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.

Input: Consider Input: Context: Specific and effective therapy for prevention or reversal of bronchiolitis obliterans (BO) is lacking. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF) gene modified mesenchymal stromal cells (MSCs) on BO.', 'A mouse model of experimental BO was established by subcutaneously transplanting the tracheas from C57BL/6 mice into Balb/C recipients, which were then administered saline, Ad-HGF-modified human umbilical cord-MSCs (MSCs-HGF) or Ad-Null-modified MSCs (MSCs-Null). The therapeutic effects of MSCs-Null and MSCs-HGF were evaluated by using fluorescence-activated cell sorting (FACS) for lymphocyte immunophenotype of spleen, enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (rt-PCR) for cytokine expression, and histopathological analysis for the transplanted trachea.', 'The histopathologic recovery of allograft tracheas was improved significantly after MSCs-Null and MSCs-HGF treatment and the beneficial effects were particularly observed in MSCs-HGF-treated mice. Furthermore, the allo-transplantation-induced immunophenotype disorders of the spleen, including regulatory T (Treg), T helper (Th)1, Th2 and Th17, were attenuated in both cell-treated groups. MSCs-HGF treatment reduced expression and secretion of inflammation cytokines interferon-gamma (IFN-γ), and increased expression of anti-inflammatory cytokine interleukin (IL)-4 and IL-10. It also decreased the expression level of the profibrosis factor transforming growth factor (TGF)-β.\Question: Does hepatocyte growth factor enhance the inflammation-alleviating effect of umbilical cord-derived mesenchymal stromal cells in a bronchiolitis obliterans model?

Output: Treatment of BO with HGF gene modified MSCs results in reduction of local inflammation and promotion in recovery of allograft trachea histopathology. These findings might provide an effective therapeutic strategy for BO.


Input: Consider Input: Context: The current standard of care for glioblastoma (GBM) involves a combination of surgery, radiotherapy, and temozolomide chemotherapy, but this regimen fails to achieve long-term tumor control. Resistance to temozolomide is largely mediated by expression of the DNA repair enzyme MGMT; however, emerging evidence suggests that inactivation of MSH6 and other mismatch repair proteins plays an important role in temozolomide resistance. Here, we investigate endogenous MSH6 mutations in GBM, anaplastic oligodendroglial tumor tissue, and corresponding brain tumor-initiating cell lines (BTIC).', 'MSH6 sequence and MGMT promoter methylation were determined in human tumor samples and BTICs. Sensitivity to temozolomide was evaluated in vitro using BTICs in the absence and presence of O(6)-benzylguanine to deplete MGMT. The influence of MGMT and MSH6 status on in vivo sensitivity to temozolomide was evaluated using intracranial BTIC xenografts.', 'We identified 11 previously unreported mutations in MSH6 in nine different glioma samples and six paired BTIC lines from adult patients. In addition, MSH6 mutations were documented in three oligodendrogliomas and two treatment-naïve gliomas, both previously unreported findings. These mutations were found to influence the sensitivity of BTICs to temozolomide both in vitro and in vivo, independent of MGMT promoter methylation status.\Question: Do novel MSH6 mutations in treatment-naïve glioblastoma and anaplastic oligodendroglioma contribute to temozolomide resistance independently of MGMT promoter methylation?

Output: These data demonstrate that endogenous MSH6 mutations may be present before alkylator therapy and occur in at least two histologic subtypes of adult glial neoplasms, with this report serving as the first to note these mutations in oligodendroglioma. These findings broaden our understanding of the clinical response to temozolomide in gliomas.


Input: Consider Input: Context: The objective of this study was to determine the utility of subjective memory decline (SMD) to predict episodic memory change and rates of clinical progression in cognitively normal older adults with evidence of high β-amyloid burden (CN Aβ+).', 'Fifty-eight CN Aβ+ participants from the Australian Imaging, Biomarkers, and Lifestyle study responded to an SMD questionnaire and underwent comprehensive neuropsychological assessments. Participant data for three follow-up assessments were analyzed.', "In CN Aβ+, subjects with high SMD did not exhibit significantly greater episodic memory decline than those with low SMD. High SMD was related to greater rates of progression to mild cognitive impairment or Alzheimer's disease (AD) dementia (hazard ratio\xa0=\xa05.1; 95% confidence interval, 1.4-20.0, P\xa0=\xa0.02) compared with low SMD. High SMD was associated with greater depressive symptomatology and smaller left hippocampal volume.\Question: Does subjective memory decline predict greater rates of clinical progression in preclinical Alzheimer 's disease?


Output: High SMD is a harbinger of greater rates of clinical progression in preclinical AD. Although SMD reflects broader diagnostic implications for CN Aβ+, more sensitive measures may be required to detect early subtle cognitive change.