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.

Q: Context: Early metastasis in node-negative breast cancer indicates that breast cancer cells obviously can bypass the lymph nodes and disseminate directly hematogenous to distant organs. For this purpose, we evaluated the prognostic value of blood-borne, HER2-positive circulating tumor cells (CTC) in the peripheral blood from 42 breast cancer patients with a median follow-up of 95 months.', 'Cells were isolated by the patented combined buoyant density gradient and immunomagnetic separation procedure and analyzed by immunocytochemistry.', 'We detected one to eight CTCs in the peripheral blood of 17 of 35 patients (48.6%) presenting no overt metastasis. As a positive control, 7 of 7 (100%) patients with metastatic disease presented positive. Healthy persons and patients (n = 32) operated for nonmalignant diseases presented negative for CTCs. The presence and frequency of HER2-positive CTCs correlated with a significantly decreased disease-free survival (P < 0.005) and overall survival (P < 0.05). Interestingly, in 12 patients with HER2-positive CTCs, the primary tumor was negative for HER2 as assessed by immunohistochemical score and fluorescence in situ hybridization.
Answer: This study provides some evidence of a prognostic effect of HER2-positive CTCs in stage I to III breast cancer. Future studies have to determine the outcome of patients treated with HER2-targeting therapies with respect to HER2-positive CTC levels because it is not unlikely that high levels of HER2-positive CTCs reflect the activity of the tumor and may predict response to trastuzumab.

A: Do hER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients?
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Q: Context: The etiology of reduced left ventricular (LV) ejection fraction after exercise, without obstructive coronary artery disease or other established causes, is unclear. The aims of this study were to determine whether patients undergoing treadmill stress echocardiography with this abnormal LV contractile response to exercise (LVCRE) without established causes have resting LV long-axis dysfunction or microvascular dysfunction and to determine associations with this abnormal LVCRE.', 'Of 5,275 consecutive patients undergoing treadmill stress echocardiography, 1,134 underwent cardiac computed tomography angiography or invasive angiography. Having excluded patients with obstructive coronary artery disease, hypertensive response, submaximal heart rate response, resting LV ejection fraction < 50%, and valvular disease, 110 with "abnormal LVCRE" and 212 with "normal LVCRE" were analyzed. Resting mitral annular velocities were measured to assess LV long-axis function. Myocardial blush grade and corrected Thrombolysis In Myocardial Infarction frame count were determined angiographically to assess microvascular function.', "Comparing normal LVCRE with abnormal LVCRE, age (mean, 59.7 11.1 vs 61.4 10.0 years), hypertension (53% vs 55%), diabetes (16% vs 20%), and body mass index (mean, 29.1 5.4 vs 29.5 6.4 kg/m(2)) were similar (P > .05). Abnormal LVCRE had reduced resting LV long-axis function with lower septal (mean, 6.1 1.9 vs 7.7 2.2 cm/sec) and lateral (mean, 8.1 2.9 vs 10.4 3.0 cm/sec) e' velocities (P < .001) and larger resting left atrial volumes (mean, 37.3 10.1 vs 31.1 7.2 mL/m(2), P < .001). On multivariate analysis, female gender (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.15-1.99; P < .001), exaggerated chronotropic response (OR, 1.49; 95% CI, 1.09-2.05; P < .001), resting left atrial volume (OR, 2.38; 95% CI, 1.63-3.47; P < .001), and resting lateral e' velocity (OR, 1.70; 95% CI, 1.22-2.49; P = .003) were associated with abnormal LVCRE, but not myocardial blush grade or corrected Thrombolysis In Myocardial Infarction frame count.
Answer: An abnormal LVCRE in the absence of established causes is associated with resting LV long-axis dysfunction and is usually seen in women.

A: Is abnormal left ventricular contractile response to exercise in the absence of obstructive coronary artery disease associated with resting left ventricular long-axis dysfunction?
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Q: Context: The aim of the present study was to study patterns in the extended spectrum of the human hearing (0.125 to 20 kHz) in order to obtain reference thresholds. Then, we compare our values with existing results at extended high-frequencies (8 to 20 kHz) in an attempt to establish new standards for potential international adoption.', 'A prospective study in a group of otologically healthy subjects.', 'A total of 645 subjects aged between 5 and 90 years were recruited. Pure-tone thresholds were determined for conventional and extended high-frequencies.', 'There was an increase in the hearing thresholds as a function of frequency and age. For the 20 to 69 years old group, thresholds were lower in females than in males, especially at 12.5 and 16 kHz. Our threshold values are comparable to those presented in previous studies that used different instrumentation and populations.
Answer: When comparing different studies the hearing thresholds were found to be similar. Therefore, it would be possible to establish international standard thresholds.

A:
Do extended high-frequency ( 9-20 kHz ) audiometry reference thresholds in 645 healthy subjects?
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