bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymptomatic Coronary Artery Disease (CAD) in a Norwegian Cohort with Type 2 Diabetes (T2D)—A Prospective Invasive Coronary Angiographic (ICA) Study
Authors: OFSTAD ANNE P. , ARORA SATISH , ULIMOEN GEIR R. , BIRKELAND KARE I. , ENDRESEN KNUT , GULLESTAD LARS L. , JOHANSEN ODD ERIK 
Published: June 2018

Effective treatment strategies to reduce the CAD burden in T2D are needed. We investigated whether progression of CAD, evaluated by ICA, could be modulated with a hospital-based multi-intervention (MULTI) to reduce cardiovascular (CV) risk. Patients with T2D and ≥ 1 CV risk factor (n=56, 21% women, age/T2D duration 57.9±7.9/5.8±5.6 years, HbA1c 7.4±1.6%, systolic BP 139±19 mmHg, LDL-cholesterol 2.8±0.9 mmol/L) were randomized to 2 years of MULTI (n=30), or standard care (STAND) by general physicians (n=26), with a pre-planned follow-up at year 7. ICA was performed at baseline (BL) and year 7. At BL 21 (36%) had no CAD, 17 (29%) wall changes, 4 (7%) 25-50% stenosis and 14 (24%) &gt;50% stenosis. Angiograms were scored as: grade 0:&lt;25% stenosis (st), 1:&lt;50% st, 2: &lt;75% st, 3: &gt;75% st, 4: occlusion. CAD burden was described by the extent score (sc) (number of segments graded ≥1, adjusted to 16 segments) and severity sc (average gr of the diseased segments graded ≥1). After 2 years of intervention, CV risk factors in MULTI (HbA1c, systolic BP, LDL-cholesterol) were reduced, without between-group differences in CAD progression at year 7 (Table). Our data indicate that asymptomatic T2D patients have extensive CAD that increases over time and is not modulated by a 2-year multi-intervention. This suggests a need for more durable CV risk management using alternative approaches.Progression of CAD from baseline to 7 years in the two treatment groupsT2D populationBaseline7 yearspMULTI (n=30)STAND (n=26)MULTI (n=30)STAND (n=26)CAD progressionExtent Score0.038±0.0670.078±0.120.050±0.0810.10±0.110.30*Severity Score0.47±0.840.83±1.110.67±0.981.18±1.060.20**p for between-group difference in change from baseline to 7 years by ANCOVA Abbreviations: CAD: coronary artery disease, T2D: type 2 diabetes, MULTI: multi-intervention, STAND: standard care. Data given as mean±standard deviation.

Disclosure
A.P. Ofstad: Employee; Self; Boehringer Ingelheim GmbH. S. Arora: None. G.R. Ulimoen: None. K.I. Birkeland: Research Support; Self; AstraZeneca, Novo Nordisk A/S, Eli Lilly and Company, Sanofi, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp.. K. Endresen: None. L.L. Gullestad: None. O. Johansen: Employee; Self; Boehringer Ingelheim GmbH.
A Machine-Learning Model Accurately Predicts Projected Blood Glucose
Authors: GOLDNER DANIEL R. , OSBORN CHANDRA Y. , SEARS LINDSAY E. , HUDDLESTON BRIAN , DACHIS JEFF 
Published: June 2018

Background: Clinical guidelines do not specify the frequency of self-monitoring of blood glucose (SMBG) for the ∼85% of people with type 2 diabetes (T2D) not on intensive insulin therapy. For these individuals, insurance covers a limited amount of testing supplies, and blood glucose (BG) checks are infrequent. With limited BG data, people may not know how foods, activity, and other factors affect their BG levels. Other, non-SMBG-dependent, approaches are needed to illustrate how self-care choices affect BG.
Objectives: 1.) Use a large dataset to train a machine learning model 2.) Use the model and minimal data inputs to predict BG values at variable times 3.) Test the accuracy of the prediction.
Methods: The One Drop | Mobile app collected 1,923,416 BG measurements from 14,706 people with noninsulin treated T2D. Contextual information (CI), when available, included demographics, health metrics (e.g., weight, A1c), and self-care. Inputs to each BG prediction included a prior BG and available CI. The model did not distinguish whether BGs with similar CI were from the same or different users. Forecast horizons were set by the time since prior BG and varied from 10 minutes to several days. Machine learning algorithms to predict BG values were trained and vetted on BGs entered prior to Sept. 2017 (83% of all BGs). BGs (17%) entered from Sept.-Nov. 2017 were held out and predicted.
Results: Users were 59% male, with 80% from North America, 9% from Europe, and 11% from elsewhere; 50% were diagnosed with T2D in the past 3 years. The median and mean absolute error of holdout predictions were 14.2 and 21.3 mg/dL respectively, with 91% of predictions within +/-50 mg/dL.
Discussion: A machine learning model with minimal inputs accurately predicts future BG values in noninsulin treated people with T2D. Whether people modify their behavior (e.g., eating less carbohydrates) after knowing a planned behavior (e.g., a 60 carbohydrate gram meal) produces an undesirable BG (&gt;140 mg/dL postprandial) is an empirical question worth investigating.

