instruction:
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: Most melanomas harbor oncogenic BRAF(V600) mutations, which constitutively activate the MAPK pathway. Although MAPK pathway inhibitors show clinical benefit in BRAF(V600)-mutant melanoma, it remains incompletely understood why 10% to 20% of patients fail to respond. Here, we show that RAF inhibitor-sensitive and inhibitor-resistant BRAF(V600)-mutant melanomas display distinct transcriptional profiles. Whereas most drug-sensitive cell lines and patient biopsies showed high expression and activity of the melanocytic lineage transcription factor MITF, intrinsically resistant cell lines and biopsies displayed low MITF expression but higher levels of NF-κB signaling and the receptor tyrosine kinase AXL. In vitro, these MITF-low/NF-κB-high melanomas were resistant to inhibition of RAF and MEK, singly or in combination, and ERK. Moreover, in cell lines, NF-κB activation antagonized MITF expression and induced both resistance marker genes and drug resistance. Thus, distinct cell states characterized by MITF or NF-κB activity may influence intrinsic resistance to MAPK pathway inhibitors in BRAF(V600)-mutant melanoma.\Question: Does a melanoma cell state distinction influence sensitivity to MAPK pathway inhibitors?
answer:
Although most BRAF(V600)-mutant melanomas are sensitive to RAF and/or MEK inhibitors, a subset fails to respond to such treatment. This study characterizes a transcriptional cell state distinction linked to MITF and NF-κB that may modulate intrinsic sensitivity of melanomas to MAPK pathway inhibitors.


question:
Context: Cannabis use disorders (CUD) may influence the course of bipolar disorder (BD), but key confounding factors such as tobacco smoking have not been adequately addressed. This study examined whether CUD was associated with a more severe illness course in tobacco smoking BD patients.', 'A sample of French and Norwegian tobacco smoking patients with BD I and II (N=642) was investigated. DSM-IV diagnoses and other characteristics were obtained through personal interviews using structured questionnaires. The association between CUD and illness course was assessed in regression analyses.', 'In bivariate analyses, CUD was associated with earlier BD onset, higher frequency of manic (in BD I) and depressive episodes and hospitalizations per illness year, and a higher occurrence of psychotic episodes. After controlling for potential confounders, the relationships with earlier BD onset (B=-5.60 95% CI=-7.65 to -3.64), and increased rates of manic episodes (OR=1.93, 95% CI: 1.15 to 3.23) and hospitalizations (OR=2.93, 95% CI: 1.85 to 4.64) remained statistically significant.\Question: Is cannabis use disorder associated with greater illness severity in tobacco smoking patients with bipolar disorder?
answer:
Despite the multivariate approach, differences between the two samples may lead to spurious findings related to hidden confounders. Substance use and mood episode information was collected retrospectively, and potential birth cohort effects could not be controlled for.


question:
Context: Traditional methods for bile culturing may miss a large number of underlying bacterial infections that could lead to acute or chronic cholecystitis.', 'to evaluate possible differences regarding the site of material collection and thus to detect the most suitable sample site for gallbladder culture.', "A cohort of 137 patients with symptomatic cholelithiasis was enrolled. After surgical excision of the gallbladder, bile cultures were separately performed from fundus, body and neck. Identification of bacteria as well as computation of mean bacterial concentrations were performed with standard microbiological techniques. Wilcoxon's paired and Chi-square tests were used for comparison between continuous and discrete parameters, respectively.", 'Thirty-one patients (22.6%) demonstrated at least one positive culture sample. Positivity was 31/31 (100.0%) in neck samples, 20/31 (64.5%) in body and 13/31 (41.9%) in fundus samples (P<0.001). The microorganisms identified were Escherichia coli (14 cases) and Enterococcus faecalis (10 cases), followed by Staphylococcus aureus (3 cases), Pseudomonas aeruginosa, Enterococcus faecium, Enterobacter aerogenes and Enterobacter cloacae (1 case each). Mean bacterial concentrations in positive samples derived from the neck (272.2 +/- 187.5) were higher (P<0.01) when compared to those derived from both the body (38.2 +/- 28.7) and the fundus (12.5 +/- 11.3). Mean bacterial concentrations in positive samples derived from the body were higher (P<0.01) than those derived from the fundus.\Question: Does the culture site of the gallbladder affect recovery of bacteria in symptomatic cholelithiasis?
answer:

The neck of the gallbladder hosts the biggest bacterial load in comparison with the body and the fundus. This difference might be attributed to the presence of Rokitansky-Aschoff sinuses, which is the main histological characteristic of the region.