bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI212 Adrenalitis Caused By Proteus Mirabilis In An Immunocompetent Patient
Authors: Abdelkarim Jumana Omar , Tarabichi Ula , Jakoby Michael 
Published: October 2023

Abstract
Disclosure: J.O. Abdelkarim: None. U. Tarabichi: None. M. Jakoby: None.
Infectious adrenalitis with Mycobacterium tuberculosis remains the leading cause of primary adrenal insufficiency in developing countries, but the incidence of adrenalitis from infection with other bacterial species is quite low. We present a patient with radiographic evidence of adrenalitis during an infection with Proteus mirabilis that resolved after antimicrobial treatment.An 86-year-old male with an indwelling Foley catheter presented to the hospital for evaluation of abdominal pain and distension. The patient was afebrile and normotensive. Examination was notable for a distended bladder and obstructed urinary catheter. Computed tomography (CT) revealed a dense right lower lobe infiltrate and bilaterally enlarged, hypointense adrenal glands with irregular margins. Radiographic findings were new compared to a CT scan obtained approximately 10 weeks before admission to hospital. Turbid and malodorous urine was drained after replacement of the patient’s urinary catheter, and urine culture grew &gt; 105 CFU/mL Proteus mirabilis. Antibiotics were dosed before blood cultures were drawn, and no organisms were grown from blood cultures. Since there was no clinical or biochemical evidence (e.g. hyponatremia or hyperkalemia) of primary adrenal insufficiency, an ACTH stimulation test was deferred. The patient responded well to replacement of his urinary catheter and antibiotics and was discharged to his extended care facility three days later. A CT scan obtained 10 days after treatment showed resolution of the changes to the patient’s adrenal glands observed on admission imaging.The radiographic changes are most plausibly due to P. mirabilis bacteremia and adrenalitis. The patient had urine culture confirmed infection with P. mirabilis and radiographic evidence of disseminated infection in the right lung and adrenal glands. Adrenal enlargement is well described in cases of acute M. tuberculosis adrenalitis, and radiographic changes of adrenalitis resolved after successful treatment of the patient’s infection. P. mirabilis has been documented as an etiology of Waterhouse-Friderichsen syndrome and cultured from an adrenal abscess. Blood cultures in this case were almost certainly negative due to timing relative to initial antibiotic doses. Injury to the adrenals in bacterial adrenalitis is thought to occur due to multiple mechanisms including direct infection of the glands, endotoxemia, vasculitis, and disseminated intravascular coagulation (DIC). Hemorrhage appears to occur in about 60% of cases. Elevated ACTH level is postulated as a factor predisposing to adrenal hemorrhage, and this prompted deferral of stimulation testing to evaluate adrenal function since there was no clinical evidence of primary adrenal insufficiency. Early management of the patient’s infection likely prevented the occurrence of adrenal insufficiency and deterioration of his clinical status.
Presentation: Friday, June 16, 2023
SAT406 Evaluation Of The Emotional And Cognitive Effects Of Hormone Therapy In Transgender Men And Women
Authors: Yaish Iris , Keltch Gali , Greenman Yona , Tordjman Karen Michele 
Published: October 2023

Abstract
Disclosure: I. Yaish: None. G. Keltch: None. Y. Greenman: None. K.M. Tordjman: None.
Background:- Sex hormones have far-reaching effects on the brain, both emotionally and cognitively.
- Varying levels of sex hormones are associated with altered emotional states and cognitive abilities.
-No longitudinal study has assessed the impact of cross-sex hormone on these issues in young transgender people.
Aim:•To prospectively evaluate the effect of gender-affirming hormonal therapy (GAHT) on cognition and emotional state in transgender men and women initiating therapy
Subjects and Methods:- Transgender men (TM) aged 24.6±7.8 y (18-37), and 11 transgender women (TW) 27.3±9.4 (19-46).- Mood questionnaires (PHQ9 and GAD-7), and cognitive tests (short-term logical memory test, sub-tests of knowledge, forward and backward digit recall, number-coding and random learning from WAIS-III, a verbal fluency test and CTMT test) were administered prior to GAHT, and 3-6 months into treatment.
- Scores were calculated for emotional stress, memory, attention, and executive functions.
- Wilcoxon tests for paired samples assessed the impact of GAHT on these variables.
Results
- In TM, GAHT significantly improved executive functions but had no effect on memory, attention, and emotional stress.
- In TW, GAHT significantly improved memory but had no effect on attention, executive functions, and emotional stress.
- Despite a trend for improved emotional stress with GAHT in both groups, over this short study period, this was not significant.
Conclusions:- - In keeping with the literature, this short preliminary study showed that estrogen contributes to memory, and testosterone to executive functions.-- This is the first time this has been shown in transgender individuals.
-The lack of effect on emotional stress is probably due to the small sample size and short duration, larger studies should elucidate this point.
Presentation: Saturday, June 17, 2023
SAT413 Feminising Gender Affirming Hormone Therapy Prolongs QTc Interval
Authors: Angus Lachlan , Lin Tina , Leemaqz Shalem , Grossmann Mathis , Zajac Jeffrey D , Cheung Ada S 
Published: October 2023

