bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLGA-based gene delivering nanoparticle enhance suppression effect of miRNA in HePG2 cells
Authors: Liang Gao Feng , Zhu Yan Liang , Sun Bo , Hu Fei Hu , Tian Tian , Li Shu Chun , Xiao Zhong Dang 
Published: July 2011

AbstractThe biggest challenge in the field of gene therapy is how to effectively deliver target genes to special cells. This study aimed to develop a new type of poly(D,L-lactide-co-glycolide) (PLGA)-based nanoparticles for gene delivery, which are capable of overcoming the disadvantages of polyethylenimine (PEI)- or cationic liposome-based gene carrier, such as the cytotoxicity induced by excess positive charge, as well as the aggregation on the cell surface. The PLGA-based nanoparticles presented in this study were synthesized by emulsion evaporation method and characterized by transmission electron microscopy, dynamic light scattering, and energy dispersive spectroscopy. The size of PLGA/PEI nanoparticles in phosphate-buffered saline (PBS) was about 60 nm at the optimal charge ratio. Without observable aggregation, the nanoparticles showed a better monodispersity. The PLGA-based nanoparticles were used as vector carrier for miRNA transfection in HepG2 cells. It exhibited a higher transfection efficiency and lower cytotoxicity in HepG2 cells compared to the PEI/DNA complex. The N/P ratio (ratio of the polymer nitrogen to the DNA phosphate) 6 of the PLGA/PEI/DNA nanocomplex displays the best property among various N/P proportions, yielding similar transfection efficiency when compared to Lipofectamine/DNA lipoplexes. Moreover, nanocomplex shows better serum compatibility than commercial liposome. PLGA nanocomplexes obviously accumulate in tumor cells after transfection, which indicate that the complexes contribute to cellular uptake of pDNA and pronouncedly enhance the treatment effect of miR-26a by inducing cell cycle arrest. Therefore, these results demonstrate that PLGA/PEI nanoparticles are promising non-viral vectors for gene delivery.
Antibodies against outer-capsid proteins of grass carp reovirus expressed in E. coli are capable of neutralizing viral infectivity
Authors: Shao Ling , Sun Xiaoyun , Fang Qin 
Published: July 2011

Abstract

Background
Grass carp reovirus (GCRV), which causes severe infectious outbreaks of hemorrhagic disease in aquatic animals, is a highly pathogenic agent in the Aquareovirus genus of family Reoviridae. The outer capsid shell of GCRV, composed of the VP5-VP7 protein complex, is believed to be involved in cell entry. The objective of this study was to produce a major neutralization antibody for mitigating GCRV infection.

Results
Recombinant plasmids of GCRV outer capsid proteins VP5 and VP7 were constructed and expressed in prokaryotic cells in our previous work. In this study, we prepared GCRV Antibody (Ab), VP5Ab and VP7Ab generated from purified native GCRV, recombinant VP5 and VP7 respectively. Immunoblotting analysis showed that the prepared antibodies were specific to its antigens. In addition, combined plaque and cytopathic effect (CPE)-based TCID50 (50% tissue culture infective dose) assays showed that both VP5Ab and VP7Ab were capable of neutralizing viral infectivity. Particularly, the neutralizing activity of VP7Ab was 3 times higher than that of VP5Ab, suggesting that VP7 might be a dominating epitope. Moreover, the combination of VP5Ab and VP7Ab appeared to enhance GCRV neutralizing capacity.

Conclusions
The results presented in this study indicated that VP7 protein was the major epitope of GCRV. Furthermore, VP5Ab and VP7Ab in combination presented an enhanced capacity to neutralize the GCRV particle, suggesting that the VP5 and VP7 proteins may cooperate with each other during virus cell entry. The data can be used not only to further define the surface epitope domain of GCRV but may also be applicable in the designing of vaccines.
Dietary fructose and risk of metabolic syndrome in adults: Tehran Lipid and Glucose study
Authors: Hosseini-Esfahani Firoozeh , Bahadoran Zahra , Mirmiran Parvin , Hosseinpour-Niazi Somayeh , Hosseinpanah Farhad , Azizi Fereidoun 
Published: July 2011

Abstract

Background
Studies have shown that the excessive fructose intake may induce adverse metabolic effects. There is no direct evidence from epidemiological studies to clarify the association between usual amounts of fructose intake and the metabolic syndrome.

