bluuebunny/crossref_metadata_2025_split huggingface dataset:
1759-P: Delta Cell Potentiates Secretion of Insulin and Glucagon in a Novel Model of Islet Paracrine Interactions
Authors: RODRIGUEZ DIAZ RAYNER , TAMAYO ALEJANDRO M. , PEREIRA ELIZABETH 
Published: June 2024

The islet δ-cell secretes SST, a peptide which is a strong paracrine inhibitor of insulin and glucagon secretion. It is conceivable, that the δ-cell, as an inner homeostatic element in the islet to prevent the spillover of both hormones.There are insufficient data to ascertain the intraislet mechanisms governing the δ-cell activity and its impact on the islet secretory output. We aimed to 1) study the correlation between insulin and somatostatin secretion in human islets from healthy and diabetic donors as well as mice fed control or high fat diet; and 2) mechanistic studies to dissect the role the δ-cell plays in the islet secretory output using transgenic mouse models. Our data allows us to propose a revised model of intraislet paracrine interactions that challenges the view of the δ-cell solely as a suppressive element on islet secretion. We propose that δ-cells paradoxically may enhance the secretion of both glucoregulatory hormones through short and sharp events inhibition driven by its pulsatile secretion, besides its canonical inhibiting role. δ-cell activation leads to peaks of somatostatin secretion appears to cause asynchronous off-responses secretory responses of neighboring α- and β- cells after somatostatin falloff, prompting a net increase in the magnitude of insulin and glucagon secretions. This model provides a comprehensive explanation for our contradictory results of the effects manipulating δ-cells has on the mouse glucose metabolism, such as, the improved glucose metabolic readouts upon activation, inhibition or even ablation of the δ-cells. Our findings emphasize the importance of understanding the mechanism that link δ-cells to pathological events in the natural history of Diabetes.

Disclosure
R. Rodriguez Diaz: None. A.M. Tamayo: None. E. Pereira: None.

Funding
National Institutes of Health (R01 DK124527)
1864-LB: Comparative Safety and Effectiveness of GLP-1RA and SGLT2i Use in Adults with Type 2 Diabetes in U.S. Clinical Practice
Authors: HOFFMAN SARAH R. , LANES STEPHAN , QUIMBO TRACEY , PAPAZIAN AANAHIT , WHITE JEFF , FISHER VICKI , CZIRAKY MARK J. , CROWLEY MATTHEW J. , WILLEY VINCENT 
Published: June 2024

GLP-1 RA use has risen sharply, a shift prompted by trial evidence and guideline recommendations in T2D and use in obesity. To inform safe prescribing for T2D, this study assessed the real-world effects of GLP-1 RA and SGLT2i on the incidence of serious clinical events. Adults with T2D who initiated a GLP-1 RA or SGLT2i agent from 1/1/16 to 9/30/23 were identified from the Healthcare Integrated Research Database (HIRD), a large national US claims database. Outcomes included GI, psychiatric, hepatic and CV events, thyroid cancer and all-cause mortality. Inverse probability of treatment weighting was used to control confounding and incidence rates and rate ratios (RR) were estimated. Differences between new users of GLP-1 RA (n=311,574) and SGLT2i (n=255,146) were observed in age, sex, prevalent conditions (obesity, ASCVD, HF, CKD and anxiety) and insulin use. After weighting, characteristics were well balanced between groups. Rates and RR are displayed in the Table. Among serious events, only GI hospitalizations occurred more frequently in GLP-1 RA users, while acute liver injury was less common. Psychiatric events, thyroid cancer and all-cause mortality rates were similar between groups, as were CV event rates in these groups having broad heterogeneity in baseline CV risk. These real-world data complement trial data and should inform GLP-1 RA prescribing decisions in T2D.

