bluuebunny/crossref_metadata_2025_split huggingface dataset:
RF03 | PMON290 Transcriptional regulation of immune-pathways by chromatin reader ZMYND8 in triple-negative breast cancer
Authors: Ramos Enrique , Swagata Adhikari , Choudhari Ramesh , Das Chandrima , Gadad Shrikanth 
Published: November 2022

Abstract
Zinc Finger transcription factors are crucial in modulating various cellular processes, including inflammation and immune response. Zinc Finger MYND (Myeloid, Nervy, and DEAF-1) type containing 8 (ZMYND8), a putative chromatin reader. We have observed this chromatin reader's unique role in regulating immune genes expression in triple-negative breast cancer (TNBC). TNBC is a very aggressive subtype of breast cancer. It is characterized as a heterogeneous group of tumors defined by the absence of estrogen receptor, progesterone receptor, and overexpression of the human epidermal growth factor receptor 2 gene. Ectopic expression and genetic deletion of ZMYND8 in triple-negative breast cancer cells modulated the expression of several genes implicated in immune response and cancer. Mechanistically, ZMYND8 regulates transcription by epigenetically modulating key promoters of target genes. Collectively our results elucidate a novel role for ZMYND8 in triple-negative cancer biology.
This work was supported by grants from the Cancer Prevention and Research Institute of Texas (RR170020) and the Lizanell and Colbert Coldwell Foundation to S.S.G.
Presentation: Saturday, June 11, 2022 1:54 p.m. - 1:59 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF07 | PSUN384 Hepatocyte Deletion of IGF2 Prevents DNA Damage and Tumor Formation in Hepatocellular Carcinoma
Authors: Das Manasi , Ellies Lesley , Jih Lily , Kumar Deepak , Oberg Alexis , Sahoo Debashis , Sauceda Consuelo , Webster Prof Nicholas , Wu Panyisha 
Published: November 2022

Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide with a 18% 5-year survival rate. Mice lacking the splicing factor SRSF3 in hepatocytes (SKO mice) overexpress IGF2 and are predisposed to developing HCC with age. Loss of Igf2 in the SKO background prevented hepatic fibrosis and inflammation, and completely prevented tumor formation. This was associated with decreased proliferation, apoptosis and DNA damage, and restored DNA repair enzyme expression. Mechanistically, IGF2 treatment of HepG2 cells in vitro caused DNA damage and decreased DNA repair enzyme expression, and tumors from the SKO mice show mutational signatures consistent with double strand break and defective mismatch repair. Looking at human data, HCC patients with high IGF2 mRNA expression had worse survival compared to patients with normal IGF2 expression. The patients also showed a switch in IGF2 promoter usage that correlated with increased expression. HCC patients having high SRSF3 mRNA expression also showed poor survival as did patients with alterations in known SRSF3-dependent splicing events. The level of SRSF3 protein was decreased 6-fold in human HCC tissues compared with normal liver tissues. The results indicate that IGF2 overexpression in conjunction with reduced SRSF3 splicing activity could be a major cause of DNA damage and driver of liver cancer.
Presentation: Saturday, June 11, 2022 1:18 p.m. - 1:23 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSAT024 A Case of Mild Autonomous Cortisol Secretion Managed with Active Surveillance
Authors: Thakkar Aditi , Greb Alexandra , Reikes Andrew 
Published: November 2022

