bluuebunny/crossref_metadata_2025_split huggingface dataset:
7676 Sex is An Influential Factor on the Conversion of Plasma Renin Activity and its Active Concentration
Authors: Tezuka Yuta , Omata Kei , Ono Yoshikiyo , Satoh Fumitoshi 
Published: October 2024

Abstract
Disclosure: Y. Tezuka: None. K. Omata: None. Y. Ono: None. F. Satoh: None.
Background: Renin is one of the essential factors to understand the cause of hypertension. In primary aldosteronism (PA), plasma renin activity (PRA) has been employed for screening and confirmation tests, while plasma active renin concentration (ARC) is being popularized due to its better reproducibility and easier technique. However, how the transition of renin measurement impacts on PA diagnosis is still unclear. Objective: To investigate the correlative relationship between PRA and ARC, and the impact of renin transition on PA screening. Methods: We retrospectively enrolled 206 hypertensive patients who underwent PA screening and/or confirmatory tests with simultaneous measurements of both PRA and ARC from 2021 to 2023. Those who had higher PRA than 3 ng/mL/h were excluded based on the context of this study. Antihypertensive drugs which interfere with renin-angiotensin-aldosterone system were withdrew before renin evaluation. Plasma samples for renin and aldosterone measurements were obtained at supine position after 30 minutes rest. PA diagnosis was established based on PRA-based confirmatory tests. The correlations between renin and other parameters were evaluated with simple linear regression and Spearman’s correlation analysis. Chi-square test was applied for categorical variables. Results: Of 206 patients, including 147 PA cases, 95 were men (46%) and, mean age and eGFR were 54 years and 72 mL/min/1.73m2, respectively. Plasma aldosterone concentrations, PRA and ARC were as follows (median [interquartile range]: 8.0 [5.4, 13.3] ng/dL, 0.40 [0.20, 0.70] ng/mL/h and 1.61 [0.79, 2.87] pg/mL, respectively. Total number of renin evaluation reviewed was 890 (median 5 times/person). PRA and ARC showed a significant positive correlation (ARC =3.97 x PRA +0.08: Spearman’s r=0.790, p&lt;0.0001), whereas there were sex differences in the slope and the intercept, particularly in ages under 50 years old (men, 5.03 and -0.19: women, 3.11 and +0.40, respectively). The renin ratio (ARC/PRA) showed weak negative and positive correlations with age (Spearman’s r=-0.073, p=0.03) and body mass index (Spearman’s r=0.113, p=0.0007), respectively. Defining low renin status as PRA&lt;1.0 ng/mL/h and ARC&lt;4.0 pg/mL, 142 (97%) out of 147 PA patients showed persistent suppressed renin for both, while 15 (10%) had controversial aldosterone-to-renin ratios (ARRs) between PRA and ARC. Overall, 24 (12%) patients had controversial ARRs, and the rate was similar between men and women (11% and 13%, respectively). Conclusions: Our current study revealed the positive correlation between PRA and ARC, affected by sex. Although the renin transition could lead to different interpretation of aldosterone-to-renin ratios regardless of sex, the replacement of PRA with ARC rarely alters renin status in PA patients.
Presentation: 6/3/2024
9364 The Deleterious Synergy Of Aldosterone And LDL Cholesterol On Major Cardiovascular Events In Chronic Kidney Disease
Authors: Solomon M , Vaidya A , Waikar S S , Verma A 
Published: October 2024

Abstract
Disclosure: M. Solomon: None. A. Vaidya: None. S.S. Waikar: None. A. Verma: None.
