Selected Skill Sets as Building Blocks for High School-to-Medical School Bridge: Longitudinal Study Among Undergraduate Medical Students.

BACKGROUND: The high school-to-medical school education transition is a significant milestone in the students' academic journey, which is characterized by multiple stressors. Although this crucial transition has been repetitively explored, the concept of proactively intervening to support this transition is still novel. OBJECTIVE: In this study, we investigated the efficacy of a web-based multidimensional resilience building intervention in developing selected soft skills that are believed to drive the learner's success in any learning setting. The association between the students' academic performance over time and their proficiency in selected modules addressing skill sets, including Time Management, Memory and Study, Listening and Taking Notes, and College Transition, was also assessed to test the impact of the intervention on the students' learning. METHODS: A longitudinal study was conducted on 1 cohort of students of a Bachelor of Medicine, Bachelor of Surgery program (MBBS). The medical students were offered a learning intervention around 4 skill sets during the first year of the 6-year program. Quantitative analyses were conducted using deidentified data, relating to the students' proficiency in the 4 skill sets and to the students' academic performance: grade point average (GPA). Descriptive analyses constituted computing an overall score of skill sets' proficiency (of all 4 selected skill sets). The mean and SD (and percentage of the mean) were also calculated for each skill set component, independently, and for the overall score of skill sets' proficiency. Bivariate Pearson correlations were used to assess the extent to which the academic performance of the students can be explained by the corresponding students' level of proficiency in each skill set component and by all 4 sets together. RESULTS: Out of the 63 admitted students, 28 participated in the offered intervention. The means and SDs of the annual GPA of the students for years 1 and 2 (GPA range 1-4) were 2.83 (SD 0.74) and 2.83 (SD 0.99), respectively. The mean and SD of the cumulative GPA toward the end of year 2 was 2.92 (SD 0.70). Correlation analysis showed that the overall score of skill sets proficiency was significantly associated with the annual GPA of year 1 (r=0.44; P=.02) but was not associated with their annual GPA of year 2. The cumulative GPA (toward the end of year 2) appeared to be significantly associated with the overall score (r=0.438; P=.02). CONCLUSIONS: Developing purposefully selected skill sets among medical students holds the potential of facilitating the high school-to-medical school education transition and is likely to improve their academic performance. As the medical student progresses, the acquired skills need to be continuously reinforced and effectively built upon.

Epigenetic status of FBXW7 gene and its role in Ovarian cancer pathogenesis.

BACKGROUND: Chromatin immunoprecipitation (ChIP) analysis revealed that the FBXW7 gene and the long non-coding RNA (LINC01588) are potential candidates in epithelial ovarian cancer (EOC) pathogenesis. However, their exact role in EOC is not yet known. Thus, the present study sheds light on the impact of the mutations/ methylation status of the FBXW7 gene. MATERIALS AND METHODS: We used public databases to assess the correlation between mutations/ methylation status and the FBXW7 expression. Furthermore, we performed Pearson's correlation analysis between the FBXW7 gene and LINC01588. We performed gene panel exome sequencing and Methylation-specific PCR (MSP) in HOSE 6-3, MCAS, OVSAHO, and eight EOC patients' samples to validate the bioinformatics results. RESULTS: The FBXW7 gene was less expressed in EOC, particularly in stages III and IV, compared to healthy tissues. Furthermore, bioinformatics analysis, gene panel exome sequencing, and MSP revealed that the FBXW7 gene is neither mutated nor methylated in EOC cell lines and tissues, suggesting alternative mechanisms for FBXW7 gene regulation. Interestingly, Pearson's correlation analysis showed an inverse, significant correlation between the FBXW7 gene and LINC01588  expression, suggesting a potential regulatory role of LINC01588. CONCLUSION: Neither mutations nor methylation is the causative mechanism for the FBXW7 downregulation in EOC, suggesting alternative means involving the lncRNA LINC01588.

Identification and validation of a novel long non-coding RNA (LINC01465) in ovarian cancer.

