bluuebunny/crossref_metadata_2025_split huggingface dataset:
1385-P: Association of Glycemic Variability with Brain Imaging Abnormalities in Persons with Type 2 Diabetes
Authors: LI TSAI-CHUNG , LIN CHENG-CHIEH , LI CHIA-ING , LIU CHIU-SHONG , YANG CHUAN-WEI 
Published: June 2024

Introduction & Objective: Persons with diabetes are prone to have atherosclerosis, stenosis, poor blood fluid properties, and other adverse blood vessel health conditions, leading to occurrence of stroke. Thus, this study aims to examine the effects of glycemic variability on brain imaging abnormalities in persons with type 2 diabetes (T2DM).
Methods: This study consisted of 2,536 persons with T2DM who underwent magnetic resonance imaging (MRI) of the brain after they attended the Diabetes Care Management Program of a medical center in Taichung from 2001-2015. After 1:1 age and sex matching, we identified 958 persons with or without white matter hyperintensity (WMH) and 1,106 persons with or without cerebrovascular abnormality (CA). Glycemic variability is estimated using the coefficient of variation in fasting plasma glucose (FPG-CV) within one year of index date (date of first MRI assessment). Logistic regression models were used to assess whether FPG-CV is associated with brain imaging abnormalities.
Results: FPG-CV was associated with CA in multivariable analysis (tertile 2 vs. 1: odds ratios [ORs] 1.48, 95% confidence intervals [95% CI] 1.20-1.83 for unmatched population and 1.35, 1.08-1.68 for matched population; tertile 3 vs. 1: 2.07, 1.65-2.60 for unmatched population and 1.83, 1.44-2.33 for matched population; both P for trend &lt;0.001) but not with WMH.
Conclusion: Our finding indicated glycemic variability may be used as markers to predict cerebrovascular abnormality in persons with T2DM. In addition, glycemic management might guide clinicians toward specific strategies to prevent cerebrovascular abnormality in clinical practice.

Disclosure
T. Li: None. C. Lin: None. C. Li: None. C. Liu: None. C. Yang: None.
1412-P: Visceral Adiposity Is an Independent Predictor of Incident Type 2 Diabetes in Japanese
Authors: HAYASHI TOMOSHIGE , KOH HIDEO , SHIBATA MIKIKO , SHIBATA IZUMI , HIKITA YONEZO , BOYKO EDWARD J. , SATO KYOKO K. 
Published: June 2024

Introduction & Objective: Visceral adiposity has been reported to be an important risk factor for type 2 diabetes (T2D). However, whether directly measured visceral adiposity is associated with the risk of developing T2D independent of other fat depots and insulin resistance and whether this association holds true in normal-weight individuals has not been investigated in a prospective cohort study of native Asians.
Methods: Study participants were 1244 Japanese men and women without diabetes at baseline. Intra-abdominal fat area (IAFA) and abdominal, thoracic, and thigh subcutaneous fat areas (SFA) were measured by CT. Total fat area (TFA) was calculated as the sum of these fat areas and total SFA as TFA minus IAFA. T2D was defined as a fasting plasma glucose level ≥126 mg/dL, or an A1c value ≥6.5%, or use of glucose-lowering medications or insulin. Cox proportional hazards model was used to estimate hazard ratios for T2D in relation to exposures.
Results: The mean BMI at baseline was 23.1 kg/m2 and the mean age was 50.2 years. During the 10520 person-years of follow-up, we confirmed 112 cases of T2D. IAFA was associated with an increased risk for T2D. The multiple-adjusted hazard ratios of T2D for tertiles of IAFA were 2.76 (95% CI, 1.20-16.36) for tertile 2 and 4.96 (2.07-11.93) for tertile 3 compared with tertile 1 after adjustment for abdominal SFA, age, sex, family history of diabetes, smoking habit, regular physical activity, daily alcohol consumption, and fasting immunoreactive insulin. IAFA remained a significant risk factor for T2D even after adjustment for TFA, total SFA, abdominal SFA, waist circumference, or BMI, but none of these measures of fat area were associated with the risk of T2D in models including IAFA. In individuals with BMI &lt;25 kg/m2, these associations did not change.
Conclusions: Greater visceral adiposity increased the risk of T2D independent of other fat depots and insulin resistance in Japanese. These associations were similar in normal-weight individuals.