Abstract
Disclosure: L. Angus: Speaker; Self; Kirin Brewery. T. Lin: None. S. Leemaqz: None. M. Grossmann: None. J.D. Zajac: None. A.S. Cheung: None.
Background: In trans people using feminising hormone therapy there is an increased risk of cardiovascular events including conduction disorders. It is known that the QTc interval is longer in cisgender women of reproductive age than cisgender men, attributed to factors including serum sex steroid concentrations. Androgen deprivation therapy in men with prostate cancer is associated with prolongation of the QTc interval, but the effects of feminising hormone therapy in trans women are unclear. Methods: We measured the automated QTc interval from a 12-lead electrocardiogram at baseline and 6 months in trans women newly commencing feminising hormone therapy. Sex steroid concentrations were measured by LCMS. Participants were part of a randomised controlled double-blind trial of spironolactone 100mg daily versus cyproterone acetate 12.5mg daily in transgender women commencing estradiol for feminisation (ANZCTR 12620000339954) and this was a prespecified secondary outcome. Statistical analysis was performed using a linear mixed effects model looking at the effects of treatment over time. Results: Sixty-three participants were randomised and 55 participants completed the trial and were included in analysis (spironolactone group n=27, cyproterone acetate group n=28). Baseline group characteristics were comparable. Overall, the QTc interval increased by 18ms (95% CI 14 - 23 ms; p&lt;0.001) at 6 months compared to baseline, but there was no between group difference (p=0.23). One participant had a QTc interval above 450ms. The mean serum total testosterone concentrations were similar between groups at baseline (spironolactone group 16.9 (13.5 - 20.3) nmol/L vs cyproterone acetate group 18.0 (15.0 - 21.0) nmol/L, p=0.60) but higher in the spironolactone group 4.3 (2.0 - 6.5) nmol/L than the cyproterone acetate group 1.5 (0.0 - 2.9) nmol/L, p&lt;0.05 at 6 months. The mean serum estradiol and serum potassium concentrations were similar between groups at baseline and 6 months. Conclusions: Feminising hormone therapy with estradiol and either spironolactone or cyproterone acetate in trans women is associated with prolongation of the QTc interval over a six-month period. Further research is required to investigate the incidence of cardiac arrhythmia in this population.
Presentation: Saturday, June 17, 2023
OR31-04 Testosterone Therapy On Gender Dysphoria, Depression, And Suicidality In Transgender And Gender Diverse Individuals Seeking Masculinisation: A Randomised Controlled Trial
Authors: Nolan Brendan J , Zwickl Sav , Zajac Jeffrey D , Cheung Ada S 
Published: October 2023

