bluuebunny/crossref_metadata_2025_split huggingface dataset:
1680-P: Methyl Dihydrojasmonate (MDJ) Induces Hallmarks of Polycystic Ovary Syndrome (PCOS) and Related Mechanisms in Female Mice
Authors: CAI MEILI , DILIMULATI DILIQINGNA , ZHANG YUQIN , SHAO XIAOWEN , QU SHEN , ZHANG MANNA 
Published: June 2023

More than half of polycystic ovary syndrome (PCOS) are overweight or obese. Environmental endocrine-disrupting chemicals (EDCs) are one of the important pathogenic factors in PCOS women. Methyl dihydrojasmonate (MDJ) is a food flavor additive, which can enter the body through several paths. However, the impact of MDJ on obese PCOS patients is still unknown. Hence, the study aims to determine whether MDJ may induce hallmarks of PCOS as new EDCs. The blood samples (33 obese PCOS patients and 30 controls) were collected for metabonomic sequencing. Sequencing results that serum MDJ level was significantly increased in obese PCOS patients, and was closely associated with the clinical phenotype of PCOS. C57BL/6J female mice fed high-fat diets were randomly divided into four groups. The PCOS model was established by subcutaneous injection of dehydroepiandrosterone for 21 days. Different concentrations of MDJ group were gavage of MDJ (60, and 120 mg/kg/d), and the control group was gavage of corn oil, once daily from pregnancy to offspring 16 weeks old. After 16 weeks, different concentrations of MDJ treatment resulted in an irregular estrus cycle and disturbed ovarian development in female mice. Serum TT and insulin resistance levels were increased in the MDJ group. At the cellular level, different concentrations of MDJ (50, and 100 μg/L) intervention mouse-primary-granulosa-cells (mpGCs) and measured supernatant TT levels after 48h. In the mouse ovarian tissue and mpGCs, we found that the expression of key genes for steroid synthesis (Star, Cyp17a1, Hsd3b1, Lhcgr) was increased significantly, while the expression of Cyp19a1 decreased after different concentrations of MDJ treatments. In preliminary experiments, we found that long-term exposure to MDJ during pregnancy and growth can induce PCOS phenotype in C57BL/6J female mice. Ongoing studies will determine how MDJ induces the hallmarks of PCOS and related mechanisms, which may help reveal the pathogenesis of PCOS.

Disclosure
M.Cai: None. D.Dilimulati: None. Y.Zhang: None. X.Shao: None. S.Qu: None. M.Zhang: None.

Funding
National Key R&D Program of China (2018YFC1314100); National Natural Science Foundation of China (81601269)
1683-P: High-Fat Diet Downregulates CREG1 in the Liver via DNA Methylation
Authors: QI YANMEI , LIU JIE , CHAO JOSHUA C. , RAHIMI SAUM A. , LEE LEONARD Y. , LI SHAOHUA 
Published: June 2023

CREG1 is an endosomal-lysosomal protein which is highly expressed in the liver. Hepatocyte-specific deletion of Creg1 in mice causes insulin resistance and elevated glycemia. To test if CREG1 is nutritionally regulated, we fed mice for 10 weeks with a high-fat diet (HFD) which progressively downregulated CREG1 in the liver at both protein and mRNA levels. The CREG1 expression was restored after switch back to a standard chow diet for two weeks. The diet-induced CREG1 changes negatively correlated with blood glucose levels. Sequence analysis revealed enrichment of CpG islands in exon 1 of both human and mouse CREG1 genes. To test if methylation of these CpG islands contributes to HFD-induced CREG1 reduction, we fed mice with a HFD for 10 weeks and treated them with the DNA methyltransferase inhibitor 5-aza-deoxycytidine, which reversed HFD-induced CREG1 downregulation in the liver. At the cellular level, overload of cultured human hepatocytes with fatty acids reduced CREG1 expression, and this was reversed by inhibiting DNA methylation. Furthermore, removal of all CpG islands in the first exon with sense mutations abolished lipid overload-induced CREG1 downregulation. These results suggest that HFD downregulates CREG1 via DNA methylation of the CpG islands in the first exon. It would be interesting to test if CREG1 reduction mediates HFD-induced insulin resistance.

