bluuebunny/crossref_metadata_2025_split huggingface dataset:
885-P: IND-Enabling Assessment of Tolerance and Safety for SAB-142—A First-in-Class Fully Human Polyclonal Antithymocyte Immunoglobulin to Delay the Progression of Type 1 Diabetes
Authors: EGLAND KRISTI A. , MAHER DIANE , SANDHURST ERIC S. , WU HUA , SAVINOV ALEXEI Y. , EZZELARAB MOHAMED , BAUSCH CHRISTOPH L. , LUKE THOMAS C. 
Published: June 2024

SAB-142, a human polyclonal anti-thymocyte immunoglobulin, is currently being evaluated for safety in a Phase 1 clinical trial for Type 1 Diabetes (T1D). Previous clinical studies showed that ThymoglobulinTM, a rabbit polyclonal anti-thymocyte immunoglobulin (rATG), significantly slowed the progression of T1D. However, rATG is highly immunogenic and causes serum sickness limiting redosing over time. Our objective is to develop a safer and efficacious immunomodulatory agent to delay the progression and/or onset of T1D. Here we demonstrate the preclinical safety and tolerance of SAB-142 in Cynomolgus macaques, as well as in vitro safety and activity assays. For in vitro assays, binding of SAB-142 to human serum proteins and Glomerular Basement Membrane (GBM) antigen was assessed by ELISA. Platelet and red blood cell (RBC) binding was determined by flow cytometry and hemagglutination assays, respectively. A single dose of SAB-142 (1, 5, and 10 mg/kg), and rATG (5 mg/kg) as an active comparator, were infused intravenously to groups of 6 macaques, which were monitored for 4-weeks post-infusion. Clinical scoring was performed; blood and tissue samples were analyzed. SAB-142 bound below detection limits to human serum proteins and GBM in vitro. As compared to rATG, SAB-142 had higher platelet binding, but lower binding to RBCs. In macaques, SAB-142 and rATG were equally well tolerated, and no adverse effects were observed. All monkeys maintained normal body weight and ability to thrive. Despite reduced white blood cell counts, as expected by both reagents, no bleeding or thrombotic complications were observed post-infusion. ECG, hematology, coagulation, urine analyses and metabolic parameters were normal during and post-infusion. At the end of the study, no pathological findings were observed in native organs. Our results indicate that SAB-142 is well tolerated and should be immunomodulatory in humans.

Disclosure
K.A. Egland: None. D. Maher: Employee; SAB Biotherapeutics, Inc. E.S. Sandhurst: Employee; SAB Biotherapeutics, Inc. H. Wu: None. A.Y. Savinov: None. M. Ezzelarab: Consultant; SAB Biotherapeutics, Inc. C.L. Bausch: None. T.C. Luke: None.
888-P: Therapy Recommendation Neural Network for Comorbid Cardiometabolic Diseases
Authors: DIBNER YARON , BRANDT NICOLAS , KRENTZ ANDREW , LOZHKINA ARINA , LUSTER ALEXANDRE , PÈRE ARTHUR , JAUN ANDRÉ 
Published: June 2024

Objectives: Type 2 diabetes, hypertension, and hypercholesterolemia often develop in tandem with risk factors that appear to be more than additive. This work studies early therapeutic intervention beyond the silos that are created when looking at each morbidity separately.
Methods: After reproducing national guidelines for three morbidities using a neural network, we rely on transfer learning to record real world evidence outcomes from 469,496 primary care patients to optimise therapeutic outcomes from a multi-morbidity perspective in the following 2 years. Single morbidity treatment recommendations are adequate for the majority, but are optimally complemented with a comorbid therapy for a minority. Shapley values explain differences and are used with digital twin cohorts to reject the null hypothesis for no clinical benefit over guidelines with 95% confidence.
Results: Applied retrospectively on a test set with 10,676 cardiometabolic therapy decisions, 807 comorbidity recommendations were identified, 575 with p&lt;0.05 after testing digital twin cohorts for statistical support. Among these, diabetes therapies with two active ingredients should sometimes be complemented, either with an angiotensin receptor blocker (167) or a statin (117), in spite of not qualifying for a formal comorbid diagnosis. Apart from systolic blood pressure and ldl-c levels, we find that ethnicity plays an important role, with individuals of Asian origins being more than twice as likely to benefit from an early comorbidity intervention.
Conclusion: In this proof-of-concept study, we demonstrated that a neural network can formulate therapy recommendations beyond clinical guidelines to improve comorbid outcomes for persons with type 2 diabetes in primary care.