Background: Elevated aldosterone and low-density lipoprotein (LDL) are both known risk factors for major cardiovascular events (MACE) in chronic kidney disease (CKD). Method: The synergistic impact of aldosterone and LDL on incident MACE was investigated among 3453 participants in the Chronic Renal Insufficiency Cohort. The primary exposure was the interaction between aldosterone and LDL as continuous variables. We also evaluated the same interaction after categorizing each variable by the median. The primary outcome was MACE [defined as the composite of heart failure (HF), myocardial infarction (MI), or stroke, whichever occurred first]. Cox proportional hazard models and confounder-adjusted survival curves were developed after adjustment for demographic, metabolic, renal, and laboratory parameters to ensure a robust interpretation of results. Results: Over a median follow-up period of 8.9 years, 1,030 participants experienced major cardiovascular events (MACE). There was a statistically significant linear interaction between aldosterone and low-density lipoprotein (LDL) in predicting incident MACE (P = 0.005). In adjusted models, participants with aldosterone and LDL levels greater than the median had a 32% increased risk of MACE (HR 1.32, 95% CI 1.08-1.61) compared to those with values below the median. The 10-year absolute risk difference for MACE was 5.8% (95% CI 1.3 -10.3) comparing individuals with aldosterone and LDL greater than the median with those below the median. Conclusion: The combination of elevated aldosterone levels and elevated LDL cholesterol imparts a heightened risk for major cardiovascular events in CKD. These findings emphasize the potential value of mineralocorticoid receptor antagonism or aldosterone synthase inhibition in combination with LDL-lowering to mitigate adverse cardiovascular events in CKD.
Presentation: 6/3/2024
6565 The NF-κB-CXCL1 Axis Mediates the Development of Nonalcoholic Steatohepatitis
Authors: Raul Mahima Chandrakant , Li Yuchang , Chen Liting , Sottas Chantal , Patel Nrupa Dinesh , Zambidis Alexander Elias , Papadopoulos Vassilios 
Published: October 2024

Abstract
Disclosure: M. Raul: None. Y. Li: None. L. Chen: None. C. Sottas: None. N. Patel: None. A. Zambidis: None. V. Papadopoulos: None.
The transcription factor nuclear factor kappa B (NF-κB) plays a crucial role in the pathogenesis of nonalcoholic steatohepatitis (NASH). CXC chemokine, (CXCL1) is one of the most selective and potent chemokines that effectively attracts neutrophils to the site of inflammation or infection, which is also regulated by the NF-κB signaling pathway. In the liver, when NF-κB is activated, it promotes the transcription of CXCL1 to recruit neutrophils to the site of inflammation. Moreover, induced expression of the CXCL1 gene in rat liver was accompanied by neutrophil infiltration, causing hepatic damage and dysfunction. Previous research has shown that NF-κB signaling can influence CXCL1 in vitro. However, the contribution of the NF-κB/CXCL1 axis to the progression of NASH has remained unclear. To verify the regulatory association between NF-κB and CXCL1, we conducted a luciferase assay by transiently transfecting Huh7 cells with a CXCL1-Luciferase plasmid and treating them with varying concentrations of human recombinant NF-κB protein. The results demonstrated a dose-dependent increase in CXCL1-luciferase activity in response to NF-κB, indicating that NF-κB regulates CXCL1 expression. Additionally, TNFɑ (10ng/ml)-induced CXCL1-luciferase activity was significantly and dose-dependently suppressed by celastrol (CEL), a compound known to counteract the TNFα-induced upregulation of NF-κB. To further investigate the regulation of CXCL1 by NF-κB in the liver in vivo, CEL was administered to rats fed with the Gubra-Amylin diet-induced NASH (GAN) diet. Histological studies revealed a substantial reduction in liver lipid accumulation and fibrosis, along with reduced inflammation in white adipose tissue with CEL treatment. As anticipated, NF-κB levels were significantly suppressed in GAN+CEL compared to the GAN+Veh (vehicle)-treated rats. CXCL1 expression was also diminished by the treatment, providing further confirmation of the regulation of CXCL1 by NF-κB in the liver. Moreover, the hallmarks of NASH, including inflammation, lipid accumulation, and fibrosis, were alleviated in the GAN+CEL group compared to the GAN+Veh group. In conclusion, these findings provide compelling evidence supporting the involvement of the NF-κB - CXCL1 signaling pathway in the development of NASH.
