bluuebunny/crossref_metadata_2025_split huggingface dataset:
319-OR: Effect of Vertical Sleeve Gastrectomy (VSG) on the Kidney Transcriptome of Youth with Type 2 Diabetes (T2D)
Authors: NAIK ABHIJIT , ALAKWAA FADHL , SCHAUB JENNIFER A. , MCCOWN PHILLIP J. , NAIR VIJI , EDDY SEAN , PYLE LAURA , VIGERS TIMOTHY B. , KELSEY MEGAN M. , FULLER KELLY N.Z. , LADD PATRICIA E. , SANDOVAL DARLEEN A. , GROSS SUSAN , ZEITLER PHILIP , NADEAU KRISTEN J. , RYDER JUSTIN R. , INGE THOMAS , HODGIN JEFFREY B. , BROSIUS FRANK C. , NELSON ROBERT G. , KRETZLER MATTHIAS , BJORNSTAD PETTER 
Published: June 2023

Introduction: VSG attenuates early diabetic kidney disease (DKD) in youth with T2D, yet the molecular mechanisms of VSG on kidney health are unknown. We analyzed single-cell RNA sequencing data from paired kidney biopsies obtained from youth with T2D before and 1-year after VSG.
Methods: Data from 5 youths with T2D who underwent kidney biopsies before and after VSG were included in this analysis (pre-VSG:17±2 years, HbA1c 7.5±2.6%, BMI 41±3 kg/m2, 40% with albuminuria (UACR≥30mg/g). A total of 23598 cells were profiled from the five paired kidney biopsies, with 19735 cells from 12 HC. Cell selective differentially expressed genes in disease (T2D vs. HC) were computed. Disease genes that reversed directionality post-VSG were termed "suppressed by VSG" or "upregulated by VSG," depending on the direction of the reversal.
Results: VSG resulted in the normalization of HbA1c and UACR in all cases at 12 months. Post VSG, 73% of proximal tubule (PT) genes that were upregulated in T2D vs. HC were suppressed in VSG vs. T2D. These suppressed genes were enriched for glycolysis, gluconeogenesis, and TCA cycle pathways (Figure). Gene and pathway changes in the PT were similar to what was recently demonstrated with SGLT2i in T2D youth.
Conclusion: VSG, like SGLT2i, is associated with reduced central carbon metabolism in the PT and other nephron segments.

Disclosure
A.Naik: Advisory Panel; CareDx. K.N.Z.Fuller: None. P.E.Ladd: None. D.A.Sandoval: Consultant; Metis Therapeutics. S.Gross: None. P.Zeitler: Consultant; Eli Lilly and Company, Boehringer Ingelheim Inc., Johnson & Johnson. K.J.Nadeau: None. J.R.Ryder: None. T.Inge: None. J.B.Hodgin: None. F.C.Brosius: Advisory Panel; Gilead Sciences, Inc. F.Alakwaa: None. R.G.Nelson: None. M.Kretzler: Research Support; Lilly, Boehringer Ingelheim Inc., Traveere Pharmaceuticals, Novo Nordisk, certa, Chinook Therapeutics Inc., Janssen Research & Development, LLC, AstraZeneca, Moderna, Inc., Gilead Sciences, Inc., Regeneron, Ionis Pharmaceuticals, Angioin, Renalytix. P.Bjornstad: Advisory Panel; AstraZeneca, Novo Nordisk, Lilly, Horizon Therapeutics plc, Boehringer Ingelheim (Canada) Ltd., LG Chem, Consultant; Bayer Inc., Bristol-Myers Squibb Company. J.A.Schaub: None. P.J.Mccown: None. V.Nair: None. S.Eddy: None. L.Pyle: None. T.B.Vigers: None. M.M.Kelsey: Other Relationship; Boehringer Ingelheim Inc., Janssen Pharmaceuticals, Inc., Rhythm Pharmaceuticals, Inc., Lilly.

