bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-564 ATG7 Overexpression Results in Reduction of Hepatocellular Lipid Content in Vitro
Authors: Tavaglione Federica , Baselli Guido , Ciociola Ester , Gentilucci Umberto Vespasiani , Valenti Luca , Romeo Stefano 
Published: May 2020

Abstract
Abstract: Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, paralleling the epidemic of obesity and type 2 diabetes. Despite the high prevalence of NAFLD, only a minority of patients progress to NASH and advanced fibrosis. The reasons for this inter-individual variability are not completely understood but can be partially accounted for by genetic risk factors (1). Although several common genetic variants associated with liver disease have been identified, there is still a proportion of NAFLD heritability that remains unknown. The rare rs143545741 C&gt;T variant in the autophagy related 7 (ATG7) gene (P426L) has been associated with a higher risk of progressive NAFLD (2). Interestingly, ATG7 encodes a E1-like ubiquitin activating enzyme which is involved in hepatic lipophagy (3). We hypothesized that the unknown heritability of NAFLD might be partially explained by rare genetic variants, therefore not identified in the GWAS studies. Moreover, we assumed that loss-of-function variants in ATG7 might confer an increased susceptibility to NAFLD by reducing autophagic catabolism of lipid droplets in the liver. To examine the underlying mechanism of the low-frequency V471A variant and the rare T86I, L127I, Q170E, and P426L variants in ATG7, we performed in vitro experiments of HepaRG cells overexpressing the human V5-tagged ATG7. We observed a reduction in intracellular lipid content in HepaRG cells overexpressing the ATG7 wild type and the 86I mutant protein (p=0.029, n=4) but not the 127I, 170E, 426L, and 471A mutant proteins. Cells with the ATG7 127I, 170E, 426L, and 471A mutants had higher intracellular lipid content compared to cells overexpressing the wild type protein (p=0.029, n=4). Our data suggested that the low-frequency V471A variant and the rare L127I, Q170E, and P426L variants in ATG7 are loss-of-function, resulting in defective lipophagy, reduced hepatocellular lipid droplets turnover, and excessive lipid accumulation. More experiments are needed to clarify the underlying mechanism of the T86I variant. In conclusion, we highlighted a role for ATG7 in reducing hepatocellular lipid content. Furthermore, we provided evidence showing non-synonymous variants in ATG7 increase the risk of NAFLD and that these variants are loss-of-function. We speculate that ATG7 might be a new susceptibility risk genetic locus for liver disease development and progression. References: (1) Eslam et al. J Hepatol. 2018;68(2):268–279. (2) Baselli et al. The Liver Meeting 2018 - AASLD. Hepatology. October 2018. Volume 68, Issue S1. (3) Martinez-Lopez and Singh. Annu Rev Nutr. 2015;35:215–37.
MON-447 Schwannoma Masquerading as Metastatic Papillary Thyroid Carcinoma in a Cervical Lymph Node
Authors: Kim Stephanie , Goldstein Ruth , Liu Lisa , Duh Quan-Yang , Liu Chienying 
Published: May 2020

Abstract
Background: Schwannomas originate from peripheral nerve sheath Schwann cells and develop in various locations, commonly seen in the head and neck in up to 45% of cases. On ultrasound, they appear hypoechoic, lack a hilum, and can resemble a metastatic lymph node in patients with thyroid cancer. We describe a case of a schwannoma masquerading as metastatic papillary thyroid carcinoma. Clinical Case: A 59-year-old woman presented to our clinic with a history of Graves’ disease and papillary thyroid cancer (PTC) for which she underwent surgery over fifteen years ago at an outside institution. Pathology revealed two microfoci of PTC (0.5 and 0.4 cm) and 0 of 3 positive lymph nodes, with no other concerning features. She underwent radioactive iodine therapy (RAI) with 100 mCi postoperatively. There was no evidence of metastasis on her post-treatment scan. She had surveillance including neck ultrasounds with no evidence of recurrence. Five years later, neck ultrasound revealed a 5 mm nodule in the right neck posterior to the jugular vein. This nodule remained stable a year later and was not mentioned on subsequent ultrasounds. Two years ago upon presentation to our institution, she was found to have a suspicious hypoechoic solid mass on neck ultrasound. It was located in the lateral neck deep to the internal jugular vein and immediately adjacent and lateral to the common carotid and measured 8 x 7 x 7 mm enlarging to 13 x 9 x 10 mm in the next year. On one of the ultrasounds, the mass was noted to be inseparable from the surrounding nerve fibers and the possibility of nerve sheath tumor was suggested although a metastatic lymph node could not be excluded. This nodule enlarged to 13 x 9 x 10 mm in the next year. Due to the location, biopsy was deemed difficult and she underwent surgical resection of the mass. Intraoperatively, the lesion was noted to be very firm and intimately involved with the vagus nerve, which had to be sacrificed as it could not be dissected off. Pathology revealed a schwannoma, which was confirmed by immunohistochemical staining. Conclusion: This case highlights the importance of recognizing subtle but important ultrasonographic features of a schwannoma in the neck as it can resemble a metastatic lymph node, especially in a patient with history of thyroid cancer. Clinicians should consider this in the differential diagnosis when there are appropriate imaging findings that may be consistent with a schwannoma, including homogeneous hypoechogeneity and nerve continuity.