Presentation: 6/2/2024
7091 Triglyceride Glucose Index Is Strongly Associated With Nonalcoholic Fatty Liver Disease in the Normal BMI US Population
Authors: Ayesh Hazem , Niswender Kevin Dean , Carranza Leon Barbara Gisella 
Published: October 2024

Abstract
Disclosure: H. Ayesh: None. K.D. Niswender: None. B.G. Carranza Leon: None.
Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) poses a growing global health threat. The surge in NAFLD, often linked to metabolic disorders such as diabetes and obesity, underscores the urgency for effective screening methods. Traditional approaches rely on indicators that involve elevated BMI and/or liver function tests to identify individuals at risk of NAFLD. The Triglyceride-Glucose Index (TyG Index), calculated as ln(Fasting Triglycerides × Fasting Glucose/2), may be a promising NAFLD risk prediction tool. Our study aims to investigate the correlation between the TyG Index and NAFLD in the normal BMI population, utilizing data from the National Health and Nutrition Examination Survey (NHANES). Methods: A total of 1130 subjects with a normal Body Mass Index (BMI) (18.5 - 24.9) were selected from the NHANES study. The primary goal was to explore the correlation between hepatic steatosis and the Triglyceride-Glucose (TyG) index. The study population was categorized into TyG quartiles. Regression analysis was conducted while controlling for confounding variables such as BMI, Hemoglobin A1c, and age. Hepatic steatosis was evaluated using the Fibroscan technique, with the Median Controlled Attenuation Parameter (CAP) as the quantitative indicator. Results/Discussion: The study found a significant correlation between steatosis and the Triglyceride-Glucose Index (TyG), with an odds ratio of 3.75, a P-value &lt; 0.001 between the lowest and highest quartile, and a confidence interval of 2.385 to 5.99. This correlation increased across higher quartiles (2-1, 3-1, 4-1) with odds ratios of 1.34, 1.91, and 3.75, revealing a dose-response relationship with higher TyG. These findings remained significant after adjusting for BMI and hemoglobin A1c, key NAFLD risk factors. The TyG index is valuable for identifying high-risk NAFLD patients, especially those with a normal BMI. Unlike other calculators like Fatty Liver Index and Hepatic Steatosis Index, TyG does not rely on BMI. The study unveiled a racial difference in the correlation between TyG and NAFLD, with a weaker TyG-NAFLD association in African Americans and a stronger one in Asians. This discovery emphasizes the need for future large-scale studies to explore potential genetic components and the potential of the TyG index to modulate genetic predisposition to NAFLD.
Presentation: 6/2/2024
7493 A Case Report of Recurrent Hypoglycemia With Polysubstance Abuse With Rhabdomyolysis and Capillary Glucose Monitoring Dilemma
Authors: Gupta Uma Datta , Prasad Parinitha , Hlaing Pwint P , Panigrahi Kalpana , Deribe Zewge 
Published: October 2024

Abstract
Disclosure: U.D. Gupta: None. P. Prasad: None. P.P. Hlaing: None. K. Panigrahi: None. Z. Deribe: None.
