TASK DEFINITION: Given a passage, 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: Aggrecanase cleavage at the 392Glu-393Ala bond in the interglobular domain (IGD) of aggrecan, releasing N-terminal 393ARGS fragments, is an early key event in arthritis and joint injuries. Here, we use a quantitative immunoassay of aggrecan ARGS neoepitope fragments in human synovial fluid to determine if this cleavage-site specific method better identifies joint pathology than previously available less specific aggrecan assays.', 'Synovial fluid (SF) from 26 people with healthy knees (reference) and 269 patients were analyzed in a cross-sectional study. Patient groups were acute inflammatory arthritis, acute knee injury, chronic knee injury and knee osteoarthritis (OA). Aggrecan ARGS fragments were assayed by ELISA using the monoclonal antibody OA-1. Total aggrecan content was analyzed by an ELISA using the monoclonal antibody 1-F21, and sulfated glycosaminoglycan by Alcian blue precipitation.', 'Aggrecan ARGS fragment concentrations in all groups differed from the reference group (P < 0.001). The acute inflammatory arthritis group had the highest median level, 177-fold greater than that of the reference group. Median levels (in pmol ARGS/ml SF) were: reference 0.5, acute inflammatory arthritis 88.5, acute knee injury 53.9, chronic knee injury 0.5 and OA 4.6. In contrast, aggrecan and sulfated glycosaminoglycan concentrations varied much less between groups, and only acute inflammatory arthritis and acute knee injury were found to have a two-fold increase in median levels compared to the reference.

SOLUTION: Is synovial fluid level of aggrecan ARGS fragments a more sensitive marker of joint disease than glycosaminoglycan or aggrecan levels : a cross-sectional study?

PROBLEM: Development of novel strategies in the treatment of advanced thyroid cancer are needed. Our laboratory has previously identified a role for nuclear factor B (NF-B) signaling in human thyroid cancer cell growth, survival, and invasion.', 'Our goal was to establish the role of NF-B signaling on thyroid cancer growth and metastases in vivo and to begin to dissect mechanisms regulating this effect.', 'We examined tumor formation of five thyroid cancer cell lines in an in vivo model of thyroid cancer and observed tumor establishment in two of the cell lines (8505C and BCPAP).', 'Inhibition of NF-B signaling by overexpression of a dominant-negative IB (mIB) significantly inhibited thyroid tumor growth in tumors derived from both cell lines. Further studies in an experimental metastasis model demonstrated that NF-B inhibition impaired growth of tumor metastasis and prolonged mouse survival. Proliferation (mitotic index) was decreased in 8505C tumors, but not in BCPAP tumors, while in vitro angiogenesis and in vivo tumor vascularity were significantly inhibited by mIkB only in the BCPAP cells. Cytokine antibody array analysis demonstrated that IL-8 secretion was blocked by mIB expression. Interestingly, basal NF-B activity and IL-8 levels were significantly higher in the two tumorigenic cell lines compared with the nontumorigenic lines. Furthermore, IL-8 transcript levels were elevated in high-risk human tumors, suggesting that NF-B and IL-8 are associated with more aggressive tumor behavior.

SOLUTION: Is nuclear factor B-dependent regulation of angiogenesis , and metastasis in an in vivo model of thyroid cancer associated with secreted interleukin-8?

PROBLEM: Although evidence suggests that antiretroviral (ARV) regimens containing nonnucleoside reverse transcriptase inhibitors (NNRTIs) are superior to single-protease inhibitor (PI)-based regimens at suppressing viral load, it is unclear how much of the improved viral suppression is due to intrinsic drug potency versus higher levels of adherence to simpler regimens. We therefore examined adherence and viral suppression in NNRTI and single-PI regimens in a cohort of largely ARV-experienced participants by using objective measures of adherence.', "Participants were recruited from the Research on Access to Care in the Homeless (REACH) Cohort and were included in the study if they were on single-PI-based or NNRTI-based highly active antiretroviral therapy (HAART) regimens for at least 3 months prior to study entry. Adherence was measured by unannounced pill counts at the participant's usual place of residence. The primary outcome was suppression of HIV viral RNA to <50 copies/mL.", 'Among 109 individuals who were followed for a median of 8.7 months, the odds of virologic suppression were approximately 8 times higher (p < .01) for participants on NNRTI-based regimens (n = 53) compared with those using single-PI-based regimens (n = 56) when controlling for adherence, as well as other potential confounders in a multivariable analysis. The only other independent predictors of viral suppression in multivariable modeling were ARV adherence (p < .01), CD4 nadir (p = .02), and continuous months on current regimen prior to the start of adherence monitoring (p < .01). There was no significant difference in adherence by unannounced pill counts in participants receiving NNRTI- versus single-PI-containing regimens.

SOLUTION:
Are higher rates of viral suppression with nonnucleoside reverse transcriptase inhibitors compared to single protease inhibitors explained by better adherence?