The functions and prognostic values of m6A RNA methylation regulators in thyroid carcinoma.

BACKGROUND: N6-Methyladenosine (m6A) is the most common RNA modification and regulates RNA splicing, translation, translocation, and stability. Aberrant expression of m6A has been reported in various types of human cancers. m6A RNA modification is dynamically and reversibly mediated by different regulators, including methyltransferase, demethylases, and m6A binding proteins. However, the role of m6A RNA methylation regulators in thyroid cancer remains unknown. The aim of this study is to investigate the effect of the 13 main m6A RNA modification regulators in thyroid carcinoma. METHODS: We obtained clinical data and RNA sequencing data of 13 m6A RNA methylation regulators from The Cancer Genome Atlas (TCGA) THCA database. We performed consensus clustering to identify the clinical relevance of m6A RNA methylation regulators in thyroid carcinoma. Then we used LASSO Cox regression analysis to generate a prognostic signature based on m6A RNA modification regulator expression. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment Analyses were performed to explore differential cellular processes and signaling pathways between the two groups based on risk signature. RESULTS: We found that most of the m6A RNA modification regulators are down-regulated in 450 patients with thyroid carcinoma. We derived a three m6A RNA modification regulator genes-based risk signature (FTO, RBM15 and KIAA1429), that is an independent prognostic biomarker in patients with thyroid carcinoma. Moreover, we found that this risk signature could better predict outcome in male than female. Functional research in vitro demonstrated that the m6A RNA methylation regulators involved in the model acted significant role in the proliferation and migration of thyroid cancer cells. CONCLUSIONS: Our study revealed the influence of m6A RNA methylation regulators on thyroid carcinoma through biological experiments and three-gene prognostic model.

The PROFILE of assessment program for internal medicine internship of Sun Yat-Sen University.

Objective: To reflectively look at the present methods by which the clinical competence of 5th-year medical students (i.e. interns) in Sun Yat-Sen University (SYSU) are assessed upon finishing internship rotation in internal medicine (IM). Methods: Current procedures for the competence assessment of end-of-rotation IM interns in the First Affiliated Hospital of SYSU were reviewed, along with a point-by-point appraisal based on the PROFILE approach to structured assessment, and, whenever possible, suggestions for future improvement. Results and discussions: On a scale of 1-10, with 10 being the best or the most ideal, our marks for current methods to assess end-of-rotation IM interns in terms of being Programmatic, Real-World, Outcome-based, Formative, Impactful, Learner-engaged, and Evaluation-guaranteed were 7, 9, 3, 4, 6, 8, and 1, respectively. The strengths, weaknesses as well as potential solutions in each of the seven aspects are also discussed separately. Conclusions: Current assessment program for IM internship is strong in being programmatic, real-world, educationally impactful and learner engaged, and has room for further improvement in its time-based arrangements, relative shortage of feedback provision, as well as a systematic lack of quality control measures.

Reflecting on Experiences of Senior Medical Students' External Clinical Teaching Visits in General Practice Placements: A Pilot Study.

Purpose: Australian general practice training uses external clinical teaching (ECT) visits for formative work-based assessments. ECT visits appoint senior general-practitioners (GPs) observe trainee GPs' consultations, provide feedback, and make performance-enhancing recommendations. As ECT visits are one of the best assessment tools in Australian GP training, there is limited evidence of its use in undergraduate teaching. This study aims to introduce ECT visits and evaluate assessment tools during senior medical students' GP placement. Methods: This study included external and internal GP supervisors and twenty-five Chinese and Australian students during GP placements. The supervisors provided structured in-person feedback, while the ECT assessment tool used a standardised, validated feedback platform to assess every component of a consultation. Students' feedback was recorded and collected by both internal and external supervisors, and then semantically analysed by external supervisors. Results: Twenty-five ECT visit feedbacks were collected and analysed semantically. All participating students rated ECT visits excellently and confirmed the relevance of assessment tools for discussions with supervisors to achieve the designed learning outcomes. Chinese students rated the assessment tools as innovative from a cultural perspective and recommended the ECT visit teaching model and assessment tools to their home university, whereas Australian students suggested more ECT visits during GP placements. Time management was a limitation for both the students and supervisors. Conclusion: ECT visit is an innovative placement teaching model and work-based assessment tool for senior medical students' GP placements, and is rated as the most preferred formative assessment tool. The limitations of this study include small group of students/supervisors and lack of patient feedback; however, all of these limitations can be overcome by involving multiple GP clinics in ongoing large-scale study. ECT visits can be introduced quantitatively into students' GP placement curricula to improve clinical reasoning, learning, and quality assurance with assessments during clinical placements.

