bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs
Authors: Nakahara Takeshi , Uchi Hiroshi , Lesokhin Alexander M. , Avogadri Francesca , Rizzuto Gabrielle A. , Hirschhorn-Cymerman Daniel , Panageas Katherine S. , Merghoub Taha , Wolchok Jedd D. , Houghton Alan N. 
Published: February 2010

AbstractCyclophosphamide (CTX), a commonly used chemotherapeutic agent can enhance immune responses. The ability of CTX to promote the proliferation of effector T cells and abrogate the function of regulatory T cells (Tregs) has been described. In this study, we examined the effects of CTX treatment on dendritic cell (DC) subsets and the subsequent outcome on the effector and suppressive arms of adaptive immunity. In secondary lymphoid tissues, tissue-derived migratory DCs (migratory DCs), lymphoid tissue–resident DCs (resident DCs), and plasmacytoid DCs (pDCs) are well described. CTX has profound and selective cytotoxic effects on CD8+ resident DCs, but not skin-derived migratory DCs or pDCs in lymph nodes (LNs) and spleen, causing an imbalance among these DC subsets. CTX treatment increases the potency of DCs in antigen presentation and cytokine secretion, and partially inhibits the suppressor activity of Tregs. Adoptive transfer of CD8+ DCs can reconstitute this population in regional draining LNs and abrogate the immune-enhancing effects of CTX in vivo. These findings demonstrate that CTX may improve immune responses by preferentially depleting CD8+ lymphoid-resident DCs, which leads to diminished Treg suppression and enhanced effector T-cell function in vivo.
A comparison of experience-dependent locomotory behaviors and biogenic amine neurons in nematode relatives of Caenorhabditis elegans
Authors: Rivard Laura , Srinivasan Jagan , Stone Allison , Ochoa Stacy , Sternberg Paul W , Loer Curtis M 
Published: February 2010

Abstract

Background
Survival of an animal depends on its ability to match its responses to environmental conditions. To generate an optimal behavioral output, the nervous system must process sensory information and generate a directed motor output in response to stimuli. The nervous system should also store information about experiences to use in the future. The diverse group of free-living nematodes provides an excellent system to study macro- and microevolution of molecular, morphological and behavioral character states associated with such nervous system function. We asked whether an adaptive behavior would vary among bacterivorous nematodes and whether differences in the neurotransmitter systems known to regulate the behavior in one species would reflect differences seen in the adaptive behavior among those species. Caenorhabditis elegans worms slow in the presence of food; this 'basal' slowing is triggered by dopaminergic mechanosensory neurons that detect bacteria. Starved worms slow more dramatically; this 'enhanced' slowing is regulated by serotonin.

Results
We examined seven nematode species with known phylogenetic relationship to C. elegans for locomotory behaviors modulated by food (E. coli), and by the worm's recent history of feeding (being well-fed or starved). We found that locomotory behavior in some species was modulated by food and recent feeding experience in a manner similar to C. elegans, but not all the species tested exhibited these food-modulated behaviors. We also found that some worms had different responses to bacteria other than E. coli. Using histochemical and immunological staining, we found that dopaminergic neurons were very similar among all species. For instance, we saw likely homologs of four bilateral pairs of dopaminergic cephalic and deirid neurons known from C. elegans in all seven species examined. In contrast, there was greater variation in the patterns of serotonergic neurons. The presence of presumptive homologs of dopaminergic and serotonergic neurons in a given species did not correlate with the observed differences in locomotory behaviors.

Conclusions
This study demonstrates that behaviors can differ significantly between species that appear morphologically very similar, and therefore it is important to consider factors, such as ecology of a species in the wild, when formulating hypotheses about the adaptive significance of a behavior. Our results suggest that evolutionary changes in locomotory behaviors are less likely to be caused by changes in neurotransmitter expression of neurons. Such changes could be caused either by subtle changes in neural circuitry or in the function of the signal transduction pathways mediating these behaviors.
Personalized medicine in psoriasis: developing a genomic classifier to predict histological response to Alefacept
Authors: Suárez-Fariñas Mayte , Shah Kejal R , Haider Asifa S , Krueger James G , Lowes Michelle A 
Published: February 2010

