The Evolution of Single Cell-derived Colorectal Cancer Cell Lines is Dominated by the Continued Selection of Tumor Specific Genomic Imbalances, Despite Random Chromosomal Instability

Intratumor heterogeneity is a major challenge in cancer treatment. To decipher patterns of chromosomal heterogeneity, we analyzed six colorectal cancer cell lines by multiplex interphase FISH (miFISH). The mismatch repair deficient cell lines DLD-1 and HCT116 had the most stable copy numbers, whereas aneuploid cell lines (HT-29, SW480, SW620 and H508) displayed a higher degree of instability. We subsequently assessed the clonal evolution of single cells in two CRC cell lines, SW480 and HT-29, which both have aneuploid karyotypes but different degrees of chromosomal instability. The clonal compositions of the single cell-derived daughter lines, as assessed by miFISH, differed for HT-29 and SW480. Daughters of HT-29 were stable, clonal, with little heterogeneity. Daughters of SW480 were more heterogeneous, with the single cell-derived daughter lines separating into two distinct populations with different ploidy (hyper-diploid and near-triploid), morphology, gene expression and tumorigenicity. To better understand the evolutionary trajectory for the two SW480 populations, we constructed phylogenetic trees which showed ongoing instability in the daughter lines. When analyzing the evolutionary development over time, most single cell-derived daughter lines maintained their major clonal pattern, with the exception of one daughter line that showed a switch involving a loss of APC. Our meticulous analysis of the clonal evolution and composition of these colorectal cancer models shows that all chromosomes are subject to segregation errors, however, specific net genomic imbalances are maintained. Karyotype evolution is driven by the necessity to arrive at and maintain a specific plateau of chromosomal copy numbers as the drivers of carcinogenesis

A Systematic Review of Integrated Learning Definitions, Frameworks, and Practices in Recent Health Professions Education Literature

International curricular redevelopment and quality improvement efforts include integration within and across disciplines as a focal point. Definitions and applications of the term ‘integration’ vary routinely in health professions education literature, weakening opportunities to enhance our educational practice through collaborative, interprofessional knowledge-sharing. This systematic review examined recent health professions education literature for reported definitions, theories or frameworks, and educational activities around integrated learning, education, curricula, or teaching. A total of 35 articles representing learners from 12 different health professions, between 2017 and 2021, were analyzed through a literature search of seven databases: PubMed, Scopus, CINAHL, JSTOR, the Cochrane Library, LGBTQ + Life, and ERIC. Full-text retrieval and data extraction of the included studies were conducted. Of the 35 articles reviewed, 13 included explicit definitions of integration (an additional six alluded to a definition), 19 referred to an educational theory or framework used to guide integration design efforts, and 27 mentioned teaching methods by which integration was implemented. Misunderstanding what is meant by integrated, how others have planned for it, or how others have sought to bring it about practically, all threaten attempts to improve the cultivation of health professionals as integrated thinkers and holistic care providers

A Systematic Review of Integrated Learning Definitions, Frameworks, and Practices in Recent Health Professions Education Literature

International curricular redevelopment and quality improvement efforts include integration within and across disciplines as a focal point. Definitions and applications of the term ‘integration’ vary routinely in health professions education literature, weakening opportunities to enhance our educational practice through collaborative, interprofessional knowledge-sharing. This systematic review examined recent health professions education literature for reported definitions, theories or frameworks, and educational activities around integrated learning, education, curricula, or teaching. A total of 35 articles representing learners from 12 different health professions, between 2017 and 2021, were analyzed through a literature search of seven databases: PubMed, Scopus, CINAHL, JSTOR, the Cochrane Library, LGBTQ + Life, and ERIC. Full-text retrieval and data extraction of the included studies were conducted. Of the 35 articles reviewed, 13 included explicit definitions of integration (an additional six alluded to a definition), 19 referred to an educational theory or framework used to guide integration design efforts, and 27 mentioned teaching methods by which integration was implemented. Misunderstanding what is meant by integrated, how others have planned for it, or how others have sought to bring it about practically, all threaten attempts to improve the cultivation of health professionals as integrated thinkers and holistic care providers

PEARLS (Perspectives on Equity Advancement: Research and Learning Symposium), a Case Report in Promoting DEI in a Medical School Setting

PEARLS (Perspectives on Equity Advancement: Research and Learning Symposium) was a student-led, faculty-mentored, year-long initiative culminating in a symposium with three components: (1) “Change Agents”, where faculty leaders presented their research and advances in DEI and the impact on the community; (2) The “15% Better” initiative, which promoted individual commitments to improving DEI in the Frank H. Netter School of Medicine at Quinnipiac University through reflection on a monthly prompt and review of selected educational resources; and (3) “Grand Rounds Pitches’’ where student-designed scholarly DEI initiatives received competitive seed grants alongside a mentorship team that help support their project to completion. The 2022 post-event survey (RR 58%) showed that 100% of respondents felt inspired to engage more deeply in DEI after seeing the faculty’s work, felt committed to at least one action that furthers their learning or promotes DEI broadly, and were better able to describe student-led DEI projects. In total, 94% of respondents felt more connected to faculty and students advancing DEI in the school of medicine community and 91% felt a greater sense of belonging. The 15% Better initiative strengthened the belief that small individual DEI commitments can result in substantial positive changes for 73%, while 27% already believed this. In total, 61% were more likely to engage in DEI efforts this year and 36% already planned to engage. Qualitative data highlighted themes of inspiration, positive impact, and actionable change. PEARLS stands as an easily reproducible way for higher education institutions to engage their community in DEI strategies through its foundational elements of promoting belonging, fostering inspiration, and encouraging commitment to action