Cancer predisposition is most often studied in the context of single cancers. However, inherited cancer predispositions can also give rise to multiple primary cancers. Yet, there is a paucity of ...studies on genetic predisposition in multiple primary cancers, especially those outside of well-defined cancer predisposition syndromes. This study aimed to identify germline variants associated with dual primary cancers of the breast and lung.
Exome sequencing was performed on germline DNA from 55 Singapore patients (52 95% never-smokers) with dual primaries in the breast and lung, confirmed by histopathology. Using two large control cohorts: the local SG10K_Health (n = 9770) and gnomAD non-cancer East Asians (n = 9626); and two additional local case cohorts of early-onset or familial breast cancer (n = 290), and lung cancer (n = 209), variants were assessed for pathogenicity in accordance with ACMG/AMP guidelines. In particular, comparisons were made with known pathogenic or likely pathogenic variants in the ClinVar database, pathogenicity predictions were obtained from in silico prediction software, and case-control association analyses were performed.
Altogether, we identified 19 pathogenic or likely pathogenic variants from 16 genes, detected in 17 of 55 (31%) patients. Six of the 19 variants were identified using ClinVar, while 13 variants were classified pathogenic or likely pathogenic using ACMG/AMP guidelines. The 16 genes include well-known cancer predisposition genes such as BRCA2, TP53, and RAD51D; but also lesser known cancer genes EXT2, WWOX, GATA2, and GPC3. Most of these genes are involved in DNA damage repair, reaffirming the role of impaired DNA repair mechanisms in the development of multiple malignancies. These variants warrant further investigations in additional populations.
We have identified both known and novel variants significantly enriched in patients with primary breast and lung malignancies, expanding the body of known cancer predisposition variants for both breast and lung cancer. These variants are mostly from genes involved in DNA repair, affirming the role of impaired DNA repair in the predisposition and development of multiple cancers.
Nowadays, digital technology has been increasingly ubiquitous, particularly in teaching pedagogy. Digital
technology-based teaching has the potential to significantly increase the students’ learning ...outcomes as
well as their critical thinking and problem-solving skills. As a result, the Ministry of Education has initiated,
supported, and promoted the incorporation of information and communications technology
(ICT) into educational policy, as well as infusing classrooms with digital learning tools and resources. The
Ministry of Education believes that implementing ICT into teaching and learning processes could assist
and improve educational standards. However, due to some barriers, ICT integration in teaching has not
yet been effectively adopted in Malaysia’s secondary schools. The aim of this study was to analyze and
rank the factors that impede the implementation of ICT in urban and rural secondary schools using the
analytic hierarchy process (AHP) approach. A t-test analysis is also carried out to determine the significant
difference between factors from both urban and rural areas. The finding shows that there is no
significant difference between factors from areas. The new mean values have been computed for each
factor in order to determine the new ranking for each factor. The workload, lack of accessibility and
network connection, and lack of support assistance are the top three factors that impede the ICT adoption
in secondary schools in Kedah according to the new mean values obtained. In contrast, a lack of
confidence has the least impact factor in this issue, accounting for only 3.5% of the total.
Abstract
Background
Acute ischemic stroke is a time-sensitive emergency where accurate diagnosis is required promptly. Due to time pressures, stroke mimics who present with similar signs and symptoms ...as acute ischemic stroke, pose a diagnostic challenge to the emergency physician. With limited access to investigative tools, clinical prediction, tools based only on clinical features, may be useful to identify stroke mimics. We aim to externally validate the performance of 4 stroke mimic prediction scales, and derive a novel decision tree, to improve identification of stroke mimics.
Methods
We performed a retrospective cross-sectional study at a primary stroke centre, served by a telestroke hub. We included consecutive patients who were administered intravenous thrombolysis for suspected acute ischemic stroke from January 2015 to October 2017. Four stroke mimic prediction tools (FABS, simplified FABS, Telestroke Mimic Score and Khan Score) were rated simultaneously, using only clinical information prior to administration of thrombolysis. The final diagnosis was ascertained by an independent stroke neurologist. Area under receiver operating curve (AUROC) analysis was performed. A classification tree analysis was also conducted using variables which were found to be significant in the univariate analysis.
Results
Telestroke Mimic Score had the highest discrimination for stroke mimics among the 4 scores tested (AUROC = 0.75, 95% CI = 0.63–0.87). However, all 4 scores performed similarly (DeLong
p
> 0.05). Telestroke Mimic Score had the highest sensitivity (91.3%), while Khan score had the highest specificity (88.2%). All 4 scores had high positive predictive value (88.1 to 97.5%) and low negative predictive values (4.7 to 32.3%). A novel decision tree, using only age, presence of migraine and psychiatric history, had a higher prediction performance (AUROC = 0.80).
Conclusion
Four tested stroke mimic prediction scales performed similarly to identify stroke mimics in the emergency setting. A novel decision tree may improve the identification of stroke mimics.
