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.
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Question: Context: Cord blood (CB) hematopoietic stem cell transplantation has often been limited by the scarcity of stem cells. Therefore, the number of CB hematopoietic stem/progenitor cells (HSPCs) should be increased while maintaining the stem cell characteristics.', 'We designed an ex vivo culture system using endothelial progenitor cells (EPCs) as stroma to determine the capacity of expanding CB-HSPCs in a defined medium, the effect on engraftment of the expanded cells in a mouse model and the underlying mechanism.', "After 7 days of culture, compared with those cultured with cytokines alone (3.25 ± 0.59), CD34+ cells under contact and non-contact co-culture with EPCs were expanded by 5.38 ± 0.61 (P = 0.003) and 4.06 ± 0.43 (P = 0.025)-fold, respectively. Direct cell-to-cell contact co-culture with EPCs resulted in more primitive CD34+ CD38- cells than stroma-free culture (156.17 ± 21.32 versus 79.12 ± 19.77-fold; P = 0.010). Comparable engraftment of day 7 co-cultured HSPCs with respect to HSPCs at day 0 in nonobese diabetic-severe combined immunodeficiency disease (NOD/SCID) mice was measured as a percentage of chimerism (13.3% ± 11.0% versus 16.0% ± 14.3%; P = 0.750). EPCs highly expressed interleukin 6 (IL6) and angiopoietin 1 (ANGPT1), the hematopoietic- related cytokines. A higher transcriptional level of WNT5A genes in EPCs and co-cultured HSPCs suggests that the activation of Wnt signaling pathway may play a role in HSPCs' expansion ex vivo.\Question: Do endothelial progenitor cells promote efficient ex vivo expansion of cord blood-derived hematopoietic stem/progenitor cells?

Answer: These data demonstrated that EPCs improve the CD34+ population but do not compromise the repopulating efficacy of the amplified HSPCs, possibly via cytokine secretion and Wnt signaling pathway activation.


Question: Context: The goal of this study was to identify genetic determinants of plasma N-terminal proatrial natriuretic peptide (NT-proANP) in the general community by performing a large-scale genetic association study and to assess its functional significance in in vitro cell studies and on disease susceptibility.', 'Genotyping was performed across 16 000 genes in 893 randomly selected individuals, with replication in 891 subjects from the community. Plasma NT-proANP1-98 concentrations were determined using a radioimmunoassay. Thirty-three genome-wide significant single-nucleotide polymorphisms were identified in the MTHFR-CLCN6-NPPA-NPPB locus and were all replicated. To assess the significance, in vitro functional genomic studies and clinical outcomes for carriers of a single-nucleotide polymorphism rs5063 (V32M) located in NPPA that represented the most significant variation in this genetic locus were assessed. The rs5063 variant allozyme in transfected HEK293 cells was decreased to 55±8% of wild-type protein (P=0.01) as assessed by quantitative western blots. Carriers of rs5063 had lower NT-proANP levels (1427 versus 2291 pmol/L; P<0.001) and higher diastolic blood pressures (75 versus 73 mm Hg; P=0.009) and were at an increased risk of stroke when compared with wild-type subjects independent of age, sex, diabetes mellitus, hypertension, atrial fibrillation, and cholesterol levels (hazard ratio, 1.6; P=0.004).\Question: Does circulating atrial natriuretic peptide genetic association study identify a novel gene cluster associated with stroke in whites?

Answer: This is the first large-scale genetic association study of circulating NT-proANP levels performed with replication and functional assessment that identified genetic variants in the MTHFR-CLCN6-NPPA-NPPB cluster to be significantly associated with NT-proANP levels. The clinical significance of this variation is related to lower NT-proANP levels, higher blood pressures, and an increased risk of stroke in the general community.


Question: Context: The aim was to review different approaches for the derivation of threshold values and to discuss their strengths and limitations in the context of minimum provider volumes.', "The following methods for the calculation of threshold values are compared and discussed: The value of acceptable risk limit, the value of acceptable risk gradient, the benchmark value proposed by Budtz-Jørgensen and Ulm's breakpoint model. The latter is extended to account for two different breakpoints. The methods are applied to German quality assurance data concerning total knee replacement.", 'The discussed methods for calculating threshold values differ in the kind of information that has to be specified beforehand. For the value of acceptable risk limit approach an absolute number, the acceptable risk, has to be predetermined. The value of acceptable risk gradient approach and the method of Budtz-Jørgensen require the specification of a relative change expressed in gradient and in odds, respectively. On the other hand, the threshold value according to the method of Ulm is defined as a parameter of a statistical model and no a priori specification is required.\Question: Are flexible regression models useful tools to calculate and assess threshold values in the context of minimum provider volumes?

Answer:
Each of the proposed methods has benefits and drawbacks. The choice of the most appropriate approach depends on the specific problem and the available data.