Epithelial Ovarian Cancer (EOC) is a heterogeneous disease usually diagnosed at advanced stages. Therefore, early detection is crucial for better survival. Despite the advances in ovarian research, mechanisms underlying EOC carcinogenesis are not elucidated. We performed chromatin immunoprecipitation sequencing to identify genes regulated by E2F5, a transcription factor involved in ovarian carcinogenesis. Results revealed several putative candidate genes (115 protein-coding genes, 20 lncRNAs, 6 pseudogenes, and 4 miRNAs). A literature review and bioinformatics analysis of these genes revealed a novel lncRNA candidate (LINC01465) in EOC. We validated LINC01465 by quantifying its expression in EOC cell lines and selected OVSAHO and SKOV3 as a model with high LINC01465 levels. We silenced LINC01465 and performed proliferation, wound healing, invasion, and drug resistance assays. Knocking-down LINC01465 resulted in reduced migration, suggesting potential involvement in EOC. Furthermore, to identify the significance of LINC01465 in chemoresistance, we assessed the LINC01465 levels in A2780 S cells treated with malformin, which revealed higher LINC01465 expression as compared to untreated A2780S cells implying the involvement of LINC01465 in cell death. Thus, this study unraveled the repertoire of E2F5 regulated candidate genes and suggested a putative role of LINC01465 in malformin-induced cell death in EOC.

Assessment as Learning in Medical Education: Feasibility and Perceived Impact of Student-Generated Formative Assessments.

BACKGROUND: Self-regulated learning (SRL) is gaining widespread recognition as a vital competency that is desirable to sustain lifelong learning, especially relevant to health professions education. Contemporary educational practices emphasize this aspect of undergraduate medical education through innovative designs of teaching and learning, such as the flipped classroom and team-based learning. Assessment practices are less commonly deployed to build capacity for SRL. Assessment as learning (AaL) can be a unique way of inculcating SRL by enabling active learning habits. It charges students to create formative assessments, reinforcing student-centered in-depth learning and critical thinking. OBJECTIVE: This study aimed to explore, from the learners' perspectives, the feasibility and perceived learning impact of student-generated formative assessments. METHODS: This study relied on a convergent mixed methods approach. An educational intervention was deployed on a cohort of 54 students in the second year of a 6-year undergraduate medical program as part of a single-course curriculum. The AaL intervention engaged students in generating assessments using peer collaboration, tutor facilitation, and feedback. The outcomes of the intervention were measured through quantitative and qualitative data on student perceptions, which were collected through an anonymized web-based survey and in-person focus groups, respectively. Quantitative survey data were analyzed using SPSS (IBM), and qualitative inputs underwent thematic analysis. RESULTS: The students' overall score of agreement with the AaL educational intervention was 84%, which was strongly correlated with scores for ease and impact on a 5-point Likert-type scale. The themes that emerged from the qualitative analysis included prominent characteristics, immediate gains, and expected long-term benefits of engagement. The prominent characteristics included individuals' engagement, effective interdependencies, novelty, and time requirements. The identified immediate gains highlighted increased motivation and acquisition of knowledge and skills. The expected long-term benefits included critical thinking, problem solving, and clinical reasoning. CONCLUSIONS: As a form of AaL, student-generated assessments were perceived as viable, constructive, and stimulating educational exercises by the student authors. In the short term, the activity provided students with a fun and challenging opportunity to dive deeply into the content, be creative in designing questions, and improve exam-taking skills. In the long term, students expected an enhancement of critical thinking and the inculcation of student-centered attributes of self-regulated lifelong learning and peer collaboration, which are vital to the practice of medicine.

Virtual Microscopy in Undergraduate Pathology Education: An early transformative experience in clinical reasoning.

OBJECTIVES: Whole-slide imaging and virtual microscopy (VM) have revolutionised teaching, diagnosis and research in histopathology. This study aimed to establish the feasibility of achieving early integration of clinical reasoning with undergraduate pathology teaching on a VM platform and to determine its student-centricity through student feedback. METHODS: This study was conducted at the Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates, between August and December 2017. A total of 38 VM-centred clinical cases were introduced to 49 students in an integrated undergraduate medical curriculum. The cases were aligned to curricular objectives, reinforced the pathologic basis of disease with critical thinking and were delivered across 15 interactive small-group sessions. A simulated cross-disciplinary integration and judicious choice of pertinent diagnostic investigations were linked to principles of management. Feedback was obtained through a mixed-methods approach. RESULTS: User-friendliness, gradual learning curve of VM and annotation-capacity were scored as 4-5 (on a Likert scale of 1-5) by 91.84%, 87.76% and 83.67% of the participants, respectively. Most students agreed that the content matched the stage of learning (81.63%), theme of the week (91.84%) and development of a strong clinical foundation (77.55%). Integration (85.71%) and clinico-pathological correlation (83.67%) were the strengths of this educational effort. High student attendance (~100%) and improved assessment scores on critical thinking (80%) were observed. Software lacunae included frequent logouts and lack of note-taking tools. Easy access was a significant student-centric advantage. CONCLUSION: A VM-centred approach with a clinico-pathological correlation has been successfully introduced to inculcate integrated learning. Using the pathologic basis of disease as a fulcrum and critical reasoning as an anchor, a digitally-enabled generation of medical students have embraced this educational tool for tutor-guided, student-centred learning.