Substance use has been correlated with impaired functioning in every bodily system. Over the last two years, our investigations into polysubstance abuse patients have revealed variations in mortality risks, particularly associated with hypoglycemia. We have presented a case of 45-year-old male with a medical history encompassing Bipolar 1 disorder, Polysubstance abuse, and schizoaffective disorder presented to the Emergency Department due to bizarre behavior. On the second day of admission, the patient experienced recurrent hypoglycemia, as indicated by a finger stick blood glucose reading of 39, which was successfully corrected with 50% glucose and D5RL drip. Nevertheless, two hours later, the BG level dropped to less than 20. Despite this, the patient remained asymptomatic and alert, and oral feeding was initiated. However, an ear lobe measurement concurrently indicated a value of 122. The patient's polysubstance use had notable impacts on cardiac, respiratory, metabolic, and renal systems. Blood glucose fluctuations were influenced by both sympathomimetic drug overdoses and underlying disease processes. Instances of hypoglycemia linked to recreational drug use, particularly with substances such as ecstasy, amphetamine, eutylone, and cannabinoids, have been documented. However, there have been a few reports of persistent refractory hypoglycemia in these cases. The probable cause of refractory hypoglycemia is linked to amphetamine and synthetic cannabinoid use, accentuated by compromised elimination due to renal dysfunction. It is noteworthy that the unique recurrent hypoglycemia in our case is evident solely in peripheral finger stick measurements, with no corresponding results in ear lobe or venous blood samples. Healthcare providers may also overestimate the accuracy of portable glucose meter readings. A study revealed widening differences in meter readings (5.7% to 32%)- which needs to be re-evaluated in every instance. Recognizing and understanding cases like this will contribute to improved diagnosis in the future, facilitating the identification of reasons for the observed discrepancy. In addition, as research, papers, and case reports addressing hypoglycemia in polysubstance abuse patients, along with its management and assessment, are notably scarce that need to be addressed with proper assessment of hypoglycemia. It is imperative to conduct thorough assessments and evaluations of such cases to establish a comprehensive management plan, aiming to prevent mortality rather than merely treating symptomatic hypoglycemia.
Presentation: 6/3/2024
8704 A DREADD-base Chemogenetic Approach to Quiz the Impact of the Delta Cell Input on Islet Hormone Secretion
Authors: Rodriguez Dayleen Hakim , Tamayo Alejandro , Diaz Rayner Rodriguez , Pereira Elizabeth , Alcazar Oscar , Makhmutova Madina 
Published: October 2024

Abstract
Disclosure: D. Hakim Rodriguez: None. A. Tamayo: None. R. Rodriguez Diaz: None. E. Pereira: None. O. Alcazar: None. M. Makhmutova: None.
The utilization of DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) that are gated by clozapine-N-oxide (CNO) enables the selective stimulation of genetically specified cell types in vivo. This chemogenetic technology has been successfully applied in various in vivo studies, including those using mice, to remotely control GPCR signaling in specific cells, such as neurons, glia cells, pancreatic β-cells, or cancer cells. Utilizing DREADDs in the study of pancreatic islets, particularly in the somatostatin-producing δ-cells, could offer insights into the complex role of this hormone. Somatostatin is known to inhibit the secretion of other islet hormones, such as insulin and glucagon, but the detailed mechanisms of its action have not been fully elucidated. To address this, we generated mice enabling the expression of either the activator-DREADD Gq or the inhibitor-DREADD Gi in the mouse somatostatin secreting cells, including the islet δ-cell. Immunohistochemical staining of pancreas sections showed that DREADD were expressed and translocated to the membrane of the islet δ-cells. Perifusion experiments with isolated islets showed that δ-cells responded to CNO stimulation as expected. Islets bearing the DREADD Gq secreted somatostatin in a dose-dependent manner, while somatostatin secretion was inhibited in those expressing DREADD Gi. Secretion of insulin and glucagon were modulated upon activation or inhibition of δ-cells via CNO/DREADD manipulation. CNO-driven pulses of somatostatin stimulation caused asynchronous off responses of neighboring α-and β-cells during the time lapses of somatostatin secretion falloff, resulting in a net increment in the magnitude of both insulin and glucagon secretion. Meanwhile, inhibition of somatostatin secretion surprisingly unleashed glucagon secretion in non-permissive 16mM glucose. These results encouraged us to explore the potential application of DREADD tools in isolated human islets. We will discuss our current approaches whilst using viral vectors to drive the expression of DREADDs in human δ-cells and its impact in the overall islet secretory output.
