bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introducing Mini Clinical Evaluation Exercise for Intern Assessment in Shahid Beheshti University's Pediatrics Department
Authors: Malek Fatemeh , Nasehi Mohammadmahdi , Vahidshahi Kourosh , Jafari Narjes , Nazari Shiva , Hosseini Amirhossein , Hajipor Mahmood , Javadzadeh Mohsen 
Published: July 2024

Abstract

Introducing the Mini Clinical Evaluation Exercise (Mini-CEX) as a workplace-based assessment tool at Shahid Beheshti University of Medical Sciences in Iran significantly advances medical education evaluation. By incorporating consistent mini-clinical evaluations, we aim to address the clinical competency gap by sensitizing faculty and interns and providing structured feedback. The brief, 10 to 20-minute encounters focus on evaluating crucial clinical skills, but the comprehensive nature of the Mini-CEX genuinely sets it apart. This comprehensive process allows for simultaneous evaluation of trainees' clinical skills and provides valuable feedback on their performance, enhancing the learning process and improving clinical competency. The comprehensive nature of Mini-CEX ensures a well-rounded evaluation, instilling confidence in its effectiveness. Multiple examiners for multiple cases are utilized to minimize inter-rater bias, making the Mini-CEX a comprehensive and practical assessment tool that positively impacts professional growth.
The greenhouse gas observation mission with Global Observing SATellite for Greenhouse gases and Water cycle (GOSAT-GW): Objectives, conceptual framework and scientific contributions
Authors: Tanimoto Hiroshi , Matsunaga Tsuneo , Someya Yu , Fujinawa Tamaki , Ohyama Hirofumi , Morino Isamu , Yashiro Hisashi , Sugita Takafumi , Inomata Satoshi , Müller Astrid , Saeki Tazu , Yoshida Yukio , Niwa Yosuke , Saito Makoto , Noda Hibiki , Yamashita Yousuke , Ikeda Kohei , Saigusa Nobuko , Machida Toshinobu , Frey Matthias Max , Lim Hyunkwang , Srivast Priyanka , Jin Yoshitaka , Shimizu Atsushi , Nishizawa Tomoaki , Kanaya Yugo , Sekiya Takashi , Patra Prabir , Takigawa Masayuki , Bisht Jagat , Kasai Yasko , Sato Tomohiro O. 
Published: July 2024

Abstract

The Japanese Global Observing SATellite for Greenhouse gases and Water cycle (GOSAT-GW) will be an Earth-observing satellite to conduct global observations of atmospheric carbon dioxide (CO2), methane (CH4), and nitrogen dioxide (NO2) simultaneously from a single platform. GOSAT-GW is the third satellite in the series of the currently operating Greenhouse gases Observing SATellite (GOSAT) and GOSAT-2. It will carry two sensors, the Total Anthropogenic and Natural emissions mapping SpectrOmeter-3 (TANSO-3), and the Advanced Microwave Scanning Radiometer 3 (AMSR3), with the latter dedicated to the observation of physical parameters related to the water cycle. TANSO-3 is a high-resolution grating spectrometer designed to measure reflected sunlight in the visible to short-wave infrared spectral ranges. It aims to retrieve the column-averaged dry-air mole fractions of CO2 and CH4 (denoted as XCO2 and XCH4, respectively), as well as the vertical column density of tropospheric NO2. The TANSO-3 sensor onboard GOSAT-GW will utilize the wavelength bands of 0.45, 0.76, and 1.61 µm for NO2, O2, and CO2 and CH4 retrievals, respectively. GOSAT-GW will fly in a sun-synchronous orbit with a local overpass time of approximately 13:30 and a 3-day ground-track repeat cycle. The TANSO-3 sensor has two observation modes in the push-broom operation: Wide Mode, which provides globally covered maps with a 10-km spatial resolution within 3 days, and Focus Mode, which provides snapshot maps over targeted areas with a high spatial resolution of 1–3 km. The objectives of the GOSAT-GW mission include (1) monitoring atmospheric global-mean concentrations of greenhouse gasses (GHGs), (2) verifying national anthropogenic GHG emissions inventories, and (3) detecting GHG emissions from large sources, such as megacities and power plants. A comprehensive validation exercise will be conducted to ensure that the sensor products’ quality meets the required precision to achieve the above objectives. With a projected operational lifetime of seven years, GOSAT-GW will provide vital space-based constraints on both anthropogenic and natural GHG emissions. These measurements will contribute significantly to climate change mitigation efforts, particularly by supporting the Global Stocktake (GST) mechanism, a key element of the Paris Agreement.
Ex vivo susceptibility to antimalarial drugs and polymorphisms in drug resistance genes of African Plasmodium falciparum, 2016-2023: a genotype-phenotype association study
Authors: Rosado Jason , Fola Abebe A. , Cojean Sandrine , Sarrasin Véronique , Coppée Romain , Zaffaroulah Rizwana , Bouzayene Azza , Cicéron Liliane , Maréchal Céline , Thaboulet Geoffrey , Moissant Camille , Wallus Léa , Houzé Ludivine , Imbert Nicolas , Crudale Rebecca , Musset Lise , Thellier Marc , Pradines Bruno , Clain Jérôme , Bailey Jeffrey A. , Houzé Sandrine , Group Investigation Study 
Published: July 2024