Disclosure
T. Hayashi: None. H. Koh: None. M. Shibata: None. I. Shibata: None. Y. Hikita: None. E.J. Boyko: None. K.K. Sato: None.
1431-P: Dramatic Reduction in Prevalence of Increase of Insulin Resistance in 14- to 15-Year-Old Students after the COVID-19 Pandemic
Authors: OHNO TAKAYUKI , ISHIGURO MIZUKI , SUGANUMA YUKA , NISHIMURA RIMEI 
Published: June 2024

Introduction & Objective: In the midst of the COVID-19 pandemic in 2020 and 2021, we reported a significant increase in homeostatic model assessment for insulin resistance (HOMA-IR) values among 14-15 years old students. In this study, we conducted prolonged surveys incorporating data until 2023.
Methods: The study included 430 students aged 14-15 who underwent health examinations between 2015 and 2023 (236 males, 194 females). Using its data, HOMA-IR, BMI, and obesity levels were calculated, and temporal changes were assessed using the Kruskal-Wallis test. Insulin resistance (IR) is defined as HOMA-IR ≥2.5 and temporal changes were assessed using the Chi-square test.
Results: A significant change in the median HOMA-IR was observed over the 8-year period (p &lt; 0.001). Conversely, no significant differences were observed in the median BMI and obesity levels over the 8-year period (p = 0.055, p = 0.064). Figure1 illustrated changes in the proportion of study participants with IR over time.
Conclusion: The significant increase in HOMA-IR observed after 2020 significantly decreased to values similar to pre-COVID-19 levels by 2023. However, BMI and obesity levels showed no temporal changes. Our findings suggest that changes in lifestyle due to the COVID-19 pandemic may have influenced insulin resistance in 14-15 years old students, irrespective of obesity status during 2020-2022.

Disclosure
T. Ohno: None. M. Ishiguro: None. Y. Suganuma: None. R. Nishimura: Speaker's Bureau; Abbott. Advisory Panel; Abbott Japan Co., Ltd. Speaker's Bureau; Boehringer-Ingelheim, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Medtronic, Sanofi, Taiho Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Eli Lilly and Company, Novo Nordisk A/S. Consultant; Terumo Corporation.

Funding
Ministry of Education, Culture, Sports, Science, and Technology, Japan (Kiban [c] 23590815 and Kiban [c] 19590600)
1440-P: C-Peptide Preservation and Diabetic Ketoacidosis (DKA) Risk in Type 1 Diabetes
Authors: ABUABAT MOHAMMAD I. , BUDHRAM DALTON R. , BAPAT PRIYA , BAKHSH ABDULMOHSEN M.K. , VERHOEFF NATASHA , MUMFORD DOUG , ORSZAG ANDREJ , FRALICK MICHAEL , WEISMAN ALANNA , ERIK LOVBLOM LEIF , PERKINS BRUCE A. 
Published: June 2024

Introduction & Objective: Endogenous insulin production in T1D, as measured by detectable C-peptide, is associated with lower HbA1c and insulin dose, as well as lower hypoglycemia and retinopathy risk. We aimed to determine if detectable C-peptide is also associated with decreased risk of DKA.
Methods: We accessed data from the Diabetes Control and Complications Trial (DCCT) from the NIDDK central repository to investigate the effects of detectable stimulated C-peptide measured annually (≥0.2 pmol/ml, exposure) on DKA incidence (outcome) over mean 6.5-year trial follow-up. Analysis was conducted using the Andersen-Gill model for recurrent DKA events with time-varying covariates; crude unadjusted models and models adjusted for age, sex, diabetes duration, and trial assignment (intensive vs. conventional) were fit. Sensitivity analysis also adjusted for HbA1c.
Results: Of the 1441 participants with a median age of 27 years and median duration of diabetes of 49 months, 53% were male, 21% had detectable C-peptide levels (&gt;0.2 pmol/ml) at baseline, and the median HbA1c level was 8.8%. During the trial, 129 participants (9%) had 180 DKA events. Only 1 of these 129 DKA events occurred in an individual with detectable C-peptide, while 128 events occurred in individuals after C-peptide became undetectable. In crude analysis, detectable C-peptide level had a 93% reduction in the hazard for recurrent DKA [hazard ratio (HR) 0.07, 95% CI 0.01 to 0.48, p=0.007]. Results were similar in the first adjusted model (HR 0.06, 95% CI 0.01 to 0.44, p=0.006) and in the final adjusted model (HR 0.08, 95% CI 0.01 to 0.60, p=0.012).
Conclusion: In addition to previously identified clinical benefits, this analysis demonstrates that endogenous insulin production dramatically lowers the risk of DKA in T1D. This implies that therapies that may preserve insulin production - such as immune, cell-based, or other therapies - are likely to reduce the burden of DKA.