Objective
The aim this study was to determine the association of fructose intake and prevalence of metabolic syndrome (MetS) and its components in Tehranian adults.

Methods
This cross-sectional population based study was conducted on 2537 subjects (45% men) aged 19-70 y, participants of the Tehran Lipid and Glucose Study (2006-2008). Dietary data were collected using a validated 168 item semi-quantitative food frequency questionnaire. Dietary fructose intake was calculated by sum of natural fructose (NF) in fruits and vegetables and added fructose (AF) in commercial foods. MetS was defined according to the modified NCEP ATP III for Iranian adults.

Results
The mean ages of men and women were 40.5 ± 13.6 and 38.6 ± 12.8 years, respectively. Mean total dietary fructose intakes were 46.5 ± 24.5 (NF: 19.6 ± 10.7 and AF: 26.9 ± 13.9) and 37.3 ± 24.2 g/d (NF: 18.6 ± 10.5 and AF: 18.7 ± 13.6) in men and women, respectively. Compared with those in the lowest quartile of fructose intakes, men and women in the highest quartile, respectively, had 33% (95% CI, 1.15-1.47) and 20% (95% CI, 1.09-1.27) higher risk of the metabolic syndrome; 39% (CI, 1.16-1.63) and 20% (CI, 1.07-1.27) higher risk of abdominal obesity; 11% (CI, 1.02-1.17) and 9% (CI, 1.02-1.14) higher risk of hypertension; and 9% (CI, 1-1.15) and 9% (1.04-1.12) higher risk of impaired fasting glucose.

Conclusion
Higher consumption of dietary fructose may have adverse metabolic effects.
Primary growth hormone insensitivity (Laron syndrome) and acquired hypothyroidism: a case report
Authors: Cotta Oana R , Santarpia Libero , Curtò Lorenzo , Aimaretti Gianluca , Corneli Ginevra , Trimarchi Francesco , Cannavò Salvatore 
Published: July 2011

Abstract

Introduction
Primary growth hormone resistance or growth hormone insensitivity syndrome, also known as Laron syndrome, is a hereditary disease caused by deletions or different types of mutations in the growth hormone receptor gene or by post-receptor defects. This disorder is characterized by a clinical appearance of severe growth hormone deficiency with high levels of circulating growth hormone in contrast to low serum insulin-like growth factor 1 values.

Case presentation
We report the case of a 15-year-old Caucasian girl who was diagnosed with Silver-Russell syndrome at the age of four and a half years. Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum growth hormone levels were high, and an insulin-like growth factor 1 generation test did not increase insulin-like growth factor 1 levels (baseline insulin-like growth factor 1 levels, 52 μg/L; reference range, 75 μg/L to 365 μg/L; and peak, 76 μg/L and 50 μg/L after 12 and 84 hours, respectively, from baseline). The genetic analysis showed that the patient was homozygous for the R217X mutation in the growth hormone receptor gene, which is characteristic of Laron syndrome. On the basis of these results, the diagnosis of primary growth hormone insensitivity syndrome was made, and recombinant insulin-like growth factor 1 therapy was initiated. The patient's treatment was well tolerated, but unexplained central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age.

Conclusion
The most important functional tests for the diagnosis of growth hormone insensitivity are the insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective treatment is daily administration of recombinant insulin-like growth factor 1 starting from early childhood. However, these patients show a dramatically impaired final height. In our case, unexplained central hypothyroidism occurred during treatment.
Prospective evaluation of serum tissue inhibitor of metalloproteinase 1 and carbonic anhydrase IX in correlation to circulating tumor cells in patients with metastatic breast cancer
Authors: Müller Volkmar , Riethdorf Sabine , Rack Brigitte , Janni Wolfgang , Fasching Peter A , Solomayer Erich , Aktas Bahriye , Kasimir-Bauer Sabine , Zeitz Julia , Pantel Klaus , Fehm Tanja ,   the DETECT study group
Published: July 2011

Abstract
Introduction
Circulating tumor cells (CTCs) reflect aggressive tumor behavior by hematogenous tumor cell dissemination. The tissue inhibitor of metalloproteinase 1 (TIMP-1) plays a role in tissue invasion and is also involved in angiogenesis, abrogation of apoptosis and in chemoresistance. Carbonic anhydrase IX (CAIX) is a metalloenzyme involved in cell adhesion, growth and survival of tumor cells. The aim of the study was to investigate whether serum concentrations of TIMP-1 and CAIX are associated with the detection of CTC in metastatic breast cancer.