Abstract
Disclosure: B.J. Nolan: None. S. Zwickl: None. J.D. Zajac: None. A.S. Cheung: None.
Background: Testosterone treatment is a necessary component of management for some transgender (trans) and gender diverse individuals. Observational studies have demonstrated improvements in gender dysphoria and depression following commencement of gender-affirming hormone therapy but there is a lack of randomised controlled trial data.
Objectives: To assess the impact of testosterone therapy compared to no treatment on gender dysphoria, depression, and suicidality in trans people seeking masculinisation.
Methods: Three-month open-label randomised controlled trial of 64 trans individuals seeking initiation of testosterone therapy comparing immediate testosterone commencement (intervention group) with no treatment (standard care waiting list of 3 months prior to commencement). This design ensured no individuals would be waiting longer than standard care. Primary outcome was gender dysphoria, as measured by the Gender Preoccupation and Stability Questionnaire (GPSQ). Secondary outcomes included the Patient Health Questionnaire-9 (PHQ-9) to assess depression and the Suicidal Ideation Attributes Scale (SIDAS) to assess suicidality. Questionnaires were undertaken at 0 and 3 months. ANCOVA was used to compare mean differences between groups.
Results: Compared to standard care, the intervention group had a decrease in gender dysphoria [mean difference -7.2 points (95% CI (-8.3, -6.1), p&lt;0.001], a clinically significant decrease in PHQ-9 [mean difference -5.6 points (-6.8, -4.4), p&lt;0.001], and a decrease in SIDAS [mean difference -6.5 points (-8.2, -4.8), p&lt;0.001]. Resolution of suicidality assessed by PHQ-9 item 9 occurred in 11 (52%) individuals with immediate testosterone commencement compared to 1 (5%) in standard care (p=0.002).
Conclusions: This randomised controlled trial supports the use of testosterone therapy to significantly reduce gender dysphoria, depression, and suicidality in trans and gender diverse individuals desiring testosterone therapy.
Presentation: Sunday, June 18, 2023
THU477 Drivers Of Estrogen Induced Invasive Lobular Carcinoma
Authors: Ufondu Chinasa , Clem Larkin , Musick Maggie , Sikora Matthew Joseph , Ostrander Julie Hanson 
Published: October 2023

Abstract
Disclosure: C. Ufondu: None. L. Clem: None. M. Musick: None. M.J. Sikora: None. J.H. Ostrander: None.
Invasive lobular carcinoma (ILC) is an estrogen-receptor (ER)-positive histologic subtype of breast cancer typically treated with anti-estrogens (i.e., tamoxifen and aromatase inhibitors). Anti-estrogen resistance and disease progression occur in about 34% of patients with ILC, but mechanisms of resistance have been underexplored. Additionally, estrogen-only hormone replacement therapy increases the risk of ILC, but not the more common invasive ductal carcinoma (IDC), highlighting a potentially unique role for estrogen in ILC initiation and progression. To identify mediators of estrogen-induced ILC progression we are using the the mouse mammary intraductal (MIND) model, which better recapitulates the progression of ILC and response to estrogen in vivo. MM134, MM330, and SUM44PE ILC cell lines were injected intraductally into the #4 mammary glands of NSG mice. Mice were monitored for up to 20 weeks with or without estrogen supplemented in the drinking water. Our results show that MIND supports an in situ-like to invasive disease progression for ILC cell lines, and that estrogen accelerated tumor growth and invasion in vivo. Current studies are aimed at identifying mediators that drive estrogen-induced tumor growth and invasion in vivo, focusing on E-cadherin (CDH1) loss as the genetic hallmark of ILC occurring in ∼95% of cases. We aim to identify how loss of E-cadherin in normal human mammary epithelial cells (HMECs) may lead to reprogramming of ER and promote the development of ILC. We are developing a CRISPR/Cas9 approach for knocking out CDH1 in HMECs. We will study estrogen response in the CDH1-knockout versus control HMECs in vitro to examine whether loss contributes to ILC-specific estrogen activity. Using the MIND model, we will engraft the control and knockout cells into the ducts of adult female NSG mice and monitor tumor growth through bioluminescence imaging. ER reprogramming will be assessed in the engrafted cells using RNAseq and CUT&RUN (Cleavage Under Target & Release Using Nuclease). We predict that E-cadherin loss will reprogram ER DNA binding, dysregulate transcription factors linked to E-cadherin, such as TCF/LEF, and confirm critical downstream regulators that mediate estrogen-driven tumorigenesis. Understanding the unique contributions of ER in ILC could lead to new therapeutic strategies for the prevention and treatment of ILC.
Presentation: Thursday, June 15, 2023
THU478 Unchecked Kinase Activation Underlies Pituitary Adenomas Causing Cushing’s Disease
Authors: Asuzu David , Mullaney Dustin , Li Yan , Mandal Debjani , Tatsi Christina , Nieman Lynnette K , Chittiboina Prashant 
Published: October 2023