SAT-423 Anti-thyroid Drug Response in Graves’ Disease: Predictors of Biochemically Persistent Disease
Authors: El Kawkgi Omar M , Li Dingfeng , Vallejo Sebastian , Lincango Eddy , Mohan Sneha , Kohlenberg Jacob , Giblon Rachel , Stan Marius , Brito Juan P 
Published: May 2020

Abstract
Introduction: Anti-thyroid Drugs (ATD) have become the most frequently used treatment for Graves’ disease (GD) in the United States. However, the response to this therapy is variable. Factors that predict biochemically responsive vs. biochemically persistent disease remain unknown. Identifying predictors of disease poorly responsive to ATD can help guide treatment decision making, follow up planning and prognosis.
Methods: From a database of patients with GD treated with ATD and receiving care at an academic medical center between 2009–2019, we selected adults with incident GD treated with ≥14 days of ATD.
Results: 172 patients (from a database of 730 patients with GD on ATD) were sampled for the purpose of this pilot and 97 of these met inclusion criteria. Patients had a median age of 50 (18–90); female, 70.1%; never smokers, 64.9%; median goiter size of 40 g (15–100); and median TRAb on presentation of 8.1 mIU/L (1.0- 60). Graves’ orbitopathy (GO) was present in 13.4% at baseline. Patients (100%) were started on methimazole at a median dose of 20 mg (2.5–60). The median time from presentation until biochemical improvement (defined as the first instance of FT4 ≤1.7 ng/dL) was 120.9 days (18–1525), and to biochemical euthyroidism (normal TSH & FT4) was 251 days (41–1259) including a median of 3 (0–17) dose adjustments. In a univariate analysis, response to ATD was divided into two groups; biochemically responsive and biochemically persistent disease (based on reaching biochemical improvement in ≤6 months, or &gt;6 months respectively). Biochemically persistent disease was more common in those with GO at presentation (38.5% vs.11.1%) (p .024). There was a trend towards greater prevalence of biochemically persistent disease in those with TRAb ≥ 8.0 mIU/L (46.2% vs. 27.8%) (p .204), and goiter estimated 30 grams or above by physical examination (30.8% vs. 19.4%) (p .460). Biochemically responsive disease was associated with higher frequency of hypothyroidism during treatment (p .047).
Conclusion: Our preliminary results illustrate the spectrum of response to ATD and predictors of biochemically persistent disease. We aim to expand this analysis utilizing a large database. As use of ATD increases, clinicians and patients can apply this data to estimate response to therapy, and identify patients that may require more aggressive therapy, thereby tailoring management plans.
MON-529 The Impact of The Association of Unnecessarily Ordered Thyroid Ultrasounds (USGS) and Unnecessarily Requested Endocrinology Consultations
Authors: Veeramachaneni Ravali , Anbari Raghda Al , Marenych Nadiia , Patel Sabah , Moid Alvia , Theckedath Boby George , Barsano Charles P 
Published: May 2020

Abstract
We have previously reported that there is a strong association between unnecessarily ordered thyroid USGs and unnecessarily requested Endocrinology (Endo) consultations. Unnecessary consults consume time and resources, delay appropriate consults, and have even been proposed as a factor in the over-diagnosis of clinically innocuous thyroid cancers. We have examined the impact on the consumption of clinical resources.
