TASK DEFINITION: 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.
PROBLEM: Context: Biological evidence reported in the literature supports the role of CELSR1 as being essential for valvular function in murine lymphatics. Yet thus far, there have been no variants in CELSR1 associated with lymphatic dysfunction in humans.', 'In this report, a rare early inactivating mutation in CELSR1 is found to be causal for non-syndromic, lower extremity lymphedema in a family across three generations. Near-infrared fluorescence lymphatic imaging shows that instead of being propelled within the lumen of well-defined lymphatic vessels, lymph moved in regions of both legs in an unusual fashion and within sheet-like structures.
Answer: CELSRI may be responsible for primary, non-syndromic lymphedema in humans.

SOLUTION: Is a novel mutation in CELSR1 associated with hereditary lymphedema?

PROBLEM: Context: There is a strong association between migraine and depression. The aim of this study is to identify migraine-specific factors involved in this association.', 'We conducted a cross-sectional study in a large, well-defined cohort of migraine patients (n=2533). We assessed lifetime depression using validated questionnaires, and diagnosed migraine based on the International Classification of Headache Disorders III-beta criteria. Multivariate regression analyses were conducted.', 'Of the 2533 migraineurs that were eligible, 1137 (45%) suffered from lifetime depression. The following independent factors were associated with an increased depression prevalence: i) migraine-specific risk factors: high migraine attack frequency and the presence of allodynia, ii) general factors: being a bad sleeper, female gender, high BMI, being single, smoking, and a low alcohol consumption.
Answer: This study identified allodynia, in addition to high migraine attack frequency, as a new migraine-specific factor associated with depression.

SOLUTION: Is allodynia associated with a higher prevalence of depression in migraine patients?

PROBLEM: Context: Chronic high-frequency electrical deep brain stimulation (DBS) of the subcallosal cingulate region is currently being investigated clinically as a therapy for treatment of refractory depression. Experimental DBS of the homologous region, the ventromedial prefrontal cortex (VMPFC), in rodent models has previously demonstrated anti-depressant-like effects. Our goal was to determine if structural remodeling accompanies the alterations of brain function previously observed as a result of chronic DBS.', 'Here we applied 6h of high-frequency bilateral VMPFC DBS daily to 8 9-week old C57Bl/6 mice for 5days. We investigated the "micro-lesion" effect by using a sham stimulation group (8 mice) and a control group (8 mice with a hole drilled into the skull only). Whole brain anatomy was investigated post-mortem using high-resolution magnetic resonance imaging and areas demonstrating volumetric expansion were further investigated using histology and immunohistochemistry.', 'The DBS group demonstrated bilateral increases in whole hippocampus and the left thalamus volume compared to both sham and control groups. Local hippocampal and thalamic volume increases were also observed at the voxel-level; however these increases were observed in both DBS and sham groups. Follow-up immunohistochemistry in the hippocampus revealed DBS increased blood vessel size and synaptic density relative to the control group whereas the sham group demonstrated increased astrocyte size.
Answer: Our work demonstrates that DBS not only works by altering function with neural circuits, but also by structurally altering circuits at the cellular level. Neuroplastic alterations may play a role in mediating the clinical efficacy of DBS therapy.

SOLUTION:
Does deep brain stimulation of the ventromedial prefrontal cortex cause reorganization of neuronal processes and vasculature?