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.

Ex Input:
Context: BAF312 (Siponimod) is a dual agonist at the sphingosine-1 phosphate receptors, S1PR1 and S1PR5. This drug is currently undergoing clinical trials for the treatment of secondary progressive multiple sclerosis (MS). Here, we investigated the effects of BAF312 on isolated astrocyte and microglia cultures as well as in slice culture models of demyelination.', 'Mouse and human astrocytes were treated with S1PR modulators and changes in the levels of pERK, pAkt, and calcium signalling as well as S1PR1 internalization and cytokine levels was investigated using Western blotting, immunochemistry, ELISA and confocal microscopy. Organotypic slice cultures were prepared from the cerebellum of 10-day-old mice and treated with lysophosphatidylcholine (LPC), psychosine and/or S1PR modulators, and changes in myelination states were measured by fluorescence of myelin basic protein and neurofilament H.', 'BAF312 treatment of human and mouse astrocytes activated pERK, pAKT and Ca(2+) signalling as well as inducing S1PR1 internalization. Notably, activation of S1PR1 increased pERK and pAKT in mouse astrocytes while both S1PR1 and S1PR3 equally increased pERK and pAKT in human astrocytes, suggesting that the coupling of S1PR1 and S1PR3 to pERK and pAKT differ in mouse and human astrocytes. We also observed that BAF312 moderately attenuated lipopolysaccharide (LPS)- or TNFα/IL17-induced levels of IL6 in both astrocyte and microglia cell cultures. In organotypic slice cultures, BAF312 reduced LPC-induced levels of IL6 and attenuated LPC-mediated demyelination. We have shown previously that the toxic lipid metabolite psychosine induces demyelination in organotypic slice cultures, without altering the levels of cytokines, such as IL6. Importantly, psychosine-induced demyelination was also attenuated by BAF312.
Answer: Overall, this study suggests that BAF312 can modulate glial cell function and attenuate demyelination, highlighting this drug as a further potential therapy in demyelinating disorders, beyond MS.

Ex Output:
Does the dual S1PR1/S1PR5 drug BAF312 ( Siponimod ) attenuate demyelination in organotypic slice cultures?


Ex Input:
Context: Increased concentrations of metalloproteinases are associated with the invasive and metastatic behavior of several human malignant tumors. Normally, enzymatic activity is tightly regulated by nonspecific mechanisms and specific inhibitors. The aim of the study was to determine the potential of a synthetic metalloproteinase inhibitor, batimastat, to show its in vitro effect on MatLyLu cancer cells and its in vivo effect on tumor growth in orthotopic cancer (R3327 Dunning tumor) in rats.', 'In vitro, a dose response curve of batimastat was generated over 4 days using the MTT assay. Prostate cancer was injected in vivo in male Copenhagen rats by inoculating R3327 Dunning tumor cells (MatLyLu) into the ventral prostatic lobe of 30 rats. Each of 10 rats received batimastat (30 mg/kg body weight) or vehicle administered once a day by i.p. application beginning the day of cell inoculation. Ten rats remained untreated. The effect on local tumor growth was evaluated by measuring tumor weights 20 days after tumor cell inoculation.', 'Significant inhibition of tumor cell proliferation in vitro occurred at 400 and 4,000 ng/ml batimastat. After orthotopic cell inoculation, tumors grew to mean weights of 18.9 g in the control group without treatment, to 22.3 g in the vehicle group, and to 11.1 g in the treated group. In comparison to the control group and to the vehicle group, tumor weights increased significantly less under treatment with batimastat.
Answer: Batimastat is able to reduce tumor growth in the standard prostate cancer model. Using this model, activity against cancer progression of future inhibitory agents can be reliably assessed.

Ex Output:
Does synthetic inhibitor of matrix metalloproteinases ( batimastat ) reduce prostate cancer growth in an orthotopic rat model?


Ex Input:
Context: Trauma centers often receive transfers from lower-level trauma centers or nontrauma hospitals. The aim of this study was to analyze the incidence and pattern of secondary overtriage to our Level I trauma center.', 'We performed a 2-year retrospective analysis of all trauma patients transferred to our Level I trauma center and discharged within 24 hours of admission. Reason for referral, referring specialty, mode of transport, and intervention details were collected. Outcomes measures were incidence of secondary overtriage as well as requirement of major or minor procedure. Major procedure was defined as surgical intervention in the operating room. Minor procedures were defined as procedures performed in the emergency department.', 'A total of 1,846 patients were transferred to our Level I trauma center, of whom 440 (24%) were discharged within 24 hours of admission. The mean (SD) age was 35 (21) years, 72% were male, and mean (SD) Injury Severity Score (ISS) 4 (4). The most common reasons for referral were extremity fractures (31%), followed by head injury (23%) and soft tissue injuries (13%).Of the 440 patients discharged within 24 hours, 380 (86%) required only observation (268 of 380) or minor procedure (112 of 380). Minor procedures were entirely consisted of fracture management (n = 47, 42%) and wound care (n = 65, 58%). The mean (SD) interfacility transfer distance was 45 (46) miles. Mean (SD) hospital charges per transfer were $12,549 ($5,863).
Answer: A significant number of patients transferred to our trauma center were discharged within 24 hours; most of them required observation and/or minor procedures. Appropriately increasing primary hospital resources, in addition to interhospital outreach in the form of education or telemedicine, should be considered to decrease the number of avoidable transfers.

Ex Output:

Do a critical analysis of secondary overtriage to a Level I trauma center?