A Scoping Review of Institutional Policies and Recommendations for Trans Inpatient Mental Health Care

Introduction: Access to culturally sensitive care is critical for addressing known mental health disparities among trans-and gender-non- conforming (TGNC) individuals. Although there has been a proliferation of TGNC healthcare guidelines from accrediting bodies, policies have failed to address the needs of TGNC patients in inpatient psychiatric settings. Aim: To identify unaddressed needs in policies and policy recommendations for the care of TGNC patients to inform recommendations for change. Method: A scoping review protocol was developed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 850 articles were reduced to seven relevant articles with six themes identified via thematic analysis. Results: Six themes were identified: lack of consistency in preferred and pronoun use, lack of communication among providers, lack of training in TGNC healthcare, personal bias, lack of formal policies, and housing segregation by sex rather than gender. Discussion: The creation of new guidelines or bolstering of existing guidelines to specifically address identified themes and gaps may improve the well-being and treatment outcomes of TGNC individuals in inpatient psychiatric settings. Implications for practice: To provide a foundation for future studies to integrate these identified gaps and inform the future development of comprehensive formal policies that generalize TGNC care in inpatient settings

Targetable genetic alterations of TCF4 (E2-2) drive immunoglobulin expression in diffuse large B cell lymphoma

The activated B cell (ABC-like) subtype of diffuse large B cell lymphoma (DLBCL) is characterized by chronic activation of signaling initiated by immunoglobulin m (IgM). By analyzing the DNA copy number profiles of 1000 DLBCL tumors, we identified gains of 18q21.2 as the most frequent genetic alteration in ABC-like DLBCL. Using integrative analysis of matched gene expression profiling data, we found that the TCF4 (E2-2) transcription factor gene was the target of these alterations. Overexpression of TCF4 in ABC-like DLBCL cell lines led to its occupancy on immunoglobulin (IGHM) and MYC gene enhancers and increased expression of these genes at the transcript and protein levels. Inhibition of TCF4 activity with dominant-negative constructs was synthetically lethal to ABC-like DLBCL cell lines harboring TCF4 DNA copy gains, highlighting these gains as an attractive potential therapeutic target. Furthermore, the TCF4 gene was one of the top BRD4-regulated genes in DLBCL cell lines. BET proteolysistargeting chimera (PROTAC) ARV771 extinguished TCF4, MYC, and IgM expression and killed ABC-like DLBCL cells in vitro. In DLBCL xenograft models, ARV771 treatment reduced tumor growth and prolonged survival. This work highlights a genetic mechanism for promoting immunoglobulin signaling in ABC-like DLBCL and provides a functional rationale for the use of BET inhibitors in this disease