Reflecting on Students' Experiences of an Innovative Teaching Model During Aged Care Visit in Clinical Placements: A Qualitative Pilot Study.

Purpose: Clinical placement teaching could be challenging due to time constraints, lack of effective teaching models and consensus approaches. Learner-centred approach facilitated deeper learning by demonstrating "seeing-patients-under-supervision" being ideal during Residential-Aged-Care-Facility (RACF)-visit in GP clinical placements. The study aimed to reflect on the students' experiences in aged-care visits by applying an innovative teaching model of "students-being-the-GP-clinician-in-charge-of-RACF-visit-ward-round-under-the-supervision-of-clinical-supervisor". Through students' reflections, this study identified 12 commonly managed RACF problems to be introduced into the curriculum to optimise clinical reasoning learning during RACF-visit. Methods: This qualitative study used online surveys and interviews. All participating students reported all the encountered cases during the RACF visit through an online survey. The participating students acted as GP in charge of all clinical interactions with patients, caregivers, and nurses during RACF visits and final management plan discussions with GP supervisors to ensure clinical-service safety and teaching-and-learning quality. The interview questionnaires applied standard-and-open-ended-questions to examine the impact of this innovative teaching model on clinical-reasoning-learning, clinical-competence-improvement, Objective Structured Clinical Exam (OSCE) preparation, limitations-from-students'-patients'-and-supervisors' perspectives, and intern readiness. Results: An online survey summarising students' encountered cases was returned by 30 students. The 12 most commonly-managed problems were tabulated. Falls, urinary tract infections, and behavioural and psychological symptoms of dementia were the three most commonly-managed problems. All thirty students' reflections indicated the positive impact of the innovative-teaching-models on "Improving-Clinical-Reasoning-Learning", "Enhancing-Clinical-Competency", "Enriching-Salient-Learning-Points", "Facilitating-Feedback-Discussion-with-Supervisor", "Strengthening-OSCE-exam-preparation", "Understanding-the-Limitation-from-students'-patients'-and-supervisors'-perspectives", "Enabling-intern-readiness". Twelve students' individual reflections were demonstrated. Conclusion: This qualitative pilot study demonstrated through students' reflection that "Student-doctor-in-charge-of-nursing-home-round" is an innovative teaching model for clinical reasoning learning. This model extended the concepts of "cognitive-apprenticeship" in the context of modern medical education. Students' reflections and summary of commonly managed problems indicated the need for further study to verify the feasibility of implementing this teaching model in the formal curriculum and creating a RACF-visit-specific curriculum for students.

Evidence of a common mechanism of disassembly of adherens junctions through Gα13 targeting of VE-cadherin.

The heterotrimeric G protein Gα13 transduces signals from G protein-coupled receptors (GPCRs) to induce cell spreading, differentiation, migration, and cell polarity. Here, we describe a novel GPCR-independent function of Gα13 in regulating the stability of endothelial cell adherens junctions (AJs). We observed that the oxidant H2O2, which is released in response to multiple proinflammatory mediators, induced the interaction of Gα13 with VE-cadherin. Gα13 binding to VE-cadherin in turn induced Src activation and VE-cadherin phosphorylation at Tyr 658, the p120-catenin binding site thought to be responsible for VE-cadherin internalization. Inhibition of Gα13-VE-cadherin interaction using an interfering peptide derived from the Gα13 binding motif on VE-cadherin abrogated the disruption of AJs in response to inflammatory mediators. These studies identify a unique role of Gα13 binding to VE-cadherin in mediating VE-cadherin internalization and endothelial barrier disruption and inflammation.