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.

Input: Consider Input: Context: SIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear.', 'The effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 µmol/L palmitic acid to induce insulin resistance. SIRT3 was knocked down and overexpressed in L6 cells. SIRT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, c-Jun N-terminal kinase 1 (JNK1), and superoxide dismutase 2 (SOD2) were evaluated by Western blotting.', 'Over expression of SIRT3 increased glucose uptake and decreased ROS production in L6-IR cells as well as in L6 cells. Knock-down of SIRT3 induced increased production of ROS while decreased glucose uptake in both L6 and L6-IR cells, and these effects were reversed by N-acetyl-L-cysteine (NAC). Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-κB p65 (1.5-fold) and JNK1 (1.5-fold). Knockdown of SIRT3 (P < 0.05) reversed the metformin-induced decreases in NF-κB p65 and JNK1 and the metformin-induced increase in SOD2 (P < 0.05).
Answer: Upregulated SIRT3 is involved in the pharmacological mechanism by which metformin promotes glucose uptake. Additionally, SIRT3 may function as an important regulator of oxidative stress and a new alternative approach for targeting insulin resistance-related diseases.

Output: Does metformin ameliorate insulin resistance in L6 rat skeletal muscle cells through upregulation of SIRT3?


Input: Consider Input: Context: Dentofacial deformities are dys-morpho-functional disorders involving the temporomandibular joints (TMJ). Many authors have reported a TMJ improvement in dysfunctional subjects with malocclusion after orthodontic or combined orthodontic and surgical treatment particularly for the relief of pain. In particular, few studies have highlighted the demographic and clinical predictors of response to surgical treatment. To date, no genetic factor has yet been identified as a predictor of response to surgical treatment. The aim of this cohort study is therefore to identify single-nucleotide polymorphisms associated with postoperative temporomandibular disorders (TMD) or with TMJ symptoms after orthognathic surgery. Here, we found the AA genotype of SNP rs1643821 (ESR1 gene) as a risk factor for dysfunctional worsening after orthognathic surgery. In addition, we have identified TT genotype of SNP rs858339 (ENPP1 gene) as a protective factor against TMD in a population of patients with dentofacial deformities. Conversely, the heterozygous genotype AT was identified as a risk factor of TMD with respect to the rest of our population. All these elements are particularly important to bring new screening strategies and tailor future treatment.
Answer: This study allows us to identify sub-populations at high risk of developing postoperative temporomandibular disorders after orthognathic surgery procedures. Many other genes of interest could be potential factors influencing the dysfunctional response to orthognathic surgery, particularly genes of the Opera cohort.

Output: Do eNPP1 and ESR1 genotypes influence temporomandibular disorders development and surgical treatment response in dentofacial deformities?


Input: Consider Input: Context: Patient portals may improve pediatric chronic disease outcomes, but few have been rigorously evaluated for usability by parents. Using scenario-based testing with think-aloud protocols, we evaluated the usability of portals for parents of children with cystic fibrosis, diabetes or arthritis. DESIGN Sixteen parents used a prototype and test data to complete 14 tasks followed by a validated satisfaction questionnaire. Three iterations of the prototype were used.', 'During the usability testing, we measured the time it took participants to complete or give up on each task. Sessions were videotaped and content-analyzed for common themes. Following testing, participants completed the Computer Usability Satisfaction Questionnaire which measured their opinions on the efficiency of the system, its ease of use, and the likeability of the system interface. A 7-point Likert scale was used, with seven indicating the highest possible satisfaction.', 'Mean task completion times ranged from 73 (+/- 61) seconds to locate a document to 431 (+/- 286) seconds to graph laboratory results. Tasks such as graphing, location of data, requesting access, and data interpretation were challenging. Satisfaction was greatest for interface pleasantness (5.9 +/- 0.7) and likeability (5.8 +/- 0.6) and lowest for error messages (2.3 +/- 1.2) and clarity of information (4.2 +/- 1.4). Overall mean satisfaction scores improved between iteration one and three.
Answer: Despite parental involvement and prior heuristic testing, scenario-based testing demonstrated difficulties in navigation, medical language complexity, error recovery, and provider-based organizational schema. While such usability testing can be expensive, the current study demonstrates that it can assist in making healthcare system interfaces for laypersons more user-friendly and potentially more functional for patients and their families.


Output: Does usability testing found problems for novice users of pediatric portals?