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.

Input: Consider Input: Doxorubicin is a cytotoxic drug with potential for severe myelosuppression that is highly variable and poorly predictable.', 'We correlated CBR1 and CBR3 genotypes with the pharmacokinetics and pharmacodynamics of doxorubicin in 101 Southeast Asian breast cancer patients receiving first-line doxorubicin.', 'A common CBR3 11G>A variant was associated with lower doxorubicinol area under the concentration-time curve (AUC)/doxorubicin AUC metabolite ratio (P=0.009, GG vs. AA; trend test, P=0.004), lower CBR3 expression in breast tumor tissue (P=0.001, GG vs. AA), greater tumor reduction (P=0.015, GG vs. AA), and greater percentage reduction of leukocyte and platelet counts at nadir (trend test, P < or = 0.03). Chinese and Malays had higher frequency of the CBR3 11G>A variant than Indians (P < or = 0.002). Another variant CBR3 730G>A was associated with higher doxorubicinol AUC (P=0.009, GG vs. AA) and CBR3 expression in breast tumor tissue (P=0.001, GG vs AA).

Output: Does genotype of human carbonyl reductase CBR3 correlate with doxorubicin disposition and toxicity?


Input: Consider Input: Dual activation by TSH of the phospholipase C and cAMP cascades has been reported in human thyroid cells. In contrast, Singh et al. reported convincing data in FRTL-5 thyrocytes arguing against such an effect in this model. Their data in FRTL-5 cells indicated no increase in inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in response to TSH. Therefore, the authors questioned results previously obtained on human cells by cruder methodology.', 'We investigated the formation of inositol phosphates by HPLC techniques in human thyroid slices to separate the inositol phosphate isomers.', 'Ins(1,4,5)P3, inositol 1,3,4-trisphosphate, and inositol 1,3,4,5-tetrakisphosphate were increased after TSH stimulation. The effect of TSH in human thyroid cells was reproduced by recombinant TSH and prevented by antibodies blocking the TSH receptor. Thyroid-stimulating antibodies at concentrations eliciting a cAMP response equivalent to TSH failed to stimulate inositol phosphate generation.

Output: Does thyrotropin stimulate the generation of inositol 1,4,5-trisphosphate in human thyroid cells?


Input: Consider Input: Adult acquired flatfoot deformity is characterized by midfoot abduction and collapse of the medial longitudinal arch. Lateral column lengthening osteotomies primarily correct the abduction deformity, but the effects of graft shape on deformity correction and forefoot loading are unclear. Therefore, the purpose of this study was to demonstrate the effect of graft shape and taper on deformity correction and forefoot loading mechanics in a cadaveric flatfoot model.', 'Flatfoot deformity was simulated in 18 cadaveric specimens. A lateral column lengthening osteotomy was performed using a triangular, trapezoidal, and rectangular graft for each specimen. During each testing condition, talonavicular joint angles and forefoot plantar pressures were measured.', 'Each graft shape corrected abduction and dorsiflexion deformity at the talonavicular joint. Coronal plane correction was affected by graft shape, and the less tapered trapezoidal and rectangular grafts overloaded the lateral forefoot compared to the intact condition. The more tapered triangular graft did not cause a lateral shift in forefoot pressures. Forefoot plantar pressures were strongly correlated with talonavicular abduction correction (R (2) = .473, P < .001).


Output: Does graft shape affect midfoot correction and forefoot loading mechanics in lateral column lengthening osteotomies?