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 Input:
Context: Lung adenocarcinomas are a heterogeneous set of diseases with distinct genetic and histologic characteristics. Besides the discovery of oncogenic mutations and introduction of the histologic classifications (2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society and 2015 WHO), increasing evidence has linked this intertumor heterogeneity\xa0to the lung lineage-specific pathways and lineage genes. Therefore, in this study, we assessed the gene expression of identified lung lineage genes to study their role in distinguishing lung adenocarcinoma diversities.', 'A total of 278 surgically resected lung adenocarcinomas were included. Each case was evaluated for genetic mutations and histologic classification. Lineage genes associated with respiratory tract differentiation (NK2 homeobox 1 gene [NKX2-1], GATA protein binding 6 gene [GATA6], foxhead box J1 gene [FOXJ1], and SAM pointed domain containing ETS transcription factor gene [SPDEF]) and stem/basal-like status (inhibitor of DNA binding 2, HLH protein gene [ID2], POU class 5 homeobox 1 gene [POU5F1], SRY-box 2 gene [SOX2], and v-myc avian myelocytomatosis viral oncogene homolog gene [MYC]) were selected. mRNA expression of these genes in each tumor sample was assessed by quantitative real-time polymerase chain reaction and normalized to paired normal lung tissue.', 'Distinct lineage gene expressions were found on the basis of genetic and histologic diversities. Expression of NKX2-1, GATA6, FOXJ1, and POU5F1 exhibited a significant linear relationship across histologic subgroups that was independent of genetic mutation status. Expression levels of NKX2-1 and POU5F1 were also associated with EGFR mutation status, independent of histologic subtypes. Further analysis revealed that the overexpression of SPDEF defined longer relapse-free survivals, especially in stage I disease.
Answer: For the first time, we showed the unique lineage backgrounds of different histologic subtypes and oncogenic mutations. Assessing this added parameter might be beneficial in discriminating intertumor heterogeneity, advancing target exploration, developing theranostic/prognostic biomarkers, and designing clinical trials.

Ex Output:
Do the Histologic Classifications of Lung Adenocarcinomas Are Discriminable by Unique Lineage Backgrounds?


Ex Input:
Context: Human induced pluripotent stem cells (iPSCs) play an important role in disease modeling and drug testing. However, the current methods are time-consuming and lack an isogenic control.', 'This study sought to establish an efficient technology to generate human PSC-based disease models with isogenic control.', 'The ion channel genes KCNQ1 and KCNH2 with dominant negative mutations causing long QT syndrome types 1 and 2, respectively, were stably integrated into a safe harbor AAVS1 locus using zinc finger nuclease technology.', 'Patch-clamp recording revealed that the edited iPSC-derived cardiomyocytes (iPSC-CMs) displayed characteristic long QT syndrome phenotype and significant prolongation of the action potential duration compared with the unedited control cells. Finally, addition of nifedipine (L-type calcium channel blocker) or pinacidil (KATP-channel opener) shortened the action potential duration of iPSC-CMs, confirming the validity of isogenic iPSC lines for drug testing in the future.
Answer: Our study demonstrates that iPSC-CM-based disease models can be rapidly generated by overexpression of dominant negative gene mutants.

Ex Output:
Does genome editing of isogenic human induced pluripotent stem cells recapitulate long QT phenotype for drug testing?


Ex Input:
Context: p53 Is known to be a tumor-suppressor gene and has been suggested to play an important role for multistep carcinogenesis of cutaneous squamous cell carcinoma (SCC). To evaluate the role of ultraviolet light (UV) in p53 mutation in squamous cell carcinogenesis, paraffin-embedded sections of SCCs were immunohistochemically stained with the CM-1 antibody for p53 protein. Positive staining suggests mutation of the p53 gene since the mutant p53 protein gains prolonged half-life to be detectable by this method. The specimen included SCCs induced by UV (SCCs on sun-exposed areas, SCCs on patients with xeroderma pigmentosum), roentgen rays, scar, and miscellaneous causes. In addition, solar keratoses that are precancerous lesions of UV-related SCCs were also analyzed.', 'Fourteen (54%) of 26 UV-related SCCs were positive, whereas five (19%) of 26 UV-unrelated SCCs were positive. Among the UV-related SCCs, five (45%) of 11 well-differentiated SCCs and nine (60%) of 15 moderately to poorly differentiated SCCs were positive. Eleven (48%) of 23 solar keratoses were positive for p53.
Answer: These results indicate that UV acts as a mutagen for the p53 gene, and this event may occur at a relatively early stage of multistep UV carcinogenesis.

Ex Output:

Is expression of p53 protein an early event in ultraviolet light-induced cutaneous squamous cell carcinogenesis?