Disclosure
S.R. Hoffman: Other Relationship; Carelon Research. S. Lanes: None. T. Quimbo: None. A. Papazian: None. J. White: None. V. Fisher: None. M.J. Cziraky: Other Relationship; Carelon Research. M.J. Crowley: None. V. Willey: Other Relationship; Carelon Research.
1865-LB: Exploring Incretin-Based Therapies as Adjunctive Treatment for Type 1 Diabetes—Real-World Insights and Future Directions
Authors: ALMARZOOQI IHSAN , ZAKARIA HALA , CACCELLI MILENA , SAID YOUSEF , HASHEMI ALI 
Published: June 2024

Incretin-based therapies, known for their efficacy in Type 2 diabetes management, are increasingly explored in the context of Type 1 diabetes due to their ability to modulate insulin and glucagon secretion. This shift in focus has prompted investigations into the potential benefits of Tirzepatide and Semaglutide, a glucagon-like peptide-1 receptor agonist, in managing Type 1 Diabetes. This case series study investigates Tirzepatide and Semaglutide's potential benefits in Type 1 Diabetes management.Our study included 10 T1D patients (30-47 years) using a hybrid care model with physical encounters and remote data monitoring. Patients on insulin were initiated on Semaglutide or Tirzepatide over three months. Data, including baseline characteristics and continuous glucose monitoring (CGM) metrics, were collected. Patients showed a substantial reduction in prandial and basal insulin doses (-25.24%, -29.16%). HbA1c improved from 8.28% to 6.95% in 3 months. Time in Range increased significantly (+42.11%, p=0.002). Overweight/obese patients lost -5.64 kg (p&lt;0.001). The initiation of incretin therapy led to a substantial decrease in both bolus and basal insulin requirements, along with noteworthy improvements in HbA1c levels, weight and TIR. These reductions in alignment with ADA recommendations for T1D patients underscore the potential benefits of incretin-based therapies. Dose adjustments, continuous monitoring, and avoiding hypoglycemia were crucial.Preliminary findings suggest incretin therapy as an adjunct to insulin in T1D management, showing reduced insulin requirements, improved glycemic control, and positive weight impacts. However, comprehensive, randomized clinical trials with a larger cohort are needed to validate these outcomes.

Disclosure
I. Almarzooqi: None. H. Zakaria: None. M. Caccelli: None. Y. Said: None. A. Hashemi: None.
1873-LB: Comparison of Adherence and Persistence between Oral Semaglutide and Once-Weekly Semaglutide Injection at 12-Month Follow-up in Japanese Real-World Data
Authors: HORII TAKESHI , MASUDO CHIKAKO , MIHARA KIYOSHI 
Published: June 2024

This retrospective, observational study aimed to compare 12-month adherence and persistence between oral semaglutide (O-SEMA) and matched Once-Weekly semaglutide Injection (SEMA-I) using real-world administrative claims data from the MDV database. The study included patients with T2D who initiated O-SEMA or SEMA-I between January 2018 and December 2022. SEMA-I initiators were 1:1 propensity-score matched to O-SEMA initiators (9,238 pairs each). Non-adherence was defined as a Proportion of Days Covered (PDC) &lt;0.8. Logistic regression analysis was used with medication adherence (PDC &lt;0.8) as the dependent variable. Persistence rates were compared using Cox regression analysis, with discontinuation of SEMA as the event. Baseline characteristics were balanced, with a mean age of 58 years and 50% females. More O-SEMA initiators were adherent compared to SEMA-I (92.5% vs. 89.8%). The odds ratio for non-adherence significantly increased with SEMA-I compared to SEMA-O (OR: 1.41). More O-SEMA initiators were persistent on therapy compared to SEMA-I (91.7% vs. 82.9%). The hazard ratio for treatment discontinuation, with O-SEMA as the reference, was 1.97 (95% CI 0.81-2.15) for SEMA-I. However, during the first 100 days of treatment, the hazard ratio for SEMA-I compared to O-SEMA was 0.67 (95% CI 0.60-0.76). O-SEMA initiators showed significantly higher adherence and greater persistence on their therapy than SEMA-I initiators in 12-month. On the other hand, it is important to be cautious of the risk of treatment discontinuation in the early stages of O-SEMA administration, as the complexity of management and the method of administration may be influencing factors.

