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: Monocytes are cellular components of wound repair, arteriogenesis, and atherogenesis. Vascular endothelial growth factor (VEGF)-A and placental growth factor recruit monocytes to sites of arteriogenesis via stimulation of VEGF receptor-1 (VEGFR-1). The chemotactic response of monocytes to VEGF-A is attenuated in individuals with diabetes mellitus (DM). This VEGF resistance correlates with impaired collateral growth. The aim of this study is to elucidate the molecular basis of VEGF resistance and impaired monocyte response in DM.', 'Phosphorylation of Akt, p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) could be stimulated with either placental growth factor-1 or VEGF-A in monocytes from non-DM but not DM individuals. In contrast, formyl-methionyl-leucyl-phenylalanine caused a comparable activation of these molecules in both DM and non-DM monocytes. Baseline phosphorylation of Akt, p38, and ERK1/2 was significantly elevated in monocytes from DM compared with non-DM subjects. Of note, H(2)O(2) activated Akt, p38, and ERK1/2 in non-DM monocytes ex vivo. Protein tyrosine phosphatases had stronger oxidative modifications in monocytes from DM than from non-DM individuals, which reflects functional protein tyrosine phosphatase inhibition, similar to that seen after H(2)O(2) challenge. Overall, protein tyrosine phosphatase and protein tyrosine phosphatase-1B activity were reduced in DM monocytes. DM monocytes revealed higher expression of the receptor for advanced glycation end products. Stimulation with advanced glycation end products ligands resulted in activation of non-DM monocytes and inhibition of VEGFR-1-mediated chemotaxis. The elevated baseline phosphorylation/activation of Akt, p38, and ERK1/2 in DM monocytes likely causes the resistance to further stimulation with specific stimuli such as VEGF-A, revealing a molecular explanation of the DM-related signal transduction defect.\Question: Does diabetes mellitus activate signal transduction pathways resulting in vascular endothelial growth factor resistance of human monocytes?

Output: We propose that elevated advanced glycation end products expression and increased oxidative stress in diabetic monocytes lead to activation of VEGFR-1-related signaling pathways and to desensitization of VEGFR-1 responses. These data establish VEGF resistance as a novel molecular concept for DM-related cellular dysfunction.


Input: Consider Input: Context: In Crohn's disease (CD), rapid response to anti-tumor necrosis factor therapy improves short- and medium-term outcomes, but the relationship between early remission (ER) and long-term remission is unclear.", 'This exploratory analysis of PRECiSE 3 (NCT00160524) assessed whether ER after initiation of certolizumab pegol predicted long-term remission.', 'Patients enrolled in PRECiSE 3 had completed PRECiSE 1 or 2, two randomized placebo-controlled studies for moderate to severe CD, and received open-label certolizumab pegol 400\u2009mg every 4 weeks for a total treatment duration of ≤7.5 years. Time to loss of remission between patients with and without ER (Harvey-Bradshaw Index ≤4 at or before Week 6 of PRECiSE 1 or 2) was compared by log-rank test of Kaplan-Meier estimates.', 'At baseline, patients with (n\u2009=\u2009242) and without (n\u2009=\u2009148) ER had mean (standard deviation [SD]) durations of CD of 6.8 (6.6) and 7.4 (7.8) years, mean (SD) CD Activity Index scores of 280.3 (53.4) and 311.1 (55.5), with 45.5% and 41.9% of patients having ileocolonic CD, and median C-reactive protein concentrations of 8.0 and 5.0\u2009mg/L, respectively. Median certolizumab pegol plasma concentrations during the first 6 weeks of therapy were similar in both groups. Mean time to loss of remission was significantly longer in patients with versus without ER (2.77 vs. 1.14 years, p\u2009<\u20090.0001).\Question: Does early remission status predict long-term outcomes in patients with Crohn 's disease treated with certolizumab pegol?

Output: In certolizumab pegol-treated patients with CD, ER appears to be an important predictor of long-term clinical remission. Prospective trials are needed to determine whether ER improves other long-term outcomes.


Input: Consider Input: Context: To evaluate the usefulness of fluorescence in situ hybridization (FISH) on peripheral-blood specimens to evaluate the cytogenetic response to treatment in patients with chronic myeloid leukemia (CML).', 'In a first attempt, we analyzed 62 bone marrow specimens using interphase FISH and compared the results with those of conventional cytogenetics. In a second step, we analyzed 60 paired sets of bone marrow and peripheral-blood specimens with interphase FISH.', 'The results of interphase FISH agreed with conventional cytogenetics on bone marrow for most patients, and only minor differences were found (r =.98). The comparison of interphase FISH on bone marrow versus peripheral-blood specimens showed a strong correlation between these two specimen sources (r =.97).\Question: Is fluorescence in situ hybridization on peripheral-blood specimens a reliable method to evaluate cytogenetic response in chronic myeloid leukemia?


Output: Our results confirmed that FISH is a sensitive technique for the evaluation of response to treatment in patients with CML. Moreover, our study suggests that follow-up of cytogenetic response to therapy can be evaluated on peripheral-blood specimens, thus enabling an easier and more frequent evaluation of patients. The next step will be to evaluate this technique in a large prospective trial to define the prognostic value of complete remissions evaluated by FISH.


