Financial Reporting, Framing Effects and Successful Investment Decision

The purpose of this study is to determine the relationship of the financial reports and investment decision and framing bias affects the relationship of financial reporting and investment decision. We collected data through 225questionnaires from individual investors of Islamabad stock exchange (ISE). Result shows that financial reporting is significantly positive associated with investment decision and framing bias affects the relationship of financial reporting and successful investment decision. Our study may help the investor to focus on present facts and choices as neutrally and consistently at the time of investment decision and to keep the big picture in mind

Classic virilizing congenital adrenal hyperplasia presenting late: case series from Pakistan

Deficiency of 21 hydroxylase enzyme deficiency (21OH) activity accounts for 90% cases of congenital adrenal hyperplasia (CAH). This results in deficient cortisol, increased ACTH, adrenal hyperplasia and increased adrenal androgen secretion. There is marked virilization in genetic females which is the hallmark of this disorder. Genetic heterogeneity in 21 OHD is well recognized, and both severe and mild forms occur. We present three cases of adult females with the disease from a larger study to establish genotype, phenotype correlation of Pakistani patients with congenital adrenal hyperplasia (CAH) and to highlight issues such as diagnostic delay, inappropriate gender assignment at birth, and high degree of consanguinity among parents, psychosexual outcome of 21 OHD females and the need to develop expertise for early case detection. The analysis was done using Amplification Refractory Mutation System (ARMS) PCR. These cases show that CAH frequently remains undiagnosed during the newborn period in our population due to lack of awareness in the society and lack of proper diagnosis by the primary physician. There is a need to develop expertise for early case detection

FOXM1 Induces a Global Methylation Signature That Mimics the Cancer Epigenome in Head and Neck Squamous Cell Carcinoma

The oncogene FOXM1 has been implicated in all major types of human cancer. We recently showed that aberrant FOXM1 expression causes stem cell compartment expansion resulting in the initiation of hyperplasia. We have previously shown that FOXM1 regulates HELLS, a SNF2/helicase involved in DNA methylation, implicating FOXM1 in epigenetic regulation. Here, we have demonstrated using primary normal human oral keratinocytes (NOK) that upregulation of FOXM1 suppressed the tumour suppressor gene p16INK4A (CDKN2A) through promoter hypermethylation. Knockdown of HELLS using siRNA re-activated the mRNA expression of p16INK4A and concomitant downregulation of two DNA methyltransferases DNMT1 and DNMT3B. The dose-dependent upregulation of endogenous FOXM1 (isoform B) expression during tumour progression across a panel of normal primary NOK strains (n = 8), dysplasias (n = 5) and head and neck squamous cell carcinoma (HNSCC) cell lines (n = 11) correlated positively with endogenous expressions of HELLS, BMI1, DNMT1 and DNMT3B and negatively with p16INK4A and involucrin. Bisulfite modification and methylation-specific promoter analysis using absolute quantitative PCR (MS-qPCR) showed that upregulation of FOXM1 significantly induced p16INK4A promoter hypermethylation (10-fold, P<0.05) in primary NOK cells. Using a non-bias genome-wide promoter methylation microarray profiling method, we revealed that aberrant FOXM1 expression in primary NOK induced a global hypomethylation pattern similar to that found in an HNSCC (SCC15) cell line. Following validation experiments using absolute qPCR, we have identified a set of differentially methylated genes, found to be inversely correlated with in vivo mRNA expression levels of clinical HNSCC tumour biopsy samples. This study provided the first evidence, using primary normal human cells and tumour tissues, that aberrant upregulation of FOXM1 orchestrated a DNA methylation signature that mimics the cancer methylome landscape, from which we have identified a unique FOXM1-induced epigenetic signature which may have clinical translational potentials as biomarkers for early cancer screening, diagnostic and/or therapeutic interventions

Data_Sheet_1_Principals' leadership styles and its impact on teachers' performance at college level.docx

