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.

[EX Q]: Context: Minimal residual disease (MRD) is defined as the presence of sub-microscopic levels of leukaemia. Measurement of MRD from bone marrow at the end of induction chemotherapy (day 28) for childhood acute lymphoblastic leukaemia (ALL) can highlight a large group of patients (>40%) with an excellent (>90%) short-term event-free survival (EFS). However, follow-up in recent published trials is relatively short, raising concerns about using this result to infer the safety of further therapy reduction in the future.', 'We examined MRD data on 225 patients treated on one of three UKALL trials between 1997 and 2003 to assess the long-term (>10\u2005years follow-up) outcome of those patients who had low-risk MRD (<0.01%) at day 28.', 'Our pilot data define a cohort of 53% of children with MRD <0.01% at day 28 who have an EFS of 91% and long-term overall survival of 97%. Of 120 patients with day-28 MRD <0.01% and extended follow-up, there was one death due to treatment-related toxicity, one infectious death while in complete remission, and four relapse deaths.
Answer: The excellent outcome for childhood ALL in patients with MRD <0.01% after induction chemotherapy is sustained for more than 10 years from diagnosis. This supports the potential exploration of further reduction of therapy in this group, in an attempt to reduce treatment-related mortality and late effects.
[EX A]: Is excellent outcome of minimal residual disease-defined low-risk patients sustained with more than 10 years follow-up : results of UK paediatric acute lymphoblastic leukaemia trials 1997-2003?

[EX Q]: Context: Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein function until the local cellular redox environment has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the Forkhead Box O4 (FOXO4) transcription factor.', 'In this study, we sought to investigate whether redox signaling differentially controls the human FOXO3 and FOXO4 paralogs.', 'We present evidence that FOXO3 and FOXO4 have acquired paralog-specific cysteines throughout vertebrate evolution. Using a proteome-wide screen, we identified previously unknown redox-dependent FOXO3 interaction partners. The nuclear import receptors Importin-7 (IPO7) and Importin-8 (IPO8) form a disulfide-dependent heterodimer with FOXO3, which is required for its reactive oxygen species-induced nuclear translocation. FOXO4 does not interact with IPO7 or IPO8.
Answer: IPO7 and IPO8 control the nuclear import of FOXO3, but not FOXO4, in a redox-sensitive and disulfide-dependent manner. Our findings suggest that evolutionary acquisition of cysteines has contributed to regulatory divergence of FOXO paralogs, and that phylogenetic analysis can aid in the identification of cysteines involved in redox signaling.
[EX A]: Does evolutionary acquisition of cysteines determine FOXO paralog-specific redox signaling?

[EX Q]: Context: PARP-1 is important for the recognition of both endogenous and exogenous DNA damage, and binds to DNA strand breaks including intermediates of base excision repair (BER). Once DNA-bound, PARP-1 becomes catalytically activated synthesizing PAR polymers onto itself and other repair factors (PARylation). As a result, BER repair proteins such as XRCC1 and DNA polymerase β (pol β) are more efficiently and rapidly recruited to sites of DNA damage. In the presence of an inhibitor of PARP activity (PARPi), PARP-1 binds to sites of DNA damage, but PARylation is prevented. BER enzyme recruitment is hindered, but binding of PARP-1 to DNA is stabilized, impeding DNA repair and leading to double-strand DNA breaks (DSB). Deficiencies in pol β(-/-) and Xrcc1(-/-) cells resulted in hypersensitivity to the PARP inhibitor 4-AN and reexpression of pol β or XRCC1, in these contexts, reversed the 4-AN hypersensitivity phenotype. BER deficiencies also showed evidence of replication defects that lead to DSB-induced apoptosis upon PARPi treatment. Finally, the clinically relevant PARP inhibitors olaparib and veliparib also exhibited hypersensitivity in both pol β(-/-) and Xrcc1(-/-) BER-deficient cells. These results reveal heightened sensitivity to PARPi as a function of BER deficiency.
Answer: BER deficiency represents a new therapeutic opportunity to enhance PARPi efficacy.
[EX A]:
Do base excision repair defects invoke hypersensitivity to PARP inhibition?