Abstract

Background: Given the altered responses to both artemisinins and lumefantrine in Eastern Africa, monitoring antimalarial drug resistance in all African countries is paramount.
Methods: We measured the susceptibility to six antimalarials using ex vivo growth inhibition assays (IC50) for a total of 805 Plasmodium falciparum isolates obtained from travelers returning to France (2016-2023), mainly from West and Central Africa. Isolates were sequenced using molecular inversion probes (MIPs) targeting fourteen drug resistance genes across the parasite genome.
Findings: Ex vivo susceptibility to several drugs has significantly decreased in 2019-2023 versus 2016-2018 parasite samples: lumefantrine (median IC50: 23·0 nM [IQR: 14·4-35·1] in 2019-2023 versus 13·9 nM [8·42-21·7] in 2016-2018, p<0·0001), monodesethylamodiaquine (35·4 [21·2-51·1] versus 20·3 nM [15·4-33·1], p<0·0001), and marginally piperaquine (20·5 [16·5-26·2] versus 18.0 [14·2-22·4] nM, p<0·0001). Only four isolates carried a validated pfkelch13 mutation. Multiple mutations in pfcrt and one in pfmdr1 (N86Y) were significantly associated with altered susceptibility to multiple drugs. The susceptibility to lumefantrine was altered by pfcrt and pfmdr1 mutations in an additive manner, with the wild-type haplotype (pfcrt K76-pfmdr1 N86) exhibiting the least susceptibility.
Interpretation: Our study on P. falciparum isolates from West and Central Africa indicates a low prevalence of molecular markers of artemisinin resistance but a significant decrease in susceptibility to the partner drugs that have been the most widely used since a decade -lumefantrine and amodiaquine. These phenotypic changes likely mark parasite adaptation to sustained drug pressure and call for intensifying the monitoring of antimalarial drug resistance in Africa.
Hospitalizations for Food-Induced Anaphylaxis Between 2016 and 2021: Population-Based Epidemiologic Study
Authors: Jimenez-Garcia Rodrigo , Lopez-de-Andres Ana , Hernandez-Barrera Valentin , Zamorano-Leon Jose J , Cuadrado-Corrales Natividad , de Miguel-Diez Javier , del-Barrio Jose L , Jimenez-Sierra Ana , Carabantes-Alarcon David 
Published: July 2024

Background
Food-induced anaphylaxis (FIA) is a major public health problem resulting in serious clinical complications, emergency department visits, hospitalization, and death.

Objective
This study aims to assess the epidemiology and the trends in hospitalizations because of FIA in Spain between 2016 and 2021.

Methods
An observational descriptive study was conducted using data from the Spanish National Hospital discharge database. Information was coded based on the International Classification of Diseases, Tenth Revision. The study population was analyzed by gender and age group and according to food triggers, clinical characteristics, admission to the intensive care unit, severity, and in-hospital mortality. The annual incidence of hospitalizations because of FIA per 100,000 person-years was estimated and analyzed using Poisson regression models. Multivariable logistic regression models were constructed to identify which variables were associated with severe FIA.

