bluuebunny/crossref_metadata_2025_split huggingface dataset:
7849 The EDC Mixture “NeuroMix” Has Developmental, Anxiolytic, And Obesogenic Effects In Rats
Authors: Morales-Grahl Elena , Thompson Lindsay M , Hilz Emily N , Gore Andrea C 
Published: October 2024

Abstract
Disclosure: E. Morales-Grahl: None. L. M. Thompson: None. E.N. Hilz: None. A.C. Gore: None.
Humans are exposed to a variety of endocrine disrupting chemicals (EDCs) on a daily basis through drinking water, food, and contact with everyday objects. Safety guidelines aim to keep exposure to individual EDCs below certain levels but don’t take into account the potentially unpredictable effects of simultaneous exposure to multiple EDCs. Furthermore, EDCs may exhibit non-monotonic dose responses. The present study assessed the effect of an EDC mixture at three different doses on two sets of behaviors implicated in EDC research: anxiety, and high fat and sugar consumption. Beginning in early pregnancy and until pups were weaned at day 21, Sprague Dawley rats were fed daily with NeuroMix, our lab’s EDC mixture containing 9 common industrial chemicals, at three doses (0.1x, 1x, 10x). The base dose (1x) contained EDCs below the no observed adverse effect level in humans (NOAEL). In adulthood, the female and male offspring were then subjected to an open field and light/dark test, followed by a high fat and high sucrose preference test. 0.1x NeuroMix exposure advanced the timing of vaginal opening in female offspring, while all doses increased anogenital distance in males, marking differences in sexual development. 1x NeuroMix exposure in male rats increased their time in the open field corners and their time immobile in the corners, indicating higher anxiety. No difference was seen in sucrose preference. Female rats exposed to 1x NeuroMix showed a higher preference for a high-fat diet, and gained more weight compared to the controls while on this diet. These findings demonstrate that a mixture of human-relevant chemicals, when administered perinatally to rats, have developmental, anxiogenic and obesogenic effects in a sexually dimorphic manner. We also show a non-monotonic response to our chemical mixture, with the 1x dose showing greater effects than the 10x dose. Overall, we provide evidence that even at levels considered safe for individual EDCs, there are adverse developmental and behavioral effects of EDCs when combined. Grant support: R35 ES035024, F32 ES034257.
Presentation: 6/1/2024
7282 Arginine-Vasopressin Deficiency And Long COVID: A Causal Or A Coincident Relationship?
Authors: Medeiros Regina Saudade , Pereira Bernardo , Pataco Andreia , Senra Catarina , Ponte Maria João , Anselmo João , Sousa Isabel 
Published: October 2024

Abstract
Disclosure: R.S. Medeiros: None.
Introduction: Arginine-vasopressin deficiency (AVP-D) has been reported in few case reports as a very rare complication of COVID-19 and SARS-COV2 immunization. Long COVID is defined as signs, symptoms, and conditions that develop after COVID-19, and it can affect several organs and systems. Autopsy studies showed SARS-COV2 genetic sequence in degenerated neurons of hypothalamus, and expression of angiotensin-converting enzyme type 2 in median eminence capillaries and paraventricular nucleus have also been demonstrated. Clinical Case: A 47-year-old male presented with polydipsia (8 L/day) and polyuria 8 weeks after non-severe COVID-19. Past medical history was relevant for untreated dyslipidemia. He denied past head trauma, surgery or radiotherapy. Family history was unremarkable. Biochemical evaluation revealed normal glucose, serum electrolytes, renal and hepatic parameters; urine osmolality was 160 mOs/Kg and 24h urinary volume was 10350 mL. Basal pituitary surveys were also normal. A water deprivation test was performed but stopped after 2 hours due to development of hypernatremia (Na+ 146 mEq/L), serum osmolality of 311 mOs/Kg (reference: 280-300) and urine osmolality of 105 mOsm/Kg. After 20 ug intranasal desmopressin urine osmolality increased to 357 mOsm/Kg. A contrast-enhanced MRI revealed an absent posterior pituitary bright spot and thickening of the pituitary stalk suggesting infundibulo-neurohypophysitis. Further biochemical and imaging surveys excluded infectious and infiltrative causes of AVP-D; however, due to elevated serum iron (204.0 ug/dL; reference: 65-175) and transferrin saturation (68%; reference: 15-45%), genetic screening of hemochromatosis by next-generation sequencing of all hemochromatosis-associated genes (HFE, HJV, HAMP, TFR2 and SLC40A1) revealed a heterozygotic variant c.187C&gt;G p.(His63Asp) in HFE, a genotype not associated with iron overload. He started oral desmopressin 0.2 mg/day, to which he showed a prompt response, titrated to 0.8 mg/day (in 3 divided doses). Conclusion: Although molecular and histologic confirmation of SARS-COV2 infundibulo-neurohypophysitis could not be investigated, a strong temporal relationship and the absence of an alternative diagnosis renders plausible the inclusion of AVP-D in the myriad of manifestations of long COVID. Further studies with patients recovered from COVID-19 are necessary to gain a better understanding on the epidemiology, pathophysiology and clinical course of this very rare endocrine association of SARS-COV2 infection with infundibulo-neurohypophysitis.