AbstractBackgroundAlefacept treatment is highly effective in a select group patients with moderate-to-severe psoriasis, and is an ideal candidate to develop systems to predict who will respond to therapy. A clinical trial of 22 patients with moderate to severe psoriasis treated with alefacept was conducted in 2002-2003, as a mechanism of action study. Patients were classified as responders or non-responders to alefacept based on histological criteria. Results of the original mechanism of action study have been published. Peripheral blood was collected at the start of this clinical trial, and a prior analysis demonstrated that gene expression in PBMCs differed between responders and non-responders, however, the analysis performed could not be used to predict response.MethodsMicroarray data from PBMCs of 16 of these patients was analyzed to generate a treatment response classifier. We used a discriminant analysis method that performs sample classification from gene expression data, via "nearest shrunken centroid method". Centroids are the average gene expression for each gene in each class divided by the within-class standard deviation for that gene.ResultsA disease response classifier using 23 genes was created to accurately predict response to alefacept (12.3% error rate). While the genes in this classifier should be considered as a group, some of the individual genes are of great interest, for example, cAMP response element modulator (CREM), v-MAF avian musculoaponeurotic fibrosarcoma oncogene family (MAFF), chloride intracellular channel protein 1 (CLIC1, also called NCC27), NLR family, pyrin domain-containing 1 (NLRP1), and CCL5 (chemokine, cc motif, ligand 5, also called regulated upon activation, normally T expressed, and presumably secreted/RANTES).ConclusionsAlthough this study is small, and based on analysis of existing microarray data, we demonstrate that a treatment response classifier for alefacept can be created using gene expression of PBMCs in psoriasis. This preliminary study may provide a useful tool to predict response of psoriatic patients to alefacept.
Efficacy of non-artemisinin- and artemisinin-based combination therapies for uncomplicated falciparum malaria in Cameroon
Authors: Whegang Solange Youdom , Tahar Rachida , Foumane Vincent Ngane , Soula Georges , Gwét Henri , Thalabard Jean-Christophe , Basco Leonardo K 
Published: February 2010

Abstract

Background
The use of drug combinations, including non-artemisinin-based and artemisinin-based combination therapy (ACT), is a novel strategy that enhances therapeutic efficacy and delays the emergence of multidrug-resistant Plasmodium falciparum. Its use is strongly recommended in most sub-Saharan African countries, namely Cameroon, where resistance to chloroquine is widespread and antifolate resistance is emerging.

Methods
Studies were conducted in Cameroonian children with acute uncomplicated P. falciparum malaria according to the standard World Health Organization protocol at four sentinel sites between 2003 and 2007. A total of 1,401 children were enrolled, of whom 1,337 were assigned to randomized studies and 64 were included in a single non-randomized study. The proportions of adequate clinical and parasitological response (PCR-uncorrected on day 14 and PCR-corrected on day 28) were the primary endpoints to evaluate treatment efficacy on day 14 and day 28. The relative effectiveness of drug combinations was compared by a multi-treatment Bayesian random-effect meta-analysis.

Findings
The results based on the meta-analysis suggested that artesunate-amodiaquine (AS-AQ) is as effective as other drugs (artesunate-sulphadoxine-pyrimethamine [AS-SP], artesunate-chlorproguanil-dapsone [AS-CD], artesunate-mefloquine [AS-MQ], dihydroartemisinin-piperaquine [DH-PP], artemether-lumefantrine [AM-LM], amodiaquine, and amodiaquine-sulphadoxine-pyrimethamine [AQ-SP]). AM-LM appeared to be the most effective with no treatment failure due to recrudescence, closely followed by DH-PP.