Disclosure
Y.Qi: None. J.Liu: None. J.C.Chao: None. S.A.Rahimi: None. L.Y.Lee: Speaker's Bureau; Abbott. S.Li: None.

Funding
Rutgers Biomedical and Health Sciences
1686-P: ER Stress Aggravates Diaphragmatic Weakness through Activating PERK/JNK Signaling in Obesity Hypoventilation Syndrome
Authors: XIANG XIAOXIN , ZHU YANHUA , PAN XUYA , XIN WEI , TANG WEIJIAN , HE XUEMIN , SHI GUOJUN , CHEN YANMING 
Published: June 2023

Obesity hypoventilation syndrome (OHS) is associated with reduced quality of life and increased risk of death. Diaphragmatic dysfunction has been implicated in the pathogenesis of OHS. We found that significant diaphragmatic weakness and lipid accumulation in people with obesity as well as mouse models of obesity, which was associated with activated endoplasmic reticulum (ER) stress indicated by increased PERK signaling and activation of JNK pathway. In cultured myotubes, inhibition of PERK and JNK signaling abrogated the lipids deposition and ameliorated insulin resistance, and inhibition of JNK signaling reversed the impaired elasticity of myotubes induced by lipotoxicity. Collectively, our data suggest that activation of PERK/JNK signaling is an important pathophysiological factor contributing to diaphragmatic contractile dysfunction in OHS.

Disclosure
X.Xiang: None. Y.Zhu: None. X.Pan: None. W.Xin: None. W.Tang: None. X.He: None. G.Shi: None. Y.Chen: None.

Funding
National Key R&D Program of China (2017YFA0105803); National Natural Science Foundation of China (82270886, 82070811); 5010 Clinical Research Projects of Sun Yat-sen University (2015015); Science and Technology Plan Project of Guangzhou City (202007040003, 202201020497); Key Area R&D Program of Guangdong Province (2019B020227003); Science and Technology Research Development Program of Guangzhou City (202007040003, 202201020497)
1692-P: Designing and Testing a Novel Weight Navigation Program to Improve Obesity Treatment in Primary Care Settings
Authors: GRIAUZDE DINA H. , TURNER CASSIE D. , HENDERSON JAMES , OTHMAN AMAL , OSHMAN LAUREN , GABISON JONATHAN , WALFORD ERIC , ARIZACA-DILEO PATRICIA K. , BECKIUS DEENA I. , KRAFTSON ANDREW T. 
Published: June 2023

Background: We developed and tested a novel Weight Navigation Program (WNP). The WNP aims to (1) integrate American Board of Obesity Medicine Diplomates into primary care teams, (2) deliver preference-sensitive weight management treatment, and (3) optimize patients’ achievement of ≥5% weight loss through remote weight monitoring with proactive outreach to support patients with &lt;5% weight loss.
Methods: This is a quality improvement program conducted at an academic primary care site from October 2020 to September 2021. WNP inclusion criteria are BMI ≥30 and ≥1 weight-related condition. Primary outcomes were measures of feasibility, including rates of referral to and engagement in the WNP. Secondary outcomes were mean weight loss and percentage of patients achieving ≥5% weight loss. We compared rates of referral to weight management treatment programs (i.e., nutrition counseling, meal replacement (MR), bariatric surgery) and prescribing of weight management medications (WMMs) among WNP-eligible patients at the pilot site and at a nearby clinic (control). Rates are also reported for patients with a completed WNP visit.
Results: Of 1,533 eligible patients, 238 (16%) were referred to the WNP and 135 (9%) completed a WNP visit. Mean percent weight change at 12-months for WNP patients was 5% and 39% achieved ≥5% weight loss. WNP-eligible patients at the WNP site (n=1,533) were referred to WMTs and prescribed WMMs at similar rates to WNP-eligible patients at the control site (n=2,913) (nutrition counseling 4.8% v. 6.8%, MR 1.0% v. 0.6%, WMM 2.0% v. 3.2%, bariatric surgery 1.2% vs. 1.8%). Patients with a completed WNP visit (n=135) received WMTs at substantially higher rates than the pilot and control sites (nutrition counseling 26.7%, MR 13.3%, WMM 11.9%, bariatric surgery 16.3%).
Discussion: A WNP is feasible and may support achievement of ≥5% weight loss. Additional work is needed to compare the efficacy of WNP vs usual care for weight loss.

