bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice
Authors: Zheng Liu , Weilun Zhang , Minghong Jiang , Yaxi Zhang , Shilian Liu , Yanxin Liu , Dexian Zheng 
Published: April 2012

Abstract

Background
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV) vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy.

Methods
Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity.

Results
The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline.

Conclusion
These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy.
Reduced lung function is independently associated with increased risk of type 2 diabetes in Korean men
Authors: Kwon Chang-Hee , Rhee Eun-Jung , Song Jae-Uk , Kim Jung-Tae , Kwag Hyon Joo , Sung Ki-Chul 
Published: April 2012

Abstract

Background
Reduced lung function is associated with incident insulin resistance and diabetes. The aim of this study was to assess the relationship between lung function and incident type 2 diabetes in Korean men.

Methods
This study included 9,220 men (mean age: 41.4 years) without type 2 diabetes at baseline who were followed for five years. Subjects were divided into four groups according to baseline forced vital capacity (FVC) (% predicted) and forced expiratory volume in one second (FEV1) (% predicted) quartiles. The incidence of type 2 diabetes at follow-up was compared according to FVC and FEV1 quartiles.

Results
The overall incidence of type 2 diabetes was 2.2%. Reduced lung function was significantly associated with the incidence of type 2 diabetes after adjusting for age, BMI, education, smoking, exercise, alcohol, and HOMA-IR. Both FVC and FEV1 were negatively associated with type 2 diabetes (P < 0.05). In non-obese subjects with BMI < 25, the lowest quartile of FVC and FEV1 had a significantly higher odds ratio for type 2 diabetes compared with the highest quartile after adjusting for age and BMI (2.15 [95% CI 1.02-4.57] and 2.19 [95% CI 1.09-4.42]).

Conclusions
Reduced lung function is independently associated with the incidence of type 2 diabetes in Korean men.
Proteomic profiling of the rat hypothalamus
Authors: Pedroso Amanda P , Watanabe Regina L H , Albuquerque Kelse T , Telles Mônica M , Andrade Maria C C , Perez Juliana D , Sakata Maísa M , Lima Mariana L , Estadella Debora , Nascimento Cláudia M O , Oyama Lila M , Rosa José C , Casarini Dulce E , Ribeiro Eliane B 
Published: April 2012

AbstractBackgroundThe hypothalamus plays a pivotal role in numerous mechanisms highly relevant to the maintenance of body homeostasis, such as the control of food intake and energy expenditure. Impairment of these mechanisms has been associated with the metabolic disturbances involved in the pathogenesis of obesity. Since rodent species constitute important models for metabolism studies and the rat hypothalamus is poorly characterized by proteomic strategies, we performed experiments aimed at constructing a two-dimensional gel electrophoresis (2-DE) profile of rat hypothalamus proteins.ResultsAs a first step, we established the best conditions for tissue collection and protein extraction, quantification and separation. The extraction buffer composition selected for proteome characterization of rat hypothalamus was urea 7 M, thiourea 2 M, CHAPS 4%, Triton X-100 0.5%, followed by a precipitation step with chloroform/methanol. Two-dimensional (2-D) gels of hypothalamic extracts from four-month-old rats were analyzed; the protein spots were digested and identified by using tandem mass spectrometry and database query using the protein search engine MASCOT. Eighty-six hypothalamic proteins were identified, the majority of which were classified as participating in metabolic processes, consistent with the finding of a large number of proteins with catalytic activity. Genes encoding proteins identified in this study have been related to obesity development.ConclusionThe present results indicate that the 2-DE technique will be useful for nutritional studies focusing on hypothalamic proteins. The data presented herein will serve as a reference database for studies testing the effects of dietary manipulations on hypothalamic proteome. We trust that these experiments will lead to important knowledge on protein targets of nutritional variables potentially able to affect the complex central nervous system control of energy homeostasis.
Treatment of adult MPSI mouse brains with IDUA-expressing mesenchymal stem cells decreases GAG deposition and improves exploratory behavior
Authors: da Silva Flávia Helena , Pereira Vanessa Gonçalves , Yasumura Eduardo G , Tenório Lígia Zacchi , de Carvalho Leonardo Pinto , Lisboa Bianca Cristina Garcia , Matsumoto Priscila Keiko , Stilhano Roberta Sessa , Samoto Vivian Y , Calegare Bruno Frederico Aguilar , Brandão Letícia de Campos , D’Almeida Vânia , Filippo Thaís RM , Porcionatto Marimélia , Toma Leny , Nader Helena Bonciani , Valero Valderez Bastos , Camassola Melissa , Nardi Nance Beyer , Han Sang Won 
Published: April 2012