Conclusion
Although AM-LM requires six doses, rather than three doses for other artemisinin-based combinations, it has potential advantages over other forms of ACT. Further studies are needed to evaluate the clinical efficacy and tolerance of these combinations in different epidemiological context.
Cigarette smoke regulates VEGFR2-mediated survival signaling in rat lungs
Authors: Marwick John A , Edirisinghe Indika , Arunachalam Gnanapragasam , Stevenson Christopher S , MacNee William , Kirkham Paul A , Rahman Irfan 
Published: February 2010

Abstract

Background
Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2)-mediated survival signaling is critical to endothelial cell survival, maintenance of the vasculature and alveolar structure and regeneration of lung tissue. Reduced VEGF and VEGFR2 expression in emphysematous lungs has been linked to increased endothelial cell death and vascular regression. Previously, we have shown that CS down-regulated the VEGFR2 and its downstream signaling in mouse lungs. However, the VEGFR2-mediated survival signaling in response to oxidants/cigarette smoke (CS) is not known. We hypothesized that CS exposure leads to disruption of VEGFR2-mediated endothelial survival signaling in rat lungs.

Methods
Adult male Sprague-Dawley rats were exposed CS for 3 days, 8 weeks and 6 months to investigate the effect of CS on VEGFR2-mediated survival signaling by measuring the Akt/PI3-kinase/eNOS downstream signaling in rat lungs.

Results and Discussion
We show that CS disrupts VEGFR2/PI3-kinase association leading to decreased Akt and eNOS phosphorylation. This may further alter the phosphorylation of the pro-apoptotic protein Bad and increase the Bad/Bcl-xl association. However, this was not associated with a significant lung cell death as evidenced by active caspase-3 levels. These data suggest that although CS altered the VEGFR2-mediated survival signaling in the rat lungs, but it was not sufficient to cause lung cell death.

Conclusion
The rat lungs exposed to CS in acute, sub-chronic and chronic levels may be representative of smokers where survival signaling is altered but was not associated with lung cell death whereas emphysema is known to be associated with lung cell apoptosis.
Detection of anatid herpesvirus 1 gC gene by TaqMan™ fluorescent quantitative real-time PCR with specific primers and probe
Authors: Zou Qing , Sun Kunfeng , Cheng Anchun , Wang Mingshu , Xu Chao , Zhu Dekang , Jia Renyong , Luo Qihui , Zhou Yi , Chen Zhengli , Chen Xiaoyue 
Published: February 2010

Abstract

Background
Anatid herpesvirus 1 (AHV-1) is known for the difficulty of monitoring and controlling, because it has a long period of asymptomatic carrier state in waterfowls. Furthermore, as a significant essential agent for viral attachment, release, stability and virulence, gC (UL44) gene and its protein product (glycoprotein C) may play a key role in the epidemiological screening. The objectives of this study were to rapidly, sensitively, quantitatively detect gC gene of AHV-1 and provide the underlying basis for further investigating pcDNA3.1-gC DNA vaccine in infected ducks by TaqMan™ fluorescent quantitative real-time PCR assay (FQ-PCR) with pcDNA3.1-gC plasmid.

Results
The repeatable and reproducible quantitative assay was established by the standard curve with a wide dynamic range (eight logarithmic units of concentration) and very good correlation values (1.000). This protocol was able to detect as little as 1.0 × 101 DNA copies per reaction and it was highly specific to AHV-1. The TaqMan™ FQ-PCR assay successfully detected the gC gene in tissue samples from pcDNA3.1-gC and AHV-1 attenuated vaccine (AHV-1 Cha) strain inoculated ducks respectively.

Conclusions
The assay offers an attractive method for the detection of AHV-1, the investigation of distribution pattern of AHV-1 in vivo and molecular epidemiological screening. Meanwhile, this method could expedite related AHV-1 and gC DNA vaccine research.
Macrophage inhibitory cytokine-1 is increased in individuals before type 2 diabetes diagnosis but is not an independent predictor of type 2 diabetes: the Whitehall II study
Authors: Carstensen Maren , Herder Christian , Brunner Eric J , Strassburger Klaus , Tabak Adam G , Roden Michael , Witte Daniel R 
Published: February 2010

