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.

Input: Consider Input: Context: Cytotechnologists and pathologists often perform onsite evaluations of thyroid fine-needle aspirations (FNAs) to provide immediate feedback regarding whether adequate material has been obtained for cytologic diagnosis. The current study was designed to determine whether onsite adequacy assessment results in a significant decrease in nondiagnostic specimens between ultrasound (US)-guided FNAs of the thyroid and those performed by palpation alone.', 'A search was performed to identify in-house thyroid FNAs performed between January 1, 2000 and December 31, 2003 that were obtained under US guidance or by palpation only. It was then recorded whether an onsite adequacy assessment was performed. The submitting physician and final diagnosis also were recorded for each case. Contingency tables were constructed and evaluated using chi-square analysis.', 'Of 1502 in-house thyroid FNAs included in the current study, 981 (65.3%) were performed under US guidance and 521 (34.7%) were performed with palpation alone. Onsite adequacy assessment of the aspirated material was performed in 323 cases (21.5%), whereas 1179 cases (78.5%) were performed without onsite evaluation. Of the 418 palpation-guided FNAs that were performed without adequacy assessment, 70 (16.7%) were reported to be nondiagnostic, whereas of the 103 palpation-guided FNAs with immediate evaluation, only 7 (6.8%) were determined to be inadequate for diagnosis. This difference was statistically significant (P < 0.025). Of 761 US-guided FNAs without immediate adequacy assessment, 54 (7.1%) were nondiagnostic, which was not statistically different from the nondiagnostic rate of 4.5% (10 of 220 cases) for US-guided FNAs with onsite evaluation. However, when these US-guided FNAs were divided further into 2 groups based on the experience of the radiologist performing the FNA, the nondiagnostic rate in the group of experienced radiologists was only 5.4% (or 32 of 592 US-guided FNAs), even though onsite evaluation was not performed. Among radiologists with less experience, adequacy assessment significantly reduced the nondiagnostic rate from 13.0% (22 of 169 FNAs without adequacy assessment) to 4.5% (10 of 220 FNAs with adequacy assessment) (P < 0.01).
Answer: The results of the current study demonstrate that onsite adequacy assessment of thyroid FNAs significantly reduces the number of nondiagnostic aspirates. However, the benefit of onsite evaluation, at least for US-guided FNAs, depends on the experience of the radiologist. In the current study, experienced radiologists with a relatively low nondiagnostic rate did not benefit from onsite adequacy assessment. This finding confirms the importance of experience in the performance of FNA, but suggests that onsite adequacy assessment may assist the less experienced operator.

Output: Is the value of onsite adequacy assessment of thyroid fine-needle aspirations a function of operator experience?


Input: Consider Input: Context: Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein function until the local cellular redox environment has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the Forkhead Box O4 (FOXO4) transcription factor.', 'In this study, we sought to investigate whether redox signaling differentially controls the human FOXO3 and FOXO4 paralogs.', 'We present evidence that FOXO3 and FOXO4 have acquired paralog-specific cysteines throughout vertebrate evolution. Using a proteome-wide screen, we identified previously unknown redox-dependent FOXO3 interaction partners. The nuclear import receptors Importin-7 (IPO7) and Importin-8 (IPO8) form a disulfide-dependent heterodimer with FOXO3, which is required for its reactive oxygen species-induced nuclear translocation. FOXO4 does not interact with IPO7 or IPO8.
Answer: IPO7 and IPO8 control the nuclear import of FOXO3, but not FOXO4, in a redox-sensitive and disulfide-dependent manner. Our findings suggest that evolutionary acquisition of cysteines has contributed to regulatory divergence of FOXO paralogs, and that phylogenetic analysis can aid in the identification of cysteines involved in redox signaling.

Output: Does evolutionary acquisition of cysteines determine FOXO paralog-specific redox signaling?


Input: Consider Input: Context: The aim of this study was to investigate PD-1/PD-L1 involvement in the hyporesponsiveness of rheumatoid arthritis (RA) synovial fluid (SF) CD4 T cells upon stimulation by thymic stromal lymphopoietin (TSLP)-primed CD1c myeloid dendritic cells (mDCs).', 'Expression of PD-1 on naïve (Tn), central memory (Tcm) and effector memory (Tem) CD4 T cell subsets was assessed by flow cytometry. PD-L1 expression and its regulation upon TSLP stimulation of mDCs from peripheral blood (PB) and SF of RA patients were investigated by quantitative RT-PCR and flow cytometry. The involvement of PD-1/PD-L1 interactions in SF T cell hyporesponsiveness upon (TSLP-primed) mDC activation was determined by cell culture in the presence of PD-1 blocking antibodies, with or without interleukin 7 (IL-7) as a recognized suppressor of PD-1 expression.', 'PD-1 expression was increased on CD4 T cells derived from SF compared with PB of RA patients. TSLP increased PD-L1 mRNA expression in both PB and SF mDCs. PD-L1 protein expression was increased on SF mDCs compared with PB mDCs and was associated with T cell hyporesponsiveness. Blockade of PD-1, as well as IL-7 stimulation, during cocultures of memory T cells and (TSLP-primed) mDCs from RA patients significantly recovered T cell proliferation.
Answer: SF T cell hyporesponsiveness upon (TSLP-primed) mDC stimulation in RA joints is partially dependent on PD-1/PD-L1 interactions, as PD-1 and PD-L1 are both highly expressed on SF T cells and mDCs, respectively, and inhibiting PD-1 availability restores T cell proliferation. The potential of IL-7 to robustly reverse this hyporesponsiveness suggests that such proinflammatory cytokines in RA joints strongly contribute to memory T cell activation.


Output: Is synovial T cell hyporesponsiveness to myeloid dendritic cells reversed by preventing PD-1/PD-L1 interactions?