Disclosure
M.I. Abuabat: None. D.R. Budhram: None. P. Bapat: None. A.M.K. Bakhsh: None. N. Verhoeff: None. D. Mumford: None. A. Orszag: None. M. Fralick: Consultant; singal1, proofdx. A. Weisman: None. L. Lovblom: None. B.A. Perkins: Advisory Panel; Abbott. Other Relationship; Novo Nordisk. Advisory Panel; Insulet Corporation, Nephris. Other Relationship; Medtronic. Advisory Panel; Sanofi, Vertex Pharmaceuticals Incorporated, Dexcom, Inc.

Funding
Diabetes Canada (Operating Grant OG-3-21-5572-BP)
1443-P: Natural History of Type 1 Diabetes (T1D)—Contrasting Adult vs. Pediatric At-Risk Populations
Authors: TEMPLEMAN ERIN , FERRAT LAURIC A. , THOMAS NICHOLAS , SPEAKE CATE , WHERRETT DIANE K. , SHERR JENNIFER L. , REDONDO MARIA J. , EVANS-MOLINA CARMELLA , SOSENKO JAY , SIMS EMILY K. , ORAM RICHARD A. 
Published: June 2024

Introduction: Adults represent over half of incident T1D cases but most studies on risk prediction focus on children.
Methods: We studied 135,970 children (&lt;18 years old) and 99,795 adult relatives in the TrialNet Pathway to Prevention study screened for autoantibody positivity (AB+). Kaplan Meier curves and log rank tests compare T1D progression. We tested discrimination of existing metabolic risk scores: Index60 (I60) and DPT1 (DPTRS) using area under time dependent receiver operating characteristic curve (ROC AUC).
Results: Adults had lower confirmed AB+ rates (adults 4.9% (n=4843); children 5.4% (n=7364), p &lt; 0.001), particularly for multiple AB+ (adults 0.9% (n=939); children 3% (n=4062), p &lt; 0.001). AB+ adults at all stages of disease exhibited lower 3 year progression risk compared to children (Table 1) but risk scores remained discriminative (DPTRS ROC AUC: adults 0.91 [0.87 - 0.94], children 0.86 [0.84 - 0.87]; I60: adults 0.87 [0.83 - 0.91], children 0.83 [0.82 - 0.85]).
Conclusion: Key differences and similarities between children and adult relatives are highlighted: fewer adults presented with early stage T1D (multiple AB+), progression rates were lower in AB+ adults, and those at highest risk can be identified with metabolic risk scores. Large datasets of AB+ adults are needed to refine and calibrate T1D prediction models in adults.

Disclosure
E. Templeman: None. L.A. Ferrat: Consultant; Johnson & Johnson Medical Devices Companies. N. Thomas: None. C. Speake: None. D.K. Wherrett: None. J.L. Sherr: Consultant; Medtronic. Advisory Panel; Medtronic, Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Vertex Pharmaceuticals Incorporated, MannKind Corporation, StartUp Health T1D Moonshot, Bigfoot Biomedical, Inc., Cecelia Health. Speaker's Bureau; Zealand Pharma A/S. M.J. Redondo: None. C. Evans-Molina: Other Relationship; Bristol-Myers Squibb Company, Nimbus Therapeutics. Research Support; Lilly Diabetes, Astellas Pharma Inc. Advisory Panel; Avotres Inc., Neurodon, DiogenX, Isla Technologies. J. Sosenko: None. E.K. Sims: Consultant; Sanofi. Board Member; American Diabetes Association. Other Relationship; American Diabetes Association, Medscape. Consultant; DRI. R.A. Oram: Research Support; Randox R & D. Consultant; Provention Bio, Inc., Sanofi.