Disclosure
D.H.Griauzde: None. A.T.Kraftson: None. C.D.Turner: None. J.Henderson: None. A.Othman: None. L.Oshman: Stock/Shareholder; Abbott, AbbVie Inc., Merck & Co., Inc., Procter & Gamble, Johnson & Johnson, Eli Lilly and Company. J.Gabison: None. E.Walford: None. P.K.Arizaca-dileo: None. D.I.Beckius: None.

Funding
University of Michigan Elizabeth Weiser Caswell Diabetes Institute; Michigan Center for Diabetes and Translational Research (P30DK092926-09 to D.H.G.); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK123416-01A1 to D.H.G.)
1698-P: The Effect of Ectopic Fat on Brain Structure and Cognitive Function—A Meta-analysis from Observational Studies of 1,003,593 Individuals
Authors: SONG ZHIHUI , LIU JING , ZHANG ZHAO , ZHOU JIANBO 
Published: June 2023

Abstract Purpose: To investigate the effects of ectopic fat on brain structure and cognitive function.
Methods: Data extraction and meta-analysis of eligible clinical studies were performed.
Results: The results showed ectopic fat was associated with the decreased total brain volume, posterior cingulate cortex volume, semioval center volume, sensorimotor cortex volume, and the increased lateral ventricle volume. Subcutaneous fat significantly was associated with the reduced risk of cerebral white matter hyperintensities (OR = 0.86, 95% CI: 0.74 to 1.00). Ectopic fat was associated with the decreased cognitive function. Visceral fat was significantly associated with poor cognitive outcomes (OR=1.42, 95% CI: 1.11 to 1.81).
Conclusion: Visceral ectopic fat was associated with the increased risk of brain structural changes and cognitive impairment. A new strategy identifying patients at risk of developing cognitive decline may be implemented timely and personalized treatment.
Fig.1 The relationship between ectopic fat and cognitive scores (WMD)

Disclosure
Z.Song: None. J.Liu: None. Z.Zhang: None. J.Zhou: None.
1709-P: Perceptions of Treatment Outcomes in People with Obesity and T2D—A Qualitative Study
Authors: LING POON JIAT , O'HARA LOUISE , KENDAL HELEN , SULLY KATE , GUY MARGARET , BRADLEY HELENA , TOLLEY CHLOE , MASON BRAD 
Published: June 2023

Background: Treatments for obesity and T2D often combine lifestyle changes (diet, physical activity) and medication. Weight reduction is an expected outcome of obesity and some T2D treatments. Individuals’ perspectives on obesity treatments, attitudes towards reduced food intake via appetite changes, and treatment-related gastrointestinal adverse events (GI AEs) are not well characterized. The current study assessed individuals’ perceptions of obesity/T2D treatments that impact appetite, eating behaviors, and weight, and concerns about GI AEs.
Methods: This cross-sectional study involved semi-structured interviews with 45 US adults (obesity, n=15; overweight, n=10; T2D, n=20). Two creative tasks explored participants’ perceptions of obesity/T2D treatment outcomes: 1) participants discussed perspectives on hypothetical obesity/T2D treatments that reduced appetite, hunger, and cravings; 2) participants indicated their choice from two hypothetical obesity/T2D treatments, which varied by degree of GI AEs, appetite changes, and weight reduction. Interviews were audio recorded and transcribed for analysis.
Results: Most participants asked (28/35; 80%) perceived the hypothetical scenarios as a positive outcome of obesity/T2D treatment. Most (30/35; 86%) considered appetite reduction to be an important treatment benefit. Many also perceived fewer cravings (13/29; 45%) and lesser desire to eat (12/29; 41%) to be positive treatment outcomes. Participants associated treatment-related appetite changes with improvements in diet (10/33; 30%), emotional well-being (9/33; 27%), and daily activities (8/33; 24%). In the choice task, participants perceived appetite and weight reduction as positive treatment outcomes, irrespective of degree of GI AEs.
Conclusions: Findings demonstrate that participants value appetite changes and/or weight reduction as treatment priorities, and are willing to accept potential GI AEs for these treatment outcomes.

