Given a passage, 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: To correlate cerebral cavernous malformations (CCMs) disease aggressiveness with peripheral blood biomarkers hypothesized mechanistically.', 'A prospective case-control study enrolled 43 CCM patients, where 25-(OH) vitamin D, HDL and non-HDL cholesterol, CRP plasma levels and leukocyte ROCK activity were correlated with parameters of disease aggressiveness reflecting chronic and acute domains.', 'Patients with one or more features of chronically aggressive disease (early age at symptom onset, two or more symptomatic bleeds, high lesion burden) had significantly lower 25-(OH) vitamin D and non-HDL cholesterol levels in comparison to patients without these features.

Output: Do peripheral plasma vitamin D and non-HDL cholesterol reflect the severity of cerebral cavernous malformation disease?


Input: Consider Input: Corticotropin-releasing factor (CRF) is the primary physiologic regulator of the hypothalamic-pituitary-adrenal (HPA) axis and serves to globally coordinate the mammalian stress response. Hyperactivity of central nervous system CRF neurotransmission, acting primarily via the CRF(1) receptor, has been strongly implicated in the pathophysiology of depression and anxiety. Furthermore, there is evidence of enhanced CRF transcription, release, and neuronal activity after the administration of and withdrawal from several drugs of abuse, including cannabis, cocaine, ethanol, and morphine. Treatment with CRF antagonists has been demonstrated to reduce the severity of certain drug withdrawal symptoms, implicating a specific role for activation of CRF neurons in mediating the anxiogenic and stress-like reactions observed after abrupt drug discontinuation.', 'To extend these findings, we investigated whether pretreatment with the selective CRF(1) receptor antagonist R121919 decreases the behavioral and neuroendocrine activation observed after the precipitation of benzodiazepine (BZ) withdrawal in BZ-dependent rats.', 'Pretreatment with R121919 attenuated the subsequent HPA axis activation, behavioral measures of anxiety, and expression of the CRF gene in the paraventricular nucleus of the hypothalamus, as measured by CRF heteronuclear RNA, which occurs after flumazenil-precipitation of withdrawal from the BZ, lorazepam.

Output: Does the CRF1 receptor antagonist R121919 attenuate the neuroendocrine and behavioral effects of precipitated lorazepam withdrawal?


Input: Consider Input: The aim of this study is to investigate the prognostic relevance of the best objective response of metastatic target lesions during sunitinib treatment in patients with metastatic renal cell carcinoma.', 'Radiographic analysis of the best objective response according to the Response Evaluation Criteria in Solid Tumors was assessed in 50 patients. Clinicopathological characteristics including the Heng risk classification and sunitinib-related adverse reactions were compared among four patient subgroups [complete response or partial response (CR/PR), stable disease (SD), progressive disease (PD), and those without treatment evaluation (NE)]. Kaplan-Meier and Cox proportional regression analyses of progression-free survival and overall survival were performed to identify prognostic variables.', 'The best objective response was CR/PR in 12 (24\xa0%) patients, SD in 22 (44\xa0%), PD in 6 (12\xa0%), and NE in 10\xa0(20\xa0%). The incidence of hypertension and hypothyroidism was associated with a better objective response. Progression-free survival was 15.0, 9.2, 6.8, and 2.2\xa0months in the CR/PR, SD, PD, and NE groups, respectively (P\xa0=\xa00.0004, log-rank test), while the corresponding median overall survival was 59.7, 24.2, 17.1, and 18.1\xa0months, respectively (P\xa0=\xa00.007). Multivariate analysis revealed that hazard ratios for risk of death of the SD, PD, and NE groups were 4.51 (P\xa0=\xa00.06), 7.93 (P\xa0=\xa00.02), and 4.88 (P\xa0=\xa00.04), respectively, as compared to the CR/PR group.


Output: Are the best objective response of target lesions and the incidence of treatment-related hypertension associated with the survival of patients with metastatic renal cell carcinoma treated with sunitinib : a Japanese retrospective study?