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.

Input: Consider Input: There is no consensus about the ideal method for diagnosis in patients who have already undergone endoscopic ultrasound fine needle aspiration (EUS-FNA), and the inconclusive material is often obtained. The aim was to evaluate the diagnostic yield of the second EUS-FNA of pancreatic lesions.', 'A retrospective analysis of prospectively collected data of patients with EUS-FNA of pancreatic lesions is performed. All patients who underwent more than one EUS-FNA for the evaluation of suspected pancreatic cancer over a 7-year period were included in the analysis.', 'A total of 296 EUS-FNAs of the pancreas were performed in 257 patients. The diagnostic yield with the first EUS-FNA was 78.6% (202/257). Thirty-nine (13.3%) FNAs were repeated in 34 patients; 17 (50%) patients were women. The mean ± standard deviation (SD) age was 58.8 ± 16.1 years. The location of the lesions in the pancreatic gland, from which the second biopsies were taken, was head of the pancreas, n = 28 (82.4%), body of the pancreas, n = 3 (8.8%), and tail, n = 3 (8.8%). The mean ± SD of the size of the lesion was 36.3 ± 14.6 mm. The second EUS-FNA was more likely to be positive for diagnosis in patients with an "atypical" histological result in the first EUS-FNA (odds ratio [OR]: 4.04; 95% confidence interval [CI]: 0.9-18.3), in contrast to patients with a first EUS-FNA reported as "normal" (OR: 0.21; 95% CI: 0.06-0.71). Overall, the diagnostic yield of the second EUS-FNA was 58.8% (20/34) with an increase to 86.3% overall (222/257).

Output: Is repeat endoscopic ultrasound fine needle aspiration after a first negative procedure useful in pancreatic lesions?


Input: Consider Input: The objective of this study was to compare health-related quality of life (HR-QoL), disability/work productivity, and health care utilization in a variety of medical disorders with and without comorbid major depressive disorder (MDD) in the general population.', 'Twelve-month MDD (Composite International Diagnostic Interview) diagnosis was determined among 4181 participants from a community sample. Medical diagnoses (respiratory, cardiovascular, allergic, endocrine/metabolic, gastrointestinal, and neurological diseases) were made after medical examination. HR-QoL was evaluated with the MOS-SF-36. Outpatient doctor visits and disability/work productivity were assessed by self-report.', 'Comorbid MDD was associated with a lower SF-36 mental summary score in all medical diagnoses and with a lower physical summary score in comorbid allergic and neurological disorders. The number of coexisting medical disorders was strongly related to lower physical and mental summary scores in cases without comorbid depression. The number of outpatient doctor visits increased by 42% when any of the medical disorders without comorbid MDD was present, and comorbid MDD was associated with a further 24-42% increase, depending on the medical disorder. Comorbid MDD was strongly associated with lower full-time working status (37.1% with MDD vs. 51.0% without MDD) and with a significant increase in disability days (45%) in the presence of any medical disorder.

Output: Do medical disorders affect health outcome and general functioning depending on comorbid major depression in the general population?


Input: Consider Input: Activation of cyclooxygenase (COX)/prostaglandin and nuclear factor κB (NFκB) pathways can promote breast tumor initiation, growth, and progression to drug resistance and metastasis. Thus, anti-inflammatory drugs have been widely explored as chemopreventive and antineoplastic agents. Aspirin (ASA), in particular, is associated with reduced breast cancer incidence but gastrointestinal toxicity has limited its usefulness. To improve potency and minimize toxicity, ASA ester prodrugs have been developed, in which the carboxylic acid of ASA is masked and ancillary pharmacophores can be incorporated. To date, the effects of ASA and ASA prodrugs have been largely attributed to COX inhibition and reduced prostaglandin production. However, ASA has also been reported to inhibit the NFκB pathway at very high doses. Whether ASA prodrugs can inhibit NFκB signaling remains relatively unexplored.', 'A library of ASA prodrugs was synthesized and screened for inhibition of NFκB activity and cancer stem-like cell (CSC) properties, an important PGE2-and NFκB-dependent phenotype of aggressive breast cancers. Inhibition of NFκB activity was determined by dual luciferase assay, RT-QPCR, p65 DNA binding activity and Western blots. Inhibition of CSC properties was determined by mammosphere growth, CD44(+)CD24(-)immunophenotype and tumorigenicity at limiting dilution.', 'While we identified multiple ASA prodrugs that are capable of inhibiting the NFκB pathway, several were associated with cytotoxicity. Of particular interest was GTCpFE, an ASA prodrug with fumarate as the ancillary pharmacophore. This prodrug potently inhibits NFκB activity without innate cytotoxicity. In addition, GTCpFE exhibited selective anti-CSC activity by reducing mammosphere growth and the CD44(+)CD24(-)immunophenotype. Moreover, GTCpFE pre-treated cells were less tumorigenic and, when tumors did form, latency was increased and growth rate was reduced. Structure-activity relationships for GTCpFE indicate that fumarate, within the context of an ASA prodrug, is essential for anti-NFκB activity, whereas both the ASA and fumarate moieties contributed to attenuated mammosphere growth.


Output: Does a novel aspirin prodrug inhibit NFκB activity and breast cancer stem cell properties?