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: Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8\xa0wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention.', 'Volunteers were supplemented daily with 36\xa0mg/kg body weight (BW) of GAA for the first 4\xa0wk of the intervention; afterward GAA dosage was titrated ≤60\xa0mg/kg BW of GAA daily. At baseline, 4, and 8\xa0wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity.', 'Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4\xa0wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P\xa0<\xa00.05). Thalamus creatine levels decreased after 4\xa0wk for 6.5% (P\xa0=\xa00.02), and increased nonsignificantly after 8\xa0wk for 8% (P\xa0=\xa00.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P\xa0<\xa00.05). No participants reported any neurologic adverse event (e.g., seizures, tingling, convulsions) during the intervention.
Answer: Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative diseases, brain tumors, or cerebrovascular disease.

Output: Does dietary guanidinoacetic acid increase brain creatine levels in healthy men?


Input: Consider Input: Context: Cancer cells frequently exhibit resistance to the cytotoxic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Pretreatment of TRAIL-resistant cells with cisplatin sensitizes them to this ligand. Cisplatin also has been shown to enhance adenoviral transgene expression.', 'This study aims to evaluate the ability of cisplatin to enhance the expression and the cytotoxic effect of the tumor-specific adenoviral vector Ad/gTRAIL, which expresses a green fluorescent protein-TRAIL fusion protein.', 'Cultured cancer cells and normal human cells were infected with Ad/gTRAIL with or without cisplatin pretreatment. Adenoviral transgene expression was determined by using flow cytometry to measure green fluorescent protein fluorescence. Cytotoxicity was measured by using thiazolyl blue tetrazolium bromide assays and an apoptosis enzyme-linked immunosorbent assay kit.', 'Green fluorescent protein-TRAIL fusion protein expression was significantly enhanced by cisplatin pretreatment in cancer cells. Cisplatin treatment before Ad/gTRAIL infection resulted in a 2- to 12-fold increase in green fluorescent protein fluorescence intensity across cancer lines. Although Ad/gTRAIL induced mild cytotoxicity in all cancer lines (inhibitory concentration of 50% values of >500 pfu/cell), pretreatment with cisplatin resulted in a dose-dependent enhancement of Ad/gTRAIL-mediated cytotoxicity, as indicated by the drastic reduction of inhibitory concentration of 50% values to 4 to 42 pfu/cell in all cell lines. There was no cytotoxicity noted in normal cells treated with both cisplatin and Ad/gTRAIL.
Answer: Cisplatin pretreatment enhances Ad/gTRAIL cytotoxicity in malignant cells while not affecting normal cells. The mechanisms underlying this effect might include both enhancement of the susceptibility of cisplatin-treated cells to TRAIL and cisplatin-mediated enhancement of TRAIL expression in Ad/gTRAIL infected cells. These findings provide a rationale for development of Ad/gTRAIL-based therapy for thoracic malignancies.

Output: Does cisplatin enhance apoptosis induced by a tumor-selective adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand?


Input: Consider Input: Context: To compare the relative value of magnetic resonance imaging (MRI) in biopsy-naive patients to those with previous negative biopsy. Although MRI-targeted biopsy has been studied in several major prostate cancer (PCa) cohorts (biopsy naive, previous negative biopsy, and active surveillance), the relative benefit in these cohorts has not been established.', 'We retrospectively reviewed biopsy-naive (n = 45) and previous negative biopsy (n = 55) patients who underwent prostate MRI prior to biopsy at our institution. Patients with an MRI suspicious region (MSR) underwent MRI-targeted biopsy as well as a systematic template biopsy, whereas those without MSR underwent only the template biopsy. All biopsies were performed with the TargetScan (Envisioneering, Pittsburgh, PA) biopsy system. MRI targeting was performed with cognitive guidance.', 'On multivariate logistic regression, the presence of an MSR was the only statistically significant and independent predictor of Gleason ≥ 7 PCa on biopsy for biopsy-naive men (odds ratio [OR] 40.2, P = .01). For men with previous negative biopsy, the presence of MSR was not a predictor of Gleason ≥ 7 PCa on biopsy (OR 4.35, P = .16), whereas PSA density > 0.15 ng/mL(2) was a significant and independent predictor (OR 66.2, P < .01).
Answer: Prostate MRI should be considered prior to biopsy in all patients presenting with clinical suspicion for PCa, as presence of a MSR will help guide prebiopsy counseling and provide an opportunity for MRI targeting during biopsy.


Output: Does presence of Magnetic Resonance Imaging Suspicious Lesion predict Gleason 7 or Greater Prostate Cancer in Biopsy-Naive Patients?