Abstract
Mild autonomous cortisol secretion is characterized by the failure to suppress cortisol sufficiently after dexamethasone administration but without the stigmata of overt Cushing's syndrome. This condition, diagnosed in up to 50% of adrenal incidentalomas, has low overall rates of progression and mild cases can present a treatment dilemma. Here we describe one such case of cortisol excess well managed with a surveillance strategy rather than surgical intervention.
A 49-year-old female with a past medical history of hypothyroidism was evaluated in the endocrine clinic for an incidental adrenal mass. CT imaging revealed a 2.7 cm left adrenal nodule, stable in size compared to prior imaging, with features typical of benign adrenocortical adenoma. Initial 1 mg DST with 8 am cortisol of 11.7µg/dl. Late night salivary cortisol (LNSC)level was found to be elevated at 130 ng/dl (nl&lt;100 ng/dL). At that time, 24-hour urine free cortisol (UFC) was found to be borderline at 23.98 µg/day (nl&lt;24 µg/day). Further testing at 6 months and 1 year from initial assessment showed persistently elevated LNSC level (110 ng/dL) and stable 24-hour UFC at 24 µg/day. Morning ACTH level was 19 pg/mL. One year after initial assessment, LNSC continued to be elevated at 0.106 µg/dL (nl &lt;0.010–0.090 µg/dL) and repeat overnight 1 mg DST with 8am cortisol was unsuppressed at 10 mcg/dL representing at least two years of autonomous, mildly elevated cortisol levels. DHEA-S was low at 13.6 µg/dl (41.2 - 243.7 µg/dL). She had no history of diabetes, hypertension, obesity, hyperlipidemia or clinical osteoporosis. Her social history was negative for tobacco or alcohol abuse. Repeated physical exams were within normal limits, and she did not have any signs of central adiposity, abdominal striae, thinning of skin or hirsutism. She continued to deny any subjective symptoms of lethargy or muscle weakness.
Given low normal range ACTH values, mildly increased midnight salivary cortisol, failure to suppress after 1 mg overnight DST with no clinical evidence of overt hypercortisolism, patient was diagnosed with mild autonomous cortisol secretion. She did not show any signs of hypertension, hyperglycemia or physical changes that would warrant concern for hypercortisolemic end organ effects. As the patient was largely asymptomatic, with stable CT imaging of left adrenal adenoma, left adrenalectomy was discussed but not recommended as patient preferred an observation surveillance strategy with laboratory evaluation every 6 months to monitor for hypercortisolemia. This case demonstrates that a surveillance strategy, rather than surgery, may be appropriate in selected cases of mild autonomous cortisol secretion from an incidentally discovered adrenocortical adenoma, especially when end organ effects of cortisol excess are clinically absent.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
OR20-1 Impact of Intra-Procedural Sedation on Outcomes of Adrenal Vein Sampling
Authors: Chee Nicholas , Chong Winston , Doery James , Fuller Peter , Lau Kenneth , Libianto Renata , Shen Jimmy , Wan Ken , Yang Jun 
Published: November 2022

Abstract

Background
The subtyping of primary aldosteronism (PA) requires interpretation of aldosterone and cortisol concentrations measured during adrenal vein sampling (AVS). The use of intravenous sedation during AVS is not standardized but may affect AVS outcomes.

Purpose
To characterize the impact of sedation on the outcomes of AVS, including cortisol and aldosterone concentrations, cannulation success and rates of lateralisation.

Materials and Methods
This is a retrospective cohort study based at a tertiary health centre. Consecutive patients who underwent AVS both before and after ACTH stimulation between June 2018 and July 2020 were included. AVS was performed without IV sedation in patient cohort 1 (n = 70), with sedation (midazolam and fentanyl) in cohort 2 (n = 34) and both before and after sedation in cohort 3 (n = 14). Comparisons were performed using the nonparametric (Mann Whitney U) test for continuous variables and the Chi square test for categorical variables.

Results
Overall, 118 patients (median age, 53 years; 67 men) were evaluated with no significant demographic differences between the three cohorts. Compared to cohort 1, patients in cohort 2 displayed significantly lower cortisol concentrations in the peripheral vein (median of 141 nmol/L vs 218 nmol/L), left adrenal vein (522 nmol/L vs 1284 nmol/L) and right adrenal vein (577 nmol/L vs 1578 nmol/L) in unstimulated AVS. Fewer patients were assessed to have successful right sided cannulation in cohort 2 (79% vs 93% in cohort 1, p = 0.047). In cohort 3, cortisol concentrations were markedly lower after sedation, with the decrease being more marked in the adrenal veins compared to peripheral veins, hence leading to lower selectivity indices. There were no clinically significant changes in aldosterone concentration or rates of lateralisation after sedation.

