bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental depletion of CD8+ cells in acutely SIVagm-Infected African Green Monkeys results in increased viral replication
Authors: Gaufin Thaidra , Ribeiro Ruy M , Gautam Rajeev , Dufour Jason , Mandell Daniel , Apetrei Cristian , Pandrea Ivona 
Published: May 2010

AbstractBackgroundIn vivoCD8+cell depletions in pathogenic SIV infections identified a key role for cellular immunity in controlling viral load (VL) and disease progression. However, similar studies gave discordant results in chronically-infected SMs, leading some authors to propose that in natural hosts, SIV replication is independent of cellular immunity. To assess the role of cellular immune responses in the control of SIV replication in natural hosts, we investigated the impact of CD8+cell depletion during acute SIV infection in AGMs.ResultsNine AGMs were infected with SIVagm.sab and were followed up to day 225 p.i. Four were intravenously infused with the cM-T807 antibody on days 0 (50 mg/kg), 6, and 13 (10 mg/kg, respectively) post infection (p.i.). CD8+cells were depleted for up to 28 days p.i. in peripheral blood and LNs in all treated AGMs. Partial CD8+T cell depletion occurred in the intestine. SIVagm VLs peaked at similar levels in both groups (107-108RNA copies/ml). However, while VLs were controlled in undepleted AGMs, reaching set-point levels (104-105RNA copies/ml) by day 28 p.i., high VLs (>106RNA copies/ml) were maintained by day 21 p.i. in CD8-depleted AGMs. By day 42 p.i., VLs were comparable between the two groups. The levels of immune activation and proliferation remained elevated up to day 72 p.i. in CD8-depleted AGMs and returned to preinfection levels in controls by day 28 p.i. None of the CD8-depleted animals progressed to AIDS.ConclusionCD8+cells are responsible for a partial control of postacute viral replication in SIVagm.sab-infected AGMs. In contrast to macaques, the SIVagm-infected AGMs are able to control viral replication after recovery of the CD8+T cells and avoid disease progression.
The development of a rapid SYBR one step real-time RT-PCR for detection of porcine reproductive and respiratory syndrome virus
Authors: Tian Hong , Wu JingYan , Shang YouJun , Cheng Yan , Liu XiangTao 
Published: May 2010

Abstract

Background
Prompt detection of PRRSV in the field samples is important for effective PRRS control, thereby reducing the potentially serious economic damage which can result from an outbreak. In this study, a rapid SYBR-based, one step real-time RT-PCR quantitative reverse transcription PCR (qRT-PCR) has been developed for the detection of porcine reproductive and respiratory syndrome virus (PRRSV). Primers were designed based on the sequence of highly conservative region of PRRSV N gene.

Results
The sensitivity of the real-time qRT-PCR assay was achieved through PRRSV ch-1a RNA for the generation of a standard curve. The detection limit of the assay was found to be 9.6 RNA copies per reaction mixture. This assay had excellent intra- and inter-assay reproducibility as in total 65 field samples were screened for the presence of PRRSV by conventional RT-PCR in parallel with qRT-PCR, and the detection rate increased from 60.0% to 76.9%. Moreover, the specificity result indicated that this assay could reliably differentiate PRRSV from the other swine viral diseases, such as classical swine fever virus (CSFV), swine vesicular disease virus (SVDV) and vesicular exanthema of swine virus (VESV).

Conclusion
The real-time qRT-PCR assay described in this report allows the rapid, specific and sensitive laboratory detection of PRRSV in field samples.
Characterization of variants in the promoter of BZLF1 gene of EBV in nonmalignant EBV-associated diseases in Chinese children
Authors: Jin Yingkang , Xie Zhengde , Lu Gen , Yang Shuang , Shen Kunling 
Published: May 2010

Abstract

Background
Diseases associated with Epstein-Barr virus (EBV) infections, such as infectious mononucleosis (IM), EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV) are not rare in Chinese children. The association of type 1 or type 2 EBV and variants of the EBV BZLF1 promoter zone (Zp) with these diseases is unclear.

Results
The objective of this study was to investigate the relationship between EBV genotypes (Zp variants and EBV type 1 and 2) and the clinical phenotypes of EBV-associated diseases in Chinese children. The Zp region was directly sequenced in 206 EBV-positive DNA samples from the blood of patients with IM, EBV-HLH, CAEBV, and healthy controls. Type 1 or type 2 EBV was examined by PCR for EBNA2 and EBNA3C subtypes. Four polymorphic Zp variants were identified: Zp-P, Zp-V3, Zp-P4 and Zp-V1, a new variant. The Zp-V3 variant was significantly associated with CAEBV (P ≤ 0.01). The frequency of co-infection with Zp variants was higher in patients with CAEBV and EBV-HLH, compared with IM and healthy controls, mostly as Zp-P+V3 co-infection. Type 1 EBV was predominant in all categories (81.3-95%) and there was no significant difference in the frequency of the EBV types 1 and 2 in different categories (P > 0.05).