Disclosure
J.Poon: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L.O'hara: Other Relationship; Lilly. H.Kendal: Other Relationship; Eli Lilly and Company. K.Sully: None. M.Guy: Employee; Adelphi Values, Other Relationship; Eli Lilly and Company. H.Bradley: Other Relationship; Eli Lilly and Company. C.Tolley: None. B.Mason: None.
171-LB: The Online Structured DSMES Program Improved Glycemic Control in Young Adults but Not in Children and Adolescence with T1DM
Authors: AN LINGWANG , JI LINONG 
Published: June 2023

Background: The COVID-19 pandemic has forced rapid reconsideration of the way in which health care is delivered in patients with T1DM. We explored the effect of an online structured DSMES program on glycemic control and self-management behavior in patients with T1DM.
Methods: The intervention included 2 modules: (1) series of online DSMES sessions based video courses and personalized discussion on diabetes management; (2) continuous interactions and support based Wechat platform through text, audio or video.
Results: A total of 36 subjects were enrolled into the final analysis, of them, 26 (72.2%) were young adults above 18 years and 10 (27.8%) were children and adolescence below 18. There were significant changes in HbA1c, TIR and hypoglycemic event in young adults; however, no significant difference were found in children and adolescence. There were significant behavior change measured using self-management scale of T1DM for Chinese adults (SMOD-CA) in participants aged ≥18, mainly in the domains of daily performance, coping with disease-related problems and goals of disease management; however, no significant behavior change were found in adolescence with T1DM (DBRS). (Table 1)
Conclusions: The online structured DSMES program improved glycemic control, self-management behavior and reduced hypoglycemic event in young adults but not in children and adolescence with T1DM.

Disclosure
L. An: None. L. Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck & Co., Inc., Bayer Inc., Sanofi-Aventis U. S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics.
172-OR: Normative CGM Glucose Levels throughout Gestation in Patients with Uncomplicated Pregnancies
Authors: CARLSON ANDERS L. , BECK ROY , LI ZOEY , NORTON ELIZABETH , BERGENSTAL RICHARD M. , JOHNSON MARY L. , DUNNIGAN SEAN , BANFIELD MATTHEW , KRUMWIEDE KATIE J. , SIBAYAN JUDY , CALHOUN PETER , DURNWALD CELESTE 
Published: June 2023

Glycemic patterns throughout pregnancy are not well described, particularly early pregnancy. CGM used throughout the gestational period in uncomplicated pregnancies may help describe glycemic patterns in more detail. Blinded CGM data were collected throughout pregnancy from 760 pregnant patients ≥18 years old, with HbA1c &lt;6.5%, no known diabetes, and gestational age &lt;17 weeks. CGM data from uncomplicated pregnancies (pregnancy without gestational diabetes, large for gestational age birth, or hypertensive disorder of pregnancy) established the normative data set. Uncomplicated pregnancies (n=427, mean±SD age 32±4 years, 73% White non-Hispanic, mean HbA1c 5.1±0.3%) showed mean glucose during the entire gestational period was 99±7 mg/dL. Trimester specific mean glucose was: 103±7, 98±7 and 98±8 mg/dL for 1st, 2nd, 3rd trimesters. Figure 1 shows mean glucose by hour/trimester. Median (quartiles) percent time in range (TIR) 63-120 mg/dL was 86% (82-89%) for gestational period, and 84% (79-89%), 87% (82-90%), and 85% (80-90%) for 1st, 2nd, 3rd trimesters. Figure 2 shows TIR 63-120 mg/dL by 4-week periods. In uncomplicated pregnancies, mean glucose and TIR 63-120 mg/dL remained consistent throughout the gestational period. These normative CGM data will help set pregnancy-specific glycemic targets and will be important to compare to those 333 women in this study with complicated pregnancies.