Disclosure
T. Horii: None. C. Masudo: None. K. Mihara: None.
1875-LB: Adjuvant Glucagon-Like Peptide 1 Receptor Agonist (GLP-1 RA) Use in HNF1A- and HNF4A-MODY
Authors: BROOME DAVID , MEHDI ALINA Z. , FOSS-FREITAS MARIA C. , CHASE COLBY , GREGG BRIGID , ORAL ELIF A. , HERMAN WILLIAM H. 
Published: June 2024

Introduction: Maturity-onset diabetes of the young (MODY) is an autosomal dominant form of monogenic diabetes. Although sulfonylurea treatment is effective early in the disease course for HNF1A-MODY and HNF4A-MODY, patients often experience sulfonylurea treatment failure. Glucagon-like peptide-1 Receptor Agonists (GLP-1 RA) have previously been used in HNF1A-MODY and HNF4A-MODY, but there is a lack of evidence for their effectiveness as adjuvant treatment.
Methods: We compiled a case series study of University of Michigan MODY patients to examine the effect of adjuvant GLP-1 RA treatment in patients with HNF1A-MODY and HNF4A-MODY treated with sulfonylureas.
Results: Of 87 patients with genetically confirmed MODY (76 HNF4A-MODY, 11 HNF1A-MODY), there were 4 patients identified who were treated with a GLP-1 RA as adjuvant treatment to a sulfonylurea. All patients were White, 3 were female, 3 had HNF1A-MODY and all patients were from different pedigrees. The average HbA1c prior to initiation of GLP-1 RA was 7.7 &lt;u&gt;+&lt;/u&gt; 0.4%, and the average BMI was 28.5 kg/m2. After GLP-1 RA initiation, there was an average decrease in HbA1c of 1.3 &lt;u&gt;+&lt;/u&gt; 0.4%, with an average body weight loss of 15.8 &lt;u&gt;+&lt;/u&gt; 10.7 lbs (BMI change of -2.6 kg/m2). Patients had the following information (sex, current age, mutation, sulfonylurea dose reduction, administration & type of GLP-1 RA, dose, treatment duration): F, 47, HNF1A-MODY, glimepiride 6 mg/day reduction, oral semaglutide, 7 mg once daily, 22 mos.; F, 55, HNF1A-MODY, glipizide 5 mg/day reduction, subcutaneous dulaglutide, 1.5 mg once weekly, 21.5 mos.; 56, F, HNF1A-MODY, glipizide 10 mg/day reduction, subcutaneous semaglutide, 0.5 mg once weekly, 24 mos.; 43, M, HNF4A-MODY, glipizide 10 mg/day reduction, subcutaneous dulaglutide, 1.5 mg once weekly, 47.5 mos.
Conclusions: These 4 patients (3 HNF1A-MODY, 1 HNF4A-MODY) demonstrate that adjuvant treatment with GLP-1 RA lowers HbA1c, body weight, and sulfonylurea dose requirements in patients with HNF1A- and HNF4A-MODY.

Disclosure
D. Broome: Research Support; Novo Nordisk, Fractyl Health, Inc., Rhythm Pharmaceuticals, Inc., T1D Exchange. Consultant; Tayco, Inc. M.C. Foss-Freitas: Research Support; Amryt Pharma Plc. Advisory Panel; PTC Pharmaceuticals. C. Chase: None. B. Gregg: Consultant; CVS Caremark. E.A. Oral: Consultant; Akcea Thearpeutics, Inc. Research Support; Akcea Thearpeutics, Inc. Consultant; Regeneron Pharmaceuticals Inc. Research Support; Regeneron Pharmaceuticals Inc., Amryt Pharma Plc. Consultant; Amryt Pharma Plc, Ionis Pharmaceuticals. Research Support; Ionis Pharmaceuticals, Rhythm Pharmaceuticals, Inc., Novo Nordisk, GI Dynamics, Fractyl Health, Inc. W.H. Herman: Consultant; Merck Sharp & Dohme Corp. Advisory Panel; American Diabetes Association. Other Relationship; National Institutes of Health. Advisory Panel; National Committee for Quality Assurance.
1883-LB: ATR-258 Is a Precision Modulator of ß2-AR Signaling That Improves Glucose Homeostasis and Is Safe in Humans
Authors: KALINOVICH ANASTASIA , WAARA ERIK , DE JONG JASPER M.A. , PELCMAN BENJAMIN , BENGTSSON TORE 
Published: June 2024