Disclosure
Y. Dibner: None. N. Brandt: None. A. Krentz: Research Support; Daiichi Sankyo. A. Lozhkina: None. A. Luster: None. A. Père: None. A. Jaun: None.
928-P: The SGLT2 Inhibitor Canagliflozin Ameliorates Polycystic Ovary Syndrome and Attenuates Inflammation by Reducing the Activation of NLRP3 Inflammasome
Authors: ZHANG YUQIN , CAI MEILI , DILIMULATI DILIQINGNA , ZHANG MANNA 
Published: June 2024

Polycystic ovary syndrome (PCOS) is closely related to chronic low-grade inflammation and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. The sodium-glucose cotransporter 2 (SGLT2) inhibitor reduces inflammation and attenuates the progression of PCOS. We assessed whether canagliflozin (CAN) alleviates PCOS by attenuating the NLRP3 inflammasome activation. C57BL/6 mice were treated with dehydroepiandrosterone and a high-fat diet to induce PCOS models for 21 days. Then PCOS mice were randomly divided into two groups: PCOS group and PCOS+CAN group, treated with vehicle or 25mg/kg/day CAN for 21 days by daily oral gavage. In vitro, NLRP3 inflammasome was induced by using lipopolysaccharides (LPS) and adenosine 5'-triphosphate (ATP) in mouse-primary-granulosa-cells (mpGCs), followed by CAN intervention. After CAN intervention, irregular estrous cycle and ovarian morphology with fewer corpora lutea and antral follicles, but more atretic follicles and cysts in PCOS mice were improved. Compared with PCOS group, the levels of testosterone, glucose metabolism, insulin resistance, and triglycerides were improved after the use of CAN. Immunohistochemical staining showed that levels of NLRP3 were down-regulated in the ovarian tissues of PCOS+CAN group compared to PCOS group. The mRNA and protein levels of NLRP3, the inflammasome adapter protein ASC and Caspase-1, N-terminal fragment of gasdermin D (GSDMD-N), downstream inflammatory factors IL-1β and IL-18 in PCOS+CAN group were significantly lower than those in PCOS group. In vitro, LPS+ATP-induced inflammation in mpGCs led to activation of the NLRP3 inflammasome, and this effect was prevented by the addition of CAN. These results showed that canagliflozin attenuated the reproductive and metabolic characteristics of PCOS and ameliorated inflammation by ameliorating activation of the NLRP3 inflammasome.

Disclosure
Y. Zhang: None. M. Cai: None. D. Dilimulati: None. M. Zhang: None.
933-P: Effects of Dapagliflozin and Metformin on Vascular Function in Newly Diagnosed Type 2 Diabetes—A Randomized Controlled Trial (DMVascular Study)
Authors: DALAN RINKOO , JIE CHEE YING , ZHANG XIAOE 
Published: June 2024

Aims: We aim to evaluate impact of Metformin vs Dapagliflozin vs combination (Dapagliflozin/Metformin) on surrogate measures of cardiovascular risk - endothelial function, artery stiffness and carotid artery intima-media thickness (CIMT) in a 12 week, randomized controlled study.
Methods: We screened 223 participants using oral glucose tolerance test. Participants with Type 2 DM were included. Primary outcome variables were arterial stiffness (cf-PWV-Sphygmocor), endothelial function (RHI-EndoPAT), and CIMT. ANCOVA model was fitted for change from baseline, to examine drug effect on the variables adjusting for baseline and change from baseline in HbA1c. Pairwise comparisons between the treatment arms were performed.
Results: We recruited 60 participants (Age: 50.2 (8.1) years, Male 30(50%)) to Metformin (n=21), Dapagliflozin (n=18) or Metformin & Dapagliflozin (n=21). We found a statistically significant difference in CIMT between the Metformin arm and the Dapagliflozin arm (difference: 0.06; 95% CI: 0.01 - 0.11; p-value=0.03 ). The difference in cf-PWV and ln-RHI did not reach statistical significance (p&gt;0.05) (Figure 1).
Conclusion: Initial treatment with Dapagliflozin gives a better response than Metformin for CIMT. Larger-scale longitudinal studies will clarify the potential of SGLT-2 inhibitors as initial diabetes pharmacotherapy.

Disclosure
R. Dalan: None. Y. Chee: None. X. Zhang: None.