Abstract

Background
Mucopolysaccharidosis type I (MPSI) is caused by a deficiency in alpha-L iduronidase (IDUA), which leads to lysosomal accumulation of the glycosaminoglycans (GAGs) dermatan and heparan sulfate. While the currently available therapies have good systemic effects, they only minimally affect the neurodegenerative process. Based on the neuroprotective and tissue regenerative properties of mesenchymal stem cells (MSCs), we hypothesized that the administration of MSCs transduced with a murine leukemia virus (MLV) vector expressing IDUA to IDUA KO mouse brains could reduce GAG deposition in the brain and, as a result, improve neurofunctionality, as measured by exploratory activity.

Methods
MSCs infected with an MLV vector encoding IDUA were injected into the left ventricle of the brain of 12- or 25-month-old IDUA KO mice. The behavior of the treated mice in the elevated plus maze and open field tests was observed for 1 to 2 months. Following these observations, the brains were removed for biochemical and histological analyses.

Results
After 1 or 2 months of observation, the presence of the transgene in the brain tissue of almost all of the treated mice was confirmed using PCR, and a significant reduction in GAG deposition was observed. This reduction was directly reflected in an improvement in exploratory activity in the open field and the elevated plus maze tests. Despite these behavioral improvements and the reduction in GAG deposition, IDUA activity was undetectable in these samples. Overall, these results indicate that while the initial level of IDUA was not sustainable for a month, it was enough to reduce and maintain low GAG deposition and improve the exploratory activity for months.

Conclusions
These data show that gene therapy, via the direct injection of IDUA-expressing MSCs into the brain, is an effective way to treat neurodegeneration in MPSI mice.
Molecular xenomonitoring of Dirofilaria immitis and Dirofilaria repens in mosquitoes from north-eastern Italy by real-time PCR coupled with melting curve analysis
Authors: Latrofa Maria Stefania , Montarsi Fabrizio , Ciocchetta Silvia , Annoscia Giada , Dantas-Torres Filipe , Ravagnan Silvia , Capelli Gioia , Otranto Domenico 
Published: April 2012

Abstract

Background

Dirofilaria immitis and Dirofilaria repens are transmitted by bloodsucking culicid mosquitoes belonging to Culex, Aedes, Ochlerotatus, Anopheles and Mansonia genera.
The detection of filarioids in mosquitoes for assessing distribution of vectors and/or of pathogens in a given area (also known as “xenomonitoring”), when based on individual dissection of wild-caught female mosquitoes is time consuming and hardly applicable in large epidemiological surveys.
Our study aimed to evaluate the recently developed duplex real-time PCR for screening large number of culicids and to assess their positivity for D. immitis and D. repens in an area where both species are endemic.

Methods
A duplex real-time PCR was used to detect and differentiate D. immitis and D. repens in mosquitoes collected in six provinces of the Veneto region using 43 carbon dioxide-baited traps under the frame of an entomological surveillance program to monitor the vectors of West Nile disease. From early May till October 2010, unfed female mosquitoes (n = 40,892) were captured in 20 selected sites.

