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.

Context: Loss-of-function mutations in the progranulin gene (PGRN) were identified in frontotemporal lobar degeneration (FTLD) with ubiquitin-immunoreactive neuronal inclusions (FTLD-U). We assessed whether PGRN also contributes to genetic risk for Alzheimer disease (AD) in an extended Belgian AD patient group (n = 779, onset age 74.7 +/- 8.7 years).', 'A mutation analysis of the PGRN coding region was performed. The effect of missense mutations was assessed using in silico predictions and protein modeling. Risk effects of common genetic variants were estimated by logistic regression analysis and gene-based haplotype association analysis.', 'We observed seven missense mutations in eight patients (1.3%). Convincing pathogenic evidence was obtained for two missense mutations, p.Cys139Arg and p.Pro451Leu, affecting PGRN protein folding and leading to loss of PGRN by degradation of the misfolded protein. In addition, we showed that PGRN haplotypes were associated with increased risk for AD.
Answer: Our data support a role for PGRN in patients with clinically diagnosed Alzheimer disease (AD). Further, we hypothesize that at least some PGRN missense mutations might lead to loss of functional protein. Whether the underlying pathology in our cases proves to be AD, frontotemporal lobar degeneration, or a combination of the two must await further investigations.
Does genetic variability in progranulin contribute to risk for clinically diagnosed Alzheimer disease?

Context: del(17p), del(11q), and associated p53 dysfunction predict for short survival and chemoresistance in B-cell chronic lymphocytic leukemia (CLL). DNA-dependent protein kinase (DNA-PK) is activated by DNA damage and mediates DNA double-strand break repair. We hypothesized that inhibiting DNA-PK would sensitize CLL cells to drug-induced DNA damage and that this approach could increase the therapeutic index of agents used to treat CLL.', 'Fifty-four CLL cases were characterized for poor prognosis markers [del(17p), del(11q), CD38, and ZAP-70]. In selected cases, DNA-PK catalytic subunit (DNA-PKcs) expression and activity and p53 function were also measured. Ex vivo viability assays established sensitivity to fludarabine and chlorambucil and also tested the ability of a novel DNA-PK inhibitor (NU7441) to sensitize CLL cells to these drugs. The effects of NU7441 on fludarabine-induced DNA damage repair were also assessed (Comet assays and detection of gammaH2AX).', 'DNA-PKcs levels correlated with DNA-PK activity and varied 50-fold between cases but were consistently higher in del(17p) (P = 0.01) and del(11q) cases. NU7441 sensitized CLL cells to chlorambucil and fludarabine, including cases with del(17p), del(11q), p53 dysfunction, or high levels of DNA-PKcs. NU7441 increased fludarabine-induced double-strand breaks and abrogated drug-induced autophosphorylation of DNA-PKcs at Ser2056. High DNA-PK levels predicted for reduced treatment-free interval.
Answer: These data validate the concept of targeting DNA-PKcs in poor risk CLL, and demonstrate a mechanistic rationale for use of a DNA-PK inhibitor. The novel observation that DNA-PKcs is overexpressed in del(17p) and del(11q) cases indicates that DNA-PK may contribute to disease progression in CLL.
Is dNA-dependent protein kinase a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia?

Context: Left ventricular hypertrophy (LVH) is common in dialysis patients, and an independent predictor of mortality. While recent studies have shown no differences in mortality between the two most common dialysis modalities, hemodialysis (HD) and peritoneal dialysis (PD), their impact on LVH is controversial. We thus performed cardiac ultrasound studies in prevalent dialysis patients receiving either HD or PD and compared LVH.', 'We included 48 HD and 62 PD patients receiving treatment for at least three months in our dialysis center. All patients underwent echocardiographic examination and blood pressure measurements immediately following therapy. Volume status was assessed by bioelectrical impedance analysis.', 'There was no baseline difference in demographics or comorbidities between HD and PD patients. As expected, extracellular water (ECW) in post-HD patients was significantly lower than that in pre-HD and PD patients, while cardiac output (CO) and systolic blood pressure (SBP) were higher in pre-HD than that in post-HD or PD patients. There was no significant difference in CO or SBP between post-HD and PD patients. Left ventricular mass index (LVMI) was markedly higher in HD patients as compared to PD patients. Thus, the prevalence of LVH according to the Framingham criteria was 68.8% in HD patients and 45.2% in PD patients. Subgroup analysis showed similar results in the patients who had been on single-modality dialysis for at least two years and in the anuric patients. Finally, in a linear regression model (r(2) = 0.364, p < 0.001), SBP, treatment modality (to be in HD), and ECW were all independent predictors of LVMI.
Answer: In a cross-sectional analysis of prevalent Chinese patients, we found a higher LVMI and a higher prevalence of LVH in HD than in PD patients. As LVMI was associated with high blood pressure and volume overload, we suggest that in these patients, PD may preserve more physiological hemodynamics even during long-term therapy.

Is the prevalence of left ventricular hypertrophy in Chinese hemodialysis patients higher than that in peritoneal dialysis patients?