Results
A total of 2161 hospital admissions for FIA were recorded in Spain from 2016 to 2021. The overall incidence rate was 0.77 cases per 100,000 person-years. The highest incidence was found in those aged <15 years (3.68), with lower figures among those aged 15 to 59 years (0.25) and ≥60 years (0.29). Poisson regression showed a significant increase in incidence from 2016 to 2021 only among children (3.78 per 100,000 person-years vs 5.02 per 100,000 person-years; P=.04). The most frequent food triggers were “milk and dairy products” (419/2161, 19.39% of cases) and “peanuts or tree nuts and seeds” (409/2161, 18.93%). Of the 2161 patients, 256 (11.85%) were hospitalized because FIA required admission to the intensive care unit, and 11 (0.51%) patients died in the hospital. Among children, the most severe cases of FIA appeared in patients aged 0 to 4 years (40/99, 40%). Among adults, 69.4% (111/160) of cases occurred in those aged 15 to 59 years. Multivariable logistic regression showed the variables associated with severe FIA to be age 15 to 59 years (odds ratio 5.1, 95% CI 3.11-8.36), age ≥60 years (odds ratio 3.87, 95% CI 1.99-7.53), and asthma (odds ratio 1.71,95% CI 1.12-2.58).

Conclusions
In Spain, the incidence of hospitalization because of FIA increased slightly, although the only significant increase (P=.04) was among children. Even if in-hospital mortality remains low and stable, the proportion of severe cases is high and has not improved from 2016 to 2021, with older age and asthma being risk factors for severity. Surveillance must be improved, and preventive strategies must be implemented to reduce the burden of FIA.
1113-P: Utilizing a Novel Telemedicine Clinic for Managing Type 2 Diabetes—A Six-Month Pilot Study
Authors: SOTOMAYOR FIORELLA , GOTHONG CHIKARA , HERNANDEZ REYNIER , CHOE MONICA Y. , ASH GARRETT I. , SCOTT WILLIAM H. , PINAULT LILLIAN , GOMEZ-PERALTA FERNANDO , SINGH LAKSHMI G. , SORKIN JOHN D. , (ELIAS) SPANAKIS ILIAS 
Published: July 2024

Introduction & Objective: RCT aimed to assess if a Diabetes Advanced Telemedicine (DAT) clinic leads to improvement in glycemic control compared to standard of care (SoC).
Methods: Patients with type 2 diabetes (T2D) randomized to DAT or SoC. DAT used continuous glucose monitoring devices, smart insulin pens, telecommunication (i.e. video visits) with physical activity (PA) counseling by an exercise physiologist. SoC used glucometers, traditional insulin pens, in-person visits and PA counseling by providers. Primary outcome was change in HbA1c. Secondary outcomes were time in range (TIR) 70-180 mg/dl, time above range (TAR)&gt;180 mg/dl, TAR&gt;250 mg/dl and time below range (TBR)&lt;70 mg/dl. ANCOVA was used, adjusted for baseline value to determine the relation between group and outcome, and report p-values of the interaction term, group*time. Exercise was evaluated by senior fitness test and assessed by Hedge’s g effect size.
Results: Twenty-four patients with T2D completed the trial. Non-statistically significant reductions in glucose metrics were seen. HbA1c decreased by 2.2% (DAT) vs 1.1% (SoC) (-1.1%, [-0.2, -1.8], p=0.076). TIR 70-180 mg/dL increased 17.3% vs 15.4% (+1.9%, [-16.1,15.5], p=0.984), TAR&gt;180 mg/dL decreased 20.5% vs 17.9% (-2.6%, [-21.5,10.5], p=0.756), TAR&gt;250 mg/dL decreased 17.1% vs 6.0% (-11.1%. [-20.3,2.7], p=0.375), TBR changed 0.41% vs -0.88% (+0.47, [-0.16,1.37], p=0.054), DAT vs. SoC, respectively. Fitness tests, completed by 60% of participants, showed improvements in medium strength (bicep curls g=0.90 /p=0.06, chair stands g=0.63/p=0.18), daily physical function (g=0.56/p=0.20), aerobic performance (6min walk test g=0.24/p=0.61), agility/flexibility (timed up and go g=-0.30/p=0.49, back stretch g=-0.51/p=0.26).
Conclusions: T2D patients managed by DAT had non-significant improvement in glucose control driven by decreased hyperglycemia &gt; 250 mg/dl. Non-significant modest increase in PA observed.