Presentation: 6/3/2024
12255 Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue And Cognitive Impairment In Mice
Authors: Dantzer R 
Published: October 2024

Abstract
Disclosure: R. Dantzer: None.
Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue and Cognitive Impairment in Mice Brandon Chelette, PhD, Anand Singh, PhD, Robert Dantzer, DVM, PhDDept. of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA Fatigue and cognitive impairments are commonly reported by cancer patients undergoing chemotherapy. The mechanisms of these neurotoxicities are still obscure. We hypothesize that they are mediated by mitokines that are released by cells undergoing mitochondrial stress in response to chemotherapy. For the present study, we have focused on growth differentiation factor 15 (GDF15) which acts in the brain by activating its receptor, GDNF family receptor alpha-like (GFRAL). Chemotherapy-induced fatigue was assessed by reduced voluntary wheel running. Cognitive impairment was assessed by altered performance in the Puzzle Box Test that measures executive function. We first checked whether commonly used chemotherapeutic drugs can induce GDF15. Mice were injected with cisplatin, paclitaxel, or bortezomib, and their effects on plasma levels of GDF15 were measured 24 h after (ELISA). Cisplatin was used in the following experiments in the form of one or two cycles of daily injections for five days with a rest of five days between cycles. To determine whether GFRAL mediates the effects of cisplatin on wheel running and performance in the puzzle box, mice were injected with a neutralizing antibody targeted to GFRAL (GFRALna) during or after cisplatin treatment. All studies were carried out in male and female C57BL/6 J mice using a 2 (+ chemotherapy) x 2 (+ GFRALna) factorial design with a minimum of 6 mice/group. Mitochondrial dysfunction was measured via Seahorse XF Analyzer Mito Stress Test. To determine whether activation of the GDF15/GFRAL axis recruits a central GDF15 compartment, Gdf15 mRNA was measured by qRT-PCR in the brain parenchyma, meninges, and choroid plexus. All the chemotherapeutic agents we tested induced statistically significant increases in circulating GDF15. GFRALna administered during cisplatin treatment (prevention) or after completion of cisplatin treatment (cure) abrogated cisplatin-induced decrease in wheel running and the deficit displayed by cisplatin-treated mice in the first hard trial run in the puzzle box. GFRALna also blocked the decrease in maximal oxygen consumption rate of mitochondrial in synaptosomes from cisplatin-treated mice. Cisplatin did not induce Gdf15 mRNA in the brain parenchyma but increased its expression in the meninges and choroid plexus. Although the role of this GDF15 brain compartment in the neurotoxicity of cisplatin remains to be determined, the present findings can be interpreted to suggest that GDF15-GFRAL signaling represents a new target for the treatment of chemotherapy-induced fatigue and cognitive impairment. Count: 2,246 characters
Presentation: 6/1/2024
8156 Exploring Gender-Specific Characteristics Of Diabetes Among Young Adults In Korea: The Korea National Health And Nutrition Examination Survey 2011-2012 And 2019-2020
Authors: Chung C 
Published: October 2024

Abstract
Disclosure: C. Chung: None.
