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.

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

Example Input: Context: Normal glucose metabolism depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilisation, glucagon excess is the principal factor in diabetic glucose overproduction. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance. We investigated the impact of acute disruption of glucagon secretin or action in a mouse model of severe diabetes by three different approaches: (1) alpha cell elimination; (2) glucagon immunoneutralisation; and (3) glucagon receptor antagonism, in order to evaluate the effect of these on glucose tolerance.', 'Severe diabetes was induced in transgenic and wild-type mice by streptozotocin. Glucose metabolism was investigated using OGTT in transgenic mice with the human diphtheria toxin receptor expressed in proglucagon producing cells allowing for diphtheria toxin (DT)-induced alpha cell ablation and in mice treated with either a specific high affinity glucagon antibody or a specific glucagon receptor antagonist.', 'Near-total alpha cell elimination was induced in transgenic mice upon DT administration and resulted in a massive decrease in pancreatic glucagon content. Oral glucose tolerance in diabetic mice was neither affected by glucagon immunoneutralisation, glucagon receptor antagonism, nor alpha cell removal, but did not deteriorate further compared with mice with intact alpha cell mass.
Answer: Disruption of glucagon action/secretion did not improve glucose tolerance in diabetic mice. Near-total alpha cell elimination may have prevented further deterioration. Our findings support insulin lack as the major factor underlying hyperglycaemia in beta cell-deficient diabetes.
Example Output: Does acute disruption of glucagon secretion or action improve glucose tolerance in an insulin-deficient mouse model of diabetes?

Example Input: Context: Child maltreatment is associated with dysregulation of stress-mediating systems and an increased risk of mental and physical health problems. Specifically, disruptions in hypothalamic-pituitary-adrenal (HPA) axis regulation have been reported in maltreated children. The current study investigates whether increased cortisol variability is responsible for inconsistent patterns in the literature.', 'This study modeled cortisol activity over 20 weeks in 187 maltreated and 154 nonmaltreated children (mean = 8.4 years, SD = 1.8 years) in order to capture week-to-week cortisol patterns. Maltreatment was assessed through coding of Department of Human Services records. Children attended an after-school program 1 day per week for 20 weeks, where saliva was collected at the same time each day and subsequently assayed for cortisol.', "Multiple-group growth curves indicated that maltreated and non-maltreated children differ in longitudinal cortisol patterns. Maltreated children showed higher variance in the initial cortisol levels and slope over time compared to nonmaltreated children, indicating greater between-person variability in the maltreated group. Maltreated children with higher cortisol at the first assessment showed cortisol suppression over time, indicating potential HPA blunting after chronic high cortisol levels. The severity, timing, and number of subtypes of maltreatment predicted individuals' cortisol variability, and both maltreatment status and greater cortisol variability predicted more behavior problems.
Answer: Interventions for maltreated children may benefit from pre- and post-intervention HPA assessments to determine a component of treatment efficacy. As maltreatment dimensions predicted differential cortisol regulation, assessment of maltreatment experiences is necessary to understand alterations in behavior and HPA regulation post-intervention.
Example Output:
Do longitudinal patterns of cortisol regulation differ in maltreated and nonmaltreated children?