ObjectiveMacrophage inhibitory cytokine-1 (MIC-1) belongs to the transforming growth factor (TGF)-β superfamily, and has been reported to be involved in energy homoeostasis and weight loss and to have anti-inflammatory properties. We hypothesized that decreased concentrations of MIC-1 would be associated with higher risk of developing type 2 diabetes.Design and methodsWe designed a nested case–control study within the Whitehall II cohort and measured serum concentrations of MIC-1 by ELISA in 180 individuals without type 2 diabetes at baseline who developed type 2 diabetes during the follow-up period of 11.5±3.0 years and in 372 controls frequency-matched for age, sex, and body mass index with normal glucose tolerance throughout the study.ResultsMIC-1 concentrations at baseline were higher in cases (median (25/75th percentiles) 537.1 (452.7–677.4) pg/ml) than in controls (499.7 (413.8–615.4) pg/ml; P=0.0044). In the age- and sex-adjusted model, a 1-s.d. increase in MIC-1 (206.0 pg/ml) was associated with an odds ratio (95% confidence interval) of 1.21 (0.997; 1.46; P=0.054) for type 2 diabetes. Adjustment for waist circumference, cardiovascular risk factors, socioeconomic status, proinflammatory mediators, and glycemia abolished the association.ConclusionsBaseline MIC-1 concentrations were increased, not decreased, in individuals before type 2 diabetes manifestation, but not independently associated with incident type 2 diabetes in multivariable analyses. This upregulation of MIC-1 could be part of an anti-inflammatory response preceding the onset of type 2 diabetes, which has been described before for interleukin-1 receptor antagonist and TGF-β1.
Prognostic Factors in Chemotherapy-Treated Patients with HIV-Associated Plasmablastic Lymphoma
Authors: Castillo Jorge J. , Winer Eric S. , Stachurski Dariusz , Perez Kimberly , Jabbour Melhem , Milani Cannon , Colvin Gerald , Butera James N. 
Published: February 2010

Abstract

Background.
Plasmablastic lymphoma (PBL) is a variant of diffuse large B-cell lymphoma commonly seen in the oral cavity of HIV-infected individuals. PBL has a poor prognosis, but prognostic factors in patients who have received chemotherapy have not been adequately evaluated.

Methods.
An extensive literature search rendered 248 cases of PBL, from which 157 were HIV+. Seventy cases with HIV-associated PBL that received chemotherapy were identified. Whenever possible, authors of the original reports were contacted to complete clinicopathological data. Univariate analyses were performed calculating Kaplan–Meier estimates and compared using the log-rank test.

Results.
The mean age was 39 years, with a male predominance. The mean CD4+ count was 165 cells/mm3. Advanced clinical stage was seen in 51% and extraoral involvement was seen in 43% of the cases. The expression levels of CD20 and Epstein-Barr virus–encoded RNA were 13% and 86%, respectively. The overall survival duration was 14 months. In a univariate analysis, early clinical stage and a complete response to chemotherapy were associated with longer survival. There was no apparent difference in survival with regimens more intensive than cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

Conclusions.
Patients with HIV-associated PBL have a poor prognosis. Prognosis is strongly associated with achieving a complete clinical response to CHOP or CHOP-like chemotherapy. The role of more intensive regimens is currently unclear. Further research is needed to improve responses using novel therapeutic agents and strategies.
Behavioral Changes Associated With Testing HIV-Positive Among Sexually Transmitted Infection Clinic Patients In Cape Town, South Africa
Authors: Kalichman Seth C. , Cain Demetria , Simbayi Leickness C. 
Published: February 2010

Objectives. We sought to examine behavioral risks and behavior changes associated with testing HIV-positive among sexually transmitted infection (STI) patients, in order to inform HIV- and STI-prevention interventions. Methods. We performed a cohort study of 29 STI patients who seroconverted from HIV-negative to HIV-positive during 1 year of observation and 77 STI patients who persistently tested HIV-negative. Computerized behavioral interviews were collected at baseline and at 1 year, and STI clinic charts were abstracted over the same 1-year period. Results. The STI patients who reported genital bleeding during sexual activity at baseline were significantly more likely to test HIV-positive. Reductions in number of sexual partners and rates of unprotected intercourse occurred for all STI clinic patients regardless of whether they tested HIV-positive. Conclusions. Although risk reductions occurred, 5% of HIV-negative STI clinic patients subsequently tested HIV-positive over 1 year. Behavioral risk-reduction interventions are urgently needed for male and female STI clinic patients.
Financial Strain and Smoking Cessation Among Racially/Ethnically Diverse Smokers
Authors: Kendzor Darla E. , Businelle Michael S. , Costello Tracy J. , Castro Yessenia , Reitzel Lorraine R. , Cofta-Woerpel Ludmila M. , Li Yisheng , Mazas Carlos A. , Vidrine Jennifer Irvin , Cinciripini Paul M. , Greisinger Anthony J. , Wetter David W. 
Published: February 2010