Background: The escalating global incidence of diabetes among young adults could be linked to dynamic socio-environmental changes including pandemic and climate shifts. In this investigation, we aimed to discern the distinct features of diabetes among young adults in Korea. Methods: This cross-sectional study included 63,489,047 Korean young adults (32,173,248 male, 31,315,799 female) aged 20-39 years who participated in the Korean National Health and Nutrition Examination Survey 2011-2012 and 2020-2021. Diabetes cases were identified through hospital diagnoses or the prescription of insulin or non-insulinemic anti-diabetic medications. The significant insulin resistance was defined as HOMA-IR above 2.9. Complex sampling design and cross-tabulation analyses were used to examine both socioeconomic and laboratory factors. Results: The prevalence of diabetes was higher in men in both 2011-2012 and 2020-2021 (Men vs. Women, 2011-2012: 2.2 ± 0.5 vs. 1.2 ± 0.3 %, p&lt;0.001; 2020-2021: 3.0 ± 0.5 vs. 1.6 ± 0.3 %, p&lt;0.001). The use of insulin and oral hypoglycemic agent (OHA) was comparable between men and women in 2011-2012 (Insulin: 18.1 ± 8.2 vs. 5.2 ± 5.1 %, p=0.305; OHA, 18.2 ± 6.3 vs. 19.5 ± 6.5 %, p=0.239), but more women used insulin and more men used OHA in 2020-2021 (Insulin: 5.3 ± 3.7 vs. 28.7 ± 9.4 %, p=0.016; OHA: 31.4 ± 7.7 vs. 19.6 ± 7.3 %, p=0.009). Execution of fundus exam (25.7 ± 10.6 vs. 68.5 ± 14.1 %, p=0.021) and diagnosis of diabetic retinopathy (0 vs. 8.9 ± 3.3 %, p=0.001) was higher in women in 2020-2021. HbA1c was higher in men in 2020-2021 (8.1 ± 0.4 vs. 7.3 ± 0.3 %, p &lt;0.001), but was similar between men and women in 2011-2012 (8.4 ± 0.6 vs. 8.1 ± 0.6 %, p=0.697). Obesity, one of the most common comorbidities of diabetes, was higher in women in 2011-2012 (24.8 ± 4.8 vs. 79.4 ± 9.3 %, p&lt;0.001), but was higher in men in 2020-2021 (94.4 ± 2.9 vs. 67.8 ± 11.0 %, p&lt;0.001). The factors associated with increase in HOMA-IR in 2020-2021 was different between men and women. Unexpectedly, men with low mental stress showed positive correlation with HOMA-IR (B = 3.9, 95% CI 0.1-7.7, p=0.047). For women, mental stress did not affect HOMA-IR, but those with regular anaerobic exercise (B = -10.5, 95% CI -18.3 - -2.6, p=0.011) and stable employment status (B = -11.9, 95% CI -19.4 - -4.8, p=0.002) presented negative correlation with HOMA-IR. Conclusion: In comparison to before the COVID-19 pandemic, men diabetic patients showed more obese tendency after COVID-19, and there was also a statistically significant difference in HbA1c disparity with women. The higher prevalence of diabetic retinopathy despite of lower HbA1c in women during pandemic era needs to be further investigated in well-designed cohort study.
Presentation: 6/3/2024
7492 Fibroblast Growth Factor 21 In The Diagnosis And Treatment Of Metabolic Disorders
Authors: Heshmati Hassan M , Abu-Lebdeh Haitham S 
Published: October 2024

Abstract
Disclosure: H.M. Heshmati: None. H.S. Abu-Lebdeh: None.
Background: Fibroblast growth factor 21 (FGF21), a member of the human FGF superfamily, is a 181 amino acid peptide hormone primarily produced by the liver. The gene of FGF21, located on chromosome 19, was cloned in 2000. FGF21 is involved in the maintenance of metabolic homeostasis. This review presents an update on the relevance of FGF21 in the diagnosis and treatment of metabolic disorders including obesity, nonalcoholic fatty liver disease (NAFLD), dyslipidemia, and type 2 diabetes. Methods: A systematic search of literature was conducted using the search terms fibroblast growth factor 21, obesity, nonalcoholic fatty liver disease, dyslipidemia, and type 2 diabetes. Results: FGF21 is a stress hormone with effects on energy expenditure and metabolism of lipids and glucose. FGF21 exerts its endocrine action in the central nervous system and adipose tissue. The serum FGF21 levels in normal subjects increase with aging. Stressful conditions (e.g., fasting status, protein restriction, exercise, metabolic disorders, kidney diseases, cardiovascular diseases, and sepsis) increase FGF21 secretion. Serum FGF21 levels are increased in obesity, NAFLD, dyslipidemia, and type 2 diabetes. Some of these patients may have a state of FGF21 resistance. The resistance to FGF21 is related, at least in part, to the presence of high circulating levels of fibroblast activation protein, a protease that inactivates FGF21. It has been suggested that the exercise-induced weight loss can be due to increased FGF21 secretion and decreased FGF21 resistance in adipose tissue. Serum FGF21 level has the potential to be used as a biomarker for early diagnosis of metabolic disorders (e.g., NAFLD and type 2 diabetes). Based on different metabolic properties of FGF21, FGF21-based therapy has been considered as an attractive approach for the treatment of metabolic disorders. Since native FGF21 has poor pharmacodynamic properties (e.g., short half-life and proteolytic cleavage by proteases), long-acting FGF21 analogs (e.g., LY2405319, PF-05231023, pegozafermin, AKR-001, and LLF580) have been synthesized and tested in clinical trials for the treatment of obesity, NAFLD, dyslipidemia, and type 2 diabetes. The available results show that FGF21 analogs can reduce body weight, liver fat, blood lipids, and fasting insulin/insulin resistance. Overall, the treatment with these analogs is safe and well tolerated. Conclusion: FGF21 is a predominantly liver-derived peptide hormone regulating energy expenditure and metabolism of lipids and glucose. Serum FGF21 levels are increased in several metabolic disorders including obesity, NAFLD, dyslipidemia, and type 2 diabetes. FGF21 is an attractive target for the treatment of these metabolic disorders. Despite some promising results observed with the use of FGF21 analogs, more clinical studies are needed before recommending FGF21-based therapies in metabolic disorders.
