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.

Context: Hypospadias is a common male congenital urethral malformation, defined as the displacement of the urethral meatus ventrally from the tip of the glans penis. The importance of androgen receptor in male external genitalia development has been well recognized. Recently, the presence of active estrogen receptors (ER) in the developing male external genitalia has also been demonstrated. There are two isoforms of the human estrogen receptor, ESR1 and ESR2, which occur, with distinct tissue and cell patterns of expression. We hypothesized that modifications in these nuclear receptors' genes could lead to hypospadias.", 'We screened 60 boys with hypospadias for mutations in the coding regions of ESR1 and ESR2 genes, by denaturing high-performance liquid chromatography and automated sequence analysis. We also genotyped the CA repeat polymorphism in ESR2 and the TA repeat polymorphism in ESR1.', 'The CA repeat polymorphism in ESR2 is prolonged in hypospadias patients compared to controls (p < 0.05). Prolongation of this CA repeat polymorphism has previously been associated with lower levels of testosterone. Six patients presented the genetic variant 2681-4A > G (rs944050) in the heterozygous form in ESR2, which was a significantly higher frequency than in the control population (p < 0.05). One of these patients also presented a 266_267insC in exon 1 of ESR2, which is also a known single nucleotide polymorphism (SNP; rs3832949). In ESR1, no significant gene alteration was found to be associated with hypospadias.
Answer: Our results suggest that variations in the ESR2 might influence susceptibility to hypospadias.
Are polymorphisms of estrogen receptor beta gene associated with hypospadias?

Context: Blood oxygen level-dependent (BOLD) MRI has been effectively used to monitor changes in renal oxygenation. However, R2* (or T2*) is not specific to blood oxygenation and is dependent on other factors. This study investigates the use of a statistical model that takes these factors into account and maps BOLD MRI measurements to blood pO2.', "Spin echo and gradient echo images were obtained in six Sprague-Dawley rats and R2 and R2* maps were computed. Measurements were made at baseline, post-nitric oxide synthase inhibitor (L-NAME), and post-furosemide administration. A simulation of each region was performed to map R2' (computed as R2*-R2) to blood pO2.", 'At baseline, blood pO2 in the outer medulla was 30.51.2 mmHg and 51.95.2 mmHg in the cortex, in agreement with previous invasive studies. Blood pO2 was found to decrease within the outer medulla following L-NAME (P<0.05) and increase after furosemide (P<0.05). Blood pO2 in the cortex increased following furosemide (P<0.05).
Answer: Model-derived blood pO2 is sensitive to pharmacological challenges, and baseline pO2 is comparable to literature values. Reporting pO2 instead of R2* could lead to a greater clinical impact of renal BOLD MRI and facilitate the identification of hypoxic regions. Magn Reson Med, 2016. ©️ 2016 International Society for Magnetic Resonance in Medicine.
Is bOLD quantified renal pO2 sensitive to pharmacological challenges in rats?

Context: One variant of multiple endocrine neoplasia type 1 (MEN1) is defined by sporadic tumors of both the parathyroids and pituitary. The prevalence of identified MEN1 mutations in this variant is lower than in familial MEN1 (7% vs. 90%), suggesting different causes. Recently, one case of this variant had a germline mutation of p27(Kip1)/CDKN1B.', 'The objective was to test p27 in germline DNA from cases with tumors of both the parathyroids and pituitary.', 'Medical record review and sequence analysis in DNA were performed.', 'This study involved an inpatient and outpatient referral program for cases of endocrine tumors.', 'Sixteen index cases had sporadic tumors of two organs, both the parathyroids and the pituitary. There were 18 additional index cases with related features of familial tumors. Five subjects were normal controls. No case had an identified MEN1 mutation.', 'Clinical status of endocrine tumors was tabulated. Sequencing of germline DNA from index cases and control cases for the p27 gene was performed by PCR.', 'Endocrine tumor types and their expressions were measured, as were sequence changes in the p27 gene.', 'Tumor features were documented in index cases and families. One p27 germline single nucleotide change was identified. This predicted a silent substitution of Thr142Thr. Furthermore, there was a normal prevalence of heterozygosity for a common p27 polymorphism, making a large p27 deletion unlikely in all or most of these cases.
Answer: The MEN1 variant with sporadic parathyroid tumors, sporadic pituitary tumor, and no identified MEN1 mutation is usually not caused by p27 germline mutations. It is usually caused by as yet unknown process(es).
Does the parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually have causes other than p27Kip1 mutations?