Disclosure
D.R. Goldner: Consultant; Self; One Drop. C.Y. Osborn: Employee; Self; One Drop. Research Support; Self; MannKind Corporation. Stock/Shareholder; Self; One Drop. L.E. Sears: Employee; Self; Informed Data Systems Inc.. Research Support; Self; MannKind Corporation. B. Huddleston: Employee; Self; One Drop. J. Dachis: Stock/Shareholder; Self; One Drop. Board Member; Self; One Drop. Employee; Self; One Drop.
Evaluation of Endothelial Function and Sympathetic Nervous Activity along the Glucose Continuum in Individuals with Habitual Low Sodium Intake
Authors: BAQAR SARA , EKINCI ELIF I. 
Published: June 2018

Objective: To assess endothelial function and sympathetic nervous activity in individuals with low sodium intake along the glucose continuum.
Research Designs and Methods: In this prospective observational study, participants (n=54) with low sodium intake (single 24hour urine sodium excretion &lt;150mmol/24h) were recruited and categorized based on an oral glucose tolerance test as: controls (n=10), with impaired glucose tolerance (IGT) (n=15) and with untreated (n=12) type 2 diabetes and were then compared to individuals with treated type 2 diabetes (n=17) with established cardio-metabolic risk factors. We assessed pulse amplitude tonometry (PAT) derived measures of endothelial function using the reactive hyperemic index and arterial stiffness using augmentation index; muscle sympathetic nerve activity (MSNA) using microneurography; cardiac baroreflex; heart rate; blood pressure; fasting glucose; glycosylated hemoglobin A1c (HbA1c) and lipid profile.
Results: The mean (SD) sodium excretion was 110.6 (26) mmol/24hour. Compared to individuals from the other groups, the treated type 2 diabetes group had a lower PAT ratio (p=0.04), lower baroreflex (p=0.0002) and higher heart rate (p=0.02) suggestive of sympatho-vascular dysfunction. This occurred despite lower MSNA (p=0.005) and appropriate glycemic (mean +/-SD): HbA1c 7.2 (1.72)% (55mmol/mol), total cholesterol 4.2 (1.0) mmol/L, LDL 2.2 (1.0) mmol/L) and blood pressure (mean +/-SD) 136 (13) systolic and 78 (12) diastolic pressure (mmHg) control.
Conclusion: In individuals with treated type 2 diabetes, despite a low sodium intake and appropriately managed cardio-metabolic risk factors, endothelial and baroreflex function were impaired. Whether sodium restriction may be associated with an attenuated sympatho-vascular response in individuals with diabetes requires further investigations.

Disclosure
S. Baqar: None. E.I. Ekinci: None.
Low Prevalence of Peripheral Arterial Disease in Type 2 Diabetes Patients in North India
Authors: MAKKAR BRIJ M. , SHARMA JUGAL K. , JAGGI SHALINI , SOOTA KIRTI , GUPTA VIPUL , KHURANA GIRISH 
Published: June 2018

