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: Autoimmune hepatitis type 2 (AIH-2), a severe juvenile liver disorder of unknown etiology and pathogenesis, is characterized by liver-kidney microsomal antibody type 1 targeting cytochrome P450IID6 (CYP2D6) and is associated to HLA DRB1*07. Although CYP2D6 B-cell reactivity has been extensively characterized, little is known about CYP2D6-specific T-cell responses. The aim of the present study was to characterize anti-CYP2D6 cellular immune responses and their possible pathogenic role in patients with AIH-2.', 'We investigated T-cell reactivity against 61 overlapping peptides spanning the full CYP2D6 protein using ex vivo cultures obtained at diagnosis, remission, and relapse. Moreover, CYP2D6-specific T-cell reactivity was investigated in the context of HLA restriction, peptide-binding affinity to HLA DRB1*07, cytokine profile, disease specificity, and clinical course.', 'Proliferative responses to CYP2D6 cluster to 7 antigenic regions in DRB1*07 and to 4 regions in non-DRB1*07 patients. Whereas distinct peptides induce production of interferon gamma, interleukin-4, or interleukin-10, peptides inducing interferon-gamma and proliferation overlap. There is also an overlap between sequences inducing T- and B-cell responses. The breadth (number of epitopes) and intensity (quantity of cytokine produced) of the T-cell response are directly correlated to disease activity (biochemical and histologic markers).
Answer: These data imply that the T-cell response to CYP2D6 in AIH-2 is polyclonal, involves multiple effector types targeting different epitopes, and is associated with hepatocyte damage, knowledge that should form the basis for a more refined therapeutic approach.

A: Are polyclonal T-cell responses to cytochrome P450IID6 associated with disease activity in autoimmune hepatitis type 2?
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Q: 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.

A: Do eNPP1 and ESR1 genotypes influence temporomandibular disorders development and surgical treatment response in dentofacial deformities?
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Q: Context: It has been contended that, during cardiopulmonary bypass at 27 degrees C, pH-stat management decreases cerebral metabolic rate for oxygen (CMRO2) more than alpha-stat management. In contrast, other studies have not found CMRO2 to differ between techniques. Using each animal as its own control, the authors assessed the effect of alpha-stat versus pH-stat management of CMRO2, cerebral blood flow (CBF), and brain oxygen extraction during cardiopulmonary bypass at 27 degrees C.', 'Fourteen New Zealand White rabbits, anesthetized with fentanyl and diazepam, underwent cardiopulmonary bypass at 27 degrees C (membrane oxygenator, centrifugal pump, and bifemoral arterial perfusion). Group 1 animals (n = 7) had alpha-stat management for the initial 65-70 min of bypass, and were then changed to pH-stat management for the remaining 30 min of bypass. Group 2 animals (n = 7) had pH-stat management for the initial 65-70 min of bypass, and were then changed to alpha-stat management for the remaining 30 min. Measurement of CBF (radiolabeled microspheres), CMRO2 (CBF x brain arterial-venous oxygen content difference), brain temperature, systemic hemodynamics, and arterial blood gases were made in each animal under both alpha-stat and pH-stat conditions.', 'CMRO2 did not differ between alpha-stat and pH-stat conditions (1.4 +/- 0.3 ml.100 g-1.min-1; median +/- quartile deviation), and was independent of order of determination. Changes in CBF between alpha-stat and pH-stat conditions were associated with proportional opposite changes in cerebral oxygen extraction. Cerebral blood flow was significantly greater with pH-stat management than with alpha-stat management (37 +/- 5 vs. 30 +/- 3 ml.100 g-1.min-1, respectively). The CBF response to changing PaCO2 was significantly greater when going from alpha-stat to pH-stat conditions (group 1) than in the reverse order (group 2).
Answer: During cardiopulmonary bypass at 27 degrees C, hypothermic acid-base management has no measurable effect on CMRO2. CMRO2 was neither extraction limited nor dependent on either PaCO2, CBF, or hemoglobin oxygen affinity differences between alpha-stat and pH-stat management. Cerebral blood flow responses to changing CMRO2 depend on the "starting" conditions, with alpha-stat management appearing to better preserve CBF reactivity than pH-stat management.

A:
Does hypothermic acid-base management affect cerebral metabolic rate for oxygen at 27 degrees C. A study during cardiopulmonary bypass in rabbits?
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