Funding
Randox Ltd
1448-P: The Role of a Glucose Fraction Independent of Insulin Secretion in Predicting Hyperglycemia Endpoints in Autoantibody-Positive Individuals (Ab+I)
Authors: NATHAN BRANDON M. , CUTHBERTSON DAVID D. , ISMAIL HEBA M. , JACOBSEN LAURA M. , SIMS EMILY K. , SOSENKO JAY 
Published: June 2024

Objective and Introduction: It has been shown that AUC glucose from oral glucose tolerance tests (OGTTs) can be divided into fractions dependent or independent of insulin secretion. We assessed whether the independent fraction is predictive of incident IGT, a pre-diagnostic marker (2-hr glucose ≥140 to &lt;200 mg/dl), and T1D among Ab+I.
Methods: AUC glucose, calculated from baseline OGTTs of 5182 normoglycemic TrialNet Pathway to Prevention participants with ≥1 Ab+, was divided into fractions dependent (dAUCGLU) or independent (iAUCGLU) of insulin secretion. Fractions were derived from linear regression of AUC glucose vs. Index60 (insulin secretion proxy). dAUCGLU was the expected AUC glucose value, while iAUCGLU was the residual value of AUC glucose above or below the regression slope. Fractions were assessed for predicting IGT and T1D.
Results: dAUCGLU and iAUCGLU were each predictive of both IGT and T1D (p&lt;0.0001 for both, Figure). iAUCGLU was a stronger predictor of IGT, while dAUCGLU was a stronger predictor of T1D. When added to dAUCGLU in regression models, iAUCGLU contributed to the prediction (p&lt;0.0001) of both IGT and T1D.
Conclusion: A glucose fraction independent of insulin secretion predicts both IGT and T1D in Ab+I. This merits investigation into other factors (e.g., insulin resistance) contributing to these hyperglycemic endpoints.

Disclosure
B.M. Nathan: None. D.D. Cuthbertson: None. H.M. Ismail: Consultant; Sanofi, Rise Therapeutics. L.M. Jacobsen: Advisory Panel; Insulet Corporation. E.K. Sims: Consultant; Sanofi. Board Member; American Diabetes Association. Other Relationship; American Diabetes Association, Medscape. Consultant; DRI. J. Sosenko: None.

Funding
National Institutes of Health (U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085461, U01 DK085465, U01 DK085466, U01 DK085476, U01 DK085499, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993, UC4 DK117009)JDRF
1454-P: Major Adverse Cardiovascular Events, Advanced Foot Complications, and Subsequent Risk of Diabetic Ketoacidosis in Type 1 Diabetes
Authors: BAPAT PRIYA , BUDHRAM DALTON R. , BAKHSH ABDULMOHSEN M.K. , ABUABAT MOHAMMAD I. , VERHOEFF NATASHA , MUMFORD DOUG , ORSZAG ANDREJ , FRALICK MICHAEL , WEISMAN ALANNA , ERIK LOVBLOM LEIF , PERKINS BRUCE A. 
Published: June 2024

Introduction & Objective: People with type 1 diabetes and diabetes-related complications, including cardiovascular disease, are at increased risk of morbidity and mortality. We aimed to determine if major adverse cardiovascular events (MACE) and microvascular complications independently predict the risk of subsequent diabetic ketoacidosis (DKA).
Methods: We accessed previously-collected data from the DCCT/EDIC Study through the NIDDK Central Repository. We used Multivariable Cox Proportional Hazard models with time-varying exposures and co-variates to examine associations of MACE and microvascular complications (early- and late-stages of neuropathy, nephropathy, and retinopathy) as the exposure, with the subsequent occurrence of DKA as the outcome.
Results: Of 1441 participants, 297 individuals experienced 488 DKA events over 34 years of follow-up. MACE [hazard ratio (HR) 3.11, 95% confidence interval (CI) 1.56-6.17, p=0.001] and late-stage neuropathy, which comprised of foot ulcer or amputation, (HR 1.61, 95% CI 1.06-2.45 p=0.026) were independently associated with higher risk of DKA. Higher DKA risk was also associated with insulin pump use (HR 3.01, 95% CI 2.28-3.98, p&lt;0.001), higher insulin dose (HR for 1 unit/kg/day 2.39, 95% CI 1.72-3.33, p&lt;0.001), female sex (HR 2.01, 95% CI 1.58-2.56, p&lt;0.001), and higher time-updated HbA1c (HR for 1 percent 1.41, 95% CI 1.32-1.51, p&lt;0.001).
Conclusion: In those with type 1 diabetes, a major cardiovascular event, foot ulcer or amputation confers the greatest risk of future DKA independent of previously-recognized risk factors. These findings imply a need to target patients with these events for DKA prevention interventions such as self-management skills for metabolic control, management of depression, and education around DKA.