Methods
Blood was obtained in a prospective multicenter setting from 253 patients with metastatic breast cancer at the time of disease progression. Serum TIMP-1 and CAIX were determined using commercial ELISA-kits (Oncogene Science). CTC were detected with the CellSearch™ system (Veridex).

Results
Five or more CTCs were detected in 122 patients out of 245 evaluable patients (49.8%). Out of 253 metastatic patients 70 (28%) had serum TIMP-1 levels above 454 ng/mL. Serum CAIX was elevated above 506 ng/mL in 90 (35%) patients. Both serum markers had prognostic significance. Median progression free survival (PFS) was 7.2 months with elevated TIMP-1 vs. 11.4 months with non-elevated levels (p < 0.01). OS was 11.5 vs. 19.1 months (p < 0.01). Median PFS was 7.5 months with elevated CAIX vs. 11.7 months with non-elevated levels (p < 0.01), overall survival (OS) was 13.4 months vs. 19.1 months (p < 0.01). In patients with five or more CTCs, serum levels were above the cut-off for CAIX in 47% vs. 25% in those with less than five CTCs (p = 0.01). For TIMP-1, 37% patients with five or more CTCs had elevated serum levels and 17% of patients with less than five CTCs (p = 0.01). Including TIMP-1, CAIX, CTC and established prognostic factors in the multivariate analysis, the presence of CTCs, the therapy line and elevated CAIX remained independent predictors of OS.

Conclusions
Elevated serum levels of the invasion markers TIMP-1 and CAIX in metastatic breast cancer are prognostic markers and are associated with the presence of CTCs. Whether increased secretion of TIMP-1 and/or CAIX might directly contribute to tumor cell dissemination remains to be elucidated in further investigations.

Trial registration
Current Controlled Trials: ISRCTN59722891
Nomograms for Predicting Local Recurrence, Distant Metastases, and Overall Survival for Patients With Locally Advanced Rectal Cancer on the Basis of European Randomized Clinical Trials
Authors: Valentini Vincenzo , van Stiphout Ruud G.P.M. , Lammering Guido , Gambacorta Maria Antonietta , Barba Maria Cristina , Bebenek Marek , Bonnetain Franck , Bosset Jean-Francois , Bujko Krzysztof , Cionini Luca , Gerard Jean-Pierre , Rödel Claus , Sainato Aldo , Sauer Rolf , Minsky Bruce D. , Collette Laurence , Lambin Philippe 
Published: July 2011

Purpose The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemotherapy and close follow-up. Patients and Methods All data (N = 2,795) from five major European clinical trials for rectal cancer were pooled and used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from one trial was used as an external validation set. The variables used in the analysis were sex, age, clinical tumor stage stage, tumor location, radiotherapy dose, concurrent and adjuvant chemotherapy, surgery procedure, and pTNM stage. Model performance was evaluated by the concordance index (c-index). Risk group stratification was proposed for the nomograms. Results The nomograms are able to predict events with a c-index for external validation of local recurrence (LR; 0.68), distant metastases (DM; 0.73), and overall survival (OS; 0.70). Pathologic staging is essential for accurate prediction of long-term outcome. Both preoperative CRT and adjuvant chemotherapy have an added value when predicting LR, DM, and OS rates. The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome. Conclusion The easy-to-use nomograms can predict LR, DM, and OS over a 5-year period after surgery. They may be used as decision support tools in future trials by using the three defined risk groups to select patients for postoperative chemotherapy and close follow-up ( http://www.predictcancer.org ).
Impact of Treatment End Point Definitions on Perceived Differences in Long-Term Outcome With Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia
Authors: Kantarjian Hagop , O'Brien Susan , Jabbour Elias , Shan Jenny , Ravandi Farhad , Kadia Tapan , Faderl Stefan , Garcia-Manero Guillermo , Borthakur Gautam , Cortes Jorge 
Published: July 2011