Clinicopathological Features and Outcomes of Gastrointestinal Stromal Tumours in Oman: A multi-centre study.

OBJECTIVES: This study aimed to report the clinicopathological features, management and long-term outcomes of patients with gastrointestinal stromal tumours (GISTs) in Oman. METHODS: This retrospective study was conducted on patients treated for GIST between January 2003 and December 2017 at three tertiary referral centres in Muscat, Oman. All patients with confirmed histopathological diagnoses of GIST and followed-up at the centres during this period were included. Relevant information was retrieved from hospital records until April 2019. RESULTS: A total of 44 patients were included in the study. The median age was 55.5 years and 56.8% were female. The most common primary site of disease was the stomach (63.6%) followed by the jejunum/ileum (18.2%). Two patients (4.5%) had c-Kit-negative, discovered on GIST-1-positive disease. A total of 24 patients (54.5%) presented with localised disease and eight (33.3%) were classified as being at high risk of relapse. Patients with metastatic disease received imatinib in a palliative setting, whereas those with completely resected disease in the intermediate and high-risk groups were treated with adjuvant imatinib. Of the six patients (13.6%) with progressive metastatic disease, of which four had mutations on exon 11 and one on exon 9, while one had wild-type disease. Overall, rates of progression-free survival and overall survival (OS) at 100 months were 77.4% and 80.4%, respectively. Rates of OS for patients with localised and metastatic disease were 89.9% and 80.2%, respectively. CONCLUSION: The presenting features and outcomes of patients with GISTs in Oman were comparable to those reported in the regional and international literature.

Introducing the 4Ps Model of Transitioning to Distance Learning: A convergent mixed methods study conducted during the COVID-19 pandemic.

Significant concern has been raised regarding the effect of COVID-19 on medical education. This study aimed to shed light on the distance learning experiences of medical students and their instructors at the Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU) in Dubai, United Arab Emirates. A convergent mixed methods approach was utilized. Qualitative and quantitative data was collected using a survey of closed-ended followed by open-ended questions. The percentage of the total average of satisfaction among stakeholders was 76.4%. The qualitative analysis led to developing the 4Ps Model of Transitioning to Distance Learning, which encapsulates four interrelated themes. It would be helpful to leverage the lessons learned to tailor blended medical programs with a reasonable mélange of experiences. The study also contributes to the mixed methods research by showcasing a means of adapting it to evaluate critical situations reliably and rapidly.

Taking a Leap of Faith: A Study of Abruptly Transitioning an Undergraduate Medical Education Program to Distance-Learning Owing to the COVID-19 Pandemic.

The COVID-19 pandemic has forced universities worldwide to immediately transition to distance-learning. Although numerous studies have investigated the effect of the COVID-19 pandemic on universities in the Middle East, none have reflected on the process through which medical education programs for health professions underwent this transition. This study aimed to elucidate the rapid transition to distance-learning of an undergraduate medical program at the College of Medicine, Mohammad Bin Rashid University of Medicine and Health Sciences (Dubai, United Arab Emirates), owing to the COVID-19 pandemic. An action research approach constituted the foundation of this collaborative effort that involved investigations, reflections, and improvements of practice, through ongoing cycles of planning, acting, observing, and reflecting. Efforts of transitioning to distance-learning were grouped into four interrelated aspects: supporting faculty members in delivering the program content, managing curriculum changes, engaging with the students to facilitate distance-learning experiences, and conducting web-based assessments. Challenges included the high perceived uncertainty, need for making ad hoc decisions, lack of experiential learning and testing of clinical skills, and blurring of work-life boundaries. Our preliminary findings show the successful generation of a strong existing digital base, future prospects for innovation, and a cohesive team that was key to agility, rapid decision-making, and program implementation.

Correlation of expression of Akt1 and E2F1 and their phosphorylated forms in breast cancer patients with clinicopathological parameters.