Disclosure
P. Bapat: None. D.R. Budhram: None. A.M.K. Bakhsh: None. M.I. Abuabat: None. N. Verhoeff: None. D. Mumford: None. A. Orszag: None. M. Fralick: Consultant; singal1, proofdx. A. Weisman: None. L. Lovblom: None. B.A. Perkins: Advisory Panel; Abbott. Other Relationship; Novo Nordisk. Advisory Panel; Insulet Corporation, Nephris. Other Relationship; Medtronic. Advisory Panel; Sanofi, Vertex Pharmaceuticals Incorporated, Dexcom, Inc.

Funding
Diabetes Canada (Operating Grant OG-3-21-5572-BP)
1468-P: Massively Parallel Reporter Assay Reveals Position-, Promoter-, and Strand-Dependent Effects in Islet TSSs Overlapping Type 2 Diabetes GWAS Loci
Authors: BOSE MAYA L. , TOVAR ADELAIDE , VARSHNEY ARUSHI , PARKER STEPHEN , KITZMAN JACOB , KYONO YASUHIRO 
Published: June 2024

Introduction & Objective: Massively parallel reporter assays (MPRAs) are an increasingly popular method of assessing the sequence-dependent activity of variants associated with complex diseases such as type 2 diabetes (T2D). Many MPRA libraries use a single plasmid configuration, a minimal promoter, and a single strand orientation, which may fail to capture the context-dependent expression of T2D-associated cis-regulatory elements. Here, we interrogate the potential activity differences introduced by variable MPRA plasmid construction.
Methods: We used an MPRA library to quantify the activity of 1,305 human pancreatic islet transcription start sites (TSSs). We cloned TSS fragments in either the upstream or downstream position of either the human insulin promoter or a synthetic housekeeping promoter. Activity was measured in the rat pancreatic islet beta cell line 832/13. We used statistical models to calculate position- and promoter-specific fragment activity and enrichment of transcription factor motifs (TFMs) and fragment strand-of-origin.
Results: The non-zero position-bias coefficients for the fragments were significantly stronger than the promoter-bias coefficients (p &lt; 0.05) and strongly biased towards the upstream configuration. Fragments that displayed preferential activity upstream of the reporter gene were enriched for TFMs such as BHLHE22, NR2E1, and E2F, which have been implicated in insulin production and glucose metabolism. 28% of fragments with significant promoter effects overlapped a 99% T2D genome-wide annotation study credible set. Positive strand-of-origin (β = 11.91, p &lt; 0.001) predicted significantly higher fragment activity.
Conclusion: Our MPRA library demonstrates the position-, promoter-, and strand-dependence of activity at islet TSSs that may contribute to T2D development. Future MPRA studies should seek to account for such factors when assaying T2D-associated regulatory element variants.

Disclosure
M.L. Bose: None. A. Tovar: None. A. Varshney: None. S. Parker: Research Support; Pfizer Inc. J. Kitzman: Advisory Panel; Myome Inc. Y. Kyono: None.

