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.

Ex Input:
Context: Nonviral vectors based on polyethylenimine (PEI) usually contain an excess of PEI that is not complexed to DNA. Since unbound PEI contributes to cellular and systemic toxicity, purification of polyplexes from unbound PEI is desirable.', 'Size exclusion chromatography (SEC) was used to purify PEI polyplexes of free PEI. Transfection properties of purified polyplexes and the effect of free PEI on gene delivery were studied in vitro and in vivo after systemic application into mice.', 'SEC did not change the size and zeta-potential of polyplexes. Independent of the amount of PEI used for complex formation, purified PEI polyplexes had the same final PEI nitrogen/DNA phosphate ratio of 2.5. Notably, purified PEI polyplexes demonstrated low cellular and systemic toxicity. High transfection efficiency was achieved with purified polyplexes at high DNA concentrations (8-15 microg/ml). At low DNA concentrations (2-4 microg/ml) gene transfer with purified particles was less efficient than with polyplexes containing free PEI both in vitro and in vivo. Mechanistic studies showed that free PEI partly blocked cellular association of DNA complexes but was essential for the following intracellular gene delivery. Adding free PEI to cells treated with purified particles with a delay of up to 4 h resulted in significantly enhanced transfection efficiency compared with non-purified particles or purified particles without free PEI.\Question: Does purification of polyethylenimine polyplexes highlight the role of free polycations in gene transfer?

Ex Output:
This study presents an efficient method to remove free PEI from PEI polyplexes by SEC. Our results from transfection experiments demonstrate that free PEI substantially contributes to efficient gene expression but also mediates toxic effects in a dose-dependent manner. Purified polyplexes without free PEI have to be applied at increased concentrations to achieve high transfection levels, but exhibit a greatly improved toxicity profile.

Ex Input:
Context: Mild hypothermia for 72 hours is neuroprotective in newborns with moderate or severe hypoxic-ischemic encephalopathy. A core temperature of 33.5 degrees C might reduce drug clearance leading to potential toxicity. Gentamicin is nephrotoxic and ototoxic at high serum concentrations. No study has investigated the influence of 72 hours of hypothermia on serum gentamicin concentrations (SGCs) in children of any age. We aimed to compare the SGCs in encephalopathic infants who underwent intensive care with therapeutic hypothermia or normothermia.', 'Data were collected retrospectively from 2 NICUs in Bristol, United Kingdom, that offered cooling therapy within clinical trials since 1998. Eligible infants (n = 55) developed grade 2/3 encephalopathy after birth and fulfilled the entry criteria defined in the CoolCap trial. Encephalopathic infants with similar demographic values were either nursed under normothermia or 72 h-hypothermia. Once-daily gentamicin dosage (4-5 mg/kg) was administered, and trough SGC was recorded with corresponding creatinine concentrations. The time and number of omitted drug doses were noted.', 'Mean trough SGC (pre-second dose) and mean plasma creatinine concentrations for both treatment groups were similar (gentamicin: 2.19 +/- 1.7 [hypothermia] and 2.30 +/- 2.0 [normothermia] mg/L; creatinine: 115.6 +/- 42.8 [hypothermia] and 121.0 +/- 45.1 [normothermia] mumol/L). Forty percent of the trough SGCs in both groups were above the recommended trough concentration of 2.0 mg/L. A significant correlation (r(2) = 0.36) was found between high SGCs and impaired renal function assessed by raised plasma creatinine levels regardless of treatment options.\Question: Are serum gentamicin concentrations in encephalopathic infants affected by therapeutic hypothermia?

Ex Output:
Our data confirm that impaired renal function is strongly associated with high SGCs. Reduced body temperatures do not affect the clearance of gentamicin.

Ex Input:
Context: Adrenocortical carcinoma (ACC) carries a poor prognosis and current systemic cytotoxic therapies result in only modest improvement in overall survival. In this retrospective study, we performed a comprehensive genomic profiling of 29 consecutive ACC samples to identify potential targets of therapy not currently searched for in routine clinical practice.', 'DNA from 29 ACC was sequenced to high, uniform coverage (Illumina HiSeq) and analysed for genomic alterations (GAs).', 'At least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC). The most frequent GAs were in TP53 (34%), NF1 (14%), CDKN2A (14%), MEN1 (14%), CTNNB1 (10%) and ATM (10%). APC, CCND2, CDK4, DAXX, DNMT3A, KDM5C, LRP1B, MSH2 and RB1 were each altered in two cases (7%) and EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN and PTCH1 were each altered in a single case (3%). In 17 (59%) of ACC, at least one GA was associated with an available therapeutic or a mechanism-based clinical trial.\Question: Does next-generation sequencing of adrenocortical carcinoma reveal new routes to targeted therapies?

Ex Output:
Next-generation sequencing can discover targets of therapy for relapsed and metastatic ACC and shows promise to improve outcomes for this aggressive form of cancer.