Disclosure
F. Sotomayor: None. C. Gothong: None. R. Hernandez: None. M.Y. Choe: None. G.I. Ash: None. W.H. Scott: None. L. Pinault: None. F. Gomez-Peralta: Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; Insulcloud S.L. Speaker's Bureau; Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Sanofi. L.G. Singh: None. J.D. Sorkin: None. I. Spanakis: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc.
121-OR: Safety, Tolerability, and Metabolic Effects of Once-Weekly GL0034 (Utreglutide) in Individuals with Obesity—A Multiple Ascending Dose Study
Authors: THENNATI RAJAMANNAR , BURADE VINOD S. , NATARAJAN MUTHUKUMARAN , SHAHI PRADEEP , NAGARAJA RAVISHANKARA , AGRAWAL SUDEEP K. , DUVAUCHELLE THIERRY , GARCIA-OCANA ADOLFO , RUTTER GUY A. , PRATLEY RICHARD E. , THORENS BERNARD , VILSBØLL TINA 
Published: July 2024

Introduction & Objective: GL0034 (GL), a once weekly glucagon-like peptide 1 receptor agonist, previously demonstrated significant reductions in body weight (BW) up to Day 22 in a single ascending dose study in individuals with obesity. This phase 1 study assessed the safety, tolerability and metabolic effects of GL after multiple ascending doses.
Methods: Individuals with BMI ≥28 kg/m2 (N=24) were randomized (9:3) to subcutaneous GL, fixed doses (4 × 680 µg; cohort 1); or increasing doses (680, 900, 1520, 2000 µg; cohort 2) or placebo, once weekly for four weeks. Safety, tolerability and key metabolic parameters were assessed.
Results: Most common adverse events (AE) were gastrointestinal (GI) with dose-dependent nausea, decreased appetite and vomiting. One individual with a GI related serious AE rapidly recovered upon treatment with intravenous rehydration. On Day 23, reduction was observed in all parameters from baseline (BL) with significant reductions in glucose area under the curve and HbA1c in both groups. In cohorts 1 & 2, BW reduction versus BL was 2.9 kg and 4.6 kg respectively on Day 29 (Table).
Conclusions: In individuals with obesity, once weekly GL dosing for four weeks, demonstrated clinically relevant reductions in glucose, insulin, HbA1c, lipids and BW with an overall good tolerability.

Disclosure
R. Thennati: None. V.S. Burade: None. M. Natarajan: None. P. Shahi: None. R. Nagaraja: None. S.K. Agrawal: None. T. Duvauchelle: Consultant; Sun Pharmaceutical Industries Ltd. A. Garcia-Ocana: Consultant; Sun Pharmaceutical Industries Ltd. G.A. Rutter: Advisory Panel; Sun Pharmaceutical Industries Ltd. R.E. Pratley: Other Relationship; Bayer AG, Dompé, Endogenex, Inc., Gasherbrum Bio, Inc., Hengrui (USA) Ltd., Intas Pharmaceuticals Ltd., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sun Pharmaceutical Industries Ltd. Consultant; AbbVie Inc., AstraZeneca. Other Relationship; Bayer HealthCare Pharmaceuticals, Inc., Biomea Fusion, Carmot Therapeutics, Inc., Corcept Therapeutics, Fractyl Health, Inc., Genprex. Consultant; Getz Pharma. Other Relationship; Lilly USA LLC, Sanofi. Consultant; Scholar Rock, Inc. B. Thorens: Advisory Panel; Sun Pharmaceutical Industries Ltd. T. Vilsbøll: Consultant; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Mundipharma. Advisory Panel; Novo Nordisk, Lilly Diabetes, Sanofi. Speaker's Bureau; Bayer Inc., Gilead Sciences, Inc. Advisory Panel; Sun Pharmaceutical Industries Ltd. Research Support; Lilly Diabetes.
1217-P: Insulin Sensitivity and Insulin Secretion Differentially Affect Birthweight and Postpartum Glucose
Authors: ROSENBERG EMILY A. , JAMES KAITLYN , PANT DEEPTI , HSU SARAH , AZEVEDO ROBIN L. , MICHALOPOULOS CHLOE , THAWEETHAI TANAYOTT , POWE CAMILLE E. , MEDINA BAEZ ARANTXA 
Published: July 2024

