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Whether EGFR mutation occurs in lung squamous cell carcinoma (SCC) remains a controversial issue. Although numerous trials have shown positive response to tyrosine kinase inhibitors in SCC, these observations have not been well correlated with presence or absence of EGFR mutation. A complicating issue is that adenosquamous carcinoma, a mimic of SCC, frequently harbours EGFR mutations. We evaluated the EGFR mutation status of 191 cases initially diagnosed as SCC of lung origin in years 2000-2011, and performed a panel of markers including p40, p63, CK5/6, TTF-1, mucicarmine on the tissue microarray or tissue blocks from each case, to ascertain the squamous differentiation of each case. Four cases were found to have EGFR mutations, with three showing typical squamous morphological features and immunohistochemical profile on all available tumour blocks, and one reclassified as adenosquamous carcinoma. Mixed responses were noted for two of the patients with EGFR-mutated SCC treated with tyrosine kinase inhibitors. In conclusion, we report that a small subset of rigorously proven SCC harbours EGFR mutation. It also appears in our cohort that EGFR-mutated tumours, in the context of SCC, may have relatively poor response to tyrosine kinase inhibitors.

Serrated polyps are a clinically and molecularly heterogeneous group of lesions that can contribute to the development of colorectal cancers (CRCs). However, the molecular mechanism underlying the development of serrated lesions is still not well understood. Here, we combined multiple approaches to analyze the genetic alterations in 86 colorectal adenomas (including 35 sessile serrated lesions, 15 traditional adenomas, and 36 conventional adenomatous polyps). We also investigated the in vitro and in vivo oncogenic properties of a novel variant of the NCOA4-RET fusion gene. Molecular profiling revealed that sessile serrated lesions and traditional serrated adenomas have distinct clinicopathological and molecular features. Moreover, we identified receptor tyrosine kinase translocations exclusively in sessile serrated lesions (17%), and the observation was validated in a separate cohort of 34 sessile serrated lesions (15%). The kinase fusions as well as the BRAF and KRAS mutations were mutually exclusive to each other. Ectopic expression of a novel variant of the NCOA4-RET fusion gene promoted cell proliferation in vitro and in vivo, and the proliferation was significantly suppressed by RET kinase inhibitors. All of these underscored the importance of mitogen-activated protein kinase (MAPK) pathway activation in the serrated pathway of colorectal tumorigenesis. In addition, we demonstrated that the kinase fusion may occur early in the precursor lesion and subsequent loss of TP53 may drives the transformation to carcinoma during serrated tumorigenesis. In conclusion, we identified kinase fusions as a significant alternative driver of the serrated pathway in colorectal cancer development, and detecting their presence may serve as a biomarker for the diagnosis of sessile serrated lesions. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Today, Global Positioning System (GPS) is widely used in almost every aspect of our daily life. Commonly, users utilize the technology to track the position of a vehicle or an object of interest. They also use it to safely navigate to the destination of their choice. As a result, there are countless number of GPS based tracking application that has been developed. But, a main recurring issue that exists among these applications are the inaccuracy of the tracking faced by users and this issue has become a rising concern. Most existing research have examined the effects that the inaccuracy of GPS have on users while others identified suitable methods to improve the accuracy of GPS based on one or two factors. The objective of this survey paper is to identify the common factors that affects the accuracy of GPS and identify an effective method which could mitigate or overcome most of those factors. As part of our research, we conducted a thorough examination of the existing factors for GPS inaccuracies. According to an initial survey that we have collected, most of the respondents has faced some form of GPS inaccuracy. Among the common issues faced are inaccurate object tracking and disconnection of GPS signal while using an application. As such, most of the respondents agree that it is necessary to improve the accuracy of GPS. This leads to another objective of this paper, which is to examine and evaluate existing methods as well as to identify the most effective method that could improve the accuracy of GPS.

