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: Nagashima-type palmoplantar keratosis (NPPK) is a distinct autosomal recessive genodermatosis characterized by diffuse transgressive palmoplantar keratoderma (PPK). Very recently, putative loss-of-function mutations in SERPINB7, which encodes a member of the serine protease inhibitor superfamily and is abundantly expressed in the epidermis, have been identified as a cause of NPPK.', 'To confirm further the role of SERPINB7 mutations in the pathogenesis of NPPK.', 'We analysed 10 Japanese families with NPPK using Sanger and/or whole-exome sequencing.', 'We identified one novel and three recurrent null mutations in SERPINB7. In all the families, the NPPK trait was inherited in an autosomal recessive manner; in one of the families, there was pseudodominant inheritance, which had not been described in NPPK.
Answer: These data clearly provide further evidence that NPPK is caused by loss-of-function mutations in SERPINB7.

Ex Output:
Does highly prevalent SERPINB7 founder mutation cause pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis?


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: Records of patients who had repair of sinus venosus defect (SVD) between 1970 and 2008 were reviewed to predict very long-term outcome.', 'Repairs occurred in 104 consecutive patients (51 men), aged 29 +/- 23 years (range, 1 to 70 years). Seven had isolated SVD and 97 had associated lesions that required concomitant operations. Five patients had preoperative arrhythmias; 24 (23%) were in New York Heart Association (NYHA) class III to V. Single-patch repair was done in 91 patients, caval translocation (Warden) in 7, and double-patch in 6.', 'Ten late deaths during 38 years of follow-up (mean, 15 +/- 20 years). Survival was 97% +/- 2% and 79% +/- 7% at 10 and 30 years. Thirty-one (29%) long-term survivors experienced 47 complications, including chronic/recurrent supraventricular tachycardia in 28, heart failure in 5, permanent pacing in 8, cerebrovascular accident in 3, and unrelated cardiac reoperation in 3. At 30 years, freedom from adverse cardiac events was 47% +/- 9%, from supraventricular tachycardia, 50% +/- 9%; from permanent pacing, 83 +/- 6%; and from cerebrovascular accident, 96% +/- 2%. Follow-up age was 42 +/- 23 years (range, 5 to 82 years); 74 patients (79%) were in NYHA class I, and 15 and 5 were in class II and III to IV, respectively. Baseline cardiac rhythm was sinus in 75 patients (84%), atrial fibrillation in 11 (12%), and paced in 8. Nine patients had moderate/severe pulmonary hypertension, and 8 had left ventricular dysfunction. Only older age at operation was associated with lower survival (p = 0.003), freedom from cardiac events (p = 0.001), supraventricular tachycardia (p = 0.009), and permanent pacing (p = 0.002). Repair before age 20 was associated with lower NYHA class at follow-up (p = 0.01).
Answer: SVD repair at an older age is associated with increased risk of late mortality, adverse cardiac events, and worse functional outcome. Repair during childhood is strongly advised.

Ex Output:

Does age at repair affect the very long-term outcome of sinus venosus defect?