Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

Fibroblasts (FIBs) within the retro-orbital space of patients with Graves' disease (GOFs) express thyrotropin receptors (TSHRs) and are thought to be an orbital target of TSHR-stimulating autoantibodies in Graves' ophthalmopathy (GO). Recently, we developed a low molecular weight, drug-like TSHR antagonist (NCGC00229600) that inhibited TSHR activation in a model cell system overexpressing TSHRs and in normal human thyrocytes expressing endogenous TSHRs. Herein, we test the hypothesis that NCGC00229600 will inhibit activation of TSHRs endogenously expressed in GOFs.", 'Three strains of GOFs, previously obtained from patients with GO, were studied as undifferentiated FIBs and after differentiation into adipocytes (ADIPs), and another seven strains were studied only as FIBs. ADIP differentiation was monitored by morphology and measurement of adiponectin mRNA. FIBs and ADIPs were treated with the TSH- or TSHR-stimulating antibody M22 in the absence or presence of NCGC00229600 and TSHR activation was monitored by cAMP production.', 'FIBs contained few if any lipid vesicles and undetectable levels of adiponectin mRNA, whereas ADIPs exhibited abundant lipid vesicles and levels of adiponectin mRNA more than 250,000 times greater than FIBs; TSHR mRNA levels were 10-fold higher in ADIPs than FIBs. FIBs exhibited higher absolute levels of basal and forskolin-stimulated cAMP production than ADIPs. Consistent with previous findings, TSH stimulated cAMP production in the majority of ADIP strains and less consistently in FIBs. Most importantly, NCGC00229600 reduced both TSH- and M22-stimulated cAMP production in GOFs.
0

The aim of the current study was to characterize β-cell function, insulin sensitivity and line of inheritance in patients with recent-onset type 2 diabetes of Yemenite and non-Yemenite Jewish origin.', 'A cohort study including 121 GAD negative diabetic patients, 59 of Yemenite and 62 of non-Yemenite origin, treated by diet\xa0±\xa0oral antihyperglycemic monotherapy who underwent 180-min meal tolerance test (MMT). Based on MMT, indexes of insulin resistance and secretion were calculated.', 'There were no significant differences in age, sex, diabetes duration, BMI, HbA1c and lipid profile. A significant difference was found in family history of diabetes: 63\xa0% of patients of Yemenite origin had maternal inheritance versus 35\xa0% in the non-Yemenite origin (p\xa0<\xa00.001). Both indexes of β-cell function, the insulinogenic and the disposition indexes were significantly lower in patients of Yemenite origin compared with non-Yemenite origin (0.66\xa0±\xa00.4 vs. 0.93\xa0±\xa00.8, p\xa0=\xa00.04; 2.3\xa0±\xa01.8 vs. 3.3\xa0±\xa03.3, p\xa0=\xa00.04, respectively) with no difference in insulin sensitivity. When females and males were analyzed separately, the difference in maternal inheritance remained significant in both, but the difference in β-cell function indexes was observed only in males (p\xa0=\xa00.03, p\xa0=\xa00.01, respectively).
1

Serum α-hydroxybutyrate (α-HB) is elevated in insulin resistance and diabetes. We tested the hypothesis that the α-HB level predicts abnormal 1\u2005h glucose levels and β-cell dysfunction inferred from plasma insulin kinetics during a 75\u2005g oral glucose tolerance test (OGTT).', 'This cross-sectional study included 217 patients at increased risk for diabetes. 75\u2005g OGTTs were performed with multiple postload glucose and insulin measurements over a 30-120\u2005min period. OGTT responses were analyzed by repeated measures analysis of variance (ANOVA). Multivariable logistic regression was used to predict 1\u2005h glucose ≥155\u2005mg/dL with α-HB added to traditional risk factors.', 'Mean±SD age was 51±15\u2005years (44% male, 25% with impaired glucose tolerance). Fasting glucose and insulin levels, but not age or body mass index (BMI), were significantly higher in the second/third α-HB tertiles (>3.9\u2005µg/mL) than in the first tertile. Patients in the second/third α-HB tertiles exhibited a higher glucose area under the receiver operating characteristics curve (AUC) and reduced initial slope of insulin response during OGTT. The AUC for predicting 1\u2005h glucose ≥155\u2005mg/dL was 0.82 for a base model that included age, gender, BMI, fasting glucose, glycated hemoglobin (HbA1c), and insulin, and increased to 0.86 with α-HB added (p=0.015), with a net reclassification index of 52% (p<0.0001).

1