This study was designed to discuss the application of job shop scheduling with greedy technique to investigate the total time delayed for completing the dental treatment in the dental clinic. The aim of this study is to identify the total number of patients delayed for completing the dental treatment as scheduled per day. Besides, this study also aims to examine the solution obtained from each greedy technique. There are three greedy techniques have been employed which are the earliest due date, shortest processing time and longest processing time. The result of the investigation indicated that the techniques of the earliest due date and shortest processing time provide optimal solution with no delays. It is shows that the solution from this study can be used as a guideline of patient scheduling in any related application.Keywords: appointment, job shop scheduling, dental clinic, number of patients delayed, total time delayed

Colorectal cancer (CRC) is a heterogeneous disease with complex mechanisms of pathogenesis. Classification systems have been proposed based on molecular features of tumors in clinical practice. Thus, more molecular markers associated with development and progression of CRC might serve as useful tools for early diagnosis even for providing more accurate molecular classification. Frequent gain of chromosome 8q was detected in CRC by array-CGH and overexpression of exosome component 4 (EXOSC4) in this region was revealed by expression microarray analysis. Through qRT-PCR and immunohistochemistry (IHC) analysis, EXOSC4 showed increased expression in CRC cell lines and clinical specimens. Higher expression of EXOSC4 was more often detected in left side, and correlated with BRAF wild type, MSI-low or MSS, CIMP-low, and MLH1-no-silence CRC patients. Functionally, EXOSC4 overexpression increased early tumorigenic capacity by promoting cell proliferation and monolayer colony formation, enhancing cell invasion and migration study and accelerating xenograft formation in nude mice. While EXOSC4 knockdown exhibited anti-oncogenic role such as inhibiting cell proliferation and invasion. EXOSC4 inhibition also resulted in G1 phase cell cycle arrest. For the downstream signaling analysis, EXOSC4 was found to be involved in multiple signaling pathways such as cell cycle, p53 pathway and Wnt pathway. In summary, our findings demonstrated the oncogenic role of EXOSC4 in development and progression of CRC. Deep understanding of EXOSC4 as a potential diagnostic molecular biomarker will provide clinical translational potential for intervention therapy.

Background Multiple international agencies, including the World Health Organization and the International Monetary Fund, have emphasized the importance of maternal mental health for optimal child health and development. Adequate social support is vital for the most vulnerable to postpartum mood disorders. Hence, an urgent need for sustainable social support programs to aid mothers ease into their new parenting role exists. Objective This study protocol aims to examine the effectiveness of a technology-based peer support intervention program among mothers at risk for postnatal depression in the early postpartum period. Methods A randomized controlled 2-group pretest and repeated posttest experimental design will be used. The study will recruit 118 mothers from the postnatal wards of a tertiary public hospital in Singapore. Eligible mothers will be randomly allocated to receive either the peer support intervention program or routine perinatal care from the hospital. Peer volunteers will be mothers who have experienced self-reported depression and will be receiving face-to-face training to support new mothers at risk of depression. Outcome measures include postnatal depression, anxiety, loneliness, and social support. Data will be collected at immediate postnatal period (day of discharge from the hospital), at fourth week and twelfth week post childbirth. Results The recruitment and training of peer support volunteers (N=20) ended in June 2017, whereas recruitment of study participants commenced in July 2017 and is still ongoing. The current recruitment for new mothers stands at 73, with 36 in the control group and 37 in the intervention group. Data collection is projected to be completed by May 2018. Conclusions This study will identify a potentially effective and clinically useful method to prevent postnatal depression in new mothers, which is the top cause of maternal morbidity. Receiving social support from others who share similar experiences may enhance the positive parenting experiences of mothers, which in turn can improve the psychosocial well-being of the mothers, tighten mother-child bond, and enhance overall family dynamics for mothers and infants. Trial Registration International Standard Randomized Controlled Trial Number ISRCTN14864807; http://www.isrctn.com/ISRCTN14864807 (Archived by WebCite at http://www.webcitation.org/6xtBNvBTX)