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.
--------
Question: Context: Oxidative stress generated within inflammatory joints can produce autoimmune phenomena and joint destruction. Radical species with oxidative activity, including reactive nitrogen species, represent mediators of inflammation and cartilage damage.', 'To assess serum nitric oxide as a marker of oxidative stress in Egyptian patients with rheumatoid arthritis and its relation to disease activity.', '80 patients with rheumatoid arthritis were divided into 2 groups, according to the DAS-28 score: Group I: 42 patients with disease activity, and Group II: 38 patients with no disease activity. Forty age- and sex-matched individuals were included as control group (Group III). Routine laboratory investigations were done, and nitric oxide was measured using Elisa. Hand plain radiographies were done for radiological status scoring using the Sharp method.', 'A comparison between nitric oxide in all three groups showed a highly significant difference (p < 0.001), significantly higher levels were obtained among rheumatoid arthritis patients in comparison to controls, and higher levels were obtained in patients with active disease (mean±SD 82.38±20.46) in comparison to patients without active disease (35.53±7.15). Nitric oxide in Group I showed a significant positive correlation with morning stiffness (r=0.45), arthritis (r=0.43), platelet count (r=0.46), erythrocyte sedimentation rate (r=0.83), C-reactive protein (r=0.76) and Disease Activity Score (r=0.85). Nitric oxide showed a significant positive correlation (r=0.43) with hand radiographies (Sharp score) in Group I.\Question: Are [ Higher nitric oxide levels associated with disease activity in Egyptian rheumatoid arthritis patients ]?

Answer: There are increased levels of nitric oxide in the serum of patients with rheumatoid arthritis. Nitric oxide correlates significantly with disease activity, inflammatory markers and radiological joint status.


Question: Context: Characteristic clinical heterogeneity and mostly slow-growing behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause problems in finding appropriate treatments. Thus, current therapy options are not satisfactory. PKI-587 is a highly potent novel dual inhibitor of PI3K and mTORC1/C2.', 'We assessed the effects of PKI-587 in different GEP-NEN tumor models, including poorly differentiated cell line LCC-18, compared with the established mTORC1 inhibitor everolimus.', 'We treated the cell lines BON, QGP1, KRJ-I and LCC-18 with increasing concentrations of the inhibitor PKI-587, and compared with everolimus and DMSO. We assessed the impact of treatments on viability (WST-1 assay), on apoptotic processes (Caspase 3/7 assay, JC-1) and on cell cycle regulation (flow cytometry). We determined alterations of signaling mediators by phosphor-specific western blot analysis and conducted multiplexed gene expression analysis (nCounter® technology).', 'In all cell lines, PKI-587 dose-dependently inhibited proliferation whereas everolimus was less effective. Treatment with PKI-587 led to cell cycle arrest, induction of apoptosis and successfully suppressed activity of direct mTORC1 target 4E-BP1, a crucial factor for tumor genesis only partially inhibited by everolimus. Gene expression analyses revealed relevant changes of RAS, MAPK, STAT and PI3K pathway genes after treatment. Treatment dependent and cell line characteristic effects on AKT/RB/E2F signaling regarding cell cycle control and apoptosis are extensively discussed in this article.\Question: Is inhibition of mTORs Catalytic Site by PKI-587 a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease?

Answer: PI3K/mTOR dual targeting is a promising new therapeutic approach in neuroendocrine tumor disease that should be evaluated in further clinical trials.


Question: Context: Severe malaria (SM) is classically associated with Plasmodium falciparum infection. Little information is available on the contribution of P. vivax to severe disease. There are some epidemiological indications that P. vivax or mixed infections protect against complications and deaths. A large morbidity surveillance conducted in an area where the four species coexist allowed us to estimate rates of SM among patients infected with one or several species.', 'This was a prospective cohort study conducted within the framework of the Malaria Vaccine Epidemiology and Evaluation Project. All presumptive malaria cases presenting at two rural health facilities over an 8-y period were investigated with history taking, clinical examination, and laboratory assessment. Case definition of SM was based on the World Health Organization (WHO) criteria adapted for the setting (i.e., clinical diagnosis of malaria associated with asexual blood stage parasitaemia and recent history of fits, or coma, or respiratory distress, or anaemia [haemoglobin < 5 g/dl]). Out of 17,201 presumptive malaria cases, 9,537 (55%) had a confirmed Plasmodium parasitaemia. Among those, 6.2% (95% confidence interval [CI] 5.7%-6.8%) fulfilled the case definition of SM, most of them in children <5 y. In this age group, the proportion of SM was 11.7% (10.4%-13.2%) for P. falciparum, 8.8% (7.1%-10.7%) for P. vivax, and 17.3% (11.7%-24.2%) for mixed P. falciparum and P. vivax infections. P. vivax SM presented more often with respiratory distress than did P. falciparum (60% versus 41%, p = 0.002), but less often with anaemia (19% versus 41%, p = 0.0001).\Question: Are plasmodium vivax and mixed infections associated with severe malaria in children : a prospective cohort study from Papua New Guinea?

Answer:
P. vivax monoinfections as well as mixed Plasmodium infections are associated with SM. There is no indication that mixed infections protected against SM. Interventions targeted toward P. falciparum only might be insufficient to eliminate the overall malaria burden, and especially severe disease, in areas where P. falciparum and P. vivax coexist.