Presentation: 6/2/2024
7902 Improvement In Follow-Up Of Post-Hospital Discharge Patients After Targeted Approach
Authors: Ward S , Aziz Q u , Champion A L , Izuora K E 
Published: October 2024

Abstract
Disclosure: S. Ward: None. Q. Aziz: None. A.L. Champion: None. K.E. Izuora: None.
Improvement in Follow-up of Post-hospital Discharge Patients after Targeted Approach Introduction: Outpatient follow up after discharge from the hospital is a well-established factor affecting health outcomes in patients with chronic medical conditions. A prior QI project at our institution utilizing a Plan-Do-Study-Act (PDSA) cycle showed that overall follow up rate was 24% in patient expected to follow up in our outpatient clinic. The aim of this QI project was to identify and implement a targeted approach to improve outpatient follow up at our clinic. Methods: This study was a second round of a PDSA cycle with the goal of improving outpatient follow up. Analysis of prior data identified 54 patients referred for outpatient follow up in our endocrinology clinic after hospital discharge (non-targeted approach). Of these 54 only 13 patients had established follow up care (24%). We looked closer at the 39 patients who did not follow up to identify areas we could act on to improve follow up; 38% of these patients did not follow due to one of the following: did not know they needed to follow up, lack of knowledge of how to contact office, unable to reach office by phone. To overcome these obstacles, we developed a targeted approach for all patients seen in the hospital who were expected to follow up in the outpatient setting. This approach included the following: clinic business card with contact information given to patient, follow up instructions included in discharge instructions including how and when to contact office, message sent from physician to outpatient clinic staff requesting staff contact patient and schedule follow up appointment. This targeted approach was implemented for all patients requiring outpatient follow up seen by the UNLV Endocrinology consult service from August 1, 2023 to September 30, 2023. Results: During the two months of recruitment we identified 34 patients who needed outpatient follow up. All 34 of these patients had the targeted approach implemented. Of the 34 patients 12 have successfully followed up and one patient has a future appointment scheduled. This is a follow up rate of 35%, an increase of 11% compared with the prior QI data that did not use a targeted approach. If all future appointments are kept the follow up rate will be 38%. Five patients who had scheduled appointments did not show up to their appointment and are not counted in the successful follow group . Conclusions: Our targeted approach showed an improvement in outpatient follow up from 24% to 35% compared to a non-targeted approach. Five patients that scheduled appointments did not keep those appointments. Future steps would include evaluating reasons for no-show and identifying approaches to improve our no-show rate. .
Presentation: 6/2/2024
6848 Improvement Of Free Thyroxine Measurement Quality Through The CDC Clinical Standardization Programs
Authors: Ribera Ashley , Vazquez Norma , Knoblock Samantha , Sugahara Otoe , Buchannan Tatiana , Collins Lynn , Spector David , Zhang Li , Danilenko Uliana , Vesper Hubert W 
Published: October 2024

Abstract
Disclosure: A. Ribera: None. N. Vazquez: None. S. Knoblock: None. O. Sugahara: None. T. Buchannan: None. L. Collins: None. D. Spector: None. L. Zhang: None. U. Danilenko: None. H.W. Vesper: None.
