Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

[Q]: Context: Spinal anesthesia can be challenging in patients undergoing total joint arthroplasty because of poorly palpable surface landmarks and age-related changes in the lumbar spine. We hypothesized that pre-procedural ultrasound imaging would be effective in identifying the lumbar intervertebral spaces and would provide an accurate measure of the depth to the intrathecal space.', "Fifty patients undergoing elective total joint arthroplasty were recruited in this prospective descriptive study. Using a curved-array 2-5 MHz transducer, the lumbar spine was imaged in two views, i.e., longitudinal parasagittal (LP) and transverse midline (TM). The intervertebral levels were identified by counting upwards from the sacrum. The locations of the interlaminar spaces were identified by visualizing the ligamentum flavum-dura mater complex and the posterior aspect of the vertebral body. The needle insertion point for a midline approach was determined from the ultrasound examination and was marked on the skin of the patient's back.", 'The mean patient age was 67 +/- 10 yr, and 46% of the patients had a body mass index >30 kg . m(-2). Surface landmarks were difficult or impossible to palpate in 38% of the patients. The scan quality on the LP and TM views was adequate or better in 100 and 98% of the patients, respectively. Dural puncture was achieved with one needle insertion attempt and within two needle insertion attempts in 84% and 98% of the patients, respectively. The ultrasound-measured depth to the intrathecal space correlated well with the actual needle insertion depth (concordance correlation coefficient = 0.82, accuracy 0.95, precision 0.86), with a tendency to overestimate the depth by just 2.1 +/- 5.4 mm.
Answer: Ultrasound imaging of the lumbar spine provides clinically useful information that can facilitate spinal anesthesia in the older orthopedic patient population.
[A]: Does an ultrasound-assisted approach facilitate spinal anesthesia for total joint arthroplasty?


[Q]: Context: The endosteum of the bone marrow provides a specialized hypoxic niche that may serve to preserve the integrity, pluripotency, longevity and stemness of resident mesenchymal stem cells (MSCs). To explore the molecular genetic consequences of such a niche we subjected human (h) MSCs to a pO2 of 4 mmHg and analyzed global gene expression and alternative splicing (AS) by genome-exon microarray and RT-qPCR, and phenotype by western blot and immunostaining.', 'Out of 446 genes differentially regulated by >2.5-fold, down-regulated genes outnumbered up-regulated genes by 243:203. Exon analyses revealed 60 hypoxia-regulated AS events with splice indices (SI) >1.0 from 53 genes and a correlation between high SI and degree of transcript regulation. Parallel analyses of a publicly available AS study on human umbilical vein endothelial cells (HUVECs) showed that there was a strong cell-specific component with only 11 genes commonly regulated in hMSCs and HUVECs and 17 common differentially spliced genes. Only 3 genes were differentially responsive to hypoxia at the gene (>2.0) and AS levels in both cell types. Functional assignments revealed unique profiles of gene expression with complex regulation of differentiation, extracellular matrix, intermediate filament and metabolic marker genes. Antioxidant genes, striated muscle genes and insulin/IGF-1 signaling intermediates were down-regulated. There was a coordinate induction of 9 out of 12 acidic keratins that along with other epithelial and cell adhesion markers implies a partial mesenchymal to epithelial transition.
Answer: We conclude that severe hypoxia confers a quiescent phenotype in hMSCs that is reflected by both the transcriptome profile and gene-specific changes of splicosome actions. The results reveal that severe hypoxia imposes markedly different patterns of gene regulation of MSCs compared with more moderate hypoxia. This is the first study to report hypoxia-regulation of AS in stem/progenitor cells and the first molecular genetic characterization of MSC in a hypoxia-induced quiescent immobile state.
[A]: Does severe hypoxia exert parallel and cell-specific regulation of gene expression and alternative splicing in human mesenchymal stem cells?


[Q]: Context: BRAF mutations occur in 5% to 10% of metastatic colorectal cancers and are biomarkers associated with a poor prognosis. However, the outcomes with standard chemotherapy over sequential lines of therapy in a large cohort of patients with BRAF-mutant tumors have not been described.', 'We searched the M.D. Anderson Cancer Center databases for patients with colorectal cancer and identified BRAF mutations between December 2003 and May 2012. Patients were analyzed for clinical characteristics, PFS, overall survival, and chemotherapeutic agents used. Survival was estimated according to the Kaplan-Meier method.', 'Among the 1567 patients tested for BRAF mutations at our institution, 127 (8.1%) had tumors with BRAF mutations. The 71 patients who presented with metastatic disease received a median of 2 lines of chemotherapy. For the first 3 lines of chemotherapy, median PFS was 6.3 months (n\xa0= 69 patients; 95% confidence interval [CI], 4.9-7.7 months), 2.5 months (n\xa0= 58 patients; 95% CI, 1.8-3.0 months), and 2.6 months (n\xa0= 31 patients; 95% CI, 1.0-4.2 months), respectively. Median PFS was not affected by the backbone chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or irinotecan-based (6.4 months vs. 5.4 months, respectively; P\xa0= .99).
Answer: PFS is expectedly poor for patients with BRAF-mutated metastatic colorectal cancer. Despite the ascertainment bias present (with testing preferentially performed in patients suitable for clinical trials in refractory disease), these data provide historic controls suitable for future study design and support the idea that novel therapeutic options are essential in this population.
[A]:
Does progression-free survival remain poor over sequential lines of systemic therapy in patients with BRAF-mutated colorectal cancer?