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.

Ex 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?

Ex 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.


Ex Input:
Context: To provide optimal treatment of heterogeneous triple negative breast cancer (TNBC), we need biomarkers that can predict the chemotherapy response.', 'We retrospectively investigated BRCAness in 73 patients with breast cancer who had been treated with taxane- and/or anthracycline-based neoadjuvant chemotherapy (NAC). Using multiplex, ligation-dependent probe amplification on formalin-fixed core needle biopsy (CNB) specimens before NAC and surgical specimens after NAC. BRCAness status was assessed with the assessor unaware of the clinical information.', 'We obtained 45 CNB and 60 surgical specimens from the 73\xa0patients. Of the 45 CNB specimens, 17 had BRCAness (38.6% of all subtypes). Of the 23 TNBC CNB specimens, 14\xa0had BRCAness (61% of TNBC cases). The clinical response rates were significantly lower for BRCAness than for non-BRCAness tumors, both for all tumors (58.8% vs. 89.3%, P\xa0= .03) and for TNBC (50% vs. 100%, P\xa0= .02). All tumors that progressed with taxane therapy had BRCAness. Of the patients with TNBC, those with non-BRCAness cancer had pathologic complete responses significantly more often than did those with BRCAness tumors (77.8%\xa0vs. 14.3%, P\xa0= .007). After NAC, the clinical response rates were significant lower for BRCAness than for non-BRCAness tumors in all subtypes (P\xa0= .002) and in TNBC cases (P\xa0= .008). After a median follow-up of 26.4 months, 6 patients-all with BRCAness-had developed recurrence. Patients with BRCAness had shorter progression-free survival than did those with non- BRCAness (P\xa0=\xa0.049).\Question: Does bRCAness predict resistance to taxane-containing regimens in triple negative breast cancer during neoadjuvant chemotherapy?

Ex Output:
Identifying BRCAness can help predict the response to taxane, and changing regimens for BRCAness TNBC might improve patient survival. A larger prospective study is needed to further clarify this issue.


Ex Input:
Context: There is no consensus about the impact of a high BMI on postoperative morbidity and survival after esophagectomy. The aim of this study was to determine the influence of a high BMI on postoperative complications and survival in a large cohort of esophageal cancer patients.', 'From January 2006 to December 2012, 1,342 consecutive esophageal cancer patients who underwent esophagectomy were included in this study. Patients were divided into three groups: 950 patients were classified as normal BMI (BMI 18.5-24.9 kg/m(2)), 279 were classified as high BMI (BMI ≥ 25 kg/m(2)), and 113 as low BMI (BMI < 18.5 kg/m(2)). Multivariate logistic regression models were used to identify confounding factors associated with postoperative complications. The impact of BMI on overall survival (OS) was estimated by the Kaplan-Meier method and Cox proportional hazard models.', 'The predominance of pathological type was esophageal squamous cell carcinoma (n = 1,280, 95.4 %). Overall morbidity, mortality, and hospital stay did not differ among groups. The incidence of pneumonia was higher in patients with high BMI compared with those with normal BMI (14.7 vs. 9.9 %, P = 0.025). However, chylothorax was less frequent in high-BMI group (0.4 % in high-BMI group, 3.1 % in normal group, and 3.5 % in low group, P = 0.011). Logistic regression analysis revealed high BMI was independently associated with decreased incidence of chylothorax [HR 0.86; 95 % confidence interval 0.76-0.97]. Overweight and obese patients had significantly better overall survival than underweight patients (median OS 55.6 vs. 32.5 months, P = 0.013), while the pathological stage was significantly higher in underweight patients (P = 0.001). In multivariate analysis, T status, N status, differentiation grade, and tumor length were identified as independent prognostic factors.\Question: Is a high body mass index in esophageal cancer patients associated with adverse outcomes following esophagectomy?

Ex Output:

A high BMI is not associated with increased overall morbidity following esophagectomy; moreover, it is associated with decreased incidence of chylothorax. The better overall survival in patients with high BMI compared with those with low BMI might be due to a relatively low pathological stage. A high BMI should therefore not be a relative contraindication for esophagectomy.