Thyroid function tests are among the most requested tests in patient care, and reliability of these measurements are crucial for appropriate diagnosis and management of thyroid disorders. In response to concerns from the clinical and research community about the quality of thyroid function tests, the CDC Clinical Standardization Programs (CSP) has created the hormone standardization (HoSt) program for free thyroxine (FT4) in partnership with the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC). As a first step, CDC CSP has completed an interlaboratory comparison study of commercial immunoassays (IA) and lab-developed tests (LDT) to determine the current agreement among assays. Participants received 40 blinded, high quality individual donor serum samples with FT4 reference values assigned by the CDC FT4 reference measurement procedure (RMP). FT4 concentrations ranged between 11-32 pmol/L. Samples were analyzed in duplicate over 2 days and results were compared to the CDC FT4 RMP. To assess the potential impact of standardizing measurements to the CDC HoSt FT4 program, reported results were normalized to the CDC RMP results (recalibrated in silico using linear regression). Mean percent bias to the reference value was evaluated pre- and post-recalibration. In addition, inter-assay agreement of classification (assignment of hypo-, eu- or hyperthyroid status according to FT4 reference intervals) were assessed pre- and post-recalibration using the assay-specific and CDC RMP reference intervals, respectively. A total of 19 methods participated, consisting of 15 IA and 4 LDT. All participants showed a negative mean bias to the RMP, with IA showing a higher magnitude of bias (average: -20.7 ± 0.9%) than LDT (average: -4.7 ± 1.1%). Of the 40 samples measured, only 53% were classified uniformly by all 19 participants. Post-recalibration, mean percent bias improved profoundly (IA average: 0.0 ± 0.8%, LDT average: 0.1 ± 1.1%), and classification agreement improved by 33% to 86% of samples with consistent classification. The CDC CSP interlaboratory comparison among FT4 assays highlights the critical need for measurement standardization to improve accuracy of FT4 measurements and increase consistency in result interpretation. This study demonstrates that it is possible to develop common FT4 reference intervals via measurement standardization, which would allow for universal evidence-based clinical guidelines to be used in patient care.
Presentation: 6/3/2024
7845 Machine Learning Methods In Differential Diagnosis Of Genetically Confirmed Multiple Endocrine Neoplasia Type 1 And Its Phenocopies
Authors: Trukhina Diana , Voronov Kirill , Mamedova Elizaveta , Solodovnikov Alexander , Belaya Zhanna 
Published: October 2024

Abstract
Disclosure: D. Trukhina: None. K. Voronov: None. E. Mamedova: None. A. Solodovnikov: None. Z. Belaya: None.
Background. MEN-1 is a rare autosomal dominant disorder caused by mutations in the MEN1 gene encoding the menin protein (gMEN1). This syndrome is characterised by the occurrence of parathyroid tumours, gastroenteropancreatic neuroendocrine tumours, pituitary adenomas, and other endocrine and non-endocrine neoplasms. If a patient with the MEN-1 phenotype does not have any mutation in the MEN1 gene, the condition is considered a phenocopy of the syndrome (phMEN1).The goal of this study was to develop a machine learning algorithm to estimate the probability of gMEN-1 vs phMEN-1 based on easily available clinical features at first line differential diagnostics. Materials and methods. A single-center, one-stage, cohort, retrospective study was carried out. Patients were randomly stratified into 2 cohorts: training (80%) and test (20%). Eight machine learning algorithms were used to develop predictive models: Logistic Regression, k-nearest neighbors (kNN), Naive Bayes, binary decision tree (CART), C5.0 decision tree algorithms, Bagged CART, Random Forest, Gradient Boosting (Stochastic Gradient Boosting, GBM). Results. The study included 95 patients with genetically confirmed gMEN-1 syndrome and 60 patients with its phenocopies. As a result of preliminary data processing and selection for the most informative features, the final variables for the classification and prediction of gMEN-1 syndrome were identified: the number of affected parathyroid glands, age at diagnostics, pancreatic tumour existence, heredity, type of pituitary adenoma secretion, and gender. The kNN algorithm demonstrated the best diagnostic performance in a training sample (ROC-AUC - 0.96, sensitivity - 84%, specificity - 100%), which was confirmed in a test sample (ROC-AUC - 1.0; sensitivity - 94.4%, specificity - 100%) to determine genetically confirmed MEN-1 syndrome. Conclusion. The k-nearest neighbours (kNN) algorithm may be used as a first-line differential diagnostics method to select patients to be refered for genetic testing for gMEN-1.
Presentation: 6/1/2024