Funding
Boettcher Foundation; National Institute of Diabetes and Digestive and Kidney Diseases (K23116720, R01DK129211); JDRF (2-SRA-2019-845-S-B)
32-OR: Reduction of Macrophage-iPLA2ß–Derived Proinflammatory Lipids Inhibit Type 1 Diabetes Development
Authors: ALMUTAIRI ABDULAZIZ , GAI YING , NADLER JERRY , CHALFANT CHARLES E. , RAMANADHAM SASANKA 
Published: June 2023

Type 1 diabetes (T1D) is a consequence of autoimmune-mediated destruction of pancreatic β-cells, but the leading causes for this process remain elusive. Our lab revealed that Ca2+-independent phospholipase A2β (iPLA2β) modulates the polarization of macrophages (MΦ). Recently, we showed that selective iPLA2β-derived lipid signals (iDLs) produced by MΦ from spontaneous-T1D prone mice (NOD) is high during the pre-diabetic phase. Therefore, we examined the impact of bone marrow-derived macrophages (BMD-MΦ)-iDLs on T1D development by generating NOD mice with conditional reduction in MΦ-iPLA2β (NOD. cM Φ iPLA2𝛽;-/- and NOD. cM Φ iPLA2𝛽;+/-). Our data show that BMD-MΦ from NOD. cM Φ iPLA2𝛽;-/- or NOD. cMΦiPLA2𝛽;+/- are skewed towards an M2 anti-inflammatory phenotype, compared with NOD BMD-MΦ. Also, BMD-MΦ from NOD.cMΦiPLA2𝛽;-/- and NOD.cMΦiPLA2𝛽;+/- have significantly less proinflammatory lipids (PGs, DHETs, and TXB2), compared to NOD BMD-MΦ. Moreover, selective inhibition of PGE2 (EP4 antagonist) or DHET (TPPU) signaling inhibits NOD BMD-MΦ polarization towards an M1 proinflammatory phenotype, as reflected by reductions in M1 markers (Arg2, CXCL10, STAT1, and TNFα) and increases in M2 markers (Arg1, RELA, STAT6, and MRC1). Furthermore, pancreata from NOD.cMΦiPLA2𝛽;-/- and NOD.cMΦiPLA2𝛽;+/- have significantly reduced immune cell (CD4, CD8 and, CD19) infiltration and a higher abundance of M2 anti-inflammatory macrophages relative to NOD pancreata. These outcomes were associated with improved glucose tolerance and significant reduction of T1D incidence in the NOD.cMΦiPLA2𝛽;-/- and NOD.cMΦiPLA2𝛽;+/-, as compared with the incidence in the NOD mice. In summary, reduction of select proinflammatory iDLs production by BMD-MΦ favors M2 anti-inflammatory phenotype, reduced T1D pathogenesis, and T1D incidence. We conclude that MΦ-iDLs contribute to T1D onset and that inhibition of selected macrophages-derived iDLs production can be targeted to counter T1D development

Disclosure
A.Almutairi: None. Y.Gai: None. J.Nadler: None. C.E.Chalfant: None. S.Ramanadham: None.
324-OR: VEGF Is a Contributing Factor for the Reduction of Retinal Function in Diabetic Retinopathy and Hypoxic Retinal Disorders
Authors: LE YUN , ZHU MEILI 
Published: June 2023

Vascular endothelial growth factor (VEGF or VEGF-A), a major therapeutic target for blood-retina barrier breakdown (BRB) in diabetic retinopathy (DR), neovascular age-related macular degeneration (AMD), and other and hypoxic retinal diseases, has been shown to act as a direct functional regulator for peripheral and central nervous system (CNS) neurons. To investigate the direct effect of VEGF on photoreceptor function in DR and hypoxic retinal diseases, we examined and compared the effect of recombinant (rVEGF) on retinal function with electroretinography (ERG) in Akita spontaneous diabetic mice and wild-type (WT) mice kept under normal environment and hypoxia (8 percent oxygen for 5 days). Retinal function was measured with ERG in dark-adapted mice immediately after rVEGF intravitreally delivery under long-wavelength illumination. While the rVEGF caused a significant reduction of scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes in a dose-dependent manner in WT mice kept under normal conditions, the effect of rVEGF on the alteration of ERG amplitudes was diminished in age-matched Akita diabetic and hypoxic mice in which retinal VEGF levels are upregulated. Our results suggest that VEGF is a most likely direct functional regulator of photoreceptors. Our data strongly support that VEGF upregulation is a likely cause of the reduced photoreceptor function in DR and hypoxic retinal disorders. As VEGF is a major therapeutic target for BRB breakdown in DR, AMD, and other hypoxic retinal BRB diseases, our work provides the mechanistic insights for the therapeutic effects on visual acuity and for the care of anti-VEGF drug treated patients.

