In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
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Question: Context: Cognitive impairment is a common feature of late-life bipolar disorder (BD). Yet, there is limited information on the biological mechanisms associated with this process. It is uncertain whether cognitively impaired patients with BD may present the Alzheimer's disease (AD) bio-signature in the cerebrospinal fluid (CSF), defined as a combination of low concentrations of the amyloid-beta peptide (Aβ1-42 ) and high concentrations of total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau). In this study, we sought to determine whether cognitive impairment in elderly patients with BD is associated with the AD CSF bio-signature.", 'Seventy-two participants were enrolled in the study. The test group comprised older adults with BD and mild cognitive impairment (BD-MCI; n\xa0=\xa016) and the comparison groups comprised patients with dementia due to AD (n\xa0=\xa017), patients with amnestic MCI (aMCI; n\xa0=\xa014), and cognitively healthy older adults (control group; n\xa0=\xa025). CSF samples were obtained by lumbar puncture and concentrations of Aβ1-42 , T-tau and P-tau were determined.', 'CSF concentrations of all biomarkers were significantly different in the AD group compared to all other groups, but did not differentiate BD-MCI subjects from aMCI subjects and controls. BD-MCI patients had a non-significant reduction in CSF Aβ1-42 compared to controls, but this was still higher than in the AD group. Concentrations of T-tau and P-tau in BD-MCI patients were similar to those in controls, and significantly lower than those in AD.\Question: Is cognitive impairment in late-life bipolar disorder associated with Alzheimer 's disease pathological signature in the cerebrospinal fluid?

Answer: Cognitively impaired patients with BD do not display the so-called AD bio-signature in the CSF. We therefore hypothesize that cognitive deterioration in BD is not associated with the classical pathophysiological mechanisms observed in AD, i.e., amyloid deposition and hyperphosphorylation of microtubule-associated tau protein.


Question: Context: The incidence and predictors of spontaneous hepatitis B surface-antigen (HBsAg) seroclearance in patients with chronic hepatitis B virus (HBV) were evaluated.', 'A total of 1427 patients with chronic HBV infection, who were followed between 1994 and 2013, were investigated in this retrospective study. All data were extracted from patient files.', 'Spontaneous HBsAg seroclearance occurred in 84 patients during 8798 person-years of follow-up. The patients were categorized into 3 groups at follow-up based on HBV DNA features as continuously <100 copies/mL (Group A), 0-10,000 copies/mL (Group B), and 0 to >10,000 copies/mL (Group C). Alanine aminotransferase features in the 2 groups were categorized as continuously normal (<40 U/L) and 0 to >40 U/L. Spontaneous HBsAg seroclearance was seen primarily in patients with Group A HBV DNA features, and continuously low HBV DNA values were the main predictor of HBsAg seroclearance (P < 0.001).\Question: Is a persistently low HBV DNA level a predictor of spontaneous HBsAg clearance in patients with chronic hepatitis B?

Answer: These results suggest that a continuously low viral load is the most important factor affecting spontaneous HBsAg seroclearance.


Question: Context: The transcription factor GATA3 is a favorable prognostic indicator in estrogen receptor-α (ERα)-positive breast tumors in which it participates with ERα and FOXA1 in a complex transcriptional regulatory program driving tumor growth. GATA3 mutations are frequent in breast cancer and have been classified as driver mutations. To elucidate the contribution(s) of GATA3 alterations to cancer, we studied two breast cancer cell lines, MCF7, which carries a heterozygous frameshift mutation in the second zinc finger of GATA3, and T47D, wild-type at this locus.', 'Immunofluorescence staining and subcellular fractionation were employed to verify cellular localization of GATA3 in T47D and MCF7 cells. To test protein stability, cells were treated with translation inhibitor, cycloheximide or proteasome inhibitor, MG132, and GATA3 abundance was measured over time using immunoblot. GATA3 turn-over in response to hormone was determined by treating the cells with estradiol or ERα agonist, ICI 182,780. DNA binding ability of recombinant GATA3 was evaluated using electrophoretic mobility shift assay and heparin chromatography. Genomic location of GATA3 in MCF7 and T47D cells was assessed by chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq).', 'GATA3 localized in the nucleus in T47D and MCF7 cells, regardless of the mutation status. The truncated protein in MCF7 had impaired interaction with chromatin and was easily released from the nucleus. Recombinant mutant GATA3 was able to bind DNA to a lesser degree than the wild-type protein. Heterozygosity for the truncating mutation conferred protection from regulated turnover of GATA3, ERα and FOXA1 following estrogen stimulation in MCF7 cells. Thus, mutant GATA3 uncoupled protein-level regulation of master regulatory transcription factors from hormone action. Consistent with increased protein stability, ChIP-seq profiling identified greater genome-wide accumulation of GATA3 in MCF7 cells bearing the mutation, albeit with a similar distribution across the genome, comparing to T47D cells.\Question: Does breast tumor specific mutation in GATA3 affect physiological mechanisms regulating transcription factor turnover?

Answer:
We propose that this specific, cancer-derived mutation in GATA3 deregulates physiologic protein turnover, stabilizes GATA3 binding across the genome and modulates the response of breast cancer cells to estrogen signaling.