Different designs of the plant tissue culture vessel, such as size, material, and shape, may alter its microenvironment atmosphere. The present study was conducted on protocorm-like bodies (PLBs) of
...Sabin Blue orchid to determine the development of PLBs on plastic and glass culture vessels of different sizes. PLBs were cultured in half-strength Murashige and Skoog (MS) medium with the same initial weight of 0.5 g in 10 replicates. The growth index of the PLBs was calculated after 11 weeks to study their growth in every vessel; additionally, biochemical analysis was performed to determine carbohydrate content, proline concentration, and photosynthesis pigments in the PLBs. Scanning electron microscopy (SEM) was performed to study stomata development on PLBs in each vessel, and histological analyses were conducted to study the cell structure. Overall, the PLBs cultured in a large 470 ml plastic vessel showed successful growth with a high growth index, high carbohydrate content, low-stress condition, and high chlorophyll content. SEM confirmed that the presence of trichome and rhizoid in PLBs cultured in the 470 ml plastic vessel. Histological analysis showed the formation of the shoot on the PLBs and the presence of starch granules. Thus, the use of plastic as a culture vessel provides a good impact for culturing PLBs and has low cost.
Despite advances in therapeutics, outcomes for hepatocellular carcinoma (HCC) remain poor and there is an urgent need for efficacious systemic therapy. Unfortunately, drugs that are successful in ...preclinical studies often fail in the clinical setting, and we hypothesize that this is due to functional differences between primary tumors and commonly used preclinical models. In this study, we attempt to answer this question by comparing tumor morphology and gene expression profiles between primary tumors, xenografts and HCC cell lines.
Hep G2 cell lines and tumor cells from patient tumor explants were subcutaneously (ectopically) injected into the flank and orthotopically into liver parenchyma of Mus Musculus SCID mice. The mice were euthanized after two weeks. RNA was extracted from the tumors, and gene expression profiling was performed using the Gene Chip Human Genome U133 Plus 2.0. Principal component analyses (PCA) and construction of dendrograms were conducted using Partek genomics suite.
PCA showed that the commonly used HepG2 cell line model and its xenograft counterparts were vastly different from all fresh primary tumors. Expression profiles of primary tumors were also significantly divergent from their counterpart patient-derived xenograft (PDX) models, regardless of the site of implantation. Xenografts from the same primary tumors were more likely to cluster together regardless of site of implantation, although heat maps showed distinct differences in gene expression profiles between orthotopic and ectopic models.
The data presented here challenges the utility of routinely used preclinical models. Models using HepG2 were vastly different from primary tumors and PDXs, suggesting that this is not clinically representative. Surprisingly, site of implantation (orthotopic versus ectopic) resulted in limited impact on gene expression profiles, and in both scenarios xenografts differed significantly from the original primary tumors, challenging the long-held notion that orthotopic PDX model is the gold standard preclinical model for HCC.
This paper analysed the effect of the design thinking approach on the student’s awareness of marine and coastal environmental sustainability. The paper employed an experimental design and utilised a ...sample of 35 students using an online questionnaire through a Google form validated by experts in educational research. Based on the analysis of their responses, the findings revealed that the respondents are fully aware of the harmful effects of marine and coastal pollution on human lives. It is imperative to prevent the proliferation of plastic products in the environment, even if it means sacrificing something to slow down marine and coastal pollution. Also, students agreed that there is a need for awareness that despite the continual contamination of rivers and oceans, nature’s purifying processes soon return to normal when they have good management. The paper concluded that even with the awareness of marine and coastal pollution, there is still a lack of understanding of the holistic consequences of marine plastic and the resulting impact on ecosystem services, as well as the implications for human health, society, and the economy. It is limited to a small sample size, quantitative data and simple statistical tools of frequency and percentages and recommended that an approach such as design thinking focusing on marine and coastal pollution could be used in schools and the government needs to introduce harsh measures to halt marine and coastal pollution since very few people will regulate themselves.
Access to capital is a critical factor in stimulating small business creation and growth especially in developing companies. The failure of small business entities in securing the needed capital ...would entail them remaining small and limit their ability to create goods, services, and innovations in the marketplace, including jobs. This study focuses on manufacturing SMEs by examining the influence of managerial characteristics (age, gender, work experience and level of education) on capital structure towards technology improvement. Based on a survey of 219 respondents, the results indicated that male managers, managers with a lot of work experience and educated managers preferred internal and external financing. Furthermore, internal and external financing also showed positive relationships to improve manufacturing technology performance. This study provides and adds new knowledge to corporate managers to serve as benchmarks in making decisions on company performance. It could also enhance company ability to deal with competitive environments.
Small and medium enterprises (SMEs) is a important contribution to boost the economies overall the world. In fact, SMEs always struggle to access the financing compared list company. There are ...several factors influence the capital structure decision in SMEs. This study focuses on manufacturing SMEs companies and examines the influence of firm characteristics (firm size, tangible asset, liquidity, profitability and firm growth) on capital structure towards technology improvement. The results showed only liquidity and firm growth were found to be positive significantly affect the external financing. Furthermore, internal and external financing also able improve the manufacturing’s technology performance. Conclusion, different firm characteristics have different leverage privileges which trying to attain optimal capital structure. The variations in the capital structures affect the costs of equity or debt and cost of capital. This study provides benchmarks for corporate managers in SMEs when making a company’s decision on the company’s performance.
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