Introduction: Peripheral Arterial Disease (PAD) is a major macrovascular complication of type 2 diabetes (T2D). Though data is limited, studies have indicated a lower prevalence of PAD in Indian diabetes patients as compared to western population. Present study assessed prevalence of PAD in T2D patients in Delhi, North India. Methodology: This study is a retrospective analysis of patient records of T2D patients. A total of 1000 patient were screened, 195 patients were excluded due to incomplete data and 8patients were included in the study. Diagnosis of PAD was based on ankle brachial index (ABI) measurement. An ABI value of &lt;0.9 indicated diagnosis of PAD, 0.9 to 1.3 was taken as normal, and ABI&gt;1.3 as indicator of non-compressible arteries.
Results: Study population consisted of 470 male and 335 female T2D patients (n=805), group 22 to 83 years. PAD (ABI &lt;0.9) was present in 12 patients (1.49%), 9males (75% of PAD) and 3 females (25% of PAD). Diabetes patients with PAD had a higher mean age (57.±10.96 vs. 50.97 ±10.03years) a longer duration of diabetes (12.67 ±7.9 vs. 8.±8.06years, p=0.02) and significantly lower BMI (24.92kg/m2±2.42 vs. 29.55±5.87 kg/m2, p=0.0066) as compared to nondiabetic patients. More patients with PAD had hypertension (58.33% vs. 47.79%, p=0.96) and coronary artery disease (16.67% vs. 7.44%, p=0.908) which, however, were not statistically significant. PAD patients had significantly higher levels of total cholesterol (198.75±66.39 vs. 162.23±44.71mg/dl, p=0.0055) and LDL cholesterol (120.66±40.48mg/dl, p=0.039). No difference was seen in triglyceride levels (165.67±70.92mg/dl vs. 165.4±110.14,p=0.99) and A1c levels (8.97±3.vs. 9.08±2.54%, p=0.87) in two groups.
Conclusion: Our study shows that prevalence of PAD in T2D patients in Delhi, North India, is much lower than that reported in western population (∼20%) and from south India (6.3%). Prevalence of PAD was higher in patients with higher age, longer duration of diabetes, lower BMI, and higher total and LDL cholesterol.

Disclosure
B.M. Makkar: None. J.K. Sharma: None. S. Jaggi: None. K. Soota: None. V. Gupta: None. G. Khurana: None.
CXCR7 Agonist TC14012 Improves Angiogenic Function of Endothelial Progenitor Cells in Diabetic Limb Ischemia
Authors: WANG KAI , DAI XIAOZHEN , CHEN JING , EPSTEIN PAUL N. , CAI LU , WINTERGERST KUPPER A. , QIAN YAN , TAN YI 
Published: June 2018

Stromal cell-derived factor 1 (SDF-1)-chemokine receptors CXCR4/7 axis plays a vital role in diabetic limb ischemia. Our previous studies demonstrated that elevated CXCR7 improves therapeutic efficacy of endothelial progenitor cells (EPCs) in diabetic limb ischemia. The effects of a specific CXCR7 agonist TC14012 on diabetic hind limb ischemia remains untested. We hypothesize that CXCR7 expression is reduced in diabetic EPCs and TC14012 improve angiogenic function of EPCs in diabetic limb ischemia. Early WT-EPCs were transfected with siRNA against CXCR7, and early db/db-EPCs were infected with CXCR7 lentivirus. Tube formation and capillary density of ischemic gastrocnemius muscle (GS) and soleus muscle (SS) at 4 weeks post-ischemic surgery were adopt for indication of angiogenesis. Diabetic hind limb ischemia (HLI) models were established by femoral artery ligation, followed by administration of TC14012 subcutaneously. Total and cell surface expression of CXCR7 were significantly decreased in EPCs from db/db mice compared with those from WT mice, whereas no significant differences of CXCR4 expression were observed. Tube formation by EPCs from db/db mice was also impaired compared with WT-EPCs. siRNA knockdown of CXCR7 was accompanied by impaired tube formation. Conversely, increasing CXCR7 levels in db/db EPCs completely reversed impaired tube formation function. High glucose (HG) dose dependently decreased the expression of CXCR7 in vitro but not that of CXCR4. HG also impaired tube formation of EPC from WT mice. Tube formation function of HUVEC was impaired after treated with HG (25mM) for 24 hours, which could be prevented by TC14012. Most importantly, TC14012 significantly improved blood flow restoration of ischemic hind limb starting from 2 weeks after ligation and promoted angiogenesis of ischemic GS and SS. Diabetes attenuates CXCR7 expression and impairs angiogenesis of EPCs. TC14012 improves blood reperfusion of diabetic hind limb ischemia.

