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.

Context: Reactive oxygen species have been implicated as signaling molecules modulating the activity of redox-sensitive transcription factors such as nuclear factor kappa B (NF-kappaB). Recently, the transcription factor hypoxia-inducible factor-1 (HIF-1), known to mediate gene expression by hypoxia, has been found to be also activated by nonhypoxic factors in a redox-sensitive manner. We therefore aimed to elucidate the link between these 2 important redox-sensitive transcription factors.', 'In pulmonary artery smooth muscle cells, reactive oxygen species generated either by exogenous H2O2 or by a NOX4-containing NADPH oxidase stimulated by thrombin activated or induced NF-kappaB and HIF-1alpha. The reactive oxygen species-mediated HIF-1alpha induction occurred on the transcriptional level and was dependent on NF-kappaB. Transfection experiments with wild-type or mutant HIF-1alpha promoter constructs revealed the presence of a yet unidentified NF-kappaB binding element. Gel shift analyses and chromatin immunoprecipitation verified binding of NF-kappaB to this site. Furthermore, reactive oxygen species enhanced expression of plasminogen activator inhibitor-1, which was prevented by dominant-negative IkappaB or mutation of the HIF-1 binding site within the plasminogen activator inhibitor-1 promoter.
Answer: These findings show for the first time to our knowledge that reactive oxygen species directly link HIF-1alpha and NF-kappaB, implicating an important pathophysiological role of this novel pathway in disorders associated with elevated levels of reactive oxygen species.
Do reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site?

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\u2009=\u2009125) or RT (n\u2009=\u200948) 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.
Is tumor invasion depth a useful pathologic assessment for predicting outcomes in cervical squamous cell carcinoma after neoadjuvant radiotherapy?

Context: To use MR spectroscopy to aid in the diagnosis of demyelinating disease and to help differentiate tumefactive demyelinating lesions from neoplastic processes.', 'MR imaging of the brain was obtained in 4 patients who presented clinically with focal neurologic deficits. MR imaging initially revealed parenchymal mass lesions. Single-voxel MR spectroscopy was then performed utilizing a point-resolved spectroscopy sequence protocol with a short echo time (30 msec).', 'MR imaging revealed a focal ring-enhancing mass in one patient, multiple ring-enhancing lesions in the second patient, a large area of edema and mass effect without associated enhancement in the third patient, and multiple solid and peripherally enhancing lesions in the fourth patient. MR spectroscopic results in all 4 patients demonstrated marked elevation of the glutamate and glutamine peaks (2.1-2.5 ppm). Other nonspecific (and in a sense confounding) findings included elevation of the choline peak (3.2 ppm), elevation of the lactate peak (1.3 ppm), elevation of the lipid peak (0.5-1.5 ppm), and decrease in the N-acetylaspartate peak (2.0 ppm). All 4 patients were eventually given the diagnosis of multiple sclerosis based on CSF analysis, brain biopsy, and/or clinical follow-up.
Answer: MR spectroscopic metabolite information may be useful in the diagnosis of demyelinating disease by demonstrating elevation of the glutamate/glutamine peaks because elevation of these peaks is typically not seen in aggressive intra-axial neoplastic processes. This is particularly beneficial in the rarer cases of tumefactive demyelinating lesions, which are very difficult to differentiate from neoplasms by imaging findings alone.

Do metabolite findings in tumefactive demyelinating lesions utilizing short echo time proton magnetic resonance spectroscopy?