Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits using LipocyteProfiler.

A primary obstacle in translating genetic associations with disease into therapeutic strategies is elucidating the cellular programs affected by genetic risk variants and effector genes. Here, we introduce LipocyteProfiler, a cardiometabolic-disease-oriented high-content image-based profiling tool that enables evaluation of thousands of morphological and cellular profiles that can be systematically linked to genes and genetic variants relevant to cardiometabolic disease. We show that LipocyteProfiler allows surveillance of diverse cellular programs by generating rich context- and process-specific cellular profiles across hepatocyte and adipocyte cell-state transitions.

Retrospective review of changes in testosterone dosing and physiologic parameters in transgender and gender-diverse individuals following hysterectomy with and without oophorectomy.

Background: As more transgender and gender-diverse patients undergo hysterectomy, gaps in knowledge remain about how testosterone dosing or other physiologic parameters change following surgery and how these are influenced by concomitant oophorectomy.

Aim: The aims of this study were to determine the incidence of testosterone dosing change after gender-affirming hysterectomy and to compare this incidence between patients who underwent oophorectomy and ovarian preservation.

Methods: This multicenter retrospective cohort study consisted of transmasculine patients who underwent hysterectomy for gender affirmation.

Retrospective Review of Sexual and Reproductive Health Conversations During Initial Visits of Adolescents Seeking Gender-Affirming Testosterone.

Study Objective: To use a retrospective review of sexual and reproductive health (SRH) counseling that occurred during initial visits of adolescents seeking testosterone gender-affirming hormone therapy to determine the feasibility of using such visits to manage SRH DESIGN: Retrospective chart review SETTING: Children's hospital, multidisciplinary gender clinic PARTICIPANTS: Transgender male and nonbinary patients assigned female at birth (TGD-M) aged 15-17 seen for initiation of testosterone between January 1, 2010, and December 31, 2019 INTERVENTIONS: Not applicable MAIN OUTCOME MEASURE(S): Counseling on (1) testosterone impact on fertility and (2) fertility preservation; assessment of (3) desire for gender-affirming surgery, (4) sexual activity, (5) sexual orientation, and (6) human papilloma virus vaccination as documented during the initial visit.

Results: Of 195 patients who met the inclusion criteria, only 3 (1.5%) had all 6 measures addressed.

Transcriptome variation in human tissues revealed by long-read sequencing.

Regulation of transcript structure generates transcript diversity and plays an important role in human disease. The advent of long-read sequencing technologies offers the opportunity to study the role of genetic variation in transcript structure. In this Article, we present a large human long-read RNA-seq dataset using the Oxford Nanopore Technologies platform from 88 samples from Genotype-Tissue Expression (GTEx) tissues and cell lines, complementing the GTEx resource.

Family Building Perspectives of Assigned Female at Birth Transgender and Gender Diverse Adolescents Seeking Testosterone Gender-Affirming Hormone Therapy.

The purpose of this study was to assess the future family building desires of assigned female at birth (AFAB) transgender and gender diverse (TGD) adolescents initiating hormone therapy, and to characterize the individuals interested in adoption. This was a retrospective chart review of AFAB TGD adolescents ages 15-17 years old initiating testosterone gender-affirming hormone therapy between 2010 and 2019, analyzing interest in adoption, demographics, and gender-affirming care. Of 195 AFAB TGD adolescents asked about family planning goals, 58% ( = 113) indicated desire for adoption in their future, and 13.

A tripartite complex of suPAR, APOL1 risk variants and αβ integrin on podocytes mediates chronic kidney disease.

Soluble urokinase plasminogen activator receptor (suPAR) independently predicts chronic kidney disease (CKD) incidence and progression. Apolipoprotein L1 (APOL1) gene variants G1 and G2, but not the reference allele (G0), are associated with an increased risk of CKD in individuals of recent African ancestry. Here we show in two large, unrelated cohorts that decline in kidney function associated with APOL1 risk variants was dependent on plasma suPAR levels: APOL1-related risk was attenuated in patients with lower suPAR, and strengthened in those with higher suPAR levels.

Dynamin Autonomously Regulates Podocyte Focal Adhesion Maturation.

Rho family GTPases, the prototypical members of which are Cdc42, Rac1, and RhoA, are molecular switches best known for regulating the actin cytoskeleton. In addition to the canonical small GTPases, the large GTPase dynamin has been implicated in regulating the actin cytoskeleton via direct dynamin-actin interactions. The physiologic role of dynamin in regulating the actin cytoskeleton has been linked to the maintenance of the kidney filtration barrier.