Purpose Different definitions of progression-free survival (PFS) and event-free survival (EFS) may result in perceived differences in outcomes with tyrosine kinase inhibitor (TKI) therapies in chronic myelogenous leukemia (CML). Patients and Methods We analyzed the outcome of 435 patients with early chronic-phase, Philadelphia chromosome–positive CML treated with imatinib (n = 281), nilotinib (n = 78), and dasatinib (n = 76) using definitions of PFS and EFS used in the International Randomized Study of Interferon Versus STI571 (IRIS), Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients (ENEST-nd), Dasatinib Versus Imatinib Study in Treatment-Naïve CML Patients (DASISION), and MD Anderson Cancer Center (MDACC) trials. Definitions for EFS-IRIS, time without progression in ENEST-nd, PFS-DASISION, and EFS-MDACC were as previously reported. The EFS-MDACC considered an event any instance of toxicity or death from any cause on or off therapy (if not counted before death as progression/event). Results Of the 435 patients, 123 (28%) were taken off TKI therapy (resistance/loss of response, n = 33; blastic phase on TKI therapy, n = 6; intolerance/toxicity, n = 29; other causes, n = 55). Thirty-three patients (7.6%) have died; eight patients died on TKI therapy, two patients died within 60 days of being off TKIs, and 23 patients died after being off TKIs for more than 60 days. Of the 33 deaths, 19 deaths (eight deaths on TKI, two deaths within 60 days, and nine deaths off for resistance/relapse/transformation) would be counted as progression/events on the IRIS/ENEST-nd/DASISION studies, whereas 14 deaths would be censored at time off TKI. On the basis of the four definitions used by IRIS, ENEST-nd, DASISION, and MDACC trials, the corresponding 5-year PFS/EFS rates were 96%, 90%, 89%, and 81%. Conclusion Uniform definitions of PFS and EFS are needed to compare the long-term efficacy and potential use of different TKIs in CML.
Mutations and Deletions of the TP53 Gene Predict Nonresponse to Treatment and Poor Outcome in First Relapse of Childhood Acute Lymphoblastic Leukemia
Authors: Hof Jana , Krentz Stefanie , van Schewick Claudia , Körner Gabriele , Shalapour Shabnam , Rhein Peter , Karawajew Leonid , Ludwig Wolf-Dieter , Seeger Karl , Henze Günter , von Stackelberg Arend , Hagemeier Christian , Eckert Cornelia , Kirschner-Schwabe Renate 
Published: July 2011

Purpose In the clinical management of children with relapsed acute lymphoblastic leukemia (ALL), treatment resistance remains a major challenge. Alterations of the TP53 gene are frequently associated with resistance to chemotherapy, but their significance in relapsed childhood ALL has remained controversial because of small studies. Patients and Methods Therefore, we systematically studied 265 first-relapse patients enrolled in the German Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Mü nster 2002 (ALL-REZ BFM 2002) trial for sequence and copy number alterations of the TP53 gene by using direct sequencing and multiplex ligation-dependent probe amplification. Results We observed copy number and sequence alterations of TP53 in 12.4% (27 of 218) of patients with B-cell precursor ALL and 6.4% (three of 47) of patients with T-cell ALL relapse. Backtracking to initial ALL in 23 matched samples revealed that 54% of all TP53 alterations were gained at relapse. Within B-cell precursor ALL, TP53 alterations were consistently associated with nonresponse to chemotherapy (P < .001) and poor event-free survival (P < .001) and overall survival rates (P = .002). TP53 alterations also had a significant impact on survival within intermediate-risk (S2) and high-risk (S3/S4) relapse patients (P = .007 and P = .019, respectively). This prognostic significance of TP53 alterations was confirmed in multivariate analysis. Besides their clinical impact, TP53 alterations were associated with a higher fraction of leukemic cells in S/G2-M phase of the cell cycle at relapse diagnosis. Conclusion Alterations of the TP53 gene are of particular importance in the relapse stage of childhood ALL, in which they independently predict high risk of treatment failure in a significant number of patients. Therefore, they will aid in future risk assessment of children with ALL relapse.
Economic and Emissions Implications of Load-Based, Source-Based, and First-Seller Emissions Trading Programs Under California AB32
Authors: Chen Yihsu , Liu Andrew L. , Hobbs Benjamin F. 
Published: July 2011