Introduction & Objective: Stimulation of β2-adrenergic receptors (β2-AR) in skeletal muscle improves glucose uptake capacity and is a promising avenue in the treatment of type 2 diabetes (T2D). To circumvent common β2-AR-associated cardiovascular side-effects through cAMP activation, we have developed a novel β2-AR agonist, ATR-258, with low cAMP induction but improved glucose tolerance and insulin sensitivity in preclinical models. Here we present preclinical efficacy data and phase 1 safety data for our candidate drug ATR-258.
Methods: We have used various in vitro models to analyze the functional characteristics of ATR-258. These include receptor selectivity, downstream signaling profiles, cAMP induction and glucose uptake. We assessed the in vivo effects of ATR-258 on glucose tolerance and insulin sensitivity in diet-induced obese C57BL/6 mice and diabetic Goto-Kakizaki rats. To test safety in humans, we performed single and multiple ascending dose studies in a total of 46 healthy male volunteers. In a third cohort, 23 male patients with T2D received either placebo (n = 8) or 2.5 mg ATR-258 (n = 15) once daily for 28 days. Safety profiles, PK, and PD variables such as HbA1c and glucose tolerance were measured.
Results: ATR-258 displayed limited cAMP induction and no promotion of β-arrestin recruitment or receptor desensitization, but a maintained ability to induce glucose uptake compared to classical β2-AR agonists in vitro. ATR-258 improved glucose tolerance and insulin sensitivity in a dose-dependent manner in mouse and rat models of obesity and diabetes. Our first-in-human phase 1 data showed that ATR-258 is safe and well-tolerated in healthy volunteers and T2D patients.
Conclusion: ATR-258 is a β2-AR agonist with a preferential signaling and safety profile resulting in beneficial effects on glucose homeostasis in preclinical models and a promising safety profile in humans. ATR-258 could lead the way of a new class of adrenergic agonists to
treat T2D.

Disclosure
A. Kalinovich: Employee; Atrogi AB. Stock/Shareholder; Atrogi AB. E. Waara: Employee; Atrogi. J.M.A. de Jong: Employee; Atrogi AB. B. Pelcman: Consultant; Atrogi AB. T. Bengtsson: Stock/Shareholder; Atrogi, Sigrid therapeutics.
19-OR: Sucralose Consumption Decreases Insulin Sensitivity and Modifies the Gut Microbiota in Healthy Individuals
Authors: ROMO-ROMO ALONSO , SANCHEZ-TAPIA MONICA , TORRES NIMBE , AGUILAR-SALINAS CARLOS A. , MARTAGON ALEXANDRO J. , GUADALUPE LÓPEZ-CARRASCO MARÍA , GUILLÉN-PINEDA LUZ E. , GOMEZ-AVILES PAOLA , BRITO GRISELDA X. , GÓMEZ-PEREZ FRANCISCO J. , ALMEDA-VALDES PALOMA 
Published: June 2024

Introduction: Sucralose is a non-nutritive sweetener that has shown to decrease insulin sensitivity through mechanisms including changes in intestinal microbiota.
Objective: To determine the impact of sucralose on insulin sensitivity and gut microbiota in healthy individuals.
Methods: Parallel triple-blind randomized clinical trial including 24 healthy individuals, not habitual users of nonnutritive sweeteners. Individuals were instructed to maintain dietary and physical activity habits and randomized to consume capsules with 30% of the acceptable daily intake of sucralose or placebo for 30 days. Hyperinsulinemic euglycemic clamp was performed before and after the intervention, M/I value change was calculated and compared. Stool samples were taken at baseline and the final visit, DNA extraction was carried out with a QIAamp DNA stool Mini Kit.
Results: The M/I value adjusted for free fat mass decreased in the sucralose group vs placebo (p&lt;0.01). Reduction in the alpha diversity of gut microbiota (p&lt;0.0002) was observed in sucralose consuming group vs placebo (p=0.2369) and an increase in the Gram (-) bacteria Bacteroides fragilis associated to a significant increase in serum LPS were documented.
Conclusion: Sucralose consumption causes a significant decrease in insulin sensitivity associated to changes in gut microbiota composition and endotoxemia in healthy individuals.

Disclosure
A. Romo-Romo: None. M. Sanchez-Tapia: None. N. Torres: None. C.A. Aguilar-Salinas: None. A.J. Martagon: None. M. López-Carrasco: None. L.E. Guillén-Pineda: None. P. Gomez-Aviles: None. G.X. Brito: None. F.J. Gómez-Perez: None. P. Almeda-Valdes: None.