Disclosure
K. Wang: None. X. Dai: None. J. Chen: None. P.N. Epstein: None. L. Cai: None. K.A. Wintergerst: None. Y. Qian: None. Y. Tan: None.
Mechanistic Role of Mitochondrial AKT1 in Kidney Injury and Diabetic Nephropathy
Authors: LIN HUGO YOU-HSIEN , CHEN YUMAY , CHEN YU-HAN , TA ALBERT , LEE HSIAOCHEN , WANG PING H. 
Published: June 2018

Diabetes increases the risks of ischemia/reperfusion kidney injury, but the etiology is not known. Mitochondrial dysfunction, which can be modulated by AKT1, may play a critical role in nephropathy and subsequent kidney failure. We hypothesized that impaired mitochondrial AKT1 signaling plays a mechanistic role in the pathogenesis of kidney injury. Insulin acutely stimulated AKT1 translocation from the cytosol to mitochondria in renal proximal tubules, however, the translocation was impaired in diet-induced diabetes. In our murine kidney ischemia-reperfusion injury (IRI) model (30 min ischemia followed by reperfusion), serum BUN increased by 2-fold (p=0.001) and creatinine by 5-fold (p=0.038). The Jablonski score of renal tubular injury was significantly elevated after reperfusion (24 hours, p=0.0004; 1 week, p=0.027). Renal fibrosis (% area) in the IRI mice was significantly higher than the sham control mice (p&lt;0.001). Rapid accumulation of phyosphorylated AKT1 in the mitochondria at proximal tubules were found 30 minutes (p=0.0303) and 60 minutes (p=0.0173) after IRI. AKT1 translocation to IRI renal tubule mitochondria was confirmed with confocal microscope and western blots of mitochondria proteins. To further dissect the role of mitochondrial AKT1 signaling during IRI in the renal tubules, we have generated novel renal tubule-specific transgenic mice harboring an inducible mitochondria-targeting dominant negative AKT1 (KiDAKT) with cre-lox strategy. After tamoxifen induction, markers for renal tubule injuries (KIM-1, and CD44) were significantly increased in the KiDAKT mice. Histology analysis confirmed renal injury with increased Jablonski score. Therefore, inhibition of mitochondrial AKT1 signaling led to development kidney injury. These findings shed new light into the mechanistic role of mitochondrial AKT1 in nephropathy, and mitochondria signaling may become a novel target to develop new strategies for the prevention and treatment of kidney diseases.

Disclosure
H. Lin: None. Y. Chen: None. Y. Chen: None. A. Ta: None. H. Lee: None. P.H. Wang: None.
A Low-Protein Calorie-Restricted Diet Attenuates Renal Injury and Facilitates Podocyte Autophagy in Type 2 Diabetic Rats
Authors: CHEN GUOFANG , GENG YAN , LIU CHAO 
Published: June 2018

Purpose: Caloric restrictionhas been shown to exert a renoprotective effect in diabetic rats. Dietary protein restriction slows the progression of nephropathy in diabetic patients.We explored whether a low-protein calorie-restricted (LPCR) diet reduces renal injury and whether the renoprotective effect of LPCR diet isrelated to the activation of podocyte autophagy.
Methods: The type 2 diabeticrat model was induced by a combination of high fat diet and low dose streptozotocin injection. The diabetic rats were randomly divided into 3 groups, normal protein (NP, 20% protein) group, low protein(LP, 8% protein) group and LPCR (8% protein, 30% restriction)group. Nondiabetic rats were used as normal control (NC). After 4 weeks of dietary intervention, urine albumin-to-creatinine ratio,creatinine clearance, serum creatinine, and kidney-to-body weight ratio, renal histologies, podocyte density, autophagy activity in glomeruli as well as glomerular basement membrane thickness and autophagic vacuoles in podocytesunder electron microscopy were estimated.
Results: TheLPCR-diettreated diabetic ratsexhibited reduced body weight, serum triglycerides, and fasting blood glucose levels, as well as improved insulin resistance comparedwith NP-diettreated diabetic rats. LPCR diet attenuated renal injury, includingpodocyte injury, in type 2 diabetic rats. The reduced number of autophagic vacuolesin podocytesand insufficient podocyte autophagyin type 2 diabetic rats were reversed by LPCR diet.
Conclusions: The findings suggest that a LPCR diet can ameliorate renal injury in type 2 diabetic rats, which maybe linked to the activation of podocyte autophagy.