The database consisted of 201 new Endo consults, each accompanied by a pre-consult thyroid USG. The consult requests were graded as appropriately requested (APPROP), optionally requested (OPT), or unnecessarily requested (UNNEC). The USG requests were likewise graded as APPROP, OPT, or UNNEC. The USGs were also graded on their degree of contribution to the request for a consultation, specifically, as having a significant role (SIGNIF), a minor role (MIN), or little or no role (NONE).
The impact of the UNNEC consults was categorized as (a) the initial Endo consult, a resource that would not have been utilized were an UNNEC consult not submitted, and (b) resources that probably would have been utilized were the UNNEC consults not submitted but would have been managed by and costed to the referring provider instead of to the Endo provider. Such resources included follow-up Endo visits and relevant USGs and blood tests,
Of the 201 consults with associated USGs, 156 (77.6%) consults were APPROP, 23 (11.4%) were OPT, and 22 (10.9%) were UNNEC. Conversely, 157 (78.1%) of the USGs were APPROP, 11 (5.5%) were OPT, and 33 (16.4%) were UNNEC. With respect to the association of consults with their accompanying USGs, Among APPROP requested consults, 87.8% of the associated USGs were also APPROP while only 7.7% were associated with UNNEC USGs. Among UNNEC requested consults, 31.8% of the associated USGs were APPROP while 68.2% were associated with UNNEC USGs.
Regarding the resource utilization borne by an Endo clinic as a consequence of the submission of 21 UNNEC consults for the two years after the initial consultation, each UNNEC consult had consumed, on average, 5.9 (1 + 2.6 + 2.3) [initial + Yr 1 + Yr 2 follow-ups] Endo clinic visits, 0.9 (0.5 + 0.4) USGs [excludes the USG associated with initial consultation] and 4.1 (2.2 + 1.9) blood work orders and reviews. No follow-up FNAs or thyroid surgeries were performed.
Endocrine care from any source would be best served by reducing both the unnecessary utilization and the unnecessary assignment of relevant resources.
MON-674 Diabetic Amyotrophy; A Rare Cause of Muscle Weakness
Authors: Abdallah Duaa , Langenhan Trek , Speer Jarod 
Published: May 2020

Abstract
Background: Diabetic amyotrophy is a rare complication of type 2 diabetes mellitus. There is little existing evidence contributing to projected outcomes for patients recovering from diabetic amyotrophy.Clinical Case: A 42 year-old man presented with lower extremity muscle pain and progressive proximal muscle weakness over 8 months. He developed asymmetrical muscle weakness in the lower extremities with diffuse pain and sensitivity to touch. He also had 80 pounds weight loss, diarrhea, and erectile dysfunction over the same time period. He had a past medical history of asthma, chronic migraines, and type II diabetes mellitus with A1c 7.1. His medications included high dose prednisone to treat his chronic migraines and asthma. Exam revealed generalized muscle atrophy, asymmetric proximal weakness, areflexia, with sensory loss in bilateral lower limbs.ESR, CRP, ANA, anti-HMG CoA reductase, CK, aldolase, SPEP, and myomarker panel were all within normal limits. Treponema pallidum and Bartonella serologies were negative. CSF evaluation was not suggestive of any demyelinating or neuromuscular disease. Full body STIR MRI demonstrated muscle edema in abductor, gluteus minimus, and paraspinal muscles bilaterally. EMG testing revealed acute to subacute active asymmetrical polyradiculoneuropathy and evidence of chronic proximal myopathy.Based on clinical presentation, EMG findings, and lack of evidence to support alternative diagnoses, he was diagnosed with diabetic amyotrophy and was started on IVIG and methylprednisolone with improvement in pain but very minimal improvement in weakness. Unfortunately, the expected clinical course following a diagnosis of diabetic amyotrophy is one of minimal improvement with treatment, as was the case in our patient.Conclusion: Diabetic amyotrophy is a rare complication of type 2 diabetes mellitus which typically presents with muscle weakness followed by severe pain in the thighs, hips, and buttocks. Compared with other neurologic complications of diabetes, amyotrophy is relatively uncommon, affecting approximately 1 percent of patients. This low prevalence and the broad differential for proximal muscle weakness makes it challenging to diagnose. It remains a diagnosis of exclusion, though EMG studies showing polyradiculoneuropathy in the proximal leg musculature is suggestive. Clinical improvement is slow and often incomplete. Physical and occupational therapy are a mainstay of treatment which may also include IVIG and steroids aimed at treating associated pain. Endocrinologists should have a high clinical suspicion for diabetic amyotrophy in the appropriate clinical context. When considering the diagnosis and discussing treatment options with patients, this case highlights the important role of endocrinologists discussing expectations associated with projected outcomes while attempting to manage diabetic amyotrophy.