In this study, we examined the impact of principals' leadership style on the performance of teachers at the college level. For this purpose, we collect data from 300 college teachers via a random sampling approach. A self-administrated questionnaire (five-point Likert Scale) was used to collect data. For detecting relationships and differences among the opinions of the study's participants, correlation and the t-test were used. This study has revealed that the majority of college principals practice a democratic style of leadership at a higher level, Laissez-faire at a moderate level, and autocratic at a low level in their colleges. Moreover, it has been also revealed that when principals increase the use of a democratic leadership style, teacher performance may progress as well. The findings revealed that principals' leadership style had a positive impact on the performance of teachers. The study exposed a strong statistically positive relationship between college principals' leadership style and teacher performance. Thus, the results of this study suggest that college principals' should adopt the leadership style according to the level of teachers. The leadership style should be changed with specific situations in the colleges.</p

Bilateral congenital cryptorchidism and unilateral Leydig cell tumor in an adult presenting with gynecomastia and primary infertility: A case report

Introduction and importance: The neoplasms of the testis are sporadic tumors among men. Furthermore, the rarest subset of these is neoplasms belonging to the stromal tumors of the sex cord. Leydig cell tumors are the most common form among the testicular stromal tumors. In our case, the underlying risk factor associated with the development of Leydig cell tumors was cryptorchidism. While mostly unilateral, cases of bilateral cryptorchidism may be present and have been rarely reported. Case presentation: We report a 36-year-old gentleman who presented to us with the inability to carry off intercourse without difficulty attaining erection on stimulation for the past two years. He had a history of left undescended testis since birth, for which he underwent left orchidopexy 20 years ago. An ultrasound of the pelvis showed an oval hypoechoic-shaped heterogeneous mass in the right mid-inguinal canal. Relevant blood investigations showed a deranged hormonal profile. He then underwent an uneventful right radical orchiectomy, histopathology of which was consistent with Leydig cell tumor. Clinical discussion: CT with a history of bilateral cryptorchidism has rarely been reported. This case highlights its clinical presentation, management, and further follow-up in such patients. Conclusion: Bilateral congenital cryptorchidism may be associated with Leydig cell tumor years later in life hence long-term follow-up is required for these patients. The clinical presentation of these tumors may vary among individuals. Any change in physical appearance, hormonal assay, and imaging studies should promptly be followed for possible surgical resection and close monitorin

An exploration of student perception toward interprofessional high-fidelity clinical simulation

OBJECTIVES: Interprofessional education is recognized for its potential for collaboration and teamwork, reflecting clinical practice; however, existing literature for simulation-based interprofessional education does not include Physician Associate (PA) students. This initiative aimed to explore the students’ perception of interprofessional clinical simulation for PA students and allied health professional (AHP) students as part of our program development. METHODS: A high-fidelity simulation session was designed and conducted for volunteering students from the PA, paramedic science, and physiotherapy courses. We used a mixed-method electronic questionnaire consisting of 15 statements rated on a numerical rating scale (0-5) and four open-ended questions with unlimited free-text responses to explore student perceptions. Inductive thematic analysis was used for qualitative analysis. The session design was underpinned by Allport’s (intergroup) contact hypothesis with an emphasis on mutual intergroup differentiation. RESULTS: Forty-six students participated in the simulation teaching, with 48% (n=22) providing feedback. Overall student perception was mainly positive toward the interprofessional simulation; however, some barriers to learning were recognized. Based on the evaluation of our initiative and existing literature, we propose 5 top tips to promote an effective learning experience for students. (1) Understand the importance of interprofessional collaboration. (2) Establish clear roles. (3) Plan the scenarios in advance. (4) Maintain equal status between groups. (5) Provide clear instructions and expectations. CONCLUSION: To our knowledge, this is the first study of high-fidelity interprofessional simulation involving PA and AHP students. We successfully explored student perception which highlighted aspects that can impact learning. This pilot study demonstrated that interprofessional simulation is a feasible and acceptable form of learning for our students and highlighted how to improve future interprofessional simulation teaching sessions

<i>FOXM1</i> induces promoter hypermethylation of <i>p16^INK4A</i> gene in primary human oral keratinocytes.