Disclosure
G. Chen: None. Y. Geng: None. C. Liu: None.
Glycemic Index and Glycemic Load of the Diet in a Sample of Pregnant Women with Type 2 Diabetes Mellitus in Northwest Brazil
Authors: FACANHA CRISTINA , PASSOS TATIANA U. , MARANHÃO LIVIANE C. , COPPOLA FRANCIELLE C. , MARTINS JULIANA D. , MELO ANA E.F. , NOGUEIRA GERLIANO , SANTOS MILIANA D. , PONTES PEDRO A.C. , MORAIS LUCIANA M. , COSTA DOUGLAS D. 
Published: June 2018

During pregnancy, women with type 2 diabetes mellitus (DM2) needs specific dietary care to improve glycemic control and improve pregnancy outcomes. The recent updated researches points to dietary assessment and prescription based on glycemic index (GI) and glycemic load (GL) as possible strategies for achieving these goals. This study evaluated the GI and GL of the diet consumed by pregnant women with DM2. It is a quantitative-descriptive study, carried out in a diabetes treatment and care reference center in Brazil, with 20 DM2 pregnant women, randomly selected and interviewed during the outpatient routine visits follow-up. Dietary data were obtained in two 24-hour food recall (one weekday and one on weekend), one of that was collected by phone. These data were taken at home measurements and converted into grams/milliliters for subsequent determination of the GI and GL of the diets (protocol: FAO/WHO,1998) and classified according to Brand-Miller; Foster-Powell and Colagiuri (2003) and Burani (2006). Statistical analysis used the program S.P.S.S version 17, with the chi-square statistical test (p &lt;0.05). The diet of the pregnant women had a low GI (46.27 ± 7.18) and a low GL (64.15 ± 22.79). There was a positive relationship between schooling and GI, and the pregnant DM2 with a lower level of education consumed a moderate GI diet. Few studies have evaluated GI and GL in pregnancy and there are no studies with DM2 pregnant women. Similar studies point to the benefits of low GI and GL diets for glycemic control during gestation to decreased maternal-fetal comorbidities. The study population’s diet had adequate GI and CG, which promotes glycemic control and reduce adverse outcomes. However, it is suggested that larger dietary assessments be performed to further deepen the relationship between diet, metabolic control and pregnancy outcomes of woman with DM2.

Disclosure
C. Facanha: None. T.U. Passos: None. L.C. Maranhão: None. F.C. Coppola: None. J.D. Martins: None. A.E.F. Melo: None. G. Nogueira: None. M.D. Santos: None. P.A.C. Pontes: None. L.M. Morais: None. D.D. Costa: None.
CKD Prevalence and Risk Are Higher in Adults with Type 2 vs. Type 1 Diabetes-An Assessment of 1.5 Million Patients Recently Evaluated in U.S. Clinical Practices
Authors: CRESSMAN MICHAEL , ENNIS JENNIFER L. , GOLDSTEIN BARRY J. , GOURGIOTIS LOUKAS , LUO DAJIE , PURI MALA , GILLESPIE BARBARA 
Published: June 2018

Background: NHANES data (2009-2014) suggests that 25% of U.S. adults with diabetes have CKD (eGFR &lt; 60 ml/min/1.73m2 or ACR ≥ 30 mg/g). However, prevalence may be different among patients evaluated in clinical practice or in adults with T1D compared to T2D.
Methods: We utilized a clinical laboratory database maintained by LabCorp® to assess CKD prevalence and classified risk (low, moderate, high or very high) based on KDIGO criteria. The population included 48,036 adults with T1D and 1,461,915 with T2D who had both an ACR and a CKD-EPI eGFR between August 2014 and August 2017. Rates of eGFR decline were calculated for patients with ≥ 3 eGFR results over at least a 1 year period.
Results: CKD prevalence was 40% higher in T2D than T1D (44.3% vs. 31.6%, p&lt;0.001). The proportion classified as high or very high risk was also higher in T2D (17.8% vs. 12.0%, p&lt;0.001). Macroalbuminuria (MA), defined as an ACR &gt; 300, was uncommon (T1D: 7.8%, T2D: 8.3%); the majority with MA had an eGFR ≥ 60 (T1D: 60%, T2D: 53%). Median eGFR decline (ml/min/year) was low in the entire population (T1D: -0.6, T2D: -0.8), and in patients with ACR &lt; 30 (T1D: -0.34, T2D: -0.47) or ACR 30-300 (T1D: -0.97, T2D: - 1.06). However, median annual rates of decline in patients with MA were -3.80 in T1D and -3.58 in T2D.
Conclusions: These findings suggest that CKD prevalence and risk are higher in T2D than T1D among adult patients recently evaluated in U.S. clinical practices. Although MA is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1D and T2D. Availability of a large clinical laboratory database may add value when eligibility criteria, enrichment strategies, study endpoints or feasibility are assessed in clinical trials of patients with diabetes and CKD.