Abstract
Disclosure: D. Asuzu: None. D. Mullaney: None. Y. Li: None. D. Mandal: None. C. Tatsi: None. L.K. Nieman: None. P. Chittiboina: None.
Introduction: Common mechanisms underlying canonically mutated (USP8, USP48 and BRAF) and ‘wildtype’ pituitary adenomas causing Cushing’s disease remain unknown. Using syngeneic, pairwise transcriptomic analysis at the single cell/nucleus resolution, we found a ubiquitous and robust overexpression of PPP1R17 in CD adenoma corticotrophs. The role of PPP1R17, an endogenous inhibitor of tumor-suppressor phosphatase PP2A in the embryonic context remains unknown in the pituitary. Here, we elucidated mechanistically, the effect of PPP1R17 on the phopshoproteome of CD adenomas.
Methods: We quantitatively profiled the proteome and phosphoproteome of three pairs of CD adenomas and their syngeneic adjacent normal pituitary glands with TMT labeling and mass spectrometry (LC-MS/MS). We validated the mechanisms with murine corticotroph cells (mCort) overexpressing R17 (mCortR17) or GFP (mCortGFP). Elevated total and phosphprotein expression was assessed using R packages by performing cross sample normalization, noise filtering and differential protein abundance or phosphorylation analyses. Pathway enrichment analysis was performed on the KEGG database using ShinyGo 0.76.2.
Results: We identified 37 proteins differentially phosphorylated in CD adenomas compared to adjacent normal pituitary glands, including the AP2-associated protein kinase 1 (Aak1) and the apoptotic chromatin condensation inducer Acin1. Of these 37 proteins, 30 (81%) were also differentially phosphorylated in mCortR17 versus mCortGFP cells, suggesting that differential phosphorylation in CD is driven by R17 hyperactivity. Of the 35 proteins overabundant in CD adenomas, 15 (43%) overlapped with mCortR17, including the Myc-associated protein (Max) and Presenilin 1 (Psen1). Proteins enriched in both human CD and mCort datasets were involved in NOTCH signaling and neurotransmitter release, while phospho-proteome profiling highlighted R17-mediated perturbation of RNA polymerase II transcription termination and mRNA processing.
Conclusions:We first discovered a heavily dysregulated phosphoproteome in CD adenomas compared to syngeneic normal glands. We found that we could replicate the signature phosphoproteomic profile by overexpressing PPP1R17 in-vitro. These data indicate a central role for phosphatase (PP2A) inhibition in CD adenomas, and suggest potential novel anti-tumor targets for patients with CD.
Presentation: Thursday, June 15, 2023
THU480 Loss Of Selenof And A Western Diet Promote Mammary Tumorigenesis
Authors: Flowers Brenna , Zigrossi Alexandra , Diamond Alan , Kastrati Irida 
Published: October 2023

Abstract
Disclosure: B. Flowers: None. A. Zigrossi: None. A. Diamond: None. I. Kastrati: None.
SELENOF is an understudied selenium-containing protein which has previously been postulated to behave as a tumor suppressor in the breast. Examination of patient databases showed that SELENOF levels were lowest in tumors from patients with aggressive late-stage breast cancers. Whether loss of SELENOF drives breast tumorigenesis remains to be determined. To address this question, we used juvenile female wild type or systemic Selenof knockout mice and exposed them to 7,12-Dimethylbenz[a]anthracene (DMBA), a carcinogen which replicates the multistep process of breast tumorigenesis. Previous reports have shown that loss of Selenof led to glucose and metabolic dysregulation in mice suggesting a link between Selenof and metabolism. Because obesity is a risk factor in breast cancer, we challenged the mice with a western diet, high in fats and in calories, to mimic obesity. We hypothesized that loss of Selenof would promote DMBA-induced tumorigenesis and the western diet would exacerbate it. We found that tumor incidence was in fact highest in the Selenof knockout mice and western diet group. The Selenof knockout mice exhibited higher weights and higher fasting glucose levels consistent with metabolic dysfunction. These findings indicate that lower or loss of SELENOF expression may predispose a subset of women, especially obese ones, to increased risk of breast cancer. The link between SELENOF, obesity, and breast cancer warrants further investigation.
Presentation: Thursday, June 15, 2023
THU488 Genetic Alterations In CREBRF Influence Prostate Cancer Survival And Impact Prostate Tissue Homeostasis In Mice
Authors: Pascal Laura E , Frahm Krystle A , Skalitzky Kegan , DeFranco Donald Benedict , Rigatti Lora , Lu Ray , Liu Teresa 
Published: October 2023