Conclusions
IV sedation reduces cortisol concentrations during unstimulated-AVS, leading to lower selectivity indices and fewer cannulations judged as successful. Importantly, radiologists are turning to point-of-care rapid cortisol tests to determine if the catheter is 'in' the adrenal vein in real-time. Adrenal vein samples collected after sedation are more likely to be considered "unsuccessful" using these semi-quantitative assays. The need for IV sedation during AVS should be carefully assessed.
Presentation: Monday, June 13, 2022 11:00 a.m. - 11:15 a.m.
OR20-6 Histopathology and Genetic Causes of Primary Aldosteronism in Young Patients
Authors: Baker Jessica , Bancos Irina , Bick Nolan , Cohen Debbie , Else Tobias , Giordano Thomas , Liu Chia-Jen , Lyden Melanie , Nanba Kazutaka , Rainey William , Reincke Martin , Udager Aaron , Wachtel Heather , Williams Tracy , Young William , Blinder Amy 
Published: November 2022

Abstract

Background
Primary aldosteronism (PA) is the most common cause of endocrine-related hypertension. However, due to its rare incidence in younger patients, the molecular features of young-onset PA have not been well defined. Recent advances in targeted mutation analysis have identified aldosterone-driver somatic mutations in aldosterone-producing lesions including aldosterone-producing adenomas (APAs) and aldosterone-producing nodules (APNs).

Objective
To determine the histologic and somatic mutation profile in young-onset PA.

Methods
Formalin-fixed paraffin-embedded adrenals from 73 patients with unilateral PA (53 women, 19 men, and one with unknown sex) under 35 years old were analyzed. Aldosterone synthase (CYP11B2) immunohistochemistry was used to define the histopathologic classification of the aldosterone-producing lesions based on the HISTALDO consensus as well as guide DNA capture. Somatic mutations were identified by direct Sanger sequencing or Ion Torrent-based targeted next-generation sequencing.

Results
We identified 48 APAs, 20 APNs, 2 multiple aldosterone-producing nodules (MAPNs), and 3 non-functioning adenomas (NFAs). Of the 45 APAs and 18 APNs with successful sequencing, 43 APAs (96%) and 17 (94%) APNs harbored somatic mutations. The most frequent alterations in APAs were KCNJ5 mutations (35/45, 78%), while CACNA1D mutations were the most common in APNs (8/18, 44%). The mutation prevalence for KCNJ5 mutations did not vary between men and women. In both MAPNs, multiple CYP11B2-expressing lesions shared an identical somatic KCNJ5 mutation (c.451G&gt;A, p.G151R). No somatic mutations were detected in the 3 NFAs.

Conclusion
APAs are the most common histologic feature of unilateral young-onset PA. Somatic KCNJ5 mutations are more commonly seen in APAs in both men and women, while somatic CACNA1D mutations are frequently seen in APNs in these younger patients.
Presentation: Monday, June 13, 2022 12:15 p.m. - 12:30 p.m.
PSUN52 Patients with Left Ventricular Hypertrophy on Echocardiography are Frequently Evaluated with Renin and Aldosterone
Authors: Lieberman Leedor , Auchus Richard , Hench Christiana , Troost Jonathan , Kolias Theodore , Byrd James Brian , LaBounty Troy 
Published: November 2022

Abstract

Background
Increased left ventricular (LV) mass is an independent predictor of cardiovascular morbidity and mortality. Primary aldosteronism (PA) is associated with increased LV mass regardless of concomitant essential hypertension. Therefore, we hypothesize that the findings of increased LV mass approximated by left-ventricular hypertrophy (LVH) on echocardiogram relate to renin-independent hyperaldosteronism.

Methods
We performed a retrospective review of patients who underwent echocardiography at our institution between April of 2013 and September of 2017 (n=98,007 individuals). Of this population, we identified patients who underwent transthoracic echocardiography who met criteria for LVH based on current American Society of Echocardiography guidelines using the interventricular septal thickness in diastole (IVSd) and left ventricular posterior wall thickness in diastole (LVPWd). We excluded patients who underwent isolated transesophageal imaging as well as those who had significant structural cardiac abnormalities other than LVH. This cohort was analyzed with an internal self-service data tool to determine if patients had undergone biochemical evaluation with serum aldosterone and renin, which defined the final analytical cohort.

Results
We identified 19,664 patients with LVH of whom 5.8% (n = 1132) underwent biochemical evaluation with serum aldosterone and corresponding plasma renin activity (PRA) or direct renin concentration (DRC). In all patients with LVH, the mean IVSd was 11.7 ± 1.2mm in those who underwent biochemical testing and 11.5 ± 1.2 mm in those who did not (p &lt;0.001); the mean LVPWd was 11.4 ± 1.1 mm mm in those who underwent biochemical testing and 11.3 ± 1.1 mm in those who did not (p &lt;0.001). Of African American patients with LVH, 9.8% underwent biochemical testing; 5.0% of Caucasian patients with LVH underwent testing. The median PRA was 0.9 ng/mL/h with a median aldosterone to renin activty ratio (ARR) of 8.9 ng/dL-ng/mL/h. . The majority (54.4%) of individuals who underwent testing with plasma renin activity had a PRA ≤ 1.0 ng/mL/h.

