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.

[Q]: A severe complication in the replacement therapy of hemophilia A (HA) patients is the development of alloantibodies (inhibitors) against factor VIII, which neutralizes the substituted factor. The primary genetic risk factors influencing the development of inhibitors are F8 gene mutations. Interleukins and cytokines that are involved in the regulation of B-lymphocyte development are other possible targets as genetic risk factors. This study assesses the possible involvement of 9 selected single nucleotide gene polymorphisms (SNPs) with interleukins (IL-4, IL-5, and IL-10), transforming growth factor beta 1 (TGF-β1), and interferon gamma (IFN-γ) in inhibitor development in severely affected HA patients carrying a null mutation in the F8 gene.', 'A total of 173 HA patients were screened for intron 22 inversion and null mutations (nonsense and deletions). Genotyping of a total of 9 SNPs in genes IL-4, IL-5, IL-10, TGF-β1, and IFN-γ in 103 patients and 100 healthy individuals was carried out.', 'An association analysis between 42 inhibitor (+) and 61 inhibitor (-) patients showed a significant association with the T allele of rs2069812 in the IL-5 gene promoter and patients with inhibitors (p=0.0251). The TT genotype was also significantly associated with this group with a p-value of 0.0082, odds ratio of about 7, and confidence interval of over 90%, suggesting that it is the recessive susceptibility allele and that the C allele is the dominant protective allele.
[A]: Is a Polymorphism in the IL-5 Gene Associated with Inhibitor Development in Severe Hemophilia A Patients?


[Q]: Some living kidney donors report lost income during recovery from surgery. Little is known about whether concern for living donor's lost income affects the decision to undergo donation evaluation and the willingness of transplant candidates to discuss living kidney donation (LKD) with others.", 'To examine whether transplant patients were told by potential donors about lost income concerns and whether patients chose not to discuss LKD with others due to lost income concerns.', "Kidney transplant patients (185 wait-listed candidates, 171 deceased donor recipients, and 100 live donor recipients) at 2 centers completed a questionnaire to assess whether concern about donor's lost income was a consideration in discussion about LKD with others.", 'One-third (32%) were told by a family member/friend that they were willing to donate but were concerned about potential lost income. The majority of those who expressed financial concern (64%) did not initiate donation evaluation. Many patients (42%) chose not to discuss living donation with a family member/friend due to concern about the impact of lost income on the donor. In the multivariable model, lower annual household income was the only statistically significant predictor of both having a potential donor expressing lost income concern and choosing not to talk to someone because of lost income concern.
[A]: Does concern for Lost Income Following Donation deter Some Patients From Talking to Potential Living Donors?


[Q]: Chemoresistance is a main obstacle to effective esophageal cancer (EC) therapy. We hypothesize that altered expression of microRNAs (miRNAs) play a role in EC cancer progression and resistance to 5-fluorouracil (5-FU) based chemotherapeutic strategies.', 'Four pairs of esophageal adenocarcinoma (EAC) cell lines and corresponding 5-FU resistant variants were established. The expression levels of miRNAs previously shown to be involved in the general regulation of stem cell pathways were analyzed by qRT-PCR. The effects of selected miRNAs on proliferation, apoptosis, and chemosensitivity were evaluated both in vitro and in vivo. We identified a particular miRNA and analyzed its putative target genes in 14 pairs of human EC tumor specimens with surrounding normal tissue by qRT-PCR as well as Wnt pathway associated genes by immunohistochemistry in another 45 EAC tumor samples.', 'MiR-221 was overexpressed in 5-FU resistant EC cell lines as well as in human EAC tissue. DKK2 was identified as a target gene for miR-221. Knockdown of miR-221 in 5-FU resistant cells resulted in reduced cell proliferation, increased apoptosis, restored chemosensitivity, and led to inactivation of the Wnt/β-catenin pathway mediated by alteration in DKK2 expression. Moreover, miR-221 reduction resulted in alteration of EMT-associated genes such as E-cadherin and vimentin as well as significantly slower xenograft tumor growth in nude mice. RT profiler analysis identified a substantial dysregulation of 4 Wnt/β-catenin signaling and chemoresistance target genes as a result of miR-221 modulation: CDH1, CD44, MYC, and ABCG2.
[A]:
Does miR-221 mediate Chemoresistance of Esophageal Adenocarcinoma by Direct Targeting of DKK2 Expression?