Funding
CONAHCYT Ciencia de Frontera 2019/316514
1972-LB: Timing of Overt Diabetes Diagnosis and Pregnancy Outcomes
Authors: REICHELT ANGELA J. , DE CAMPOS MARIA A. , GUERRA GIULIA L. , HIRAKATA VÂNIA N. , OPPERMANN MARIA LÚCIA R. 
Published: June 2024

Introduction and Objective: Overt diabetes is becoming frequent in pregnancy. We aim to describe pregnancy outcomes in women with overt diabetes according to the timing of diagnosis.
Methods: From a retrospective cohort of 646 women with diabetes, we selected those with hyperglycemia diagnosed for the first time in pregnancy. We evaluated baseline characteristics, prenatal care, and pregnancy outcomes comparing women diagnosed up to 13 gestational weeks (GW), between 13 - 20 GW, and after 20 GW. We used ANOVA with post-hoc Tukey test to compare groups.
Results: Overt diabetes was diagnosed in 217 women (33.6%, 95% CI 30.0%-37.0%) (Table). An earlier diagnosis led to fewer maternal hospital admission, less weight gain and a lower third trimester HbA1c compared to the diagnosis in the third trimester. Pregnancy outcomes were similar among the groups.
Conclusions: Women with overt diabetes diagnosed up to the 13th gestational week attained better metabolic control. Nevertheless, timing of diagnosis did not impact on pregnancy outcomes in this cohort.

Disclosure
A.J. Reichelt: None. M.A. de Campos: None. V.N. Hirakata: None.
1988-LB: Effects of Alcohol Consumption among Patients with Hepatic Steatosis and Prediabetes or Diabetes
Authors: BANTU SRAVANI S. , PETRIE ERIN , GRAY MEAGAN , BRIL FERNANDO 
Published: June 2024

In December of 2023, a multisociety Delphi consensus on fatty liver disease nomenclature was published renaming nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) and introduced the term MetALD, which identifies patients with MASLD, who also are moderate consumers of alcohol. However, the effects of moderate alcohol consumption among patients with hepatic steatosis and prediabetes/diabetes are not well known.In order to better understand the effects of alcohol consumption in these patients, we analyzed data from NHANES 2017-2020 including self-report alcohol intake, and transient elastography (TE). Hepatic steatosis was defined based on controlled attenuation parameter ≥ 288 dB/m.A total of 1,757 patients with diabetes (47%) or prediabetes (53%) were included in the study (age: 55 ± 15 years; Sex: 44% female; BMI: 34.0 ± 7.0 kg/m2; A1c: 6.5 ± 1.4%). Based on self-reporting, patients were divided in 7 groups according to alcohol grams consumed per week (no alcohol consumption, 0-10, 10-50, 50-100, 100-200, 200-500, &gt;500). Increasing alcohol consumption was associated with decreased insulin resistance by HOMA-IR (from 6.9 ± 6.0 to 3.7 ± 1.9, p=0.042) and A1c (from 6.7 ± 1.5 to 5.7 ± 0.5%, p&lt;0.001), but increased BP (SBP: from 129 ± 19 to 137 ± 17 mmHg, p=0.006; DBP: from 76 ± 12 to 85 ± 11 mmHg, p&lt;0.001), TG (from 153 ± 118 to 209 ± 193 mg/dL, p=0.056), and HDL-C (from 47 ± 11 to 57 ± 18 mg/dL, p&lt;0.001). Alcohol consumption was associated with worse liver enzymes (AST, ALT, and GGT, all p&lt;0.001) without concomitant changes in hepatic steatosis or fibrosis by imaging.In patients with hepatic steatosis and prediabetes or diabetes, moderate alcohol consumption was associated with improvement in insulin sensitivity, but worsening of other cardiometabolic risk factors (i.e., blood pressure and triglycerides). This can result in an overclassification of patients with MetALD, even in patients where alcohol may be the only driver of the disease.