Presentation: 6/2/2024
8616 A Novel Mutation of Maturity Onset Diabetes of the Young
Authors: Weerasinghe K H , Branis N 
Published: October 2024

Abstract
Disclosure: K.H. Weerasinghe: None. N. Branis: None.
Background: Maturity onset diabetes of the young (MODY) is an autosomal dominant condition characterized by various subsets (Nkonge et al., 2020). A mutation in the glucokinase gene (GCK), otherwise known as MODY type 2, is often characterized by mild hyperglycemia managed with lifestyle modifications (Nkonge et al., 2020). Novel mutations in this gene may differ in their clinical course and need close clinical monitoring. Clinical Case: A 19 year old male presented for evaluation of his diabetes mellitus. In 2020, the patient was hyperglycemic on routine blood work, with asymptomatic features. His condition was managed with lifestyle modifications. The HbA1c was 6.8 and 7; while fructosamine was 338 mmol/L (normal 205-285 mmol/L). Subsequent workup revealed GAD 65 to be less than 5 U/ml(normal range being 0-5 U/ml) with negative islet antibodies. C-peptide was similarly measured and found to be 1.5 ng/ml, within the limits of 1.1-4.4 ng/ml, demonstrating a good pancreatic reserve. A MODY genetic profile was then conducted which revealed a novel mutation in the GCK gene, variant c.1064T&gt;C (p.L355P). As this is a novel mutation, the probability of MODY was calculated, and found to be 75% using the Exeter maturity-onset diabetes of the young (MODY) probability calculator (EMPC).The patient’s clinical course thus far has been managed conservatively as his hyperglycemia has been mild. However, recently the patient’s post prandial sugars were found to be persistently elevated. Pharmacotherapy such as sulfonylureas was discussed however, as per the patient’s wishes, stricter dietary modifications will be applied prior to the initiation of medication. Conclusion: Patients with novel mutations should be closely monitored as the general expected clinical course may vary. These changes are demonstrated in this case report as the patient started developing elevation in postprandial sugar levels uncharacteristically. Close monitoring of the patient’s future clinical status will be essential in learning more about the differences in prognosis and long term management. References: Nkonge, K. M., Nkonge, D. K., & Nkonge, T. N. (2020a). The epidemiology, Molecular Pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY). Clinical Diabetes and Endocrinology, 6(1). https://doi.org/10.1186/s40842-020-00112-5
Presentation: 6/2/2024
8348 A Rare Case Of Liraglutide-Associated Angioedema Requiring Emergent Intubation
Authors: Amin Tasnuva , Mararenko Anton , Cheng Jennifer , Ong Raquel , Holland Soemiwati , Hu Katherine 
Published: October 2024

Abstract
Disclosure: T. Amin: None. A. Mararenko: None. J. Cheng: None. R. Ong: None. S. Holland: None. K. Hu: None.
Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used in the management of type 2 diabetes mellitus to enhance glycaemic control. While generally considered safe, recent reports indicate an increasing frequency of adverse drug reactions, with gastrointestinal symptoms such as pancreatitis becoming more prevalent. This case report highlights a rare occurrence of angioedema induced by the GLP-1 receptor agonist, Liraglutide. Case A 58-year-old Type 2 diabetic male presented with rapidly progressing tongue swelling, abdominal discomfort, and watery diarrhea, six hours after initiating Liraglutide therapy. On presentation, he was hemodynamically stable, afebrile, maintaining adequate oxygenation on room air. On examination, the patient was in moderate distress with generalized tongue swelling protruding out, with no swelling of eyelids or lips. No rashes were noted on exposed skin and clear breath sounds without wheezing on lung examination. Due to concern for an impending airway compromise, the patient was intubated. Chart review showed he had an episode of self-resolving tongue swelling a few months back, at which time he was taken off his Angiotensin receptor blocker. 2 weeks ago, he was started on a new brand of GLP-1 receptor agonist (Liraglutide) to achieve optimal glycemic control. No other drug allergies or allergic reactions were reported. C1-Esterase panel, eosinophil count, and inflammatory markers were within normal limits.On admission, Liraglutide was discontinued, he was placed on a basal-bolus insulin regimen, received methylprednisolone, famotidine, and diphenhydramine Subsequent improvement allowed for extubation on the third day, and the patient was discharged with plans to discontinue Liraglutide and an epinephrine pen for precautionary use. Conclusion: This case represents a rare and severe manifestation of angioedema associated with Liraglutide use in a diabetic patient. While angioedema has been infrequently reported with other GLP-1 receptor agonists such as Exenatide and Dulaglutide , our case underscores the importance of clinicians' awareness regarding this potential life-threatening complication with Liraglutide. Post-marketing surveillance data suggest that anaphylactic reactions with Liraglutide may occur rarely, emphasizing the need for vigilance among healthcare providers.