<p>(<b>A</b>) Bisulfite modification and methylation specific absolute qPCR for the quantification of <i>p16^INK4A</i> promoter methylation status. Genomic DNA was first treated with sodium bisulfite prior to PCR pre-amplification of the promoter region of <i>p16^INK4A</i> (PCR^BS, 273 bp). Methylation specific (p16M-R/F) and methylation-independent (p16U-F/R) primers were then used to quantify the relative levels of methylated and unmethylated products within the PCR^BS sample using standard-curve based absolute qPCR method for each product, respectively. Melting analysis was performed to validate the qPCR specificity in detecting the two M and U products. (<b>B</b>) Bisulfite conversion and methylation specific qPCR were performed to measure the relative levels of unmethylated (U, melting temperature at 85.8°C) and methylated (M, 91.2°C) in either EGFP- or FOXM1-transduced primary NOK treated with either vehicle (DMSO) or 5Aza (1 µM, 3-day incubation with fresh drug replenishment daily). A total of n = 11 replicates from at least 4 independent experiments were performed. Statistical t-test significance notations *P<0.05 and ***P<0.001.</p

Upregulation of <i>FOXM1</i> (isoform B) induces a global shift in methylation pattern that mimics the cancer epigenome.

<p>(<b>A</b>) Genome-wide promoter microarray analysis of primary normal oral human keratinocytes expressing either <i>EGFP</i> (NOKG, black dots) or <i>FOXM1</i> (NOKF, yellow dots) and an established squamous cell carcinoma cell line (SCC15, red dots). Each dot represents a single gene. (<b>B</b>) A non-linear 2^nd order polynomial regression analyses were performed on the relative methylation patterns between NOKG vs NOKF (inverse correlation), NOKG vs SCC15 (inverse correlation) and NOKF vs SCC15 (positive correlation). (<b>C</b>) Gene selection criteria for differentially methylated genes between control (NOKG) and tests groups (NOKF and SCC15). 100-most hypermethylated and 100-most hypomethylated genes were inversely matched with differentially methylated genes from NOKF and SCC15. The adjacent gene lists show the shortlisted FOXM1-induced (also found in SCC15) differentially hypermethylated (red) and hypomethylated (green) genes compared to control NOKG cells. The CDKN2A (encodes <i>p16^INK4A</i>) gene, its promoter known to be hypermethylated in HNSCC, was included as a positive control for promoter hypermethylation. (<b>D</b>) Clinical tumour tissue sample correlation between the relative levels of methylation and gene expression of each shortlisted gene in a cohort of 10 patients with paired normal margin and HNSCC tumour tissue samples. Each dot represents mean ± SEM of each gene. Vertical error bars were derived from relative gene expression of 10 margin-tumour tissue pairs and horizontal error bars were derived from relative promoter methylation of 3 independent primary NOK (NOKG/NOKF) experiments. Correlation coefficient (R²) of a non-linear 2^nd order polynomial regression analyses were performed on all 30 candidate genes (left panel), 16 hypermethylated genes (middle panel) or 14 hypomethylated genes (right panel), respectively.</p

Upregulation of FOXM1 suppressed <i>p16^INK4A</i> expression in primary human oral keratinocytes.

<p>(<b>A</b>) FOXM1 significantly supresses <i>p16^INK4A</i> mRNA and protein expression (inset figure) in primary normal human keratinocytes. GAPDH was used as a control for protein loading. Control cells (mock-transduced with empty retroviral particles or EGFP-transduced) did not show significant suppression of p16^INK4A expression. (<b>B</b>) Knockdown of a FOXM1-target gene <i>HELLS</i>, which regulates genome-wide methylation <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034329#pone.0034329-Dennis1" target="_blank">[14]</a>, induced <i>p16^INK4A</i> and simultaneously suppressed <i>DNMT1</i> and <i>DNMT3B</i>, but not <i>DNMT3A</i> mRNA expression in a FOXM1-transformed malignant cell line (SVFN5) expressing constitutive levels of endogenous <i>HELLS </i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034329#pone.0034329-Gemenetzidis1" target="_blank">[8]</a>. Each bar represents a mean ± SEM of triplicate transfection (48 h) with either siCTRL or siHELLS. *P<0.05, **P<0.01 and ***P<0.001 indicate the level of statistical significance compared to controls. (<b>C</b>) Endogenous <i>FOXM1</i> (isoform B) mRNA expression levels in 8 strains of primary human normal oral keratinocytes, 5 dysplastic and 11 HNSCC cell lines. Total <i>FOXM1</i> mRNA expression levels were measured in the EGFP and FOXM1-transduced NOK (NOKG and NOKF), respectively. (<b>D</b>–<b>J</b>) Third-order polynomial regression analyses were performed to obtain the R² coefficient of determination values which indicate the significance of co-expression between each gene with <i>FOXM1</i> across the 24 cell strains/lines indicated in panel C.</p