bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT013 Characterization Of CRISPR/Cas9 Induced RXR Isotype Mutants In Xenopus Laevis
Authors: Furlow J David , Saini Simran , Mengeling Brenda J , Horb Marko E 
Published: October 2023

Abstract
Disclosure: J.D. Furlow: None. S. Saini: None. B.J. Mengeling: None. M.E. Horb: None.
Retinoid-X receptors (RXRs) occupy a unique position in the nuclear receptor (NR) superfamily. While some actions of the highly conserved RXRs may be independent, RXRs most often are heterodimer partners for several NRs that regulate development, reproduction and metabolism. As such, environmental chemicals interfering with the activity of RXRs and their partners may have significant deleterious effects on human health, often in developmental window, cell-type, and gene selective ways. The frog Xenopus has long served as an excellent model for studying vertebrate development including thyroid hormone action, and recent advances in genome editing have greatly enhanced its utility for investigating basic cell and organismal biology as well as human disease processes. To determine isotype specific roles in response to natural and synthetic ligands as well as candidate environmental chemicals interacting with RXRs in vivo, we created targeted germline mutations in the Xenopus tropicalis RXRα (rxra), RXRβ (rxrb), and RXRγ (rxrg) genes. For CRISPR/Cas9 mediated genome editing, guide RNAs were designed to target sequences just prior to or within the first RXR DNA binding domains. We raised all three RXR homozygous null mutants up to and through metamorphosis. The rxrb and rxrg homozygous null mutants completed metamorphosis and allowed us to establish adult null lines, but the rxra homozygous null mutants die at metamorphic climax, reminiscent of the thyroid hormone receptor (thra/thrb) double mutants. Some rxra mutant froglets also lack forearms or have forelimb defects, implying a role for rxra in RA mediated forelimb specification. The X. tropicalis rxrg homozygous null mutants show a trend toward an increased rate of metamorphosis versus matched wild-type controls, with significantly elevated tshb gene expression as newly metamorphosed froglets suggesting impaired negative feedback by TH. Significantly altered opsin gene expression in the froglet eye was also observed in rxrg mutant retinas: elevated short wave opsins opn1sw1 and opn1sw2 and sharply reduced long wave opsin opn1lw. This elevated tshb and opn1sw1 expression is highly similar to what is found in mouse rxrg null mutants; thus RXRγ action in the eye and pituitary appears to be highly conserved between mammals and amphibians. The establishment of these new RXR isotype mutant specific lines will support the expanded use of Xenopus to study basic biology and environmental toxicology involving TR-RXR and other NR-RXR partnerships.
Presentation: Saturday, June 17, 2023
SAT015 Improving The Quality Of Disease Biomarker Measurements In Patient Care And Research-CDC's Clinical Standardization Programs
Authors: Sugahara Otoe , Buchannan Tatiana , Danilenko Uliana , Ribera Ashley , Collins Lynn , Vasquez Norma , Dahya Komal , Pokuah Fidelia , Zhou Hui , Zhang Li , Lyle Alicia N , Vesper Hubert W , Long Lindsey , Knoblock Samantha , Flores Elias , Doty Alex 
Published: October 2023

Abstract
Disclosure: O. Sugahara: None. T. Buchannan: None. U. Danilenko: None. A. Ribera: None. L. Collins: None. N. Vasquez: None. K. Dahya: None. F. Pokuah: None. H. Zhou: None. L. Zhang: None. A.N. Lyle: None. H.W. Vesper: None.
High-quality disease biomarker tests are critical for the correct diagnosis and treatment of patients, accurate interpretation of research data, and effective use of research findings in health care. CDC’s Clinical Standardization Programs (CDC CSP) assist researchers and laboratories with assessing and improving the analytical performance of biomarker tests performed in patient care, public health, and research. CDC CSP develops and applies reference methods, materials, and protocols to consistently calibrate biomarker tests across instruments and laboratories and to assess and improve other analytical performance characteristics, such as analytical specificity. CDC CSP works with test manufacturers and laboratories operating in-house developed tests to correctly calibrate tests. Additional programs help clinical and research laboratories monitor the accuracy and reliability of tests over time. Furthermore, CDC CSP collaborates with researchers on the development of reference intervals and on using new and emerging biomarkers in patient care and public health. CDC CSP provides comprehensive programs for traditional blood lipids, testosterone, estradiol, vitamin D, and free thyroxine. Programs for free testosterone, parathyroid hormones, apolipoproteins, and angiotensin peptides will be available soon. CDC CSP collaborated with members of the Partnership for the Accurate Testing of Hormones (PATH) and established reference intervals for testosterone in men. CDC CSP is currently working to develop reference intervals for testosterone in women and for estradiol in postmenopausal women. A CDC CSP interlaboratory study on free thyroxine measurements showed high variability in calibration accuracy among free thyroxine assays. CDC CSP is using its reference methods and materials to minimize this variability. It is anticipated that assay recalibration may change measurement values for some tests by up to 50%. CDC CSP is working with PATH and the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) to educate stakeholders about the upcoming change in free thyroxine measurements.
Presentation: Saturday, June 17, 2023
OR22-03 Enhanced Endothelial Mineralocorticoid Receptor Signaling Mediates Diet - Induced Soleus Fat Infiltration And Insulin Resistance
Authors: Homan Carlton , Habibi Javad , Chen Dongqing , Whaley-Connell Adam , Sowers James R , Jia Guanghong 
Published: October 2023