In response to Assembly Bill 32, the state of California considered three types of carbon emissions trading programs for the electric power sector: load-based, source-based, and first-seller. They differed in terms of their point of regulation and in whether in-state-to-out-of-state and out-of-state-to-in-state electricity sales are regulated. In this paper, we formulate a market equilibrium model for each of the three approaches, considering power markets, transmission limitations, and emissions trading, and making the simplifying assumption of pure bilateral markets. We analyze the properties of their solutions and show the equivalence of load-based, first-seller, and source-based approaches when in-state-to-out-of-state sales are regulated under the cap. A numeric example illustrates the emissions and economic implications of the models. In the simulated cases, “leakage” eliminates most of the emissions reductions that the regulations attempt to impose. Furthermore, “contract reshuffling” occurs to such an extent that all the apparent emissions reductions resulting from changes in sources of imported power are illusory. In reality, the three systems would not be equivalent because there will also be pool-type markets, and the three systems provide different incentives for participating in those markets. However, the equivalence results under our simplifying assumptions show that load-based trading has no inherent advantage compared to other systems in terms of costs to consumers, contrary to claims elsewhere.
Charlemagne's Challenge: The Periodic Latency Problem
Authors: Coene Sofie , Spieksma Frits C. R. , Woeginger Gerhard J. 
Published: July 2011

Latency problems are characterized by their focus on minimizing the waiting time for all clients. We study periodic latency problems, a nontrivial extension of standard latency problems. In a periodic latency problem each client has to be visited regularly: there is a server traveling at unit speed, and there is a set of n clients with given positions. The server must visit the clients over and over again, subject to the constraint that successive visits to client i are at most qi time units away from each other. We investigate two main problems. In problem PLPP the goal is to find a repeatable route for the server visiting as many clients as possible without violating their qis. In problem PLP the goal is to minimize the number of servers needed to serve all clients. Depending on the topology of the underlying network, we derive polynomial-time algorithms or hardness results for these two problems. Our results draw sharp separation lines between easy and hard cases.
High Folate Intake Is Related to Better Academic Achievement in Swedish Adolescents
Authors: Nilsson Torbjörn K. , Yngve Agneta , Böttiger Anna K. , Hurtig-Wennlöf Anita , Sjöström Michael 
Published: July 2011

BACKGROUND:Adolescents are vulnerable to increased plasma total homocysteine (tHcy) and to insufficient folate status. Folate status and Hcy metabolism are linked to cognitive functions, but academic achievement by adolescents has not been studied in this respect.OBJECTIVE:To assess a possible link between academic achievement in adolescents and tHcy and its determinants, dietary folate intake, MTHFR 677 TT homozygosity, and socioeconomic status (SES).SUBJECTS AND METHODS:A study of 386 Swedish adolescents aged 15 years in whom plasma tHcy and MTHFR 677C →T genotype were assayed. The sum of school grades in 10 core subjects obtained in the final semester of compulsory 9 years of schooling was used as outcome measure of academic achievement. Lifestyle and SES data were obtained from questionnaires.RESULTS:Academic achievement was strongly correlated to tertiles of tHcy (negatively; P = .023) and to tertiles of folate intake (positively; P &lt; .001). Other significant predictors were gender, smoking, and SES (proxied by school, mother's education, and father's income). When these were controlled for, tertiles of folate intake (P &lt; .002) but not tertiles of tHcy (P = .523) or MTHFR genotype remained significantly related to academic achievement.CONCLUSION:Folate intake had a positive association with academic achievement in the 15-year-olds, which was not attenuated by SES or MTHFR 677 TT homozygosity. These results provide new information that points to the importance of keeping a closer watch on folate status in childhood and adolescence. They may also have direct implications for school meal provisions, school teaching programs, and information to parents.