Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Input: Consider Input: Context: PTH stimulates bone formation in Fgfr3 knockout mice through promotion of proliferation and differentiation in osteoblasts.', 'Previous studies showed that endogenous fibroblast growth factor 2 (FGF-2) is required for parathyroid hormone (PTH)-stimulated bone anabolic effects, however, the exact mechanisms by which PTH stimulate bone formation and the function of FGF receptors in mediating these actions are not fully defined. FGF receptor 3 (FGFR3) has been characterized as an important regulator of bone metabolism and is confirmed to cross-talk with PTH/PTHrP signal in cartilage and bone development.', 'Fgfr3 knockout and wild-type mice at 2-month-old and 4-month-old were intraperitoneally injected with PTH intermittently for 4 weeks and then the skeletal responses to PTH were assessed by dual energy X-ray absorptiometry (DEXA), micro-computed tomography (CT) and bone histomorphometry.', 'Intermittent PTH treatment improved bone mineral density (BMD) and femoral mechanical properties in both Fgfr3 (-/-) and wild-type mice. Histomorphometric analysis showed that bone formation and bone resorption were increased in both genotypes following PTH treatment. PTH treatment increased trabecular bone volume (BV/TV) in WT and Fgfr3-deficient mice. The anabolic response in Fgfr3-deficient and wild-type bone is characterized by an increase of both bone formation and resorption-related genes following PTH treatment. In addition, we found that Fgfr3 null osteoblasts (compared to wild-type controls) maintained normal abilities to response to PTH-stimulated increase of proliferation, differentiation, expression of osteoblastic marker genes (Cbfa1, Osteopontin and Osteocalcin), and phosphorylation of Erk1/2.
Answer: Bone anabolic effects of PTH were not impaired by the absence of FGFR3, suggesting that the FGFR3 signaling may not be required for osteoanabolic effects of PTH activities.

Output: Does fibroblast Growth Factor Receptor 3 Deficiency Impair the Osteoanabolic Action of Parathyroid Hormone on Mice?

Input: Consider Input: Context: After ingestion of phosphatidylcholine, l-carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk.', 'A newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease.', "Betaine concentrations in males were significantly higher than in females (42.0 vs. 35.9mol/L; p<0.001). Plasma concentrations of TMAO but not of betaine or choline were higher in patients with diabetes compared to euglycemic patients (2.39 vs. 0.980mol/L; p=0.001) as well as in patients with metabolic syndrome as compared to patients without metabolic syndrome (2.37 vs. 1.43mol/L; p=0.002). Plasma concentrations of TMAO or choline increased significantly with decreasing renal function (Spearman's rho:-0.281; p<0.001). However, plasma levels of TMAO or betaine were associated with neither a history of myocardial infarction nor the angiographically assessed presence of coronary heart disease, nor incident cardiovascular events during 8 years of follow-up. Plasma levels of choline were significantly lower in patients with a history of acute myocardial infarction as compared to those without such history (10.0 vs. 10.8mol/L; p=0.045).
Answer: Plasma levels of TMAO are confounded by impaired kidney function and poor metabolic control but are not associated with the history, presence or incidence of symptoms or events of coronary heart disease.

Output: Are plasma levels of trimethylamine-N-oxide confounded by impaired kidney function and poor metabolic control?

Input: Consider Input: Context: Total bilirubin (TB) was recently recognized as an endogenous anti-inflammatory and anti-oxidant molecule. Uric acid (UA) takes part in cardiovascular diseases by inducing oxidative stress, inflammation, and endothelial dysfunction. We assessed the relationship between serum TB levels, serum UA levels, and inflammatory status assessed by neutrophil-to-lymphocyte ratio (N/L) and arterial stiffness and arterial wave reflection in patients with a clinical diagnosis of coronary artery disease (CAD).', 'We included 145 consecutive patients admitted with stable angina pectoris (SAP) or acute coronary syndrome (ACS). Blood samples were drawn at admission for complete blood count and biochemistry. Non-invasive pulse waveform analysis for the determination of augmentation index (AIx) and carotid-femoral pulse wave velocity (PWV) measurements were performed with the commercially available SphygmoCor system.', 'When patients were divided into tertiles of PWV and AIx, median N/L and median serum UA levels were the highest and mean TB levels were the lowest in the third tertile (p<0.001 for all). AIx and PWV were positively associated with serum UA and N/L and negatively associated with serum TB levels (p<0.001 for all). After adjustments for age, gender, heart rate, systolic blood pressure, and presence of diabetes, significant correlations persisted for N/L, UA, and TB in ACS patients (p<0.05). In the SAP group, TB was significantly negatively correlated with AIx and PWV, and UA was significantly positively correlated with PWV (p<0.05).
Answer: N/L ratio and serum UA and TB levels might be used to risk-stratify patients with respect to arterial stiffness in CAD patients, especially in the presence of ACS.
Output: Are arterial stiffness and central arterial wave reflection associated with serum uric acid , total bilirubin , and neutrophil-to-lymphocyte ratio in patients with coronary artery disease?