Abstract
Disclosure: C. Homan: None. J. Habibi: None. D. Chen: None. A. Whaley-Connell: None. J.R. Sowers: None. G. Jia: None.
Skeletal muscle is an important organ in the storage and release of lipids in response to physiological changes in free fatty acid (FFA) supply and demand. Once fat tissue mass expansion exceeds its blood supply excess lipids are stored ectopically as small lipid droplets in non-adipose tissues such as skeletal muscle. Recently, our data found that mineralocorticoid receptors (MRs) mediate Western diet (WD)-induced lipid infiltration of skeletal muscle and insulin resistance. Related to this, MRs, the principal receptors for the hormone aldosterone in the kidney, also exist in vascular cells, including endothelial cells (ECs). Moreover, enhanced MR signaling in ECs (ECMR) induces arterial stiffening and impairs microcirculation. However, our understanding of the precise mechanisms by which enhanced ECMR activation promotes skeletal muscle insulin resistance remains unclear. In this study we investigated the roles of ECMR in soleus lipid accumulation and corresponding insulin resistance in diet-induced obesity. Six-week-old ECMR wild type (ECMR+/+) and knockout (ECMR-/-) mice were fed either a mouse chow diet or WD for 16 weeks. 16 weeks of WD induced increases in glucose intolerance, fasting plasma insulin levels, HOMA-IR and insulin resistance index were found to be blunted in ECMR-/- mice. ECMR-/- prevented WD-induced increase in soleus FFA levels without changing serum FFA levels. Meanwhile, WD also increased soleus intramyocellular lipid content, plasma EC derived exosomal CD36 and soleus CD36 protein levels. These abnormalities were related to reduced soleus insulin metabolic signaling in PI3K/Akt pathways, as these pathways were blunted in ECMR-/- mice. These findings indicate that EC specific MR activation contributes to diet-induced increases in CD36 expression, soleus fat infiltration, as well as systemic and skeletal muscle insulin resistance.
Presentation: Saturday, June 17, 2023
OR33-02 The Effects Of Timing And Patterns Of Hormone Stimulation On Single Molecule Dynamics And Gene Regulation In Vivo
Authors: Stavreva Diana A , Hoang Le , Wagh Kaustubh , Chari Raj , Upadhyaya Arpita , Hager Gordon L 
Published: October 2023

Abstract
Disclosure: D.A. Stavreva: None. L. Hoang: None. K. Wagh: None. R. Chari: None. A. Upadhyaya: None. G.L. Hager: None.
Even though most studies on hormonal signaling are performed under continuous stimulation, secretion of many hormones follows a circadian pattern, comprised of periodic (ultradian) pulses with short duration. Using glucocorticoid receptor (GR) signaling as a model system we have previously demonstrated that receptor occupancy of regulatory elements precisely tracks the hormonal pulses resulting in cyclic GR-mediated transcription (gene pulsing) (Stavreva et al., NCB 2009). Using various genomic approaches, we have also uncovered the impact of ultradian and constant stimulation on the lifetimes of chromatin accessibility and long-range promoter/enhancer interactions (Stavreva et al., Genome Res. 2015). By visualizing RNA synthesis from single-copy GR-regulated transcription sites (TSs) we demonstrated treatment-specific RNA bursting patterns. Moreover, our single molecule tracking (SMT) experiments showed that transcription factor (TF) dynamics determine burst duration and frequency (Stavreva et al., 2019). To further study the in vivo dynamics of various TFs we tagged the endogenous GR as well as the estrogen, progesterone receptor (ER and PR, respectively), and the large Pol II subunit (Rpb1) with Halo tag in MCF7 cells. We use SMT in combination with other microscopy and biochemical approaches to i) map the dynamics of TFs in response to constant and ultradian hormone stimulations, and ii) determine their effects on transcription regulation. These studies will help us better understand the importance of timing and pattern of hormone treatment for proper gene regulation in different physiological contexts.
Presentation: Sunday, June 18, 2023
THU674 Papillary Thyroid Carcinoma Presenting As A Benign Ectopic Thyroid Mass In The Anterior Mediastinum. A Case Report
Authors: Valdecanas David-Santos Mary Lourdes Grace , Narvacan-Montano Carolyn 
Published: October 2023

