bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation of a diacidic motif in SIV-PBj Nef impairs T-cell activation and enteropathic disease
Authors: Tschulena Ulrich , Sanzenbacher Ralf , Mühlebach Michael D , Berger André , Münch Jan , Schindler Michael , Kirchhoff Frank , Plesker Roland , Coulibaly Cheick , Panitz Sylvia , Prüfer Steffen , Muckenfuss Heide , Hamdorf Matthias , Schweizer Matthias , Cichutek Klaus , Flory Egbert 
Published: March 2011

AbstractBackgroundThe non-pathogenic course of SIV infection in its natural host is characterized by robust viral replication in the absence of chronic immune activation and T cell proliferation. In contrast, acutely lethal enteropathic SIVsmm strain PBj induces a strong immune activation and causes a severe acute and lethal disease in pig-tailed macaques after cross-species transmission. One important pathogenicity factor of the PBj virus is the PBj-Nef protein, which contains a conserved diacidic motif and, unusually, an immunoreceptor tyrosine-based activation motif (ITAM).ResultsMutation of the diacidic motif in the Nef protein of the SIVsmmPBj abolishes the acute phenotype of this virus.In vitro, wild-type and mutant PBj (PBj-Nef202/203GG) viruses replicated to similar levels in macaque PBMCs, but PBj-Nef202/203GG no longer triggers ERK mitogen-activated protein (MAP) kinase pathway including an alteration of a Nef-associated Raf-1/ERK-2 multiprotein signaling complex. Moreover, stimulation of IL-2 and down-modulation of CD4 and CD28 were impaired in the mutant virus. Pig-tailed macaques infected with PBj-Nef202/203GG did not show enteropathic complications and lethality as observed with wild-type PBj virus, despite efficient replication of both virusesin vivo. Furthermore, PBj-Nef202/203GG infected animals revealed reduced T-cell activation in periphery lymphoid organs and no detectable induction of IL-2 and IL-6.ConclusionsIn sum, we report here that mutation of the diacidic motif in the PBj-Nef protein abolishes disease progression in pig-tailed macaques despite efficient replication. These data suggest that alterations in the ability of a lentivirus to promote T cell activation and proliferation can have a dramatic impact on its pathogenic potential.
Management of HIV-1 associated hepatitis in patients with acquired immunodeficiency syndrome: role of a successful control of viral replication
Authors: Esposito Antonella , Conti Valentina , Cagliuso Maria , Pastori Daniele , Fantauzzi Alessandra , Mezzaroma Ivano 
Published: March 2011

Abstract
In HIV-1 infected patients, increase of liver enzymes may be mainly due to viral coinfections, alcohol intake, hepatotoxic drugs or autoimmune diseases. Three cases of aminotransferase elevation occurred during a phase of uncontrolled viral replication combined with a severe immunodeficiency and resolved by an effective HAART are described, focusing on the etio-pathogenetic role possibly played by HIV-1 infection.
Complexity of VTA DA neural activities in response to PFC transection in nicotine treated rats
Authors: Chen Ting Y , Zhang Die , Dragomir Andrei , Akay Yasemin M , Akay Metin 
Published: March 2011

AbstractBackgroundThe dopaminergic (DA) neurons in the ventral tegmental area (VTA) are widely implicated in the addiction and natural reward circuitry of the brain. These neurons project to several areas of the brain, including prefrontal cortex (PFC), nucleus accubens (NAc) and amygdala. The functional coupling between PFC and VTA has been demonstrated, but little is known about how PFC mediates nicotinic modulation in VTA DA neurons. The objectives of this study were to investigate the effect of acute nicotine exposure on the VTA DA neuronal firing and to understand how the disruption of communication from PFC affects the firing patterns of VTA DA neurons.MethodsExtracellular single-unit recordings were performed on Sprague-Dawley rats and nicotine was administered after stable recording was established as baseline. In order to test how input from PFC affects the VTA DA neuronal firing, bilateral transections were made immediate caudal to PFC to mechanically delete the interaction between VTA and PFC.ResultsThe complexity of the recorded neural firing was subsequently assessed using a method based on the Lempel-Ziv estimator. The results were compared with those obtained when computing the entropy of neural firing. Exposure to nicotine triggered a significant increase in VTA DA neurons firing complexity when communication between PFC and VTA was present, while transection obliterated the effect of nicotine. Similar results were obtained when entropy values were estimated.ConclusionsOur findings suggest that PFC plays a vital role in mediating VTA activity. We speculate that increased firing complexity with acute nicotine administration in PFC intact subjects is due to the close functional coupling between PFC and VTA. This hypothesis is supported by the fact that deletion of PFC results in minor alterations of VTA DA neural firing when nicotine is acutely administered.
Hepatitis Associated Aplastic Anemia: A review
Authors: Rauff Bisma , Idrees Muhammad , Shah Shahida Amjad Riaz , Butt Sadia , Butt Azeem M , Ali Liaqat , Hussain Abrar , Irshad-ur-Rehman  , Ali Muhammad 
Published: March 2011