Presentation: 6/2/2024
7284 Ablation of hexose-6-phosphate dehydrogenase in mice causes skeletal muscle atrophy and dramatically impairs exercise capacity
Authors: Zogg M , Grötsch A D , Birk J , Pelczar P , Bouitbir J , Odermatt A 
Published: October 2024

Abstract
Disclosure: M. Zogg: None. A.D. Grötsch: None. J. Birk: None. P. Pelczar: None. J. Bouitbir: None. A. Odermatt: None.
Hexose-6-phosphate dehydrogenase (H6PD) catalyzes the first two steps of the pentose-phosphate pathway (PPP) within the endoplasmic reticulum (ER), generating the redox equivalent NADPH. It has been shown that mice lacking H6PD develop defects mainly in skeletal muscles [1]. Nevertheless, the mechanisms underlying the myopathy in H6PD KO mice is unknown. Here, we further assessed muscle responses to H6PD deficiency and aimed to uncover the mechanisms that may cause myopathy in mice. We conducted a detailed characterization of the muscle structure and function as well as energy metabolism in oxidative and glycolytic muscles of H6PD KO mice. At the age of 15 weeks, H6PD KO mice displayed lower body weight than WT mice, despite similar food and water intake. Grip strength was significantly lower in H6PD KO than in WT mice. This was associated with decreased weight of the mixed (gastrocnemius, quadriceps) and fast fiber type rich muscles of the hind leg (extensor digitorum longus, tibialis anterior) in H6PD KO animals. Atrogin1 and Murf1 mRNA expression, markers of atrophy, increased only in the white (glycolytic) quadriceps. In this context, fast-twitch fibers in WT mice displayed higher H6pd mRNA expression than slow-twitch fibers. Electron microscopy analysis of red and white gastrocnemius muscles displayed the presence of large intramyofibrillar vacuoles, and morphologic changes of the sarcoplasmic reticulum and mitochondria in H6PD KO muscle. Metabolically, H6PD KO muscles presented an accumulation of glycogen granules and significantly decreased mRNA expression of glucose transporter Glut4, glucose-6-phosphate transporter G6pt and glycogen phosphorylase Pygm. The exercise capacity, measured by maximal running distance, decreased by more than 50% in H6PD KO mice. Upon exercise, both WT and H6PD KO animals were able to mobilize the majority of glycogen stored in their muscles. However, immediately after exercise, there was a significant increase in plasma lactate and glucose levels in H6PD KO animals. Disturbances in glucose metabolism were further supported by in vitro experiments using stable C2C12 H6PD KO myoblasts, revealing a shift in basal state mitochondrial fuel oxidation usage from glucose to fatty acid and glutamine in metabolic dependency assays. In conclusion, our findings revealed that H6PD seems to play a key role in proper function and energy metabolism of skeletal muscles. References:[1] Lavery G. G. et al. 2008 J. Biol. Chem. 283, 8453-8461.
Presentation: 6/1/2024