TASK DEFINITION: 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.
PROBLEM: Context: Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments.', 'ECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle.\Question: Does visual gene-network analysis reveal the cancer gene co-expression in human endometrial cancer?

SOLUTION: The results of this study provide a powerful biomarker discovery platform to better understand the progression of ECs and to uncover potential therapeutic targets in the treatment of ECs. This information might lead to improved monitoring of ECs and resulting improvement of treatment of ECs, the 4th most common of cancer in women.

PROBLEM: 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?

SOLUTION: 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.

PROBLEM: Context: Approximately one third of stable patients with significant intra-abdominal injury do not have significant intraperitoneal blood evident on admission. We hypothesized that a delayed, repeat ultrasound study (Secondary Ultrasound--SUS) will reveal additional intra-abdominal injuries and hemoperitoneum.', 'We performed a prospective observational study of trauma patients at our Level I trauma center from April 2003 to December 2003. Patients underwent an initial ultrasound (US), followed by a SUS examination within 24 hours of admission. Patients not eligible for a SUS because of early discharge, operative intervention or death were excluded. All US and SUS exams were performed and evaluated by surgical/emergency medicine house staff or surgical attendings.', 'Five hundred forty-seven patients had both an initial US and a SUS examination. The sensitivity of the initial US in this patient population was 31.1% and increased to 72.1% on SUS (p < 0.001) for intra-abdominal injury or intra-abdominal fluid. The specificity for the initial US was 99.8% and 99.8% for SUS. The negative predictive value was 92.0% for the initial US and increased to 96.6% for SUS (p = 0.002). The accuracy of the initial ultrasound was 92.1% and increased to 96.7% on the SUS (p < 0.002). No patient with a negative SUS after 4 hours developed clinically significant hemoperitoneum.\Question: Does secondary ultrasound examination increase the sensitivity of the FAST exam in blunt trauma?

SOLUTION:
A secondary ultrasound of the abdomen significantly increases the sensitivity of ultrasound to detect intra-abdominal injury.