Funding
National Medical Research Council (MOH-000014)
951-P: The t:slim X2 with Control-IQ Technology Overcomes Missed Boluses for Moderate Meals
Authors: FU LARRY , TRAHAN ALEX , MESSER LAUREL H. , CONSTANTIN ALEXANDRA 
Published: June 2024

Introduction & Objective: People with diabetes frequently miss mealtime insulin boluses. The t:slim X2 pump with Control-IQ technology (CIQ) delivers automatic correction insulin, which is thought to help improve glycemia when users do not consistently bolus for meals. This study uses simulations of a virtual population representative of CIQ users to evaluate the benefits of CIQ for users who do not bolus for small or moderate meals, as compared to those on multiple daily injections (MDI).
Methods: We leveraged 500,000 user years of real-world CGM, pump, and behavior data from over 420,000 customers to develop Tandem’s Statistical Simulator (TSS). TSS includes statistical models of user and population physiologies, behaviors, aleatory uncertainty, and CIQ system components. It can be used to run in silico clinical trials on populations representative of CIQ users in the real world. The TSS was used to compare glycemic outcomes for a group of 1000 virtual users under 4 scenarios: MDI vs. CIQ when bolusing for every meal, and CIQ vs MDI when not bolusing for small/moderate sized meals (≤40g carbs).
Results: Virtual MDI subjects who bolused for every meal had a median (IQR) of 58% (26-76%) TIR and 0.9% (0.2-2.3%) TBR. These same virtual subjects using CIQ who bolused for every meal had 69% (58-79%) TIR and 0.7% (0-3%) TBR. Virtual MDI subjects who did not bolus for meals ≤40 g of carbs had a 14% (2-37%) TIR and 0.1% (0-0.8%) TBR. These same virtual subjects using CIQ had 63% (53-71%) TIR and 0.6% (0.1-1.9%) TBR under same conditions.
Conclusion: CIQ significantly improves TIR regardless of bolus scenario, but is especially effective for individuals who miss boluses for moderate meals (more than tripling TIR). This suggests that MDI users who are prone to missing boluses would benefit greatly from CIQ use even if they continued not to bolus or count carbs accurately. This further provides evidence in line with ADA guidelines 2024 that diabetes technology should be offered to everyone (and not just the “best” candidates).

Disclosure
L. Fu: None. A. Trahan: Employee; Tandem Diabetes Care, Inc. L.H. Messer: Employee; Tandem Diabetes Care, Inc. A. Constantin: Employee; Tandem Diabetes Care, Inc.

Funding
Tandem Diabetes Care
967-P: The Use of Hybrid Closed-Loop Insulin Delivery in Adolescents and Young Adults with High-Risk Acute Lymphoblastic Leukemia during Induction Chemotherapy
Authors: JOST EMILY , CHO SOOHEE , LANGE SAMANTHA , BERGET CARI , PINSKER JORDAN E. , HARTMAN LISA , FORLENZA GREGORY P. 
Published: June 2024

Introduction & Objective: Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) are at risk of iatrogenic hyperglycemia during induction chemotherapy due to exposure to high dose corticosteroids and asparaginase, two cornerstones of ALL therapy. While hyperglycemia has been associated with adverse clinical outcomes, it is often underrecognized and undertreated. We evaluated the use of a hybrid closed-loop (HCL) insulin delivery system in this novel population at risk for severe hyperglycemia.
Methods: In this prospective trial, participants with newly diagnosed high-risk ALL received treatment with the Tandem t:slim X2 insulin pump with Control-IQ technology and Dexcom G6 continuous glucose monitor (CGM) during the 5-week chemotherapy induction period. The primary outcome was safety of HCL insulin delivery, as measured by hypoglycemia and adverse device events. Insulin usage and time in range (TIR) were also measured.
Results: A total of 5 participants, aged 13-18 years with no history of diabetes, received treatment with HCL insulin delivery. All participants started the system within 2 days after initiation of chemotherapy with high dose corticosteroids and prior to administration of asparaginase. Participants wore the system for a mean of 21 days and CGM for a mean of 23 days. The mean total daily insulin dose was 34.2 ± 24.9 units/day. Mean TIR was 84 ± 13% while on HCL, and mean time below range (TBR) was 0.9% ± 1.2%. One adverse event was related to bleeding at the CGM insertion site, and there were no severe hypoglycemic events.
Conclusion: The use of an HCL insulin delivery system for AYA patients with newly diagnosed ALL during induction chemotherapy met all feasibility and safety goals during this pilot trial. Rapid changes in insulin resistance caused by chemotherapy agents require close monitoring and prompt adjustments in HCL settings in this novel population.

Disclosure
E. Jost: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. S. Cho: None. S. Lange: None. C. Berget: Speaker's Bureau; Dexcom, Inc., Insulet Corporation, embecta. J.E. Pinsker: Employee; Tandem Diabetes Care, Inc. L. Hartman: None. G.P. Forlenza: Research Support; Abbott, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Medtronic. Advisory Panel; Medtronic. Research Support; Tandem Diabetes Care, Inc. Consultant; Tandem Diabetes Care, Inc.

