Hormonal control during infancy and testicular adrenal rest tumor development in males with congenital adrenal hyperplasia: a retrospective multicenter cohort study

IMPORTANCE Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development. OBJECTIVE This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. DESIGN AND PARTICIPANTS This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. RESULTS TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. CONCLUSIONS AND RELEVANCE A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life

The DOE E3SM Coupled Model Version 1: Overview and Evaluation at Standard Resolution

This work documents the first version of the U.S. Department of Energy (DOE) new Energy Exascale Earth System Model (E3SMv1). We focus on the standard resolution of the fully coupled physical model designed to address DOE mission-relevant water cycle questions. Its components include atmosphere and land (110-km grid spacing), ocean and sea ice (60 km in the midlatitudes and 30 km at the equator and poles), and river transport (55 km) models. This base configuration will also serve as a foundation for additional configurations exploring higher horizontal resolution as well as augmented capabilities in the form of biogeochemistry and cryosphere configurations. The performance of E3SMv1 is evaluated by means of a standard set of Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima simulations consisting of a long preindustrial control, historical simulations (ensembles of fully coupled and prescribed SSTs) as well as idealized CO2 forcing simulations. The model performs well overall with biases typical of other CMIP-class models, although the simulated Atlantic Meridional Overturning Circulation is weaker than many CMIP-class models. While the E3SMv1 historical ensemble captures the bulk of the observed warming between preindustrial (1850) and present day, the trajectory of the warming diverges from observations in the second half of the twentieth century with a period of delayed warming followed by an excessive warming trend. Using a two-layer energy balance model, we attribute this divergence to the model’s strong aerosol-related effective radiative forcing (ERFari+aci = -1.65 W/m2) and high equilibrium climate sensitivity (ECS = 5.3 K).Plain Language SummaryThe U.S. Department of Energy funded the development of a new state-of-the-art Earth system model for research and applications relevant to its mission. The Energy Exascale Earth System Model version 1 (E3SMv1) consists of five interacting components for the global atmosphere, land surface, ocean, sea ice, and rivers. Three of these components (ocean, sea ice, and river) are new and have not been coupled into an Earth system model previously. The atmosphere and land surface components were created by extending existing components part of the Community Earth System Model, Version 1. E3SMv1’s capabilities are demonstrated by performing a set of standardized simulation experiments described by the Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima protocol at standard horizontal spatial resolution of approximately 1° latitude and longitude. The model reproduces global and regional climate features well compared to observations. Simulated warming between 1850 and 2015 matches observations, but the model is too cold by about 0.5 °C between 1960 and 1990 and later warms at a rate greater than observed. A thermodynamic analysis of the model’s response to greenhouse gas and aerosol radiative affects may explain the reasons for the discrepancy.Key PointsThis work documents E3SMv1, the first version of the U.S. DOE Energy Exascale Earth System ModelThe performance of E3SMv1 is documented with a set of standard CMIP6 DECK and historical simulations comprising nearly 3,000 yearsE3SMv1 has a high equilibrium climate sensitivity (5.3 K) and strong aerosol-related effective radiative forcing (-1.65 W/m2)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151288/1/jame20860_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151288/2/jame20860.pd

Going viral? Linking the etiology of human prostate cancer to the PCA3 long noncoding RNA and oncogenic viruses

The hypothesis is discussed that prostate cancer marker lncRNA PCA3 was introduced into the human genome by an oncogenic virus, and that viral infection‐related mechanisms might underlie its overexpression and prostate cancer initiation and/or progression

Diagnostic yield of pediatric and prenatal exome sequencing in a diverse population

The diagnostic yield of exome sequencing (ES) has primarily been evaluated in individuals of European ancestry, with less focus on underrepresented minority (URM) and underserved (US) patients. We evaluated the diagnostic yield of ES in a cohort of predominantly US and URM pediatric and prenatal patients suspected to have a genetic disorder. Eligible pediatric patients had multiple congenital anomalies and/or neurocognitive disabilities and prenatal patients had one or more structural anomalies, disorders of fetal growth, or fetal effusions. URM and US patients were prioritized for enrollment and underwent ES at a single academic center. We identified definitive positive or probable positive results in 201/845 (23.8%) patients, with a significantly higher diagnostic rate in pediatric (26.7%) compared to prenatal patients (19.0%) (P = 0.01). For both pediatric and prenatal patients, the diagnostic yield and frequency of inconclusive findings did not differ significantly between URM and non-URM patients or between patients with US status and those without US status. Our results demonstrate a similar diagnostic yield of ES between prenatal and pediatric URM/US patients and non-URM/US patients for positive and inconclusive results. These data support the use of ES to identify clinically relevant variants in patients from diverse populations