Disclosure
A.L.Carlson: Advisory Panel; MannKind Corporation, Novo Nordisk, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Insulet Corporation, UnitedHealth Group, Sanofi. J.Sibayan: None. P.Calhoun: None. C.Durnwald: None. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. Z.Li: None. E.Norton: None. R.M.Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. M.L.Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research. S.Dunnigan: None. M.Banfield: None. K.J.Krumwiede: None.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust; United Health Group
1734-P: Polyhormonal Cells of the Pancreatic Islets in Congenital Hyperinsulinism
Authors: KRIVOVA YULIYA , PROSHCHINA ALEXANDRA E. , GUBAEVA DILIARA , MELIKYAN MARIA , OTLYGA DMITRY 
Published: June 2023

One of the possible causes of insulin deficiency in diabetes is dedifferentiation of β-cells into immature phenotypes with decreased insulin content or into the polyhormonal cells containing both insulin and glucagon. Polyhormonal cells have been detected in the pancreas in diabetic animal models as well as in humans with type 2 diabetes and longstanding type 1 diabetes, suggesting this phenomenon is a consequence of hyperglycemia. However, there is no information about the presence of polyhormonal cells in opposite metabolic conditions such as hypoglycemia in infants with congenital hyperinsulinism (CHI). We examined pancreatic biopsies from 6 infants with diffuse CHI and 5 infants with focal CHI using double immunofluorescence with antibodies to insulin and glucagon. In focal CHI, we found a significant proportion of α-cells containing glucagon and insulin within the focal lesion and in the rest of the tissue. Similarly, in diffuse CHI, we found the majority of α-cells contained glucagon and insulin in all pancreatic islets. The proportion of insulin and glucagon varied in the polyhormonal cells - from cells with equal expression of these hormones to cells with the prevalence of insulin or glucagon. In one diffuse case and in two focal lesions, we observed polyhormonal cells with significantly decreased glucagon expression and normal insulin expression. Outside the latter focal lesions, cells had normal level of glucagon expression. Our results indicate that polyhormonal cells are not exclusive for diabetes and hyperglycemia. We found polyhormonal cells in the pancreas of infants with CHI under hypoglycemic conditions. We suggest that this indicates high degree of the plasticity of the pancreatic cells. The role of plasticity in infants with CHI is yet to be established.

Disclosure
Y.Krivova: None. A.E.Proshchina: None. D.Gubaeva: None. M.Melikyan: None. D.Otlyga: None.
1737-P: Novel Interaction between Nkx6.1 and Pdx1 Is Needed for Proper Beta-Cell Function
Authors: TESSEM JEFFERY S. , LITTLEFIELD CONNOR C. , HILL JONATHON T. 
Published: June 2023