Funding
Tandem Diabetes and Dexcom Inc.
974-P: High Time in Closed Loop for Control-IQ Technology with New Interoperable iCGM Sensors
Authors: HABIF STEPHANIE , MUFTI SABAH , MANNING MICHELLE L. , WU KEVIN , MESSER LAUREL H. 
Published: June 2024

Background: The FDA defines medical device interoperability as “the ability to safely, securely, and effectively exchange and use information among one or more devices⋯ technologies, or systems.” Interoperability helps address barriers to diabetes device use such as lack of access, high cost, and preferences for use, by offering users choice for their diabetes care.  The t:slim X2 with Control-IQ technology is the first automated insulin delivery (AID) system in the U.S. with an interoperable continuous glucose monitor (iCGM) option. In late 2023, Tandem users participated in a first access launch and remote software update of their AID system, enabling use of iCGMs including the Dexcom G7, G6, and Abbott Freestyle Libre 2 Plus (FSL2Plus). Here we report on system performance and perceptions on usefulness, and ease of use.
Methods: 154 existing Tandem pumpers elected to update their pump software to use the Dexcom G7 or FSL2Plus integrated with their t:slim X2 pump. These users had 1+ sensor changes and ≥ 18 days of system use at time of analysis. Daily qualitative feedback from email surveys were analyzed along with back-end system performance data.
Results: The t:slim X2 pump median time in automation was ≥92% (excluding CGM warm-up time) irrespective of CGM brand. User satisfaction was high, and primary qualitative themes included ease of use and perceptions of performance. Specifically, ease of the software update process and device pairing, as well as perceptions around system connectivity and accuracy were main contributors to positive user feedback.
Conclusion: This is a first report of people with diabetes using an AID system with multiple iCGMs in the U.S. Time in automation was high in this real-world setting, and users reported positive experiences, in line with published evidence for Control-IQ technology. An AID system with the ability to choose sensor type enables people with diabetes to optimize their device experience, and reduces barriers due to cost, access, or wearability.

Disclosure
S. Habif: Employee; Tandem Diabetes Care, Inc. S. Mufti: Employee; Tandem Diabetes Care. M.L. Manning: Employee; Tandem Diabetes Care, Inc. K. Wu: None. L.H. Messer: Employee; Tandem Diabetes Care, Inc.

Funding
Tandem Diabetes Care
976-P: Diabetes Technology Use in U.S. Hospitals
Authors: HUGHES MICHAEL S. , MORGAN MARCI , HSU LIANA , LIU YING-TING , YEH LEE MING , HANES SARAH , FIELDING-SINGH VIKRAM , HOOD KOREY K. , BUCKINGHAM BRUCE A. , LAL RAYHAN 
Published: June 2024

Introduction: Outpatient use of diabetes devices, including continuous glucose monitors (CGM), insulin pumps, and automated insulin delivery (AID) is increasing, and guidelines suggest continuation during hospitalization, despite off label use and limited guidance. We conducted an online survey to understand current real world diabetes technology continuation and use in hospital.
Methods: From May-Nov 2023, a survey was distributed via diabetes-related networks and social media. Eligible participants were living with or caring for someone with diabetes who experienced a hospitalization in the prior year and used a CGM and/or insulin pump at that time.
Results: Of 540 responses, 283 were excluded for ineligibility, incompleteness, or duplication. The remaining cohort (N=258) was mostly ≥18 years (92%), female (69%), white (94%), privately insured (62%), and had type 1 diabetes (93%). Hospitalizations occurred in 45 US states, commonly for surgery (32%), glycemia (20%), or infection (12%). A majority used their devices for ≥90% of their stay (fig). Among inpatient AID users (n=133), 74% felt glucoses were well-controlled vs. 49% of those who discontinued AID (n=33) (p=0.005).
Conclusion: Outpatient diabetes technology is commonly used in hospital glucose management, with users reporting more in target glycemic control. Further research should explore hospital implementation and how effectiveness and operational demands compare to traditional methods.

Disclosure
M.S. Hughes: Consultant; Dexcom, Inc. M. Morgan: None. L. Hsu: None. Y. Liu: None. M. Lee: None. S. Hanes: None. V. Fielding-Singh: None. K.K. Hood: Consultant; Cecelia Health, Sanofi. B.A. Buckingham: Advisory Panel; Medtronic. Research Support; Medtronic. Advisory Panel; Arecor. R. Lal: Consultant; Abbott, Adaptyx Biosciences, Biolinq, Capillary Biomedical, Inc., Deep Valley Labs, Gluroo, PhysioLogic Devices, Portal Insulin, Tidepool. Advisory Panel; Lilly Diabetes.