Results
Mosquitoes identified as Culex pipiens, Ochlerotatus caspius, Aedes vexans and Culex modestus were grouped into 995 pools according to species, day and site of collection (from minimum of 1 to maximum of 57). Out of 955 pools, 23 (2.41 %) scored positive for Dirofilaria spp. of which, 21 (2.2 %) for D. immitis and two (0.21 %) for D. repens. An overall Estimated Rate of Infection (ERI) of 0.06 % was recorded, being higher in Och. caspius and Ae. vexans (i.e., 0.18 % and 0.14 %, respectively). At least one mosquito pool was positive for Dirofilaria spp. in each province with the highest ERI recorded in Vicenza and Padova provinces (i.e., 0.42% and 0.16 %, respectively). Mosquitoes collected in all provinces were positive for D. immitis whereas, only two (i.e., Padova and Rovigo) provinces scored positive for D. repens. All mosquito species, except for Cx. modestus, were positive for D. immitis, whereas D. repens was only found in Cx. pipiens.

Conclusions
The results suggest that both Dirofilaria species are endemic and may occur in sympatry in the examined area. The molecular approach herein used represents a powerful tool for surveillance programs of D. immitis and D. repens in the culicid vectors towards a better understanding of the epidemiology of the infections they cause and their seasonal transmission patterns.
Using angiogenic factors and their soluble receptors to predict organ dysfunction in patients with disseminated intravascular coagulation associated with severe trauma
Authors: Wada Takeshi , Jesmin Subrina , Gando Satoshi , Sultana Sayeeda N , Zaedi Sohel , Yokota Hiroyuki 
Published: April 2012

Abstract
Introduction
Disseminated intravascular coagulation (DIC) is characterized by the concomitant activation of coagulofibrinolytic disorders and systemic inflammation associated with endothelial dysfunction-induced microvascular permeability. Angiogenic factors, including vascular endothelial growth factor (VEGF), angiopoietin (Ang), and their receptors, play crucial roles in angiogenesis and microvascular permeability. The aim of the study was to assess the relationship between angiogenic factors, their soluble receptors and organ dysfunction associated with DIC after severe trauma.

Materials and methods
A total of 57 patients with severe trauma were divided into two subgroups; 30 DIC patients and 27 non-DIC patients. The DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC and the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. The serum levels of angiogenic factors were measured at the time of admission (Day 1), Day 3 and Day 5. This study compared levels of these angiogenic factors between the two DIC groups, and evaluated their predictive value for organ dysfunction.

Results
DIC patients, especially those with ISTH DIC, showed higher Sequential Organ Failure Assessment (SOFA) scores and lactate levels. There were lower levels of VEGF, Ang1 and the soluble Tie2 in the ISTH DIC patients than the non-DIC patients. The levels of soluble VEGF receptor-1 (sVEGFR1), Ang2 and the Ang2/Ang1 ratio in the ISTH DIC patients were higher than in non-DIC patients. The relationship between the presence of massive transfusion and angiogenic factors indicated the same results. The levels of sVEGFR1, Ang2 and the Ang2/Ang1 ratio correlated with the SOFA scores. In particular, sVEGFR1 and Ang2 were independent predictors of an increase in the SOFA score. The lactate levels independently predicted increases in the levels of sVEGFR1 and Ang2. The decrease in the platelet counts also independently predicted the increase in Ang2 levels in DIC patients.

Conclusions
Angiogenic factors and their soluble receptors, particularly sVEGFR1 and Ang2, are considered to play pivotal roles in the development of organ dysfunction in DIC associated with severe trauma. DIC-induced tissue hypoxia and platelet consumption may play crucial roles in inducing sVEGFR1 and Ang2, and in determining the prognosis of the severity of organ dysfunction.
Impact of a Bladder Cancer Diagnosis on Smoking Behavior
Authors: Bassett Jeffrey C. , Gore John L. , Chi Amanda C. , Kwan Lorna , McCarthy William , Chamie Karim , Saigal Christopher S. 
Published: April 2012

