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: Early inflammatory arthritis is clinically heterogenous and biologically-based indicators are needed to distinguish severe from self-limited disease. Anti-cyclical citrullinated peptides (CCP) have been identified as potential prognostic markers in early arthritis cohorts. Since cytokine networks are known to play a critical role in the pathogenesis of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, a panel of pro- and antiinflammatory cytokines was measured to identify biologically-based subsets of early arthritis, relating cytokine profiles to clinical measures and to the presence of RA-associated autoantibodies.', 'Plasma concentrations of cytokines [interleukin 1beta (IL-1beta), IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL-8), IL-10, IL-12p70, IL-13, IL-17, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-g (IFN-g), CCL2 (monocyte chemoattractant protein-1, MCP-1), CCL4 (MIP-1beta), and tumor necrosis factor-a (TNF-a)] were measured in patients with early, untreated inflammatory arthritis [symptom duration < or = 12 months; > or = 1 swollen joint; RA, n = 41; undifferentiated arthritis (UA), n = 23]. Cytokine expression patterns were determined using cluster analysis.', 'Both pro- and antiinflammatory cytokines were elevated in patients over controls (n = 21). RA clustered into subgroups based solely on cytokine profiles. The "mild" RA subgroup (n = 23) had higher CCL4 (MIP-1beta), CXCL8 (IL-8), IL-2, IL-12, IL-17, IL-5, and IL-10 levels, lower IL-6, IFN-g, GM-CSF, and IL-4 levels, less CCP positivity (52% vs 82%; p < 0.05), and lower CCP titers [71 (78) vs 153 (94); p < 0.01], but similar erythrocyte sedimentation rate, C-reactive protein, and joint counts compared to the "severe" RA groups. CCL4 (MIP-1beta), IL-13, IL-12, TNF-a, and IL-4 best distinguished the groups. Combining UA with RA samples preserved cytokine subgroups and strengthened the autoantibody associations. Fewer UA patients in the "mild" cluster (n = 16) were RF-positive (24% vs 100%; p < 0.002) or CCP-positive (24% vs 66%; p < 0.08) compared to the "severe" group.
Answer: Early untreated inflammatory arthritis can be categorized into distinct subgroups based on cytokine profiles. These subgroups are associated with CCP and RF autoantibodies. Integration of cytokine profiles with autoantibody status may assist prognostication and treatment decisions in these patients.

SOLUTION: Is a distinct multicytokine profile associated with anti-cyclical citrullinated peptide antibodies in patients with early untreated inflammatory arthritis?

PROBLEM: Context: TECPR2 was first described as a disease causing gene when the c.3416delT frameshift mutation was found in five Jewish Bukharian patients with similar features. It was suggested to constitute a new subtype of complex hereditary spastic paraparesis (SPG49).', 'We report here 3 additional patients from unrelated non-Bukharian families, harboring two novel mutations (c.1319delT, c.C566T) in this gene. Accumulating clinical data clarifies that in addition to intellectual disability and evolving spasticity the main disabling feature of this unique disorder is autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events.
Answer: We suggest that the disease should therefore be classified as a new subtype of hereditary sensory-autonomic neuropathy. The discovery of additional mutations in non-Bukharian patients implies that this disease might be more common than previously appreciated and should therefore be considered in undiagnosed cases of intellectual disability with autonomic features and respiratory symptoms regardless of demographic origin.

SOLUTION: Do tECPR2 mutations cause a new subtype of familial dysautonomia like hereditary sensory autonomic neuropathy with intellectual disability?

PROBLEM: Context: Cells of the myeloid lineage comprise a very heterogeneous population with many phenotypes and functional activities including macrophages and dendritic cells. To investigate the status, differentiative potential and lineage commitment of monocytic cells in systemic lupus erythematosus (SLE) patients, this study isolated and cultured peripheral blood monocytes from patients and healthy donors.', 'Monocytes were isolated by gradient centrifugation and adherence to plastic dishes. The cells were then cultured for three days, partially supplemented with GM-CSF and interleukin 4 (IL4) to obtain dendritic cells. The differentiation status was monitored by the expression of surface markers using flow cytometry and cytokine secretion.', 'Monocytes from SLE patients expressed significantly lower numbers of the monocytic marker CD14 and HLA-DR while secreting significantly more tumour necrosis factor alpha (TNFalpha) than monocytes from healthy donors. The addition of GM-CSF and IL4 resulted in an inhibition of TNFalpha secretion, but was not sufficient to generate monocytederived dendritic cells.
Answer: Monocytes from SLE patients are severely altered in phenotype and function and have a limited differentiation flexibility towards the accessory type of monocytic cells.

SOLUTION:
Are monocytes from systemic lupus erythematous patients severely altered in phenotype and lineage flexibility?