Disclosure
Y.Le: None. M.Zhu: None.

Funding
National Institutes of Health (R01EY26970, P30EY021725, P30GM122744); Oklahoma Center for the Advancement of Science and Technology (HR20-065)
33-OR: Epigenetic Reader BRD4 Directs Fast-Twitch Myofiber Gene Programs Influencing Skeletal Muscle Endurance Capacity and Systemic Glucose Homeostasis
Authors: ZHOU ZHENG , LIU LIN , XU ZHISHENG , FU TINGTING , YANG LIKUN , YAN MAO , GAN ZHENJI 
Published: June 2023

Skeletal myofibers exhibit remarkable diversity and plasticity in contractile and metabolic functions and play a key role in controlling systemic metabolism. Previous studies of muscle fiber-type switching have centered on the specification of slow-twitch myofibers. However, mechanisms that drive fast-twitch myofibers formation remain unclear. Here, we showed that BRD4, an epigenetic reader enriched in fast myofibers, plays a critical role in controlling fast-twitch myofiber identity as well as systemic glucose homeostasis. BRD4 levels are associated with fast-twitch myofiber gene expression in human muscle. Skeletal muscle-specific ablation of BRD4 in mice (Brd4f/fHSA-Cre, BRD4 mKO) resulted in downregulation of the fast-twitch myofiber gene program, increased number (~100%) of type I myofibers and mitochondrial oxidative capacity. This led to enhanced muscle endurance capacity. In adult mice, acute and inducible BRD4 deletion using a tamoxifen-inducible Cre elicited a similar fast-to-slow fiber type switch in muscle. Mechanically, genome-wide ChIP-seq and mRNA-seq analyses revealed that BRD4 directly binds to and activates transcriptional of fast-twitch myofiber genes through cooperating with MEF2. Furthermore, mice lacking muscle BRD4 were protected against high-fat-diet (HFD)-induced obesity, glucose intolerance and insulin resistance. HFD-fed BRD4 mKO mice had significantly less fat mass (∼50%) compared with HFD-fed WT controls. Histological and biochemical measurements confirmed a pronounced (~60%) decrease in fat deposition in BRD4 mKO livers. Thus, our results uncover a previously unrecognized mechanism underlying the determination of fast-twitch myofiber and provide new therapeutic opportunities for driving muscle fiber-type switch to combat metabolic diseases.

Disclosure
Z.Zhou: None. L.Liu: None. Z.Xu: None. T.Fu: None. L.Yang: None. M.Yan: None. Z.Gan: None.
346-OR: IL-10–Treated Adipose Stromal Vascular Fractions Reverse Insulin Resistance in a Type 2 Diabetes Mellitus Mouse Model
Authors: CHEN LEE-WEI 
Published: June 2023

Low IL-10 production capacity is associated with type 2 diabetes. Targeting IL-10 in diabetes patients has resulted in inconsistent results. To test if IL-10-treated adipose stromal vascular fraction could be used to reverse diabetes-induced gluconeogenesis and insulin resistance, we purified stromal vascular fractions (SVFs) from adipose tissue from diabetic (Lepdb/db ) and nondiabetic (Lep+/+) mice, treated them with IL-10, and injected them into adipose tissue of diabetic mice. Injection of IL-10 into adipose tissue of diabetic mice decreased mRNA expression of IL-6 and IL-1β of adipose SVFs but did not change G6PC and PCK1 expression in liver. Injection of IL-10-treated SVFs into adipose tissue of diabetic mice significantly decreased CCL2 and IL-1β expression and increased IL-10 and Foxp3 expression of SVFs of Lepdb/db mice. Moreover, injection of IL-10-treated SVFs significantly increased IL-10 levels of adipose tissue and decreased G6PC and PCK1 and insulin resistance of liver in diabetic mice. Altogether, our data suggest that IL-10-treated adipose SVFs could be used to reverse diabetes-induced gluconeogenesis gene expression and insulin resistance in diabetes. These data suggest that modified-adipose stromal vascular fractions could be used as a promising cell therapy tool in alleviating insulin resistance in diabetes mellitus.