Breast cancer is the leading cancer worldwide among women. Traditional clinicopathological prognostic and predictive markers need refining to improve clinical outcomes. This study explored the association between traditional clinicopathological factors and the expression of Akt1 and E2F1 transduction proteins and their phosphorylated forms in breast cancer, to determine their value as novel biomarkers and potential therapeutic targets. Tumor tissues from 94 female breast cancer patients were examined for immunophenotypic expression of total Akt1, pAkt1 (Serine 473), pAkt1 (Threonine 308), total E2F1, pE2F1 (Thr433) and pE2F1 (Ser337). The expression of pAkt1 (Ser473) was significantly associated with ER/PR positive status and total E2F1 with older age (> 50), lymph node involvement and HER2 positivity. There was a significant association between triple negative cancers and total and pAkt1 (Thr308). pAkt1 (Ser473) showed an inverse relationship with Luminal B cancers and pE2F1 (Thr433) showed an inverse association with triple negative cancers. Higher expression of pE2F1 (Ser337) was associated with better OS. Both pAkt1 (Ser473 and Thr308) proteins showed significant association with poorer patient outcomes. E2F1 (Ser337) showed a significant positive correlation with response to chemotherapy. The study suggests that a pAkt1-/pE2F1+ phenotype could indicate an opportunity to minimize chemotherapeutic options in older women; conversely a pAkt1+/pE2F1- phenotype could prompt a more aggressive regimen. Further exploration of this phenotype in younger women with breast cancer and triple-negative breast cancers is warranted.

E2F5 Promotes the Malignancy of Ovarian Cancer Via the Regulation of Hippo and Wnt Pathways.

Background: E2F5 is a transcription factor that is overexpressed in the early stages of ovarian cancer and has been suggested as a potential biomarker for early detection. In this study, we aimed to examine the role of E2F5 in invasion and proliferation of ovarian cancer cells. Materials and Methods: We performed cell viability, colony formation, and invasion assays using ovarian cancer cells treated with siRNA to knock down the E2F5 gene. The regulatory effects of E2F5 on proteins involved in the apoptotic, Wnt, Hippo, and retinoblastoma signaling pathways were evaluated by western blotting following E2F5 repression. In addition, we analyzed data available on Gene Expression Profiling Interactive Analysis for correlations between E2F5 and YAP, ß-catenin, cyclin D1, cdk4, and caspase-9. Results: E2F5 was highly expressed in ovarian cancer cell lines and samples when compared to the nonmalignant tissues. Downregulation of E2F5 inhibited cell viability and invasion and promoted the phosphorylation of YAP, GSK-3-ß, ß-catenin, and retinoblastoma. However, cyclin D1, cdk4, and caspase-9 were downregulated when compared to control. Conclusion: Overall, E2F5 promotes ovarian carcinogenesis via the regulation of Hippo and Wnt pathways.

FAT4 silencing promotes epithelial-to-mesenchymal transition and invasion via regulation of YAP and ß-catenin activity in ovarian cancer.

BACKGROUND: The adhesion molecule, FAT4, has a tumor suppressor function with a critical role in the epithelial-to-mesenchymal-transition (EMT) and anti-malignant growth in several cancers. No study has investigated yet its role in epithelial ovarian cancer (EOC) progression. In the present study, we examined the role of FAT4 in proliferation and metastasis, and its mechanisms of interaction in these processes. METHODS: We have performed cell viability, colony formation, and invasion assays in ovarian cancer cells treated with siRNA to knockdown FAT4 gene expression. The regulatory effects of FAT4 on proteins involved in apoptotic, Wnt, Hippo, and retinoblastoma signaling pathways were evaluated by Western blotting following FAT4 repression. Also, 426 ovarian tumor samples and 88 non-tumor samples from the Gene Expression Profiling Interactive Analysis (GEPIA) database were analyzed for the expression of FAT4. Pearson's correlation was performed to determine the correlation between FAT4 and the E2F5, cyclin D1, cdk4, and caspase 9 expressions. RESULTS: Lower expression of FAT4 was observed in ovarian cancer cell lines and human samples as compared to non-malignant tissues. This down-regulation seems to enhance cell viability, invasion, and colony formation. Silencing FAT4 resulted in the upregulation of E2F5, vimentin, YAP, ß-catenin, cyclin D1, cdk4, and Bcl2, and in the downregulation of GSK-3-ß, and caspase 9 when compared to control. Furthermore, regulatory effects of FAT4 on the EMT and aggressive phenotype seem to occur through Hippo, Wnt, and cell cycle pathways. CONCLUSION: FAT4 downregulation promotes increased growth and invasion through the activation of Hippo and Wnt-ß-catenin pathways.