Abstract
Hepatitis-associated aplastic anemia (HAAA) is an uncommon but distinct variant of aplastic anemia in which pancytopenia appears two to three months after an acute attack of hepatitis. HAAA occurs most frequently in young male children and is lethal if leave untreated. The etiology of this syndrome is proposed to be attributed to various hepatitis and non hepatitis viruses. Several hepatitis viruses such as HAV, HBV, HCV, HDV, HEV and HGV have been associated with this set of symptoms. Viruses other than the hepatitis viruses such as parvovirus B19, Cytomegalovirus, Epstein bar virus, Transfusion Transmitted virus (TTV) and non-A-E hepatitis virus (unknown viruses) has also been documented to develop the syndrome. Considerable evidences including the clinical features, severe imbalance of the T cell immune system and effective response to immunosuppressive therapy strongly present HAAA as an immune mediated mechanism. However, no association of HAAA has been found with blood transfusions, drugs and toxins. Besides hepatitis and non hepatitis viruses and immunopathogenesis phenomenon as causative agents of the disorder, telomerase mutation, a genetic factor has also been predisposed for the development of aplastic anemia. Diagnosis includes clinical manifestations, blood profiling, viral serological markers testing, immune functioning and bone marrow hypocellularity examination. Patients presenting the features of HAAA have been mostly treated with bone marrow or hematopoietic cell transplantation from HLA matched donor, and if not available then by immunosuppressive therapy. New therapeutic approaches involve the administration of steroids especially the glucocorticoids to augment the immunosuppressive therapy response. Pancytopenia following an episode of acute hepatitis response better to hematopoietic cell transplantation than immunosuppressive therapy.
Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale
Authors: Shmelkov Evgeny , Tang Zuojian , Aifantis Iannis , Statnikov Alexander 
Published: March 2011

Abstract

Background
Pathway databases are becoming increasingly important and almost omnipresent in most types of biological and translational research. However, little is known about the quality and completeness of pathways stored in these databases. The present study conducts a comprehensive assessment of transcriptional regulatory pathways in humans for seven well-studied transcription factors: MYC, NOTCH1, BCL6, TP53, AR, STAT1, and RELA. The employed benchmarking methodology first involves integrating genome-wide binding with functional gene expression data to derive direct targets of transcription factors. Then the lists of experimentally obtained direct targets are compared with relevant lists of transcriptional targets from 10 commonly used pathway databases.

Results
The results of this study show that for the majority of pathway databases, the overlap between experimentally obtained target genes and targets reported in transcriptional regulatory pathway databases is surprisingly small and often is not statistically significant. The only exception is MetaCore pathway database which yields statistically significant intersection with experimental results in 84% cases. Additionally, we suggest that the lists of experimentally derived direct targets obtained in this study can be used to reveal new biological insight in transcriptional regulation and suggest novel putative therapeutic targets in cancer.

Conclusions
Our study opens a debate on validity of using many popular pathway databases to obtain transcriptional regulatory targets. We conclude that the choice of pathway databases should be informed by solid scientific evidence and rigorous empirical evaluation.

Reviewers
This article was reviewed by Prof. Wing Hung Wong, Dr. Thiago Motta Venancio (nominated by Dr. L Aravind), and Prof. Geoff J McLachlan.
Effect of a single dose of pregabalin on herpes zoster pain
Authors: Jensen-Dahm Christina , Rowbotham Michael C , Reda Haatem , Petersen Karin Lottrup 
Published: March 2011

Abstract

Background
The effect of pregabalin on acute herpes zoster pain has not been previously evaluated.

Methods
In a randomized, double-blind, placebo-controlled, two-session crossover study the effect of a single oral dose of pregabalin (150 mg) on pain and allodynia was evaluated in 8 subjects with herpes zoster.

Results
Over 6 hours of observation, pain decreased by a mean of 33% with pregabalin and 14% with placebo (p < 0.10). Effects on allodynia and SF-MPQ were not significant.