Abstract
Disclosure: M.V. David-santos: None. C. Narvacan-montano: None.
Background: Ectopic Thyroid Tissue (ETT) is a rare developmental anomaly that is due to the failure of the thyroid gland to assume its position in front of the trachea. Ectopic Thyroid tissue in the mediastinum is very rare, with only a few cases reported in the literature. An incidental Papillary Thyroid Carcinoma presenting as a mediastinal mass that turns out to be benign ectopic thyroid cells is even rarer. Case: This is the case of a 33-year-old female who presented with sudden onset difficulty of breathing and chest heaviness. On workup, she was found to have an anterior mediastinal mass, which showed ectopic thyroid cells on biopsy. Further evaluation of the neck area revealed a 1.25 cm x 1 x 1.13 cm nodule on the thyroid gland which showed suspicious for Papillary Thyroid Carcinoma on Fine needle aspiration biopsy. The patient underwent Total Thyroidectomy and Excision of the Anterior Mediastinal Mass. The histopathologic report of the thyroid mass revealed a Conventional Unifocal Papillary Thyroid Carcinoma, while the excised tissues comprising the mediastinal mass were consistent with benign ectopic thyroid tissues with colloid goiter. Conclusion: The presence of the ectopic thyroid mass in the anterior mediastinum may be a potential area for metastasis. The final pathologic report nevertheless, categorizes this Papillary thyroid carcinoma as having a low risk of metastasis as per the American Thyroid Association Classification of 2015. Hence the conservative approach of Suppression therapy and active surveillance is the choice of management for this unusual case.
Presentation: Thursday, June 15, 2023
FRI466 Toxic Retrosternal Goiter Following SARS-CoV-2 Vaccination
Authors: Schipper Joslyn , Abdul Sater Zahraa 
Published: October 2023

Abstract
Disclosure: J. Schipper: None. Z. Abdul Sater: None.
Since the outbreak of the SARS-CoV-2 pandemic, there have been reports of autoimmune thyroid diseases related to COVID inflection and SARS-CoV-2 vaccination. We report a case of SARS-CoV-2 mRNA vaccination (mCoVvax)-induced Graves with retrosternal extension. A 21-year-old Hispanic male with no previous history of thyroid illness presented with a 4-month history of tachycardia, tremors, agitation, unintentional weight loss, night sweats, low-grade fever, and orthopnea that developed 62 days after receiving the first dose of mCoVvax. His physical examination was significant for sinus tachycardia, hypertension, a resting tremor, brisk deep tendon reflexes, and diffuse nonpruritic maculopapular rash. His thyroid gland was diffusely enlarged with an unpalpable lower margin and positive Pemberton sign. TSH was undetectable with elevated Free T4 and Total T3 [11.0 (NL 0.8-1.8 ng/dL) and 800 (76-181 ng/dL), respectively]. Thyroid-stimulating immunoglobulin (TSI) was 337% (NL&lt;140%), and thyroid peroxidase antibody was 653 IU/mL (NL &lt; 9 IU/mL). Thyroid ultrasound showed a diffusely enlarged thyroid gland with diffusely increased thyroid uptake on technetium thyroid scan (95% and 85% uptake after 6 and 24 hrs, respectively), consistent with Graves’ disease. CT scan of the neck and chest confirmed retrosternal Goiter without tracheal deviation. He was treated with high-dose of Methimazole, Atenolol, and Prednisone. A literature search revealed five cases of Graves’ disease after mCOVvax, all of which did not have a retrosternal extension of the thyroid. Our case represents a rare complication of mCoVvax. Clinicians should consider retrosternal goiter in patients with thyrotoxicosis and orthopnea after mCoVvax exposure.
Presentation: Friday, June 16, 2023
FRI475 The Impact Of Suppression Of Androgen Signaling On Thyroid Hormone Homeostasis In Prostate Cancer Patients
Authors: David Karel , Devos Gaetan , Devlies Wout , Narinx Nick , Antonio Leen , Deboel Ludo , Schollaert Dieter , Vanderschueren Dirk M , Claessens Frank A , Joniau Steven , Decallonne Brigitte 
Published: October 2023