The beta cell transcription factor Nkx6.1 is critical in pancreatic progenitor cells and mature beta cells. The pathways regulated by Nkx6.1 that results in these phenotypes are still being defined. We sought to define the transcriptional factors that interact with Nkx6.1 and may be harnessed to expand functional beta cell mass. INS-1 832/13 beta cells were transduced with AdCMV-Nkx6.1-BioID, AdCMV-GFP-BioID or left untreated. Biotinylated proteins were isolated and the Nkx6.1 interactome was defined using liquid chromatography-tandem mass spectrometry. We defined 176 biotinylated proteins in cells transduced with AdCMV-Nkx6.1-BioID that were not observed with AdCMV-GFP-BioID or naturally biotinylated proteins from untreated lysates. These potential Nkx6.1 interacting proteins are enriched in nucleotide binding, ribosomal proteins, and transcription factors. Among the enriched transcription factors, we validated that Pdx1 is biotinylated in response to transduction with AdCMV-Nkx6.1 using biotin-targeted immunoprecipitation and western blot. To examine if Pdx1 is likely to interact with Nkx6.1 on the genome, we analyzed the frequency of proximal binding sites for Nkx6.1 and Pdx1, and demonstrated that Pdx1 and Nkx6.1 binding sites in close proximity were statistically overrepresented in the genome. Given the role of Pdx1 on functional beta cell mass, we further characterized the interaction of endogenous Nkx6.1 and Pdx1 by co-immunoprecipitation (Co-IP). Our data demonstrates significant Pdx1 binding by Nkx6.1 Co-IP and significant Nkx6.1 binding by Pdx1 Co-IP, as compared to Co-IP with the IgG control. Finally, we demonstrate coregulation of Unc3 expression by Nkx6.1 and Pdx1 and demonstrate that CRISPR mediated deletion of either Nkx6.1 or Pdx1 is sufficient to impair INS-1 832/13 mediated expression of Unc3. These data define potential Nkx6.1 binding partners in INS-1 832/13 cells, as well as novel interaction between Nkx6.1 and Pdx1 in the regulation of Unc3.

Disclosure
J.S.Tessem: None. C.C.Littlefield: None. J.T.Hill: None.
1738-P: Instrument-Free Single-Cell Resolution of Transcriptome in Mouse Pancreatic Islet Cells
Authors: DIMITROVA DILYANA G. , LIBOZ ALEXANDRINE , LIPIN STANISLAV , BEAUPERE CARINE , ROBLOT NATACHA , KOMATSU JUN , GUILLEMAIN GHISLAINE , BLONDEAU BERTRAND 
Published: June 2023

Type 1 diabetes is characterized by an almost complete depletion of insulin-producing beta cells. Thus, regeneration of beta cells through beta-cell neogenesis represents a major therapeutic strategy to cure the disease. We previously reported a mouse model of severe insulin resistance that leads to high insulin secretion and massive beta-cell neogenesis. To understand the origins of the newly formed beta cells and the genic programs involved in high insulin secretion, we aimed at defining the pancreatic islet cells transcriptome at high resolution cell by cell. Here, we tested the compatibility of the novel instrument-free 3’ single-cell RNA-sequencing benchtop kit Asteria™, recently released by Scipio bioscience (Paris, France), on pancreatic islet cells isolated from adult mice, which underwent cell dissociation by trypsin treatment. In the Asteria™ procedure, differently from the microfluidic-based single-cell one, coupling of solid polymer-barcoded beads and cells occurs in homogenous phase in a reversible hydrogel named RevGel™. Such conditions are claimed by the vendor to be causing less mechanical stress to cells for an expected more preserved transcriptome. Successive steps were classic molecular biology and bioinformatic analysis using Scipio bioscience’s data analysis cloud-based software Cytonaut™. We profiled the transcriptome of 938 single cells from healthy mice and identified a total of 12 cell subtypes. SingleR annotation based on reference data revealed all the major cell types commonly described in the literature, including a well-represented beta cell population and some rare cell types such as ductal and stellate cells. We demonstrate 3’ single-cell RNA-sequencing using Scipio bioscience’s kit Asteria™ as an effective strategy to dissect the heterogeneity and the complexity of mouse pancreatic islets and identify the gene expression signatures of each cell.

Disclosure
D.G.Dimitrova: None. A.Liboz: None. S.Lipin: None. C.Beaupere: None. N.Roblot: None. J.Komatsu: None. G.Guillemain: None. B.Blondeau: None.