Background: Insulin deficiency and insulin resistance are two fundamental mechanisms that lead to hyperglycemia. Despite variation in the underlying physiology, individuals with hyperglycemia in pregnancy are treated similarly.
Methods: Pregnant women with diabetes risk factors completed a 2-hr 75-gram oral glucose tolerance test (OGTT) at 10-15 weeks’ gestation, 24-32 weeks’ gestation, and postpartum. We tested for associations between insulin sensitivity (opposite of insulin resistance, Matsuda index) or insulin secretory response (Stumvoll estimate) in the 1st trimester with birthweight percentile (for gestational age and sex) or 2-hr post-OGTT glucose postpartum. We used linear regression, adjusting for age, race/ethnicity, education, gestational age, BMI, GDM treatment (birthweight analyses), weeks postpartum (glucose analyses) and insulin sensitivity (insulin secretory response analyses).
Results: We studied N=151 pregnant women at a median [IQR] =12 [11-13] weeks’ gestation. N=107 had data at median [IQR] 9 [7-13] weeks postpartum. A 1-unit increase in 1st trimester insulin sensitivity (log Matsuda) was associated with a decrease of 6.9 in birthweight percentile (95% CI [-13.7, -0.05] P=0.045). 1st trimester insulin secretory response (log Stumvoll) was not associated with birthweight (β=-12.7 95% CI [-28.3, 2.9] P=0.11). 1st trimester insulin sensitivity was not associated with postpartum 2-hr OGTT glucose (β=-0.80 95% CI [-9.6, 8.0] mg/dL P=0.86), while a 1 unit increase in 1st trimester insulin secretory response was associated with a 36 mg/dL decrease in 2-hr OGTT glucose (95% CI [-53.7, -18.8] P=&lt;0.001).
Conclusion: Early pregnancy insulin sensitivity is more strongly associated with birthweight, while insulin secretory response has a stronger relationship with postpartum glycemia. Insulin resistance may confer more risk for perinatal complications, while insulin deficiency may confer more risk for postpartum hyperglycemia.

Disclosure
E.A. Rosenberg: None. K. James: None. D. Pant: None. S. Hsu: None. R.L. Azevedo: None. C. Michalopoulos: None. T. Thaweethai: None. C.E. Powe: Consultant; Mediflix. Other Relationship; Wolters Kluwer Health. A. Medina Baez: None.
1229-P: Blood Glycated Albumin or Fructosamine (GA/Fruc) Rather Than Hemoglobin A1c (A1C) Is Useful for Specifying Individuals Having a Macrosomic Baby—Meta-analysis
Authors: KODAMA SATORU , YAMADA TAKAHO , YAGYUDA NORIKO , FUJIHARA KAZUYA , MON KHIN LAY , KITAZAWA MASARU , YAMAMOTO MASAHIKO , MATSUBAYASHI YASUHIRO , KATO KIMINORI , SONE HIROHITO 
Published: July 2024

Introduction & Objective: Poor glycemic control (GC) increases the risk of various pregnancy complications. Both A1C and GA/Fruc are convenient as they require only one measurement and do not impose fasting. However, GA/Fruc is possibly a better predictor of complications than A1C during pregnancy when GC quickly changes. This meta-analysis compared the predictive ability of pregnancy complications between A1C and GA/Fruc.
Methods: We comprehensively searched for studies of prediction of maternal or neonatal adverse outcomes using both A1C and GA/Fruc and for their best cut-off values in each study presenting 2 x 2 data (i.e., true-positive, false-negative, true-negative, and false-positive cases).
Results: Of 9 eligible studies, 7 predicted macrosomia and could be meta-analyzed using a hierarchical summary receiver-operating characteristic (HSROC) model. Other complications were impossible to be analyzed because of an insufficient number of data. Pooled specificity (95% confidence interval [CI]) was significantly higher (P=0.02) for GA/Fruc (0.83 [0.70-0.91]) compared with A1C (0.57 [0.35-0.77]) while pooled sensitivity (95% CI) was 0.44 (0.26-0.63) for GA/Fruc and 0.67 (0.50-0.81) for A1C (P for difference, 0.17).
Conclusion: Compared with A1C, GA/Fruc is useful for specifying individuals having a macrosomic baby.