Purpose Bladder cancer is the second most common tobacco-related malignancy. A new bladder cancer diagnosis may be an opportunity to imprint smoking cessation. Little is known about the impact of a diagnosis of bladder cancer on patterns of tobacco use and smoking cessation among patients with incident bladder cancer. Patients and Methods A simple random sample of noninvasive bladder cancer survivors diagnosed in 2006 was obtained from the California Cancer Registry. Respondents completed a survey on history of tobacco use, beliefs regarding bladder cancer risk factors, and physician influence on tobacco cessation. Respondents were compared by smoking status. Those respondents smoking at diagnosis were compared with general population controls obtained from the California Tobacco Survey to determine the impact of a diagnosis of bladder cancer on patterns of tobacco use. Results The response rate was 70% (344 of 492 eligible participants). Most respondents (74%) had a history of cigarette use. Seventeen percent of all respondents were smoking at diagnosis. Smokers with a new diagnosis of bladder cancer were almost five times as likely to quit smoking as smokers in the general population (48% v 10%, respectively; P < .001). The bladder cancer diagnosis and the advice of the urologist were the reasons cited most often for cessation. Respondents were more likely to endorse smoking as a risk factor for bladder cancer when the urologist was the source of their understanding. Conclusion The diagnosis of bladder cancer is an opportunity for smoking cessation. Urologists can play an integral role in affecting the patterns of tobacco use of those newly diagnosed.
Both asymmetric mitotic segregation and cell-to-cell invasion are required for stable germline transmission of Wolbachia in filarial nematodes
Authors: Landmann Frédéric , Bain Odile , Martin Coralie , Uni Shigehiko , Taylor Mark J. , Sullivan William 
Published: April 2012

Summary
Parasitic filarial nematodes that belong to the Onchocercidae family live in mutualism with Wolbachia endosymbionts. We developed whole-mount techniques to follow the segregation patterns of Wolbachia through the somatic and germline lineages of four filarial species. These studies reveal multiple evolutionarily conserved mechanisms that are required for Wolbachia localization to the germline. During the initial embryonic divisions, Wolbachia segregate asymmetrically such that they concentrate in the posteriorly localized P2 blastomere, a precursor to the adult germline and hypodermal lineages. Surprisingly, in the next division they are excluded from the germline precursor lineage. Rather, they preferentially segregate to the C blastomere, a source of posterior hypodermal cells. Localization to the germline is accomplished by a distinct mechanism in which Wolbachia invade first the somatic gonadal cells close to the ovarian distal tip cell, the nematode stem cell niche, from the hypodermis. This tropism is associated with a cortical F-actin disruption, suggesting an active engulfment. Significantly, germline invasion occurs only in females, explaining the lack of Wolbachia in the male germline. Once in the syncytial environment of the ovaries, Wolbachia rely on the rachis to multiply and disperse into the germ cells. The utilization of cell-to-cell invasion for germline colonization may indicate an ancestral mode of horizontal transfer that preceded the acquisition of the mutualism.
Comparative efficacy and safety of intravenous ferric carboxymaltose (Ferinject) and iron(III) hydroxide dextran (Cosmofer) in pregnancy
Authors: Myers B , Myers O , Moore J 
Published: April 2012

Background Iron-deficiency anaemia is common in pregnancy, with well-described maternal morbidities. When oral iron therapy has failed, intravenous (IV) preparations are considered. Ferric carboxymaltose (ferinject) is a new IV preparation which can be given quickly. There are no published data on Ferinject use in pregnancy. This study analyses historical data from women given Cosmofer, compared with those given Ferinject in pregnancy, to assess comparative efficacy and safety. Methods Pregnant women treated with Cosmofer and Ferinject, were identified from pharmacy records. Records for all cases were reviewed and those which fulfilled inclusion criteria selected. The inclusion criteria included: symptomatic iron-deficient anaemia unresponsive to oral iron; age ≥18; second to third trimester; full blood count taken at least once at two, four and/or six weeks post-infusion. Data were collected on the pre-treatment Hb, ferritin, and same data collected at two, four and six weeks after the infusion. Side-effects or adverse reactions were noted for both the Cosmofer and Ferinject patients. Results Results were obtained for 92 women (44 received Ferinject and 48 Cosmofer). Pre-infusion Hb and ferritin levels were comparable in the two groups. At two weeks, the mean Hb rise in the Ferinject group was 1.73 g/dL and 1.34 g/dL in the Cosmofer group. At four weeks, the total rise in Hb was 2.57 g/dL Ferinject, 2.34 g/dL Cosmofer. At six weeks the rise was 3.01 g/dL and 3.2 g/dL respectively. No serious adverse events were reported in either group. Conclusion Both preparations appear effective and safe, with low risk of serious adverse effects and side-effects.
Hyperglycosylated Human Chorionic Gonadotropin in Serum of Testicular Cancer Patients
Authors: Lempiäinen Anna , Hotakainen Kristina , Blomqvist Carl , Alfthan Henrik , Stenman Ulf-Håkan 
Published: April 2012