Funding
National Institutes of Health (5K12DK122550, 1K23DK122017, T32DK007217, P30DK116074)
986-P: Identifying Patterns of Glycemic Control from Wearable Device Data
Authors: OKUNO TOMOKI , SORT LUCAS , MACWAN SHARON , ZHOU HUA , MILLER DONALD R. , NORMAN GREGORY J. , REAVEN PETER , ZHOU JIN 
Published: June 2024

Introduction & Objective: To identify temporal patterns of glucose control measured by continuous glucose monitoring (CGM) devices for type 1 and type 2 diabetes (T1D and T2D) patients in Veterans Affairs Healthcare System.
Methods: Observational study using Dexcom CGM device data linked with patients' electronic health records from 2015-2020 to identify temporal and regional patterns of glycemic control.
Results: Using a cohort of 785 T1D and 1,466 T2D patients and their 1,551,644 CGM readings over nearly 3-years, we found that glycemic control deteriorated significantly during weekends. Average glucose differed between Sundays (highest) and Wednesdays (lowest) by 2.7mg/dL (Figure). Additionally, time-in-range (between 70 mg/dL and 180 mg/dL) and time-above-range (time above 180 mg/dL) showed similar temporal patterns. We also observed seasonal variations in glycemic trends, with patients having worse glycemic control from October to February and better control from April to August. The average glucose difference between April (lowest) and December (highest) was 4mg/dL and varied regionally, with these patterns accentuated in the Northeast compared to the Southwest. These patterns were generally similar in both T1D and T2D patients.
Conclusions: Identifying and understanding these real-world glucose fluctuations may help patients and providers better manage overall glucose control.

Disclosure
T. Okuno: None. L. Sort: None. S. Macwan: None. H. Zhou: None. D.R. Miller: None. G.J. Norman: Employee; Dexcom, Inc. P. Reaven: Research Support; Dexcom, Inc. J. Zhou: None.

Funding
This work was supported by the Veterans Affairs Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development. Additional support was received from the National Institutes of Health R01-067690 and 5R01-094775 to P.D.R., and the American Diabetes Association to P.D.R.; J.J.Z was supported by NIH (K01DK106116, R21HL150374, R01HG006139), National Science Foundation (DMS-2054253, IIS-2205441).
Karakterisasi Molekuler Tumbuhan Sidingin (Kalanchoe sp.) Asal Riau Menggunakan Empat Penanda Barkode DNA
Authors: Herman  
Published: June 2024

Sidingin (Kalanchoe sp.) merupakan tumbuhan sukulen dari famili Crassulaceae yang tumbuh liar namun memiliki beberapa manfaat sebagai tumbuhan obat. Sidingin asal Riau belum dapat ditentukan nama spesiesnya. Penentuan nama spesies tumbuhan dapat dilakukan menggunakan beberapa barkode DNA, seperti matK, rbcL, dan ITS. Penelitian barkoding DNA pada sidingin asal Riau belum pernah dilakukan. Penelitian ini bertujuan menganalisis empat barkode DNA pada tumbuhan sidingin (Kalanchoe sp.) asal Riau, yaitu ITS, trnL-trnL-trnF intergenic spacer (IGS), ndhC-trnV IGS, dan rpl16 intron. Pada penelitian ini telah diperoleh sekuens DNA untuk ITS, trnL-trnL-trnF IGS, ndhC-trnV IGS, dan rpl16 intron dengan panjang basa secara berturut-turut 662 pb, 909 pb, 949 pb, dan 944 pb. Keempatnya telah didaftarkan dengan nomor registrasi, secara berturut-turut, MW297180, MW297177, MW297178, dan MW297179. Komposisi nukleotida pada ITS berbeda dengan ketiga barkode DNA lainnya. Tidak ada aksesi di GenBank yang memiliki kemiripan 100% dengan sidingin sehingga nama spesies dari sidingin belum dapat ditentukan. Variasi nukleotida paling sedikit dijumpai pada daerah trnL-trnL-trnF IGS (9,65%) dengan jumlah mutasi subtitusi dan indels relatif mirip. Namun uniknya, nukleotida kritis yang merupakan nukleotida penciri paling banyak dijumpai pada daerah trnL-trnL-trnF IGS (1,41%). Kesimpulan, barkode DNA trnL-trnL-trnF IGS dapat digunakan untuk mengidentifikasi tumbuhan sidingin dibandingkan ketiga sekuens lainnya yang diteliti.