SUN-370 Validation of a Deep Learning Based Algorithm to Diagnose Vertebral Compression Fractures
Authors: Page John , Moser Franklin , Maya Marcel , Prasad Ravi , Pressman Barry 
Published: May 2020

Abstract
Vertebral Compression Fractures are common in patients above age 50, but are often undiagnosed. Patients with one VCF are at higher risk of other osteoporotic fractures. Zebra Medical Imaging developed a VCF detection algorithm, utilizing a combination of traditional machine vision segmentation and convolutional neural network (CNN) technology, to detect VCFs from evaluating CT images of the chest, and/or abdomen/pelvis.
We conducted an independent and blinded validation study to estimate the operating characteristics of the Zebra VCF detection algorithm in identifying VCFs on de-identified data from previously completed CT scans of chest and/or abdomen/pelvis from 1200 women and men aged 50 or older who had those scans (for multiple reasons) at the clinics and hospitals affiliated with the Cedars Sinai Medical Center. Each set of scans were independently read by two of three board certified, practicing neuroradiologists to identify and grade VCF at each evaluable vertebra (using the semiquantitative scale of Genant and colleagues). When there was disagreement between radiologists, the respective scans were reviewed by a senior neuroradiologist who provided a final evaluation. The final determination of presence and severity of VCF by the neuroradiologists was used as the reference standard. The Zebra VCF detection algorithm evaluated the CT scans in a separate workstream from that used by the neuroradiologists (The algorithm and neuroradiologists were blind to each other’s evaluations).
The Zebra VCF algorithm was not able to evaluate CT scans for 113 patients. Of the remaining 1087 CT patients, 588 (54%) were women. Median age was 73 (range 51, 102; interquartile range 66, 81). The four neuroradiologists who evaluated the CT scans each had over 10 years of experience in neuroradiology. For the 1087 Zebra evaluated patients, 227 had at least one VCF (90 with mild VCF, 81 with moderate VCF, and 56 with severe VCF; 115 of the 1087 Zebra evaluated patients (10.6%) presented with two or more VCFs). The sensitivity and specificity of the Zebra VCF algorithm in diagnosing any VCF were 0.66 (95% confidence interval 0.59, 0.72) and 0.90 (95% confidence interval 0.88, 0.92) respectively; and for diagnosing moderate/severe VCF were 0.78 (95% confidence interval 0.70, 0.85) and 0.87 (95% confidence interval 0.85, 0.89) respectively.
The Zebra VCF algorithm works to identify approximately three-quarters of moderate to severe VCF in patients, aged 50 and above, who receive CT scans for other reasons. Implementing the Zebra VCF algorithm within radiology systems may help to identify patients at increased fracture risk and could support the diagnosis of osteoporosis, and thus be a valuable adjunct for population health.