Abstract
Disclosure: L.E. Pascal: None. K.A. Frahm: None. K. Skalitzky: None. D.B. DeFranco: None. L. Rigatti: None. R. Lu: None. T. Liu: None.
Background: Risk factors for prostate cancer include age, environmental factors, race and ethnicity. Genetic variants in cyclic-adenosine-monophosphate-response-element-binding protein 3 regulatory factor (CREBRF) gene are frequently observed in Pacific Islanders, a population with elevated prostate cancer incidence. CREBRF has been shown to play a role in other cancers, however its function in prostate homeostasis and tumorigenesis has not been previously explored. Methods: Alterations in CREBRF were identified in prostate cancer patients via in silico analysis of several publicly available datasets through cBioPortal. Male Crebrf knockout mice were generated and examined for prostate defects at 4 months of age. Immunohistochemical staining of murine prostate sections was used to determine the impact of Crebrf knockout on proliferation, apoptosis, inflammation and blood vessel density in the prostate. Serum adipokine levels were measured using a Luminex Multiplex Assay. Results: CREBRF alterations were identified in up to 4.05% of prostate tumors and the mutations identified were categorized as likely damaging. Median survival of patients with CREBRF alterations was 41 months, compared to 131 months for patients without CREBRF alterations. In the murine model, the prostates of Crebrf knockout mice had reduced epithelial proliferation and increased TUNEL+ apoptotic cells. Circulating adipokines PAI-1 and MCP-1 were also altered in Crebrf knockout mice compared to age-matched controls. Conclusions: Prostate cancer patients with CREBRF alterations were associated with decreased overall survival suggesting that CREBRF may play a role in prostate tumorigenesis and progression. The murine knockout model demonstrated that CREBRF could modulate proliferation and apoptosis and macrophage density in the prostate. Serum levels of adipokines PAI-1 and MCP-1 were also altered and could contribute to the phenotypic changes observed in the prostates of Crebrf knockout mice. Future studies focused on populations susceptible to CREBRF mutations and mechanistic studies will be required to fully elucidate the potential role of CREBRF in prostate tumorigenesis.
Presentation: Thursday, June 15, 2023
THU489 The Role Of Noncoding Genes With The Bidirectional Promoter In Triple-negative Breast Cancer
Authors: Yang Barbara , Sedano Melina , Jimenez Maria Vanessa , Ramos Enrique Ivan , Gadad Shrikanth 
Published: October 2023

Abstract
Disclosure: B. Yang: None. M. Sedano: None. M.V. Jimenez: None. E.I. Ramos: None. S. Gadad: None.
Breast cancer is the second leading cause of cancer mortality in women after lung cancer. Breast cancer is grouped into different molecular subtypes; triple-negative breast cancer (TNBC) accounts for 20%. TNBC is a highly aggressive histologic subtype; the lack of unique therapeutic targets makes it harder to treat. Recent studies have implicated genes involved in cancers that are transcribed using a process known as divergent transcription. The expression of these genes is tightly regulated; however, many escape regulation and become aberrantly expressed in tumors. Interestingly, our genomic analysis suggests that several of these genes encode noncoding transcripts. Analysis of transcriptome from different tissue types, including cancer and normal, revealed that many are upregulated in various cancers. Selected divergent transcript, such as lncRNA67, has been completely characterized (transcription start and stop site, 5’ cap, polyA tail, and exon/intron structure) and cloned. In functional assays, overexpression of lncRNA67 regulates gene expression, cell proliferation, and tumor growth. Our molecular analyses indicate that lncRNA67 plays a vital role in triple-negative breast cancer biology. Collectively, our results suggest that divergent transcripts are an integral component of cancer biology and present a new repertoire of diagnostic and potential therapeutic targets.
Presentation: Thursday, June 15, 2023