Objectives. We evaluated the influence of financial strain on smoking cessation among Latino, African American, and Caucasian smokers of predominantly low socioeconomic status. Methods. Smokers enrolled in a smoking cessation study (N = 424) were followed from 1 week prequit through 26 weeks postquit. We conducted a logistic regression analysis to evaluate the association between baseline financial strain and smoking abstinence at 26 weeks postquit after control for age, gender, race/ethnicity, educational level, annual household income, marital status, number of cigarettes smoked per day, and time to first cigarette of the day. Results. Greater financial strain at baseline was significantly associated with reduced odds of abstinence at 26 weeks postquit among those who completed the study (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.62, 0.94; P = .01). There was a significant association as well in analyses that included those who completed the study in addition to those lost to follow-up who were categorized as smokers (OR = 0.78; 95% CI = 0.64, 0.96; P = .02). Conclusions. Greater financial strain predicted lower cessation rates among racially/ethnically diverse smokers. Our findings highlight the impact of economic concerns on smoking cessation and the need to address financial strain in smoking cessation interventions.
Selective Schools and Academic Achievement
Authors: Clark Damon 
Published: February 2010

Abstract
In this paper I consider the impact of attending a selective high school in the UK. Students are assigned to these schools on the basis of a test taken in primary school and, using data on these assignment test scores for a particular district, I exploit this rule to estimate the causal effects of selective schools on test scores, high school course taking and university enrollment. Despite the huge peer advantage enjoyed by selective school students, I show that four years of selective school attendance generates at best small effects on test scores. Selective schools do however have positive effects on course-taking and, more suggestively, university enrollment, evidence suggesting they may have important longer run impacts.
Kinematics of Rising From a Chair: Image-Based Analysis of the Sagittal Hip-Spine Movement Pattern in Elderly People Who Are Healthy
Authors: Fotoohabadi Mohammad R. , Tully Elizabeth A. , Galea Mary P. 
Published: February 2010

BackgroundRehabilitation of elderly patients with sit-to-stand (STS) dysfunction includes retraining coordinated movement among participating body segments. Although trunk position is considered important, spinal movement has not been measured.ObjectiveThe aim of this study was to describe the sagittal thoracolumbar kinematics and hip-lumbar interaction during the STS task in elderly people who were healthy in order to guide physical therapists in developing treatment strategies.DesignThis was an observational study.MethodsTen retroreflective markers were attached to the midline thoracolumbar spine, pelvis, and right lower limb of 41 elderly people who were healthy. A 2-dimensional video analysis system was used to measure sagittal thoracic, lumbar, hip, and knee joint angles during the STS task. Maximal available flexion-extension angles in these joints and regions also were determined.ResultsPrior to buttocks lift-off, forward trunk lean comprised concurrent hip and lumbar flexion and thoracic extension. Hip flexion dominated, with a hip/lumbar ratio of 4.7:1 and a thoracic/lumbar ratio of 1.7:1. The hip and lumbar spine contributed 90% and 23% of their maximal available flexion angle, respectively, and the thoracic spine contributed 86% of its maximal extension range of movement. After lift-off, the hips and lumbar spine extended (ratio of 5.2:1), and the thoracic spine flexed (thoracic/lumbar ratio of 0.4:1). At lift-off, the hips and knees were similarly flexed (96°) and then locked together in a linear pattern of extension. Following lift-off, there was a brief transition phase (5% of STS duration) in which, although the hips, knees, and lumbar spine were extending, the trunk continued to flex forward a few degrees.LimitationsResults may differ in elderly people who are less active.ConclusionsThe revised model for image-based analysis demonstrated concurrent hip and thoracolumbar movement during the STS task. Close to full available hip flexion and thoracic extension were needed for optimal STS performance.