SAT-303 3D Mapping of the Human Growth Hormone Locus Identifies Putative Regulatory Hubs for Genes Involved in Cellular Signalling and Cancer-Related Pathways
Authors: Jain Lekha , Fadason Tayaza , Schierding William , Vickers Mark Hedley , O’Sullivan Justin M , Perry Jo Kate 
Published: May 2020

Abstract
Growth hormone (GH) is a peptide hormone predominantly produced in the pituitary that is crucial for normal growth and metabolism. Downstream effects of GH are mediated through binding to the GH receptor (GHR) and consequent activation of key signalling cascades including JAK-STAT, MAPK, PI3K-Akt and mTOR. The GH locus is comprised of five evolutionarily related genes under the control of an upstream locus control region which coordinates tissue-specific expression of these genes in the pituitary and placenta (1). Compromised GH signalling and genetic variation in these genes has been implicated in various disorders including cancer. We hypothesised that polymorphisms which occur within the GH locus have the potential to impact on disease phenotypes by altering or disrupting gene regulation. We used the CoDeS3D (Contextualize Developmental SNPs using 3D Information) algorithm to analyse 529 common single nucleotide polymorphisms (SNPs) across the locus. This algorithm identifies colocalised Hi-C and eQTL associations to determine which SNPs are associated with a change in gene expression at loci that physically interact within the nucleus. We identified 181 common SNPs that interacted with 292 eGenes in 48 different tissues. 145 eGenes were regulated in trans. We performed pathway enrichment of identified eGenes and found these to be enriched in GH/GHR-related downstream cellular signalling pathways including MAPK, PI3K-Akt-mTOR, and ErbB signalling. Enrichment was also observed in the Wnt and Hippo signalling pathways. There was also a significant representation of these eGenes in pathways associated with hepatocellular, colorectal, breast and non-small cell lung carcinoma. 33 eQTL SNPs identified in our study were found to be of regulatory importance in a genome-wide Survey of Regulatory Elements (SuRE) reporter screen (2). In addition, 7 eQTL SNPs were located in known enhancer regions. Our data suggests that regions within the GH locus form regulatory hubs for multiple genes in cis and trans (intra and inter-chromosomal), many of which are involved in mediating GH function in normal and pathogenic states.
Reference: (1) Tsai et al. Nucleic Acids Res 2016, 44, 10, 4651 (2) van Arensbergen et al. Nat Genet 2019, 51, 7, 1160.
SUN-217 Skin Glucocorticoid Metabolism in Burn Injury: Towards Novel Treatments That Reduce Scarring
Authors: Tsai Kevin Hung-Yueh , Parungao Roxanne Janine , Shi Huaikai , Issler-Fisher Andrea , Wang Xiaosuo , Maitz Peter , Cooper Mark Stuart , Wang Yiwei 
Published: May 2020

Abstract
The most common and severe complication of burn injury is the development of excessive scarring/tissue fibrosis. No current treatments reduce scarring after burns. Prolonged exposure to high levels of glucocorticoids (Cushing’s syndrome) detrimentally impacts skin, leading to reduced collagen production and impaired wound healing. Skin can generate active glucocorticoids locally through expression and activity of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). We hypothesised that local glucocorticoid activation by 11β-HSD1 is an important regulator of wound healing, fibrosis and scarring after burn injury. We additionally proposed that pharmacological manipulation of this system would improve outcomes of burn wound healing.
We examined glucocorticoid metabolism (by RT-PCR, immunohistochemistry and specific enzyme activity assays) in burn and non-burn skin from burn injury patients (n=14) and mouse models of burn injury (1cm2 full thickness burn in C57Bl/6 mice). We utilised mice with genetic or pharmacological deletion of 11β-HSD1 in skin to evaluate the effects of 11β-HSD1 on burn injury healing, wound fibrosis and skin properties (by atomic force microscopy and tensile property testing) after wound healing. We also developed slow release scaffolds containing therapeutic agents including inactive glucocorticoids (prednisone) that are selectively reactivated in skin cells expressing 11β-HSD1.
The expression of 11β-HSD1 in human and mouse skin increased substantially after burn injury (7.1+/-1.8 fold increase on day 4–9 post burn compared to non-burn skin, p&lt;0.05). Early after injury, expression was primarily in immune cells but at later stages in fibroblasts. Mice with 11β-HSD1 deletion experienced faster wound healing post burn (17% reduced wound area at day 7 compared to wildtype, p&lt;0.0001) but when healed these wounds had excessive collagen density and skin thickening, and abnormal collagen fibre organisation (assessed by Masson’s Trichrome staining). The post burn scars formed in 11β-HSD1 knockout mice demonstrated different skin elastic properties compared to those formed in wildtype mice. In wildtype mice application of scaffolds loaded with inactive glucocorticoid (prednisone) significantly impacted wound healing demonstrating the feasibility of using enzyme substrates to improve wound outcomes.
The findings demonstrate the importance of skin 11β-HSD1 in wound healing and scarring after burn injury and indicate ways in which excessive scarring might be prevented.