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.

[EX Q]: Context: Women with a family history of breast cancer face considerable uncertainty about whether to pursue standard screening, intensive screening, or prophylactic surgery. Accurate and individualized risk-estimation approaches may help these women make more informed decisions. Although highly penetrant genetic variants have been associated with familial breast cancer (FBC) risk, many individuals do not carry these variants, and many carriers never develop breast cancer. Common risk variants have a relatively modest effect on risk and show limited potential for predicting FBC development. As an alternative, we hypothesized that additional genomic data types, such as gene-expression levels, which can reflect genetic and epigenetic variation, could contribute to classifying a person's risk status. Specifically, we aimed to identify common patterns in gene-expression levels across individuals who develop FBC.", 'We profiled peripheral blood mononuclear cells from women with a family history of breast cancer (with or without a germline BRCA1/2 variant) and from controls. We used the support vector machines algorithm to differentiate between patients who developed FBC and those who did not. Our study used two independent datasets, a training set of 124 women from Utah (USA) and an external validation (test) set from Ontario (Canada) of 73 women (197 total). We controlled for expression variation associated with clinical, demographic, and treatment variables as well as lymphocyte markers.', 'Our multigene biomarker provided accurate, individual-level estimates of FBC occurrence for the Utah cohort (AUC = 0.76 [0.67-84]) . Even at their lower confidence bounds, these accuracy estimates meet or exceed estimates from alternative approaches. Our Ontario cohort resulted in similarly high levels of accuracy (AUC = 0.73 [0.59-0.86]), thus providing external validation of our findings. Individuals deemed to have "high" risk by our model would have an estimated 2.4 times greater odds of developing familial breast cancer than individuals deemed to have "low" risk.
Answer: Together, these findings suggest that gene-expression levels in peripheral blood cells reflect genomic variation associated with breast cancer risk and that such data have potential to be used as a non-invasive biomarker for familial breast cancer risk.
[EX A]: Do gene-expression patterns in peripheral blood classify familial breast cancer susceptibility?

[EX Q]: Context: Women have poorer outcomes after vascular surgery as compared to men as shown by studies recently. Frailty is also an independent risk factor for postoperative morbidity and mortality. This study examines the interplay of gender and frailty on outcomes after infrainguinal vascular procedures.', 'The American College of Surgeons National Surgical Quality Improvement Program database was used to identify all patients who underwent infrainguinal vascular procedures from 2005-2012. Frailty was measured using a modified frailty index (mFI; derived from the Canadian Study of Health and Aging). Univariate and multivariate analysis were performed to investigate the association of preoperative frailty and gender, on postoperative outcomes.', 'Of 24,645 patients (92% open, 8% endovascular), there were 533 deaths (2.2%) and 6198 (25.1%) major complications within 30 d postoperatively. Women were more frail (mean mFI = 0.269) than men (mean mFI = 0.259; P < 0.001). Women and frail patients (mFI>0.25) were more likely to have a major morbidity (P < 0.001) or mortality (P < 0.001) with the highest risk in frail women. On multivariate logistic regression analysis, female gender and increasing mFI were independently significantly associated with mortality (P < 0.05) as well as major complications. The interaction of gender and frailty in multivariate analysis showed the highest adjusted 30-d mortality and morbidity in frail females at 2.8% and 30.1%, respectively and that was significantly higher (P < 0.001) than nonfrail males, nonfrail females and frail males.
Answer: Female gender and frailty are both associated with increased risk of complications and death following infrainguinal vascular procedures with the highest risk in frail females. Further studies are needed to explore the mechanisms of interaction of gender and frailty and its effect on long-term outcomes for peripheral vascular disease.
[EX A]: Do gender and frailty predict poor outcomes in infrainguinal vascular surgery?

[EX Q]: Context: Whole-grain cereals and diets with a low glycemic index may protect against the development of type 2 diabetes and heart disease, but the mechanisms are poorly understood. We studied the effect of carbohydrate modification on serum metabolic profiles, including lipids and branched chain amino acids, and dependencies between these and specific gene expression pathways in adipose tissue.', 'Twenty subjects with metabolic syndrome were selected from the larger FUNGENUT study population, randomized either to a diet high in oat and wheat bread and potato (OWP) or rye bread and pasta (RP). Serum metabolomics analyses were performed using ultra-performance liquid chromatography coupled to electrospray ionization mass spectrometry (UPLC/MS), gas chromatography (GC) and UPLC. In the OWP group multiple proinflammatory lysophosphatidylcholines increased, while in the RP group docosahexaenoic acid (DHA 22:6n-3) increased and isoleucine decreased. mRNA expression of stress reactions- and adipose tissue differentiation-related genes were up-regulated in adipose tissue in the OWP group. In the RP group, however, pathways related to stress reactions and insulin signaling and energy metabolism were down-regulated. The lipid profiles had the strongest association with the changes in the adipose tissue differentiation pathway when using the elastic net regression model of the lipidomic profiles on selected pathways.
Answer: Our results suggest that the dietary carbohydrate modification alters the serum metabolic profile, especially in lysoPC species, and may, thus, contribute to proinflammatory processes which in turn promote adverse changes in insulin and glucose metabolism.
[EX A]:
Does dietary carbohydrate modification alter serum metabolic profiles in individuals with the metabolic syndrome?