Conclusion
Patients with LVH are being evaluated with renin and aldosterone at a higher frequency than patients with resistant hypertension and other guideline based indications for PA screening. Individuals evaluated with renin and aldosterone had increased IVSD and LVPWd, suggestive of more extensive LVH, compared with other individuals with LVH. LVH may be a sensitive screening criterion for PA. Additional prospective studies are necessary.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
OR08-1 PROP1 Is Not Essential For Pituitary Cells Terminal Differentiation
Authors: Carvalho Luciani , Chang Claudia , Mendoca Berenice , Marques Juliana 
Published: November 2022

Abstract

Introduction
The pituitary gland controls several mechanisms as metabolism, growth, and reproduction, in response to hypothalamic stimuli. The adequate temporal/ spatial expression of transcription factors is mandatory for a normal pituitary development. PROP1 transcription factor is widely known as a key pituitary regulator. Pathogenic variants in the PROP1 gene are the main familial causes of hypopituitarism accounting for about 54% of the cases.

Aim
To characterize the expression of genes involved in pituitary cells determination and specification during pituitary high demand period such as sexual maturation compared to adulthood in the Ames mice.

Methods
Weight and naso-anal length were measured. Pituitary glands were collected from 5 wild type (WT) and 5 prop1 mutant (Mut) animals with 30 (P30), 40, (P40), and 60 (P60) days after birth. RT-qPCR was performed to analyze the pituitary transcription factors Sox2, Sox3, Hesx1, Otx2, and genes codifying the hormones GH, TSH, LH/ FSH, CGA, and PRL by SYBR® Green (QIAGEN, Valencia, CA). They were normalized by endogenous genes and performed in triplicate. The target genes relative quantification was performed using the mutant related to its age paired wild type as a calibrator and the results were expressed as fold change. Immunofluorescence of SOX2 (ab97959, Abcam, UK) (1: 1600) and pituitary hormones GH, LH, and FSH (1: 250) were done in pituitaries at P60 and its aged paired control, stained with propidium iodide (1: 1000) for nucleus and the secondary antibody Alexa FluorÒ488 (ab150077, Abcam, UK) (1: 1000).

Results
All mutant mice presented decreased weight and naso-anal length at the three analyzed periods. The expression of the pituitary stem/ progenitor cell marker Sox2 was increased at P30 and P60 and decreased at P40. Sox3 was increased at P30 and decreased at P40 and P60. Hesx1 was increased at P30 and P60 and decreased at P40. Otx2 was increased at all periods. At P30 the genes codifying pituitary hormones was decreased, except for Tsh and Fsh. At P40 it was observed increased expression of the genes codifying Gh, Lh, Fsh and Prl, while Tsh and Cga expression was reduced. At P60 all pituitary hormones codifying genes presented decreased expression. The immunofluorescence at P60 showed increased expression of SOX2, similar expression of FSH, and decreased expression of GH and LH related to their age paired WT.

Conclusion
Despite the absence of PROP1, Hesx1 is downregulated at P40. Pituitary cell subtype differentiation and hormonal production is observed at transcriptional and protein levels, showing that pituitary cells can differentiate and produce hormones in the absence of Prop1. The recovery of pituitary capacity to differentiate in mutant suggests the involvement of another factor in the pituitary cell differentiation pathway that could compensate the lack of Prop1.
Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.
OR22-4 Homing of Antigen-specific Engineered Regulatory T Cells To Human Pancreatic Islets
Authors: Imam Shahnawaz 
Published: November 2022