Abstract

BACKGROUND
Hyperglycosylated human chorionic gonadotropin (hCG-h) contains larger and more complex carbohydrate chains than regular human chorionic gonadotropin (hCG). hCG-h is thought to be the major form of hCG produced by testicular cancers and it has been suggested to play a key role in tumor invasion, but studies on hCG-h in testicular cancer are limited. We studied whether serum hCG is hyperglycosylated, and whether measurement of hCG-h in serum offers clinical value in the management of testicular cancer.

METHODS
We determined the serum concentrations of hCG-h, hCG, and the free β subunit of hCG (hCGβ) by time-resolved immunofluorometric assays in 176 serum samples (preoperative n = 67, relapse n = 20, follow-up n = 89) obtained from 84 testicular cancer patients. We analyzed the association between preoperative serum concentrations of hCG, hCG-h, and hCGβ with known prognostic factors and progression-free survival time.

RESULTS
A major proportion of hCG was hyperglycosylated preoperatively, at relapse, and shortly after treatment. The serum concentrations of hCG-h and hCG correlated strongly with each other and had similar diagnostic value. The preoperative serum concentration of hCG-h correlated with prognostic factors and outcome in the same way as hCG. Increased preoperative hCGβ concentration predicted shorter progression-free survival.

CONCLUSIONS
Most of the hCG expressed by testicular cancers is hyperglycosylated and therefore it is important that hCG assays used for management of testicular cancer recognize hCG-h.
The Option Value of Innovation
Authors: Thornton Snider Julia , Romley John A. , Vogt William B. , Philipson Tomas J. 
Published: April 2012

Abstract
Standard techniques of cost effectiveness analysis measure a technology’s benefits in terms of expected life years (or quality-adjusted life years) gained at today’s life expectancies. However, this approach ignores the gains which derive from the possibility that a health technology allows an individual to survive long enough to benefit from other technological innovations which raise life expectancy (and quality of life) in the future. Borrowing a term from the finance literature, we refer to this source of value as the “option value” of innovation. We explain where this value comes from and how to calculate it in a variety of standard cost effectiveness analysis contexts. We provide a proof-of-concept using the example of the drug tamoxifen, which delayed the onset of breast cancer for some patients until more effective adjuvant treatment was available. We find that incorporating option value can increase the conventionally estimated value of tamoxifen with better adjuvant treatment by nearly a quarter (from $200,000 to $248,000 for those who initiated tamoxifen in 1999). We expect similar results for other drugs in therapeutic areas of rapid technological advancement.
Tax Morale and Compliance Behavior: First Evidence on a Causal Link
Authors: Halla Martin 
Published: April 2012

Abstract
Recent literature on tax evasion emphasizes the importance of moral considerations to explain compliance behavior. As a consequence scholars aim to identify factors that shape this so-called tax morale. However, the causal link between tax morale and actual compliance behavior is not established yet. Exploiting exogenous variation in tax morale – given by the inherited part of tax morale of American-born from their ancestors country of origin – our Two-Stage Least Square Estimation provides first evidence on a causal effect of tax morale on the size of the underground production.