Disclosure
L. Chen: None.

Funding
National Science and Technology Council, Taiwan (110-2314-B-A49A-540-MY3)
355-OR: Targeting a Lipid Droplet Hydrolase-Mediated Lipid Signaling for Treatment of Type 2 Diabetes
Authors: LI XIN , SUN KAI 
Published: June 2023

Lipid droplets (LDs) are cytosolic organelles that serve as the major energy reservoir in adipocytes. Excessive accumulation of neutral lipids in LDs has been linked to obesity-associated type 2 diabetes. The dynamics of LDs is regulated by multiple proteins bound to their surfaces. Recently, carboxylesterase 1d (Ces1d) was identified as a LD-targeting lipid hydrolase. It has been showed that blockage of Ces1d in adipose tissue led to not only decreased lipolysis, but also impaired β-adrenergic signaling-stimulated thermogenesis. The goal of the current study is to define the mechanism governing the function of Ces1d on lipid metabolism. The hypothesis is that the LD-targeting Ces1d generates free fatty acids (FFA) “third messenger” that trigger specific lipid signaling in adipose tissue which further affect the whole-body metabolic homeostasis. To test this hypothesis, an adipose tissue specific Ces1d knockout mouse model (Adipo-Ces1d KO) was generated. Mass Spectrometry analysis revealed that circulating docosahexaenoic acid (DHA, C22:6 n=3), an established PPARγ ligand, was dramatically decreased in Adipo-Ces1d KO mice. The production of DHA was confirmed by an in vitro lipid digestion assay on the recombinant Ces1d. Lack of DHA signaling further led to decreased transactivation of PPARγ in adipose tissue of the Adipo-Ces1d KO mice. As a result, the expression of thermogenic gene, UCP1 was significantly downregulated. The result agrees with previous observation that Adipo-Ces1d KO mice lost their ability to defense body temperature when exposed to coldness. More interestingly, the Adipo-Ces1d KO mice gained more body weight with increased fat mass during a HFD challenge, suggesting they experienced decreased energy expenditure in the whole process. The findings thus highlight the key role of a novel lipid signaling pathway mediated by Ces1d in energy expenditure and hence pinpoint it as a potential target for treatment of obesity-induced type 2 diabetes.

Disclosure
X.Li: None. K.Sun: None.

Funding
National Institutes of Health (R56DK124419, R01DK129815)
36-OR: The Effect of Glucagon-Like Peptide-1 Receptor Blockade on the ß-Cell Response to Glucagon Bolus in People With and Without Type 2 Diabetes
Authors: EGAN AOIFE M. , ZEINI MAYA , WELCH ANDREW A. , FARAHANI RAHELE A. , LAURENTI MARCELLO C. , COBELLI CLAUDIO , DALLA MAN CHIARA , VELLA ADRIAN 
Published: June 2023

Glucagon acts as an insulin secretagogue in part via the glucagon-like peptide-1 receptor (GLP1R) expressed on β-cells. Type 2 diabetes (DM2) is characterized by increased (and inappropriate) glucagon secretion for the prevailing hyperglycemia. Increased islet glucagon staining has also been observed in DM2. This suggests that increased glucagon signaling via GLP1R is a mechanism to maintain β-cell secretion in DM2. To ascertain if this is the case, we quantified the relative contribution of GLP1R signaling to the insulin response to glucagon in the presence and absence of DM2. We studied 12 individuals without DM2 (54 ± 2 yrs, 33 ± 1 kg/m2) and 11 with DM2 (58 ± 2 yrs, 34 ± 2 kg/m2) on 2 occasions in random order. On one occasion Exendin-9,39 (300pmol/kg/min) was infused to block GLP1R, while on the other study day saline was infused. Following an overnight fast and a 3-hour hyperglycemic clamp (~9 mmol/L), 1 mg glucagon bolus was administered intravenously with subsequent measurement of insulin, and C-peptide over 30 minutes during hyperglycemia. Exendin-9,39 infusion decreased peak and integrated insulin and C-peptide concentrations in response to the glucagon bolus in both those with and without DM2. The symmetric % change in insulin (-49 ± 8 vs -32 ± 8, DM2 vs. subjects without diabetes respectively, p = 0.2) and C-peptide (-24 ± 5 vs -15 ± 4, p = 0.18) did not differ between groups. In addition, six of the subjects without DM2 completed two additional study days (± exendin-9,39) with infusion of Intralipid® and heparin to raise free fatty acids (FFA) and cause acute insulin resistance. Acute FFA elevation also did not alter the net contribution of GLP1R stimulation to the response to glucagon in individuals without DM2 (% change insulin: -34 ± 10, p = 0.42; C-peptide: -23 ± 7, p = 0.38). These data suggest that the % contribution of glucagon to the stimulation of β-cell secretion via GLP1R does not change significantly in the presence or absence of DM2 or of FFA elevation.