Disclosure
M. Cressman: Employee; Self; Covance Inc. J.L. Ennis: Employee; Self; LabCorp. Stock/Shareholder; Self; LabCorp. B.J. Goldstein: Employee; Self; Covance Inc.. L. Gourgiotis: None. D. Luo: None. M. Puri: Employee; Self; Covance Inc.. B. Gillespie: None.
Mechanisms of Therapeutic Effects of Conditioned Media from Cultured Dental Pulp Stem Cells on Diabetic Polyneuropathy
Authors: MAKINO ERIKO , NAKAMURA NOBUHISA , MIYABE MEGUMI , ITO MIZUHO , KANADA SAKI , HATA MASAKI , SAIKI TOMOKAZU , KAMIYA HIDEKI , NAKAMURA JIRO , MIYAZAWA KEN , GOTO SHIGEMI , MATSUBARA TATSUAKI , NARUSE KEIKO 
Published: June 2018

Stem cell transplantation is expected to become a novel therapy for diabetic polyneuropathy. Dental pulp stem cells (DPSC) are an attractive cell source because they can be easily isolated from teeth extracted for general orthodontic reasons. We reported earlier that DPSC transplantation was effective for diabetic polyneuropathy. However, most of the transplanted DPSCs from this study are gone from the transplanted site and the mechanism of cell transplantation may have been due to the abundant secreted factors from stem cells. We confirmed that conditioned media from DPSCs (DPSC-CM) ameliorated diabetic polyneuropathy. We, therefore, examined the mechanism of therapeutic effects of DPSC-CM on diabetic polyneuropathy.
DPSCs were isolated and cultured from the mandibular incisors of 6-week-old male Sprague-Dawly (SD) rats. Diabetes was induced at 6-weeks by administering STZ. DPSC-CM was administered to the unilateral hindlimb skeletal muscles of both the diabetic and normal rats 8 weeks after the administration of STZ, and the measurements were performed 4 weeks after DPSC-CM administration. Administration of DPSC-CM significantly improved the delay of the sciatic nerve motor/sensory conduction velocity and reduced sciatic nerve blood flow in diabetic rats. TNF-α and CD68 gene expression in the sciatic nerves tended to increase in the diabetic group, which showed a decreasing trend by administration of DPSC-CM. Capillary density in the hindlimb skeletal muscle was decreased in diabetic rats. DPSC-CM significantly increased capillary/muscle ratio in the hindlimb skeletal muscles in the diabetic rats. It was revealed that intramuscular administration of DPSC-CM was effective for diabetic polyneuropathy at least in part by improving nerve/muscle blood flow and suppressing inflammation. These results indicate that DPSC-CM could be a novel therapy for diabetic polyneuropathy.

Disclosure
E. Makino: None. N. Nakamura: None. M. Miyabe: None. M. Ito: None. S. Kanada: None. M. Hata: None. T. Saiki: None. H. Kamiya: Other Relationship; Self; MSD K.K., Ono Pharmaceutical Co., Ltd., Sanofi K.K., AstraZeneca, Astellas Pharma KK, Eli Lilly and Company, Novartis Pharma K.K., Dainippon Sumitomo Pharma Co., Ltd, Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd. J. Nakamura: Other Relationship; Self; Astellas Pharma US, Inc., AstraZeneca, Ono Pharmaceutical Co., Ltd., MSD K.K., Kyowa Hakko Kirin Co., Ltd., Kowa Pharmaceuticals America, Inc., Sanofi K.K., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Mitsubishi Tanabe Pharma Corporation, Eli Lilly and Company, Novartis Pharma K.K., Pfizer Inc.. K. Miyazawa: None. S. Goto: None. T. Matsubara: None. K. Naruse: None.