Abstract
Disclosure: K. David: None. G. Devos: None. W. Devlies: None. N. Narinx: None. L. Antonio: None. L. Deboel: None. D. Schollaert: None. D.M. Vanderschueren: None. F.A. Claessens: None. S. Joniau: None. B. Decallonne: None.
Next to the classical androgen deprivation therapy (ADT) with GnRH-(ant)agonists, androgen receptor signaling inhibitors (ARSIs) such as apalutamide (APA) have become available for the treatment of prostate cancer (PC) patients in the last years. Hypothyroidism was more frequent in APA-treated patients compared to placebo in the SPARTAN trial (NCT01946204) (8.1% vs 2%). We collected serum of PC patients included in a RCT (ARNEO; NCT03080116) before and after 12 weeks of neo-adjuvant ADT (GnRH-antagonist degarelix (DGX) with APA or placebo). We aimed to explore changes in thyroid homeostasis under deep androgen suppression with combined GnRH-antagonist and ARSI. Of the 88 patients ending the trial, 1 was excluded because of history of hypothyroidism for which he received levothyroxine. 43 and 44 patients were included in the DGX+placebo and DGX+APA group, respectively. Mean age was 66.3y. Sex steroid levels measured by LC-MS/MS decreased significantly to castrate range with median testosterone 10.5 ng/dL and estradiol 3.6 ng/L. TSH levels increased in both treatment groups, but more pronounced in the DGX+APA group (DGX+placebo before: 1.18 mIU/L and after: 1.33 mIU/L, p 0.0351 vs. DGX+APA before: 1.07 mIU/L and after: 1.87 mIU/L, p &lt;0.0001; difference between groups after treatment: p &lt;0.0001). Free T4 and total T4 levels decreased in the DGX+APA group, but remained unaltered in the DGX+placebo group (free T4 after: 16.53 vs 13.87 pmol/L, p&lt;0.0001 and total T4 after: 8.77 vs. 7.78 µg/dL, p 0.0055). Total T3 and free T3 increased in the DGX+APA group, and again did not differ after treatment in the DGX+placebo group. (free T3 after: 5.03 vs 5.41 pmol/L, p 0.0066 and total T3 after: 132.30 vs 149.50 ng/dL, p 0.0003). As a result, the total and free T3/T4 ratio increased in the DGX+APA group with 32% and 35%, respectively. Reverse T3 decreased in both treatment arms, but greater in the DGX+APA group (19.55 vs 14.20 ng/dL, p 0.0157). Thyroxine binding globulin (TBG) increased in both treatment arms, with 6.9% and 8.4%, respectively. In conclusion, interference with androgen signaling alters thyroid homeostasis in PC patients, and is most pronounced under deep androgen suppression with combined GnRH-antagonist and ARSI therapy. The increase in T3 and decrease in rT3 may indicate additional effects of ARSI on deiodinase activity. Longer follow-up trials are needed to confirm these findings and assess the clinical implications of these changes in thyroid homeostasis.
Presentation: Friday, June 16, 2023
FRI477 The Effect Of Gestational Selective Serotonin Reuptake Inhibitor (SSRI) Treatment On Newborn Thyroid Screen
Authors: Brener Avivit , Raviv Orian , Cohen-Sela Eyal , Yackobovitch-Gavan Michal , Almashanu Shlomo , Marom Ronella , Hiersch Liran , Lebenthal Yael 
Published: October 2023