Disclosure
A.M.Egan: None. M.Zeini: None. A.A.Welch: None. R.A.Farahani: None. M.C.Laurenti: None. C.Cobelli: None. C.Dalla man: Research Support; Sanofi-Aventis Deutschland GmbH, Becton, Dickinson and Company. A.Vella: Advisory Panel; Rezolute, Inc., Consultant; Crinetics Pharmaceuticals, Inc., Hanmi Pharm. Co., Ltd., Zealand Pharma A/S, Other Relationship; Novo Nordisk.

Funding
National Institutes of Health (DK126206)
361-OR: Hybrid Care Model Combining Telemedicine and Office Visits for Diabetes Management Is Effective in Older Adults with Type 1 Diabetes (T1D) Using Continuous Glucose Monitors (CGM)
Authors: TOSCHI ELENA , ADAM ATIF , HURLBERT REBECCA , FRIMPONG NANA , SLYNE CHRISTINE , LAFFEL LORI M. , MUNSHI MEDHA 
Published: June 2023

Objective: CGM improves glycemic control and mitigates hypoglycemia using office visits for older adults with T1D. During COVID-19 pandemic, a hybrid (in-office and telemedicine) care model was implemented. Data on impact of hybrid care model on glycemic control in older adults with T1D are limited.
Methods: Demographic, clinical characteristics, and CGM metrics of older adults (age ≥65 yrs) with T1D were retrieved from electronic health records from 2 periods: pre-pandemic (April 1, 2019-March 1, 2020) and during pandemic (September 1, 2020 to August 31, 2021) (adjusted for length of follow-up).
Results: 299 (47% male; mean age 72±4 years; 51% pump users) older adult CGM users were seen in both periods. Comparison of CGM metrics (Table) between time periods showed no changes in overall control (mean glucose 170±31 vs 168±33 mg/dL; p=0.75), glucose management indicator (GMI) (7.4 vs 7.3% p=0.65) or coefficient of variation (CV) (36% vs 35%; p=0.82). During hybrid model of care, time in-range (64±15 vs 72±15%; p&lt;0.001) improved, while time &lt;70 mg/dL did not increase.
Conclusion: Glycemic control using a hybrid-care model was maintained compared with in-person visits in older adults with T1D using CGM without impacting risk of hypoglycemia. Further studies can clarify how to routinely use a hybrid-care model in older adults with T1D.

Disclosure
E.Toschi: Advisory Panel; Eli Lilly and Company. A.Adam: None. R.Hurlbert: None. N.Frimpong: None. C.Slyne: None. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. M.Munshi: Consultant; Sanofi.