Conclusions
Type 1 EBV and BZLF1 Zp-P of EBV were the predominant genotypes in nonmalignant EBV associated diseases in Chinese children and Zp-V3 variant may correlates with the developing of severe EBV infection diseases, such as CAEBV and EBV-HLH.
FoxP3 and Bcl-xL cooperatively promote regulatory T cell persistence and prevention of arthritis development
Authors: Haque Rizwanul , Lei Fengyang , Xiong Xiaofang , Wu Yuzhang , Song Jianxun 
Published: May 2010

Abstract
Introduction
Forkhead box p3 (FoxP3)-expressing regulatory T cells (Tregs) have been clearly implicated in the control of autoimmune disease in murine models. In addition, ectopic expression of FoxP3 conveys a Treg phenotype to CD4+ T cells, lending itself to therapeutic use in the prevention of rheumatoid arthritis (RA). In this study, we generated therapeutically active Tregs with an increased life span and hence greater therapeutic potential.

Methods
We used retrovirus-mediated transduction to introduce FoxP3 or FoxP3 with anti-apoptotic Bcl-2 family molecule Bcl-xL linked by a 2A picornavirus self-cleaving peptide into CD4+ T cells to generate Tregs. In addition, by using in vitro functional analyses and adoptive immunotherapy in a murine model of RA, we demonstrated that these Tregs were highly reactive.

Results
We found that CD4+ T cells expressing both FoxP3 and Bcl-xL were able to differentiate into functional Tregs, which have a long-term survival advantage over cells transduced with FoxP3 alone. In an in vivo murine model, adoptive transfer of Tregs expressing both FoxP3 and Bcl-xL demonstrated more effective suppression of RA than CD4+ T cells expressing FoxP3 alone.

Conclusions
FoxP3 and Bcl-xL can cooperatively promote the differentiation and persistence of Tregs, with the capacity to prevent arthritis. Our results provide a novel approach for generating highly reactive Tregs for augmenting cellular immunotherapy for autoimmune disease.
Association between length of storage of red blood cell units and outcome of critically ill children: a prospective observational study
Authors: Karam Oliver , Tucci Marisa , Bateman Scot T , Ducruet Thierry , Spinella Philip C , Randolph Adrienne G , Lacroix Jacques 
Published: May 2010

Abstract
Introduction
Transfusion is a common treatment in pediatric intensive care units (PICUs). Studies in adults suggest that prolonged storage of red blood cell units is associated with worse clinical outcome. No prospective study has been conducted in children. Our objectives were to assess the clinical impact of the length of storage of red blood cell units on clinical outcome of critically ill children.

Methods
Prospective, observational study conducted in 30 North American centers, in consecutive patients aged <18 years with a stay ≥ 48 hours in a PICU. The primary outcome measure was the incidence of multiple organ dysfunction syndrome after transfusion. The secondary outcomes were 28-day mortality and PICU length of stay. Odds ratios were adjusted for gender, age, number of organ dysfunctions at admission, total number of transfusions, and total dose of transfusion, using a multiple logistic regression model.

Results
The median length of storage was 14 days in 296 patients with documented length of storage. For patients receiving blood stored ≥ 14 days, the adjusted odds ratio for an increased incidence of multiple organ dysfunction syndrome was 1.87 (95% CI 1.04;3.27, P = 0.03). There was also a significant difference in the total PICU length of stay (adjusted median difference +3.7 days, P < 0.001) and no significant change in mortality.

Conclusions
In critically ill children, transfusion of red blood cell units stored for ≥ 14 days is independently associated with an increased occurrence of multiple organ dysfunction syndrome and prolonged PICU stay.
Modeling non-uniformity in short-read rates in RNA-Seq data
Authors: Li Jun , Jiang Hui , Wong Wing Hung 
Published: May 2010

AbstractAfter mapping, RNA-Seq data can be summarized by a sequence of read counts commonly modeled as Poisson variables with constant rates along each transcript, which actually fit data poorly. We suggest using variable rates for different positions, and propose two models to predict these rates based on local sequences. These models explain more than 50% of the variations and can lead to improved estimates of gene and isoform expressions for both Illumina and Applied Biosystems data.
Breast Cancer Survival in Relation to the Metastatic Tumor Burden in Axillary Lymph Nodes
Authors: Andersson Yvette , Frisell Jan , Sylvan Maria , de Boniface Jana , Bergkvist Leif 
Published: May 2010