Funding
National Human Genome Research Institute (T32HG000040-22)
1471-P: Impaired Delta Opioid Receptor Function Protects against Type 2 Diabetes and Results in Enhanced Insulin Secretion—A Functional Genetic Study
Authors: BONNEFOND AMELIE , GROUP RADIO , SCHARFMANN RAPHAEL , MARCHETTI PIERO , CNOP MIRIAM , FROGUEL PHILIPPE 
Published: June 2024

Introduction & Objective: Human genetics has proven powerful to pinpoint novel drug targets for metabolic disorders. While the influence of opioids on metabolic homeostasis has been largely acknowledged, the underlying mechanisms remain unclear. We used functional genomics focusing on OPRD1 encoding delta opioid receptor (DOP), aiming to unravel its effects on type 2 diabetes (T2D).
Methods: OPRD1 was sequenced in 7K participants from the French RaDiO study followed by functional investigation of rare and frequent variants. Association analyses between OPRD1 variants and metabolic traits were performed in RaDiO and confirmed in up to 222K individuals. Glucose-stimulated insulin secretion assays were done in human beta cells and islets utilizing DOP agonist or DOP antagonist. RNA-sequencing was done in human beta cells upon DOP antagonist treatment and in human islets subjected to various diabetogenic treatments.
Results: Loss-of-function OPRD1 variants were associated with higher adiposity and lower hyperglycemia risk, while gain-of-function variants were associated with lower adiposity and higher T2D risk. OPRD1 is expressed in human pancreatic islets and beta cells, but not in rodents, and this expression is decreased when exposed to diabetogenic conditions. DOP activation in human beta cells inhibited insulin secretion while DOP inhibition by a specific antagonist strongly enhanced insulin secretion in human islets and beta cells. We identified several pathways regulated by DOP antagonism in human beta cells, including nerve growth factor, circadian clock and nuclear receptor pathways.
Conclusion: Our study highlights the delta opioid receptor as a major link between opioids and metabolic homeostasis in humans, which directly modulates insulin secretion. A peripherally acting DOP antagonist unable to cross the blood-brain barrier might represent a new drug to restore optimal insulin secretion in response to glucose.

Disclosure
A. Bonnefond: None. R. Scharfmann: Consultant; Human Cell Design, Adocia. P. Marchetti: Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. M. Cnop: None. P. Froguel: None.
1484-P: Six-Class Clustering and Its Complication Prediction in Chinese Aged Diabetes Cohorts Based on Deep Contrast Clustering Analysis
Authors: WANG WEIHAO , GUO LIXIN 
Published: June 2024

Aims: This work aims to establish an innovative clustering method predicting variable categories of diabetic complications in aged Chinese diabetes cohort.
Methods: We selected and extracted data of elderly diabetic patients (n=4980) from a medical examination group of 51,400 people followed-up yearly from 2014 to now in Kunshan, China.
Result: The patients were clustered into 6 categories by analyzing 20 indicators. Cluster 1 (n=592) was characterized by heavy smoking and high risk of complications of CVD (Cumulative 10-year incidence rate was 6%). Cluster 2 (n=1130) was characterized by high alcohol consumption, high aminotransferases, the highest risk of complications of stroke (Cumulative 10-year incidence rate was 12.3%) and high risk of FLD (60.5%). Cluster 3 (n=837) was characterized by high blood lipids, high risk of complications of FLD (69.6%) and stroke (11.8%). Cluster 4 (n=886) was characterized by good healthy indicators and a low risk of complications such as FLD (Cumulative 10-year incidence rate was 27.3%), stroke (Cumulative 10-year incidence rate was 6.9%) and CVD. Cluster 5 (n=749) was characterized by older age, higher uric acid, higher creatinine, and the highest risk of complications of CVD. Cluster 6 (n=786) was characterized by high waist circumference, high BMI, high blood pressure and the highest risk of complications of FLD. All three complications, stroke, CVD, and FLD, were analyzed by the Kruskal-Wallis test (p&lt;0.05). The gene of nonalcoholic fatty liver disease (NAFLD) in the cluster 2 was the highest risk coefficient: 1.277 (95% CI:1.522-1.165, P&lt;0.05). It was consistent with the cluster 2 having a higher prevalence of FLD.
Conclusions: A new clustering method has been developed in two large Chinese cohorts of aged diabetes, which may effectively predict complications by clustered in different categories.

Disclosure
W. Wang: None. L. Guo: Consultant; Abbott, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Eli Lilly and Company, Hengrui (USA) Ltd., Dreisamtech, Dongbao, Gan & Lee, Hansoh.