Funding
Thomas J. Beatson, Jr. Foundation
382-P: Comparison of Intranasal and Injectable Glucagon Administration among Pediatric Population Responders
Authors: WANG YUE PEI , BERNATCHEZ FRANCESCA , CHOUINARD-CASTONGUAY SARAH , TREMBLAY MARIE-CLAUDE , VANASSE ANDRÉANE , MEGALLI MELISSA , MILLETTE MAUDE , BOULET GENEVIEVE , HENDERSON MÉLANIE , BRAZEAU ANNE-SOPHIE , RABASA-LHORET RÉMI , GAGNON CLAUDIA 
Published: June 2023

Context: Intranasal glucagon (INg) might improve the management of severe hypoglycemia (SH) at school in children with type 1 diabetes (T1D), which is a major concern of our patient partners.
Objectives: We compared the performance of parents of children with T1D & school workers (SW) for INg and injectable glucagon (IJg) administration. We also assessed the enablers and barriers associated with each glucagon and preferred teaching methods.
Methods: After watching a video on glucagon administration, Patients and SW (30/group) administered both glucagon in random order in 2 simulated scenarios, followed by an individual interview. Performance was rated by a direct observer: completion time, successful execution of predefined key steps and critical steps.
Results: Both groups had a better performance with INg than IJg (Fig 1). The majority preferred INg for its ease of use, safety in the pediatric context and better acceptability by SW. Some participants thought that IJg is more effective and useful for off-label smaller doses to prevent SH. Preferred teaching methods were videos and workshops, but only videos could be sufficient for INg.
Conclusions: INg is faster and more likely to be successfully administered than IJg by. Implementing mandatory video-based trainings for SW could improve SH management and the involvement of SW.

Disclosure
Y.Wang: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. C.Gagnon: Advisory Panel; Novo Nordisk, Other Relationship; Ascendis Pharma A/S, Research Support; Novo Nordisk. F.Bernatchez: None. S.Chouinard-castonguay: None. M.Tremblay: None. A.Vanasse: None. M.Megalli: None. M.Millette: Advisory Panel; Novo Nordisk Canada Inc., Pfizer Inc. G.Boulet: Other Relationship; Dexcom, Inc. M.Henderson: None.

Funding
Canadian Institutes of Health Research (157204); JDRF (2018651)
400-P: Spatial Metabolomics Analysis by MSI-DeepPath Identifies Key Pathways in ZDF Diabetic Kidney Disease Model
Authors: HEJAZI LEILA , SHARMA SHOBA , RUIZ AARON , ZHANG GUANSHI , TUCCI FABIO C. , SHARMA KUMAR 
Published: June 2023

Background: The Zucker Diabetic Fatty (ZDF) rat is a popular model of type 2 diabetes as it develops pathologic changes in the kidney similar to human diabetic nephropathy. To identify metabolic pathways linked to pathologic features MALDI mass spectrometry imaging (MSI) can be a powerful platform. However, quantification of metabolites from MALDI-MSI is very challenging. Our MSI-DeepPath computational platform enables spatial quantitation of metabolites from any tissue section size.
Methods: Control and obese ZDF male rats (age 6mo, n=5/group) were studied. Spatial metabolomics analysis of kidney tissue sections was performed using MALDI-MSI at 20 µm resolution. Metabolites were detected at mass accuracy &lt;2 ppm using Q-Exactive orbitrap MS followed by annotations using METASPACE. SygnaMap’s MSI-DeepPath computational platform was used to quantify the annotated metabolites.
Results: Of 400 metabolites annotated at m/z range 70-500 Da the top features were selected using t-test, p value and fold change analysis. The top 20 biomarkers that separated ZDF from controls included glucose, serine, histidine, and glutamate. The most significantly upregulated metabolite was tyrosinamide (8.2-fold, p=8.02 x 10-9 ). The most significant downregulated metabolite was L-threonine (0.3-fold, p=2.03 x 10-9). Pathway analysis revealed that aminoacyl-tRNA biosynthesis, galactose, glyoxylate and dicarboxylate metabolic pathways can discriminate healthy from diabetic kidney samples.
Conclusion: MSIDeepPath enables quantification of spatial metabolomics of tissue sections using MALDI-MSI data. This new tool can be applied across normal and diseased samples allowing for robust statistical analysis of spatial omics data. Using MSI-DeepPath on kidney sections from the ZDF rat we identified regulation of metabolites linked to key pathways of diabetic kidney disease.

Disclosure
L.Hejazi: None. S.Sharma: None. A.Ruiz: None. G.Zhang: None. F.C.Tucci: None. K.Sharma: Advisory Panel; Reata Pharmaceuticals, Inc., Otsuka America Pharmaceutical, Inc.

Funding
National Institutes of Health (1R43DK130732-01A1)