Conclusions
Compared to an earlier study of gabapentin 900 mg for acute zoster pain and allodynia that followed a nearly identical protocol, pregabalin had a similar effect on pain and was well tolerated, with no difference from placebo on sleepiness. Common side effects of light-headedness, unsteady gait, and slowed thinking were almost identical to that observed in the earlier study of gabapentin. Subject recruitment proved difficult in part due to the widespread off-label use of gabapentin and pregabalin for acute zoster pain in our region of the USA.

Trial Registration
ClinicalTrials.gov Identifier: NCT00352651
Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design
Authors: Khattab Ahmed A , Windecker Stephan , Jüni Peter , Hildick-Smith David , Dudek Dariusz , Andersen Henning R , Ibrahim Reda , Schuler Gerhard , Walton Antony S , Wahl Andreas , Mattle Heinrich P , Meier Bernhard 
Published: March 2011

Abstract

Background
Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events.

Methods
The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism.

Discussion
patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011).

Trial Registration
Trial listed in ClinicalTrials.gov as NCT00166257 and sponsored by AGA Medical, Plymouth, MN, USA
Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: study protocol for a multicentre randomized controlled trial
Authors: Longo Umile Giuseppe , Banerjee Sughran , Barber Julie , Chambler Andrew , Cobiella Carlos , Corbett Steven , Crowther Mark , Drew Steven , Francis Andrea , Lee Marcus , Garlick Nicholas , Packham Iain , Pearse Yemi , Richards Andrew , Roberts Chris , Tennent Duncan , Tims Emily , Ahrens Philip Michael 
Published: March 2011

Abstract

Background
Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.

Methods/Design
We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.

Discussion
This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.

Trial Registration
United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007.
A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn
Authors: Ramírez-Vélez Robinson , Romero Miryam , Echeverri Isabella , Ortega José Guillermo , Mosquera Mildrey , Salazar Blanca , Girón Sandra Lorena , Saldarriaga Wilmar , Aguilar de Plata Ana Cecilia , Mateus Julio Cesar 
Published: March 2011

Abstract

Background
Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn.

Methods and design
320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: 1. Control group: usual prenatal care (PC) and placebo (maltodextrine). 2. Exercise group: PC, placebo and aerobic physical exercise. 3. Micronutrients group: PC and a micronutrients capsule consisting of zinc (30 mg), selenium (70 μg), vitamin A (400 μg), alphatocopherol (30 mg), vitamin C (200 mg), and niacin (100 mg). 4. Combined interventions Group: PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions.

Discussion
Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population.

Trial registration

NCT00872365.
Revision of a nonunited subtrochanteric femoral fracture around a failed intramedullary nail with the use of RIA products, BMP-7 and hydroxyapatite: a case report
Authors: Tzioupis Christopher , Panteliadis Pavlos , Gamie Zakareya , Tsiridis Eleftherios 
Published: March 2011

Abstract

Introduction
Femoral subtrochanteric fractures are commonly treated using intramedullary devices. Failure of the implant and subsequent nonunion is still an issue, however, and limited evidence exists regarding the most appropriate treatment.

Case presentation
We report the case of an 80-year-old Caucasian woman with a subtrochanteric fracture originally treated using a trochanteric gamma nail which failed, resulting in a nonunion and fracture of its proximal end. The nonunion was revised with the removal of the broken trochanteric gamma nail, application of a condylar blade plate, ipsilateral Reamer/Irrigator/Aspirator autografting, recombinant human bone morphogenetic protein-7 and injectable hydroxyapatite cement. The fracture united fully at ten months following revision surgery, with no signs of femoral head avascular necrosis at 18-month follow-up.

Conclusion
The essential requirements for success when revising a nonunited fracture are to provide anatomical reduction, mechanical stability, bone defect augmentation and biological stimulation to achieve healing. Current advances in molecular biology, such as recombinant human bone morphogenetic protein-7, and biotechnology such as the Reamer/Irrigator/Aspirator system and hydroxyapatite injectable cement can improve patient outcomes over the use of our traditional revision techniques.
Two-step synthesis of fatty acid ethyl ester from soybean oil catalyzed by Yarrowia lipolytica lipase
Authors: Meng Yonghong , Wang Guili , Yang Na , Zhou Zhiqi , Li Yuejuan , Liang Xiaomei , Chen Jinnan , Li Ying , Li Jilun 
Published: March 2011

Abstract

Background
Enzymatic biodiesel production by transesterification in solvent media has been investigated intensively, but glycerol, as a by-product, could block the immobilized enzyme and excess n-hexane, as a solution aid, would reduce the productivity of the enzyme. Esterification, a solvent-free and no-glycerol-release system for biodiesel production, has been developed, and two-step catalysis of soybean oil, hydrolysis followed by esterification, with Yarrowia lipolytica lipase is reported in this paper.

