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.

Input: Consider Input: Context: Macroprolactinemia is a frequent finding in hyperprolactinemic individuals, usually without clinical impact. Data on biological activity of macroprolactin (bbPRL) are controversial and mostly based on a heterologous rat Nb2 cell bioassay. Biological activity of bbPRL observed in vitro but not in vivo may be due to its high molecular weight, preventing its passage through capillary barrier. Alternatively, bbPRL bioactivity may differ depending on the prolactin (PRL) receptor (PRLR) species specificity.', 'The objective of the study was to characterize the bioactivity of bbPRL in a homologous bioassay: Ba/F-3 cells stably expressing the human PRLR.', "Chromatography-purified bbPRL from macroprolactinemic individuals (group I, n = 18) and monomeric PRL from hyperprolactinemic patients without macroprolactinemia (group II, n = 5) were tested in Nb2 and Ba/F-LLP bioassays. Both groups were followed up at the neuroendocrinology outpatients' clinic.", 'Biological activity of bbPRL presented in the two bioassays was measured.', 'In group I, no patient had hypogonadism. Mean ratio bioactivity to immunoactivity of bbPRL in the Nb2 assay was 0.69. There was no dose-response in 15 of the 18 samples tested in Ba/F-LLP assay. In group II, three patients had galactorrhea and all five had hypogonadism. Mean ratio bioactivity to immunoactivity of monomeric PRL samples was 1.35 in Nb2 and 0.91 in Ba/F-LLP assay.
Answer: Whereas both bioassays achieve similar results with respect to monomeric PRL activity, our results indicate that the activity displayed by bbPRL toward the rat receptor may be inappropriate because it is not observed in the human PRLR-mediated assay, consistent with the apparent absence of bioactivity in vivo.

Output: Does human macroprolactin display low biological activity via its homologous receptor in a new sensitive bioassay?


Input: Consider Input: Context: del(17p), del(11q), and associated p53 dysfunction predict for short survival and chemoresistance in B-cell chronic lymphocytic leukemia (CLL). DNA-dependent protein kinase (DNA-PK) is activated by DNA damage and mediates DNA double-strand break repair. We hypothesized that inhibiting DNA-PK would sensitize CLL cells to drug-induced DNA damage and that this approach could increase the therapeutic index of agents used to treat CLL.', 'Fifty-four CLL cases were characterized for poor prognosis markers [del(17p), del(11q), CD38, and ZAP-70]. In selected cases, DNA-PK catalytic subunit (DNA-PKcs) expression and activity and p53 function were also measured. Ex vivo viability assays established sensitivity to fludarabine and chlorambucil and also tested the ability of a novel DNA-PK inhibitor (NU7441) to sensitize CLL cells to these drugs. The effects of NU7441 on fludarabine-induced DNA damage repair were also assessed (Comet assays and detection of gammaH2AX).', 'DNA-PKcs levels correlated with DNA-PK activity and varied 50-fold between cases but were consistently higher in del(17p) (P = 0.01) and del(11q) cases. NU7441 sensitized CLL cells to chlorambucil and fludarabine, including cases with del(17p), del(11q), p53 dysfunction, or high levels of DNA-PKcs. NU7441 increased fludarabine-induced double-strand breaks and abrogated drug-induced autophosphorylation of DNA-PKcs at Ser2056. High DNA-PK levels predicted for reduced treatment-free interval.
Answer: These data validate the concept of targeting DNA-PKcs in poor risk CLL, and demonstrate a mechanistic rationale for use of a DNA-PK inhibitor. The novel observation that DNA-PKcs is overexpressed in del(17p) and del(11q) cases indicates that DNA-PK may contribute to disease progression in CLL.

Output: Is dNA-dependent protein kinase a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia?


Input: Consider Input: Context: Onychomycosis is a common cause of nail dystrophy and may be associated with tinea pedis. The presence of dermatophyte fungi in clinically normal nails is unknown.', 'To assess the presence of dermatophyte fungi in normal-appearing toenails and to compare the risk of subclinical dermatophytosis in patients without and with concurrent tinea pedis.', 'This is a prospective, University-based study of adults without and with microscopically confirmed tinea pedis. Subjects with dystrophy of any toenail were excluded, as were those ever previously diagnosed as having onychomycosis and those who had used topical antifungals in the past year. A great toenail clipping obtained from each subject was submitted for periodic acid-Schiff histology.', 'One hundred and one subjects (63 men and 38 women, mean +/- SD age 45.4 +/- 15.7 years) were included. Overall, septate hyphae (ostensibly dermatophyte) were identified in seven specimens. Of the 66 control subjects, one case (1.5%) of nail dermatophyte was identified. Of the 35 subjects with tinea pedis, six cases (17%) of nail dermatophyte were identified (P = 0.0066; odds ratio 13.4, 95% confidence interval 1.6-117). There were no significant differences in age or gender between the experimental and control groups or between the nail dermatophyte-positive and negative cohorts.
Answer: Dermatophyte fungi may be isolated from normal-appearing toenails. The presence of dermatophytes in this situation is strongly associated with the presence of tinea pedis. Subclinical dermatophyte in the nail plate may serve as a reservoir for ongoing local infection.


Output: Is subclinical onychomycosis associated with tinea pedis?