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.
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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-B signaling and the receptor tyrosine kinase AXL. In vitro, these MITF-low/NF-B-high melanomas were resistant to inhibition of RAF and MEK, singly or in combination, and ERK. Moreover, in cell lines, NF-B activation antagonized MITF expression and induced both resistance marker genes and drug resistance. Thus, distinct cell states characterized by MITF or NF-B 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-B that may modulate intrinsic sensitivity of melanomas to MAPK pathway inhibitors.

Question: Context: Endothelial Microparticles (EMP) are small fragments of endothelial cell membrane shed during apoptosis or activation. Our group has previously reported elevations of EMP in patients with coronary artery disease (CAD), thrombotic thrombocytopenic purpura (TTP), pre-eclampsia, multiple sclerosis (MS), and severe hypertension (HTN). In the present study, we evaluate the possible relationship between EMP levels and the angiographic severity and characteristics of coronary obstructive lesions.', 'We studied a total of 43 patients undergoing coronary angiography. Fifteen had presented with acute myocardial infarction (MI), 20 with unstable anginas (UA), 5 with stable angina (SA) and 3 with congestive heart failure. Coronary angiography was reviewed and coronary lesions were classified using the Ambrose classification. Coronary stenoses were classified as high and low risk. High-risk included lesions with eccentric appearance (type II), presence of thrombi, or multiple irregularities. Low-risk lesions were defined as concentric or type I. Lesions were also analyzed by degree of stenosis and history of acute coronary syndrome (ACS). EMP in plasma was assayed by flow cytometry.', 'EMP in eccentric type II or multiple irregular lesions (high-risk) were 2.5-fold higher than in type I or concentric (low-risk) lesions, p<0.05. Lesions with thrombi had three-fold higher EMP than those without (p=0.05). Mild stenosis (>20%-<45%) had three-fold higher EMP than more severe (>45%), and five-fold higher than those without stenosis (p<0.01). Among patients with type II lesions, those with first ACS episode had four-fold higher EMP levels than those with recurrent ACS (p<0.01).\Question: Do endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes?

Answer: High EMP was associated with high-risk angiographic lesions including eccentric type II, multiple irregular, and lesions with thrombi. Mild to moderate stenosis was associated with higher EMP levels than severe stenosis. EMP may be a useful marker in detecting endothelial injury and risk of ACS as defined by angiography.

Question: Context: The results of studies examining the influence of subclinical hypothyroidism (SCH) and levothyroxine (L-T4) replacement therapy on bone have generated considerable interest but also controversy. The present research aims to evaluate the effects of L-T4 treatment on different skeletal sites in women.', 'A group of 45 premenopausal (mean age: 43.62 6.65 years) and 180 postmenopausal (mean age: 59.51 7.90 years) women with SCH who were undergoing L-T4 replacement therapy for at least 6 months were compared to 58 pre- and 180 postmenopausal women with SCH (untreated) matched for age. The mean doses of L-T4 were 90.88 42.59 g/day in the premenopausal women and 86.35 34.11 g/day in the postmenopausal women. Bone measurements were obtained using quantitative bone ultrasound (QUS) for the phalanx, dual-energy X-ray absorptiometry (DXA) for the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT) for the non-dominant distal forearm.', 'No differences were observed between patients and untreated controls in these bone measurements except in the bone mineral density (BMD) of the spine (p = 0.0214) in postmenopausal women, which was greater in treated women than in untreated controls.\Question: Does treatment of subclinical hypothyroidism affect bone mass as determined by dual-energy X-ray absorptiometry , peripheral quantitative computed tomography and quantitative bone ultrasound in Spanish women?

Answer:
Our results indicate that adequate metabolic control through replacement treatment with L-T4 in pre- and postmenopausal women does not affect bone mass.