Abstract
Disclosure: A. Brener: None. O. Raviv: None. E. Cohen-Sela: None. M. Yackobovitch-Gavan: None. S. Almashanu: None. R. Marom: None. L. Hiersch: None. Y. Lebenthal: None.
Background: Clinical depression treated by selective serotonin reuptake inhibitors (SSRIs) has become relatively common in women of childbearing age. The effect of gestational exposure to SSRIs on the newborn’s hypothalamic-pituitary-thyroid postnatal adaptation has not yet been determined. We aimed to investigate the characteristics of the mother–infant dyad of term infants of mothers treated with SSRIs for depression during pregnancy. Methods: This observational study included mother-infant dyads of infants delivered at term in a single tertiary medical center between 2011 and 2021. Data on maternal, pregnancy, delivery, and perinatal characteristics of the mother-infant dyads were retrieved from the hospital’s electronic database. The clinical data were linked with the newborn thyroid screening results of total thyroxin (TT4) obtained at 48-72 hours since delivery. Excluded from analysis were mothers with other chronic medical conditions and newborns with genetic syndromes. Primary outcome measures were newborn TT4 levels and fetal growth as expressed by neonatal birthweight z-scores (WHO charts). Results: SSRI anti-depression treatment during gestation was reported in 2577 (2.4%) out of 106,173 infant-mother dyads. Mothers treated with SSRIs were older (35.0±4.8 vs 32.6±4.8 years, p&lt;0.001), had a higher pre-pregnancy body mass index (23.4±4.5 vs 22.7±4.1, p&lt;0.001) and a similar mean weight gain of 13 kg during pregnancy. Elective and emergent cesarean deliveries were more common among SSRI-treated mothers (14.8% vs 11.1% and 16.5% vs 8.6%, respectively, p&lt;0.001). Infants of those mothers were born earlier (gestational age [GA] 38.7±1.9 vs 39.5±11.5 weeks, p&lt;0.001), had lower birthweight z-scores (-0.48±1.24 vs -0.04±0.92, p&lt;0.001) and lower TT4 levels (14.7±3.9 vs 15.0±3.7, p=0.001). A multivariate linear regression model revealed that sex, GA and birthweight z-score were highly significant contributors to TT4 levels (p&lt;0.001 for all), while SSRI treatment during pregnancy was not (p=0.497). Conclusions: Our findings suggest that anti-depressant use of SSRIs during pregnancy does not have a direct effect on the postnatal adaptation of the hypothalamic-pituitary-thyroidal axis. However, differences in fetal growth and in characteristics of delivery may determine newborn thyroid function.
Presentation: Friday, June 16, 2023
FRI480 Uncovering The Mystery Of Macro TSH
Authors: Anwar Farrah , Saeed Zeb I 
Published: October 2023

Abstract
Disclosure: F. Anwar: None. Z.I. Saeed: None.
Introduction: An isolated elevation in TSH level, while uncommon, may result in incorrect diagnosis and improper treatment. We present a case of suspected hypothyroidism that was later found to be caused by macroTSH in the blood. Clinical Case: A 21-year-old asymptomatic female was diagnosed with hypothyroidism and started on levothyroxine at age 16 when routine lab work revealed TSH of 34.2 MCU (0.550-4.780 MCU) and free T4 of 1.1 ng/dl (0.89-1.76 ng/dl). She denied any personal or family history of thyroid disorders in the past. Patient later reported symptoms including palpitations and weight loss leading to discontinuation of levothyroxine. Repeat lab work showed TSH of 0.112 MCU and free T4 of 1.71 ng/dl. After discontinuing levothyroxine, TSH levels were found in range of 89.26 MCU to 106 MCU (0.550-4.780 MCU). Free T4 levels remained normal, even when tested using dialysis method. Total T3 level also remained normal at 87 ng/dl (80-200 ng/dl). TPO antibodies were slightly elevated at 9.3 IU/mL (0.0-9.0 IU/ml), TSI and TSH receptor antibodies were negative. Patient's high TSH level, lack of symptoms, and normal free T4 levels prompted the use of different assays to test TSH. We contacted Mayo Clinic Lab for further testing. One assay (Roche Elecsys) showed TSH level of 90.8 mIU/L, but this result was not significantly changed when sample was incubated with a commercial heterophile antibody blocking reagent. Another assay (Beckman Coulter Access TSH) produced a significantly different but still elevated result of 43.1 mIU/L. For research purposes, the sample was further tested for macroTSH using polyethylene glycol (PEG) precipitation, which resulted in TSH level of 5.8 mIU/L which was reduced from 90.8 mIU/L (94% reduction). These results were higher than the mean +/- 2 standard deviations of the control group (range 0% to 65% reduction in TSH with PEG in controls). This suggested presence of macroTSH, although the assay's performance characteristics and reference ranges had not been established at the time of testing for this patient.
Patient's TSH levels remain high and she was advised not to begin the medication unless circulating thyroid hormone levels are abnormal. Conclusion: Macro TSH is a combination of monomeric TSH and anti-TSH antibodies, similar to macro-prolactin. It is considered inactive and has an estimated prevalence of 0.6-1.6%. In a review of over 150 patients, more than 50% of documented thyroid interferences, including macro TSH, led to incorrect diagnosis and improper treatment. This case demonstrates the significance of identifying macro TSH to avoid misdiagnosis and inappropriate management of euthyroid patients with isolated TSH elevation.
Presentation: Friday, June 16, 2023