Ophthalmology Faculty Diversity Trends in the US.

Importance: Enhancing the diversity of ophthalmologists can potentially contribute to diminishing disparities in eye care. Objectives: To investigate longitudinal trends in the representation of individuals underrepresented in medicine (URiM) and women among ophthalmology faculty compared with other specialties and to assess disparities between ophthalmology faculty demographic characteristics and the US population. Design, Setting, and Participants: In this cross-sectional study, a comprehensive analysis of Association of American Medical Colleges Faculty Roster data between 2000 and 2021 was conducted, using data from the US Medical School Faculty report on 56 438 ophthalmology faculty members. Main Outcomes and Measures: The data set was used to differentiate ophthalmology faculty members by gender, rank, and designation as a URiM individual. Outcome measures included changes in URiM and non-URiM faculty proportions, faculty rank, gender, department chair positions, and the US population between 2000 and 2021. Results: A total of 56 438 ophthalmology faculty members (37 511 men [66.5%]) were included in the study. The number of ophthalmology faculty increased from 1820 in 2000 to 3151 in 2021. Across all years, URiM female faculty represented 3.1% of ophthalmologists (1733 of 56 438), while URiM men accounted for 3.5% (1983 of 56 438). Overall, non-URiM men constituted 63.0% of ophthalmologists (35 528 of 56 438), and non-URiM women accounted for 30.5% (17 194 of 56 438). The proportion of URiM male faculty remained stable from 2000 to 2021 (63 of 1820 [3.5%] vs 104 of 3151 [3.3%]), with a small increase in URiM women faculty at junior faculty positions (2000, 40 of 1820 [2.2%]; 2021, 129 of 3151 [4.1%]; difference, 1.9% [95% CI, 0.9%-2.9%]). Proportions of non-URiM men decreased from 71.2% (1295 of 1820) in 2000 to 55.3% (1743 of 3151) in 2021 (difference, 15.8% [95% CI, 13.1%-18.6%]) and proportions of non-URiM women increased from 23.2% (422 of 1820) in 2000 to 37.3% (1175 of 3151) in 2021 (difference, 14.1% [95% CI, 11.5%-16.7%]). In terms of faculty rank, there were increases in representation of women from 2000 to 2021 at assistant professor (from 11.2% [203 of 1819] to 19.7% [622 of 3165]; difference, 8.5% [95% CI, 6.5%-10.5%]), associate professor (from 4.6% [83 of 1819] to 8.6% [271 of 3165]; difference, 4.0% [95% CI, 2.6%-5.4%]), and professor levels (from 2.8% [51 of 1819] to 7.1% [223 of 3165]; difference, 4.3% [95% CI, 3.9%-6.1%]). URiM representation remained stable at most ranks. Compared with other specialties, ophthalmology had among the lowest percentage change in URiM faculty. The expansion of ophthalmology's URiM faculty representation was less than one-third that of the diverse US population. Conclusion and Relevance: These findings highlight substantial growth in ophthalmology faculty and an increase in women's representation across several faculty ranks. However, URiM representation has remained largely unchanged, despite an increase at the associate professor level. This finding emphasizes the need for continued efforts to enhance diversity in academic ophthalmology.

Large DNA Methylation Nadirs Anchor Chromatin Loops Maintaining Hematopoietic Stem Cell Identity.

Higher-order chromatin structure and DNA methylation are implicated in multiple developmental processes, but their relationship to cell state is unknown. Here, we find that large (>7.3 kb) DNA methylation nadirs (termed "grand canyons") can form long loops connecting anchor loci that may be dozens of megabases (Mb) apart, as well as inter-chromosomal links. The interacting loci cover a total of ∼3.5 Mb of the human genome. The strongest interactions are associated with repressive marks made by the Polycomb complex and are diminished upon EZH2 inhibitor treatment. The data are suggestive of the formation of these loops by interactions between repressive elements in the loci, forming a genomic subcompartment, rather than by cohesion/CTCF-mediated extrusion. Interestingly, unlike previously characterized subcompartments, these interactions are present only in particular cell types, such as stem and progenitor cells. Our work reveals that H3K27me3-marked large DNA methylation grand canyons represent a set of very-long-range loops associated with cellular identity.

t(3;8)(q26.2;q24) Often Leads to MECOM/MYC Rearrangement and Is Commonly Associated with Therapy-Related Myeloid Neoplasms and/or Disease Progression.

t(3;8)(q26.2;q24) is a rare recurrent cytogenetic abnormality that is associated with myeloid neoplasms. Of 20 patients with t(3;8)(q26.2,q24), 8 had therapy-related acute myeloid leukemia (AML), 3 therapy-related myelodysplastic syndrome, 4 blast phase of chronic myeloid leukemia, 1 relapsed AML, 1 AML transformed from chronic myelomonocytic leukemia, 1 blast phase of an unclassifiable myeloproliferative neoplasm, 1 de novo myelodysplastic syndrome, and 1 de novo AML. Nineteen patients presented with cytopenia. Multilineage dysplasia was observed in 16/18 patients, and megakaryocytes were markedly decreased in 11/20 patients. Blasts showed a primitive myeloid immunophenotype in 17 patients, negative for myeloperoxidasein in 14/17, and aberrant CD7 expression in 5/17 patients. Fluorescence in situ hybridization showed MECOM rearrangement in 18/19 and MYC in 16/18 patients. Myc was shown to be expressed in all 14 cases assessed. Gene mutation testing was performed in 14 patients, and 7 showed at least one mutation including ASXL1 (2/6), TET2 (2/6), SRSF2 (2/6), and NRAS (2/13). At last clinical follow-up, 18 patients died and 2 were alive with persistent disease, with a median survival of 6 months. The authors conclude that t(3;8)(q26.2;q24) often leads to MECOM and MYC rearrangement, occurs predominantly in therapy-related myeloid neoplasms or at disease progression, and shares some similarities with myeloid neoplasms associated with inv(3)/GATA2-MECOM. Patients with myeloid neoplasms associated with t(3;8)(q26.2;q24) have a dismal outcome.