'Walk with Us ' Student Peer-Mentoring in Interdisciplinary Cancer Education.

'Walk with us…' reflects on a series of innovative educational journeys that have offered value addition in cancer education of health professions students. It provides an insight into interdisciplinary peer education through extra-curricular pathways. It taps on student creativity and inspirational techniques in health education that stimulate student-centered learning.

Epithelial Mesenchymal Transition (EMT) in Metastatic Breast Cancer in Omani Women.

Breast cancer (BC) in Oman affects younger women and has a more aggressive course. Clinical and biological variables like age, pregnancy, tumor size, type, grade, receptor expression and proliferation predict disease aggression but there is no direct predictor of metastasis except lymphovascular invasion. Epithelial-mesenchymal transition (EMT) is characterized by epithelial cells losing epithelial and acquiring mesenchymal morpho-immunophenotypic characteristics. In tumors, EMT-like transitions may signify a metastatic phenotype and have features in common with cancer stem cells (CSC) which show resistance to chemotherapy. This study aimed to identify EMT and CSC phenotypes in metastatic and non-metastatic breast cancer in Omani women and their association with conventional clinico-pathological predictors of BC. In a retrospective study of ninety-six Omani women with breast cancer, the association of age, pregnancy/lactation, tumor size, type, grade, ductal carcinoma insitu (DCIS), lymphovascular invasion, hormone/ HER2 receptor expression and Ki67 proliferation index (Ki67 PI) was tested with EMT/ CSC phenotype and metastasis. Young age ≤ 40 years, lymphovascular invasion and EMT had a strong association with metastasis; CSC approached significance. Vimentin expression in tumor cells, fibronectin and MMP-11 in stroma were reliable markers of EMT; dual EMT and CSC phenotype (Vim+/ CD44+/ CD 24-/low) had a strong association with apocrine variant, basal-like tumors and triple negative cancers. EMT had a strong association with Ki67 proliferation index (PI) and CSC with HER2-like tumors and distant metastasis. These select markers may be useful in metastasis-prediction in pre-treatment biopsies.

Gleason's Grading of Prostatic Adenocarcinoma: Inter-Observer Variation Among Seven Pathologists at a Tertiary Care Center in Oman

Prostatic adenocarcinoma is the commonest solid malignancy seen in Omani elderly males 60-80 years of age. The Gleason grade is the most widely used grading system for prostatic carcinoma and is recommended by the World Health Organization. A peer review was carried out at the Pathology Department of Sultan Qaboos University Hospital (SQUH), Oman, to assess the quality of reporting at the center. The aim of this study was to determine inter-observer variation among 7 pathologists working at a tertiary care center in Oman. A total of 47 consecutive prostatic biopsies were interdependently reviewed by seven pathologists and the results obtained were compared with each other and the original diagnosis. This peer review indicated a fair inter-observer agreement (0.482) among 7 pathologists in the department, with fair to moderate agreement when the results were compared to the reported diagnosis, comparable to the published literature. Dual and sub-specialty reporting are being instituted to improve the performance in this vital aspect of pathology.

Localised Skin Hyperpigmentation as a Presenting Symptom of Vitamin B12 Deficiency Complicating Chronic Atrophic Gastritis.

Vitamin B12 deficiency is common in developing countries and should be suspected in patients with unexplained anaemia or neurological symptoms. Dermatological manifestations associated with this deficiency include skin hyper- or hypopigmentation, angular stomatitis and hair changes. We report a case of a 28-year-old man who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in November 2013 with localised hyperpigmentation of the palmar and dorsal aspects of both hands of two months' duration. Other symptoms included numbness of the hands, anorexia, weight loss, dizziness, fatigability and a sore mouth and tongue. There was no evidence of hypocortisolaemia and a literature search revealed a possible B12 deficiency. The patient had low serum B12 levels and megaloblastic anaemia. An intrinsic factor antibody test was negative. A gastric biopsy revealed chronic gastritis. After B12 supplementation, the patient's symptoms resolved. Family physicians should familiarise themselves with atypical presentations of B12 deficiency. Many symptoms of this deficiency are reversible if detected and treated early.