Disclosure
S.S. Bantu: None. E. Petrie: None. M. Gray: Consultant; Novo Nordisk. F. Bril: Consultant; Novo Nordisk.
199-OR: Beta-Cell IRS1 Deficiency Predisposes Female Mice to Developing Gestational Diabetes
Authors: WANG XINGCHUN , USMAN TAOFEEK , CHHETRI GOMA , QUAN ZHENG WEN , YEH HSUAN , WHITE MORRIS F. , HENRY DONG H. 
Published: June 2024

Gestational diabetes mellitus (GDM) is characterized by glucose intolerance in pregnant women without previously diagnosed diabetes. To understand the mechanism of GDM, we characterized the role of IRS1 in β-cell compensation for pregnancy. We generated β-cell conditional IRS1-knockout (βIRS1-KO) mice. While virgin βIRS1-KO mice maintained normal metabolism, pregnant βIRS1-KO mice developed GDM, culminating in the onset of fasting hyperglycemia and glucose intolerance at gestational day 15.5. These effects were attributable to the reduction of glucose-stimulated insulin secretion in pregnant βIRS1-KO mice. Anti-insulin immunohistochemistry revealed that pregnant βIRS1-KO vs. WT mice had significantly diminished islet size and reduced β-cell mass. Anti-Ki67 immunostaining showed that βIRS1-KO vs. WT mice had minimal β-cell replication during pregnancy. Islet RNA transcriptome analysis demonstrated that IRS1-deficient islets were associated with a significant downregulation of GATA4 and its targets Reg1 and Reg3a, key factors critical for β-cell replication. In pregnant WT mice, β-cell IRS1 along with GATA4, Reg1 and Reg3a was upregulated in islets, coinciding with the physiological induction of β-cell mass expansion during pregnancy. These effects were totally abolished in IRS1-deficient islets, correlating with impaired β-cell compensation in pregnant βIRS1-KO mice. Mechanistically, IRS1 underwent prolactin-stimulated phosphorylation at Tyr632. This effect correlated with the induction of GATA4, Reg1 and Reg3a expression in islets of pregnant WT mice. We recapitulated these findings in INS1 cells in response to prolactin. Our studies uncovered a new IRS1-GATA4-Reg1/Reg3a signaling cascade in integrating gestational hormones to β-cell compensation, an adaptive mechanism that acts to overcome maternal insulin resistance and protect against GDM.

Disclosure
X. Wang: None. T. Usman: None. G. Chhetri: None. W. Zheng: None. H. Yeh: None. M.F. White: Board Member; Housey Pharmaceutical Research Laboratories. H. Dong: None.
1994-LB: Metabolites Link Infections to Type 2 Diabetes in the Multiethnic Study of Atherosclerosis (MESA)
Authors: WOOD ALEXIS , GOODARZI MARK O. , CHEN ZSU-ZSU , GUO XIUQING , RICH STEPHEN S. , CLISH CLARY B. , GERSZTEN ROBERT E. , ROTTER JEROME I. , TAYLOR KENT 
Published: June 2024

Introduction & Objective: Prior to T2D, patients experience increased infections, yet no pathways account for this immune/endocrine system cross-talk. We aimed to identify metabolites that link pathogens to T2D.
Methods: Using plasma from 4,424 adults (61 ±9 y; 53% female), taxonomic classification was conducted on reads from sequencing that aligned with a microbial reference panel, and metabolites quantified. Incident T2D (ADA 2003 criteria) was assessed over ~18 y. A cox-proportional hazard model identified baseline microbes as ‘variables of importance’ to incident T2D, with a penalty function to minimize sparse data bias. Metabolome-wide associations identified metabolites shared between T2D-related microbes at baseline, and incident T2D. All models adjusted for age, gender, race/ethnicity, education, and AHA’s Life’s Simple 8 score.
Results: Total microbes differed by race/ethnicity (X2= 30.4, df = 9, P= 3.8*10-4), but not any other covariates (all P&gt;.05). Incident T2D was associated with 2 microbes: Rahnella (HR=1.90 (1.09-3.30), P=.02) and Plasmodium falciparum (HR=1.34 (1.05-1.73), P=.02). 23 metabolites were associated with incident T2D (P&lt;.05 after an FDR-correction) and at least one of these microbes (P&lt;.05; Fig).
Conclusions: These analyses indicate molecules linking exposure to, and / or continued presence in the plasma of, infectious microbes, and increased risk of T2D.

Disclosure
A. Wood: Research Support; Beef Checkoff. Consultant; Lundquist. M.O. Goodarzi: Advisory Panel; Nestlé Health Science, Organon. Z. Chen: None. X. Guo: None. S.S. Rich: None. C.B. Clish: None. R.E. Gerszten: None. J.I. Rotter: None. K. Taylor: None.

Funding
USDA/ARS cooperative agreement (#58-3092-5-001). Advancing Translational Sciences (UL1TR001420, UL1TR001881).