Results
First, soybean oil was hydrolyzed at 40°C by 100 U of lipase broth per 1 g of oil with approximately 30% to 60% (vol/vol) water. The free fatty acid (FFA) distilled from this hydrolysis mixture was used for the esterification of FFA to fatty acid ethyl ester by immobilized lipase. A mixture of 2.82 g of FFA and equimolar ethanol (addition in three steps) were shaken at 30°C with 18 U of lipase per 1 gram of FFA. The degree of esterification reached 85% after 3 hours. The lipase membranes were taken out, dehydrated and subjected to fresh esterification so that over 82% of esterification was maintained, even though the esterification was repeated every 3 hours for 25 batches.

Conclusion
The two-step enzymatic process without glycerol released and solvent-free demonstrated higher efficiency and safety than enzymatic transesterification, which seems very promising for lipase-catalyzed, large-scale production of biodiesel, especially from high acid value waste oil.
Time course analysis of gene expression identifies multiple genes with differential expression in patients with in-stent restenosis
Authors: Ganesh Santhi K , Joo Jungnam , Skelding Kimberly , Mehta Laxmi , Zheng Gang , O'Neill Kathleen , Billings Eric M , Helgadottir Anna , Andersen Karl , Thorgeirsson Gudmundur , Gudnason Thorarinn , Geller Nancy L , Simari Robert D , Holmes David R , O'Neill William W , Nabel Elizabeth G 
Published: March 2011

Abstract

Background
The vascular disease in-stent restenosis (ISR) is characterized by formation of neointima and adverse inward remodeling of the artery after injury by coronary stent implantation. We hypothesized that the analysis of gene expression in peripheral blood mononuclear cells (PBMCs) would demonstrate differences in transcript expression between individuals who develop ISR and those who do not.

Methods and Results
We determined and investigated PBMC gene expression of 358 patients undergoing an index procedure to treat in de novo coronary artery lesions with bare metallic stents, using a novel time-varying intercept model to optimally assess the time course of gene expression across a time course of blood samples. Validation analyses were conducted in an independent sample of 97 patients with similar time-course blood sampling and gene expression data. We identified 47 probesets with differential expression, of which 36 were validated upon independent replication testing. The genes identified have varied functions, including some related to cellular growth and metabolism, such as the NAB2 and LAMP genes.

Conclusions
In a study of patients undergoing bare metallic stent implantation, we have identified and replicated differential gene expression in peripheral blood mononuclear cells, studied across a time series of blood samples. The genes identified suggest alterations in cellular growth and metabolism pathways, and these results provide the basis for further specific functional hypothesis generation and testing of the mechanisms of ISR.
Sphingosine-1 phosphate receptor (S1p1), a critical receptor controlling human lymphocyte trafficking, is expressed in hen and human ovaries and ovarian tumors
Authors: Bradaric Michael J , Barua Animesh , Penumatsa Krishna , Yi Yu , Edassery Seby L , Sharma Sameer , Abramowicz Jacques S , Bahr Janice M , Luborsky Judith L 
Published: March 2011

AbstractBackgroundSphingosine-1 receptor 1 (S1P1) plays a major role in regulating lymphocyte egress from peripheral lymph tissue. Lymphocyte trafficking is potentially a critical response to tumors and to tumor vaccines. Also, the receptor has been shown to influence metastasis. However, there is little information on its expression in the aged ovary or ovarian tumors. As a basis for further studies in the laying hen model of spontaneous ovarian cancer, the objective of this study was to determine if S1P1 is expressed in hens, and if the morphological distribution of S1P1 is similar in hen and human ovary and ovarian tumors.MethodsS1P1 mRNA was ascertained in hen tissue by RT-PCR using hen specific primers. S1P1 protein expression and localization was evaluated in hen and human tissue with a human S1P1 antibody by Western blot and immunohistochemistry.ResultsS1P1 mRNA was expressed in all hen tissues examined. Protein was detected in human and hen ovary and ovarian tumors at 47, 72 and 108 kDa in Western blots. S1P1 was similarly expressed on endothelial cells, lymphocytes and surface epithelial cells in normal ovaries and tumor-containing ovaries of the hen. In addition, S1P1 distribution was heterogeneous in both hen and human ovarian tumors by immunohistochemistry.ConclusionThe results show that S1P1 is expressed in the hen and human ovary as well as in ovarian tumors. These findings support the use of the hen in further studies of the role of S1P1 in metastasis and immune cell trafficking in ovarian tumor development.