Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
One example is below.
Q: In 1582 the united provinces invited francis, duke of anjou to lead them; but after a failed attempt to take antwerp in 1583, the duke left the netherlands again. after the assassination of william of orange (10 july 1584), both henry iii of france and elizabeth i of england declined the offer of sovereignty. however, the latter agreed to turn the united provinces into a protectorate of england (treaty of nonsuch, 1585), and sent the earl of leicester as governor-general. this was unsuccessful and in 1588 the provinces became a confederacy. the union of utrecht is regarded as the foundation of the republic of the seven united provinces, which was not recognized by the spanish empire until the peace of westphalia in 1648.
A: In what year did francis, duke of anjou leave the netherlands?
Rationale: The generated question is perfect. Because the question is based on second sentence of the input passage and its answer is 1583.
Q: Restless legs syndrome is a neurological disorder characterized by an urgency to move the legs during periods of rest. Data from a variety of sources provide a compelling argument that the amount of iron in the brain is lower in individuals with restless legs syndrome compared with neurologically normal individuals. Moreover, a significant percentage of patients with restless legs syndrome are responsive to intravenous iron therapy. The mechanism underlying the decreased iron concentrations in restless legs syndrome brains is unknown. We hypothesize that the source of the brain iron deficit is at the blood-brain interface. Thus we analysed the expression of iron management proteins in the epithelial cells of the choroid plexus and the brain microvasculature in post-mortem tissues. The choroid plexus, obtained at autopsy, from 18 neurologically normal controls and 14 individuals who had primary restless legs syndrome was subjected to histochemical staining for iron and immunostaining for iron management proteins. Iron and heavy chain ferritin staining was reduced in the epithelial cells of choroid plexus in restless legs syndrome. Divalent metal transporter, ferroportin, transferrin and its receptor were upregulated in the choroid plexus in restless legs syndrome. Microvessels were isolated from the motor cortex of 11 restless legs syndrome and 14 control brains obtained at autopsy and quantitative immunoblot analyses was performed. Expression of heavy chain ferritin, transferrin and its receptor in the microvessels from restless legs syndrome was significantly decreased compared with the controls but divalent metal protein 1, ferroportin, prohepcidin, mitochondrial ferritin and light-chain ferritin remained unchanged. The presence of an iron regulatory protein was demonstrated in the brain microvasculature and the activity of this protein is decreased in restless legs syndrome; a finding similar to our earlier report in neuromelanin cells from the substantia nigra of restless legs syndrome brains. This study reveals that there are alterations in the iron management protein profile in restless legs syndrome compared with controls at the site of blood-brain interface suggesting fundamental differences in brain iron acquisition in individuals with restless legs syndrome. Furthermore, the decrease in transferrin receptor expression in the microvasculature in the presence of relative brain iron deficiency reported in restless legs syndrome brains may underlie the problems associated with brain iron acquisition in restless legs syndrome. The consistent finding of loss of iron regulatory protein activity in restless legs syndrome brain tissue further implicates this protein as a factor in the underlying cause of the iron deficiency in the restless legs syndrome brain. The data herein provide evidence for regulation of iron uptake and storage within brain microvessels that challenge the existing paradigm that the blood-brain barrier is merely a transport system.
A:
Which deficiency is the cause of restless leg syndrome?