite Frobenius non-chain ring R-p,R-m = F-pm [u, v]/(u(2) = v(2) = 0, uv = vu), where m is a positive integer, alpha = a + ub + vc + uvd is a unit of R-p,R-m,R- a, b, c, d is an element of F-pm, and a is nonzero. We then find a Gray map from R-p,R-m[x]/(x(n) - alpha) (with respect to homogeneous weights) to F-pm [x]/(x(p3m+1n) - a) (with respect to Hamming weights), which is linear and preserves minimum weights. We present an efficient algorithm for finding the Gray images of alpha-constacyclic codes over R-p,R-m of length n, which produces infinitely many quasi-cyclic self orthogonal codes over F-pm of length p(3m+1) and index p(3m). In particular, some family turns out to be "Griesmer" codes; these Griesmer quasi-cyclic self-orthogonal codes are "new" codes compared with previously known Griesmer codes of dimension 4. (C) 2021 Published by Elsevier Inc

A study of elder abuse in Korea

This study investigates the state of elder abuse in Korea, and its related factors in a population-based survey. A total of 15,230 persons were interviewed at their homes in 1999. The rate of old people who experienced any one category of abuse was 6.3%, and emotional abuse was the most frequent while physical abuse was least prevalent. The experience of abuse seemed to be associated with personal characteristics such as age, gender, educational level, and economic dependency as well as the physical and mental health status. In addition, family characteristics such as the type of household, the family\u27s economic level, and the quality of family relations were found to be associated with the presence of abuse. © 2005 Elsevier Ltd. All rights reserved

Core temperature measurement in therapeutic hypothermia according to different phases: Comparison of bladder, rectal, and tympanic versus pulmonary artery methods

Purpose: Comparisons of bladder, rectal and tympanic temperatures versus pulmonary artery (PA) temperature during different therapeutic hypothermia (TH) phases. Methods: Twenty-one patients admitted to our emergency department (ED) after out-of-hospital cardiac arrests were included in this study. For comparison, the temperature of four different sites, urinary bladder (BL), rectal (RE), tympanic membrane (TM) digital thermometers, and a Swan-Ganz catheter were used during TH, which were controlled by a surface cooling method. TH is divided into three phases: induction, maintenance, and rewarming phase. Results: In the induction phase, the mean differences between PA temperatures and those of the other methods studied were: BL (-0.24 +/- 1.30 degrees C), RE (-0.52 +/- 1.40 degrees C), and TM (1.11 +/- 1.53 degrees C). The mean differences between PA temperatures and those of the other methods in the maintenance phase were BL (0.06 +/- 0.79 degrees C), RE (-0.30 +/- 1.16 degrees C), and TM (1.12 +/- 1.29 degrees C); in the rewarming phase: BL (0.08 +/- 0.86 degrees C), RE (-0.03 +/- 1.71 degrees C), and TM (0.89 +/- 1.62 degrees C); and in the total phase: BL (0.04 +/- 0.90 degrees C), RE (-0.22 +/- 1.44 degrees C), and TM (1.03 +/- 1.47 degrees C). Conclusions: The mean difference between BL and PA temperatures is lower than those in other sites during TH. On the contrary, there are larger differences between TM and PA temperatures when compared to other sites. The differences between RE and PA temperatures are comparatively less than those between TM and PA. However, RE temperature tends to be higher than the temperature recorded by a BL thermometer or Swan-Ganz catheter during the rapid induction phase. Crown Copyright (C) 2013 Published by Elsevier Ireland Ltd. All rights reserved.N

Plant Extracts for Type 2 Diabetes: From Traditional Medicine to Modern Drug Discovery

Type 2 diabetes mellitus (T2DM) is one of the largest public health problems worldwide. Insulin resistance-related metabolic dysfunction and chronic hyperglycemia result in devastating complications and poor prognosis. Even though there are many conventional drugs such as metformin (MET), Thiazolidinediones (TZDs), sulfonylureas (SUF), dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon like peptide 1 (GLP-1) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, side effects still exist. As numerous plant extracts with antidiabetic effects have been widely reported, they have the potential to be a great therapeutic agent for type 2 diabetes with less side effects. In this study, sixty-five recent studies regarding plant extracts that alleviate type 2 diabetes were reviewed. Plant extracts regulated blood glucose through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. The anti-inflammatory and antioxidant properties of plant extracts suppressed c-Jun amino terminal kinase (JNK) and nuclear factor kappa B (NF-κB) pathways, which induce insulin resistance. Lipogenesis and fatty acid oxidation, which are also associated with insulin resistance, are regulated by AMP-activated protein kinase (AMPK) activation. This review focuses on discovering plant extracts that alleviate type 2 diabetes and exploring its therapeutic mechanisms