Disclosure
S. Kodama: None. T. Yamada: None. N. Yagyuda: None. K. Fujihara: None. L. Khin: None. M. Kitazawa: None. M. Yamamoto: None. Y. Matsubayashi: None. K. Kato: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.
155-OR: Genetic Variation and Time to Progression in TN10 (Teplizumab)
Authors: MICHALEK DOMINIKA A. , ONENGUT-GUMUSCU SUNA , CHEN WEI-MIN , BRUSKO TODD M. , STECK ANDREA , GOTTLIEB PETER , ORAM RICHARD A. , KRISCHER JEFFREY , PARIKH HEMANG M. , REDONDO MARIA J. , HEROLD KEVAN C. , RICH STEPHEN S. 
Published: July 2024

Introduction & Objective: TN10 Anti-CD3 Prevention (TN10) was a randomized phase 2 clinical trial that showed teplizumab delayed progression to type 1 diabetes (T1D) in high-risk participants. Both HLA and non-HLA variants could influence time to progression. Here, genome-wide analysis identified variants and pathways that influence time to progression in TN10 participants.
Methods: In TN10, relatives with stage 2 T1D (i.e., multiple autoantibodies and dysglycemia) received either teplizumab (N = 44) or placebo (N = 32). Samples were genotyped with a genome-wide array followed by imputation. Cox proportional hazards regression models were used to determine the effect of teplizumab, SNPs, and their interaction on time to progression to stage 3 T1D. Thousands of Polygenic Scores (PGSs) from the PGS catalogue were inferred for each of the TN10 samples, and we identified PGS traits that shared common genetic modifiers with time to progression with teplizumab.
Results: A genome-wide analysis identified three loci associated with time to progression (p &lt; 5 x 10-6). Two loci contain genes implicated in the inflammatory response (NFKBIZ) and drug metabolism effect (FMO3). SNP-drug interaction analysis identified four known T1D regions that account for progression differences in teplizumab vs placebo: CCR9 (rs34549672), SH2B3 (rs3184504), UBASH3A (rs9984852), and INS (rs3842761). Within the teplizumab group, novel loci (p &lt; 5 x 10-6) were associated with time to progression, including ZNF385D, CCDC38, SHH, ZNF366, ITPKB and RABGAP1L. Traits with similar genetic contribution to teplizumab time to progression were vitamin B12 (AUC = 0.76) and vitamin D (AUC = 0.72).
Conclusions: In individuals with stage 2 T1D, variants in inflammatory, immune-relevant, and drug-responsive genes are associated with teplizumab time to progression. Similarity of the teplizumab-responsive polygenic score with other traits implicate novel pathways that could influence teplizumab treatment.

Disclosure
D.A. Michalek: None. S. Onengut-Gumuscu: None. W. Chen: None. T.M. Brusko: None. A. Steck: None. P. Gottlieb: Other Relationship; IM Therapeutics. Research Support; Imcyse. Advisory Panel; Imcyse. Consultant; Juvenile Diabetes Research Foundation (JDRF). Research Support; Hemsley Charitable Trust, Novartis AG, Provention Bio, Inc., Precigen, Inc. Advisory Panel; ViaCyte, Inc. Research Support; Nova Pharmaceuticals. R.A. Oram: Research Support; Randox R & D. Consultant; Provention Bio, Inc., Sanofi. J. Krischer: None. H.M. Parikh: None. M.J. Redondo: None. K.C. Herold: Consultant; Sanofi. S.S. Rich: None.

Funding
National Institutes of Health (1R01DK121843-01)