TASK DEFINITION: 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.
PROBLEM: 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.

SOLUTION: Are polymorphisms of estrogen receptor beta gene associated with hypospadias?

PROBLEM: Context: To evaluate whether tumor invasion depth can be a reliable and easily applicable pathologic assessment strategy to predict outcomes using surgically resected cervical squamous cell carcinoma specimens from patients who have received neoadjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT).', "We included 173 patients with cervical squamous cell carcinoma who received neoadjuvant CCRT (n=125) or RT (n=48) and underwent subsequent radical hysterectomy. Data for the pre-operative clinical International Federation of Gynecology and Obstetrics (FIGO) stage, post-operative pathologic FIGO stage, World Health Organization (WHO) double diameter measurement evaluation, response evaluation criteria in solid tumors (RECIST 1.1) criteria, tumor necrosis rate (TNR), and tumor regression grade (TRG) were investigated to identify correlations with outcomes related to distant metastasis and survival. The tumor invasion depth (TID) and the tumor invasion depth with cytokeratin immunostaining correction (TIDC) at the cervical internal surface were measured to assess their relations to patients' outcomes.", 'Based on measurements taken via transvaginal ultrasound, the pre-operative clinical and post-operative pathologic FIGO staging as well as the WHO double diameter measurement evaluation and RECIST 1.1 criteria were predictive of distant metastasis and survival-related outcomes. Also, lymph node involvement was found to be an independent prognostic factor for recurrence and distant metastasis. Finally, univariate analysis showed both the TID and TIDC were highly related to distant metastasis, overall survival, and progression-free survival, irrespective of the clinical stage of carcinomas.
Answer: The TID or TIDC measured at the cervical internal surface is a useful and easily applied pathologic prognostic factor for distant metastasis and survival outcomes in patients with cervical squamous cell carcinoma treated with neoadjuvant RT or CCRT.

SOLUTION: Is tumor invasion depth a useful pathologic assessment for predicting outcomes in cervical squamous cell carcinoma after neoadjuvant radiotherapy?

PROBLEM: Context: Irritable bowel syndrome is a frequently diagnosed gastrointestinal condition in general practice. Managing this chronic condition requires a co-ordinated effort between patient and doctor.', 'To explore the patterns of treatment and healthcare utilization of irritable bowel syndrome cases in a Swedish primary care setting.', 'All cases with a registered diagnosis of irritable bowel syndrome were identified retrospectively for a 5-year period through computerized medical records at three primary healthcare centres in Sweden. Documentation of diagnosis, healthcare visits, treatments, investigations, medications, referrals, laboratory tests, mental and demographic data were retrieved from the records.', 'Of all 723 irritable bowel syndrome patients identified, only 37% had a follow-up appointment to their General Practitioner during the study period. For 80%, the General Practitioner initiated some treatment during the initial consultation and 75% were prescribed medication. Fibre and bulking laxatives and acid-suppressive drugs were the most common medication. Almost a quarter was referred for complementary investigations at hospital, only 8.9% of the irritable bowel syndrome patients were referred to a specialist investigation. Laboratory investigations varied and were ordered more frequently (P = 0.05) for men.
Answer: Irritable bowel syndrome patients appear not to be heavy utilizers of primary care and, of those who attend, the majority are managed by their General Practitioner.

SOLUTION:
Appear patients with irritable bowel syndrome in primary care to be heavy healthcare utilizers?