Abstract
The therapeutic application of regulatory T cells (Tregs) for the treatment of autoimmune disorders, although efficacious, has been limited by the scarcity of antigen-specific Tregs. If antigen-specific Tregs, capable of reaching the desired autoimmune target, could be produced on demand, antigen-specific immune suppression of autoimmune diseases would be achievable. One approach to endow T cells with a desired antigen-specificity uses chimeric T cell antigen-receptors (CAR) with antibody-type specificity. Adoptive cell transfer therapies with CAR-re-directed cytotoxic T cells, have shown impressive efficacy in the treatment of hematologic malignancies. Accordingly, employing such technology to re-direct Tregs to sites of autoimmune attack may be a useful therapeutic approach to alleviate a broad spectrum of diseases in which uncontrolled auto and alloimmune responses play a major role. We recently developed pancreatic beta-cell, antigen-specific, CAR Tregs (1) and explored their therapeutic potential against T1D in our humanized mouse model (2). Ours is the first successful, antigen-specific CAR-Treg treatment of T1D in a humanized mouse model that closely resembles the human disease. Based on our mice data, we believe treatment with pancreatic beta-cell, antigen-specific CAR-Tregs will allow for recovery and reconstitution of beta cells in human T1D patients as well. The purpose of this study was to determine if antigen-specific human CAR Tregs could also identify target and home to human pancreatic islets in culture as they do in mice. The study involved drawing 10 cc of blood 1-2 weeks prior to pancreas surgery; followed by collection of a small piece of pancreas (5 cc wedge) once the pancreas was removed for a clinical indication (cancer, pancreatitis). We first isolated Tregs from peripheral blood of these human donors and expanded them in vitro. Treg cells were genetically modified to express either a beta-cell antigen-specific (GAD65) CAR or an irrelevant (EPCAM) CAR construct together with GFP marker. CAR Tregs were selectively expanded in the presence of rhGAD65 antigen. Once pancreas tissue became available, it was processed for islet separation using the collagenase method. Pancreatic islets were then co-cultured with syngeneic CAR Tregs for 7 days. IncuCyte S3 Live-cell System (Sartorius) is a real-time system that automatically acquires and analyzes HD, phase and fluorescent images of cell cultures, around the clock, for 7 days, while cells remain undisturbed. Live immunofluorescence microscopy demonstrated the distinct homing of GAD65 CAR Tregs to islets as compared to control EPCAM CAR Tregs as early as 24 hours of co-culture. Importantly, proliferation of GAD65 CAR Tregs was clearly demonstrated within 72 hours. GAD65 CAR Treg cytokine profile from co-culture supernatant was characteristic of activated Tregs. 1 PATENT #WO2020097546 2 PATENT #US20200037586
Presentation: Monday, June 13, 2022 11:45 a.m. - 12:00 p.m.
LBMON172 Impact Of Photoperiodic Green Light During Incubation On Change Hormone In The Embryo Of Chicken
Authors: Abdulateef Salwan , Farhan Sufyan M , Awad Muthanna M , Mohammed Thafer T , Al-Ani Mohammed Q , Al-Hamdani Adel 
Published: November 2022

Abstract

Background
The poultry industry discovered that an increase in light intensity can accelerate embryonic development. In nature, chicken embryos of different ages and species certainly receive some light during incubation, while, in industrial hatcheries, eggs are incubated in darkness for 21 days, so exposing fertile eggs to light can increase the embryo's growth and decrease the incubation period.

Objectives
The aim of this study was to assess the effect of exposure of fertile Ross 308 eggs to a photoperiod of green on accelerates embryo development and alters hatch-related hormones (growth hormone, thyroid, and corticosterone).

Methods
This study was carried out to evaluate the impact of the photoperiod of green light from day 1 to day 18 of incubation time, on embryo growth, and hormone concentration (growth hormone, thyroid, and corticosterone). In the Three groups, no light-dark cycle was used in the first group (LD), the second group was used 12-h light, 12-h dark (LDL), and the third group was used 24-h light (LL), the third group. The light was provided by light wavelength green LED light (522 nm) mounted in a frame that was placed above the top tray of eggs to give an even spread of illumination. Eggs (n=300/group) with four replicates (n=25/replicate) from fertile Ross 308 broiler breeders were used in this experiment. Hormones were measured using a kit supplied by the (Sunlong Biotech Co., Ltd) company for all hormones using an ELISA device, samples were taken at the age of 7, 14, and 18 days of hatching using blood drawn from the eggshell using a 1 ml syringe with a 23-gauge needle.

Results
The results showed a significant improvement (P&lt;0. 01) in the concentration of growth hormone, thyroid, and corticosterone) to the second group was used 12-h light, 12-h dark (LDL), compared to the other of groups.

Conclusions
The results of this study indicate that green light accelerates embryo development and alters hatch-related hormones (growth hormone, thyroid, and corticosterone).
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.