Purpose The aim of this study was to determine the prognostic significance of lymph node micrometastases in patients with breast cancer. Patients and Methods Between September 2000 and January 2004, 3,369 patients with breast cancer were included in a prospective cohort. According to their lymph node status, they were classified in the following four groups: 2,383 were node negative, 107 had isolated tumor cells, 123 had micrometastases, and 756 had macrometastases. Median follow-up time was 52 months. Kaplan-Meier estimates and the multivariate Cox proportional hazard regression model were used to analyze survival. Results Five-year cause-specific and event-free survival rates were lower for patients with micrometastases (pN1mi) than for node-negative (pN0) patients (94.1% v 96.9% and 79.6% v 87.1%, respectively; P = .020 and P = .032, respectively). There was no significant survival difference between node-negative patients and those with isolated tumor cells. The overall survival of pN1mi and pN0 patients did not differ. Conclusion This study demonstrates a worse prognosis for patients with micrometastases than for node-negative patients.
Intense Dose-Dense Sequential Chemotherapy With Epirubicin, Paclitaxel, and Cyclophosphamide Compared With Conventionally Scheduled Chemotherapy in High-Risk Primary Breast Cancer: Mature Results of an AGO Phase III Study
Authors: Moebus Volker , Jackisch Christian , Lueck Hans-Joachim , du Bois Andreas , Thomssen Christoph , Kurbacher Christian , Kuhn Walther , Nitz Ulrike , Schneeweiss Andreas , Huober Jens , Harbeck Nadia , von Minckwitz Gunter , Runnebaum Ingo B. , Hinke Axel , Kreienberg Rolf , Konecny Gottfried E. , Untch Michael 
Published: May 2010

Purpose Patients with primary breast cancer who have extensive axillary lymph node involvement have a poor prognosis after conventional adjuvant therapy. We compared intense dose-dense (IDD) adjuvant chemotherapy with conventionally scheduled adjuvant chemotherapy in patients with high-risk primary breast cancer. Patients and Methods In this randomized, phase III trial, a total of 1,284 eligible patients with four or more involved axillary lymph nodes were randomly assigned to receive IDD sequential epirubicin, paclitaxel, and cyclophosphamide (IDD-ETC) every 2 weeks or conventionally scheduled epirubicin/cyclophosphamide followed by paclitaxel every three weeks. The primary end point was event-free survival (EFS). Results At a median follow-up of 62 months, 5-year event-free survival rates were 62% in the conventional arm and 70% in the IDD-ETC arm, representing a 28% reduction of the relative risk of relapse (P < .001). This benefit was independent of menopausal, hormone receptor, or human epidermal growth factor receptor 2 status. The 5-year overall survival rates were 77% versus 82%, representing a 24% reduction of the relative risk of death (P = .0285). IDD therapy was associated with significantly more nonhematologic and hematologic toxicities, but no treatment-related death occurred. Four occurrences of acute myeloid leukemia or myelodysplastic syndrome (MDS) were observed in the IDD-ETC arm. No severe congestive heart failure was reported. Conclusion IDD-ETC was less well tolerated compared with conventional chemotherapy but significantly improved event-free and overall survivals in patients with high-risk primary breast cancer who had four or more positive axillary lymph nodes.
Phase I Dose-Escalation Study of Recombinant Human Apo2L/TRAIL, a Dual Proapoptotic Receptor Agonist, in Patients With Advanced Cancer
Authors: Herbst Roy S. , Eckhardt S. Gail , Kurzrock Razelle , Ebbinghaus Scot , O'Dwyer Peter J. , Gordon Michael S. , Novotny William , Goldwasser Meredith A. , Tohnya Tanyifor M. , Lum Bert L. , Ashkenazi Avi , Jubb Adrian M. , Mendelson David S. 
Published: May 2010

PurposeApoptosis ligand 2/tumor necrosis factor–related apoptosis-inducing ligand (Apo2L/TRAIL)—a member of the tumor necrosis factor cytokine family—induces apoptosis by activating the extrinsic pathway through the proapoptotic death receptors DR4 and DR5. Recombinant human Apo2L/TRAIL (rhApo2L/TRAIL) has broad potential as a cancer therapy. To the best of our knowledge, this is the first in-human clinical trial to assess the safety, tolerability, pharmacokinetics, and antitumor activity of multiple intravenous doses of rhApo2L/TRAIL in patients with advanced cancer.Patients and MethodsThis phase I, open-label, dose-escalation study treated patients with advanced cancer with rhApo2L/TRAIL doses ranging from 0.5 to 30 mg/kg/d, with parallel dose escalation for patients without liver metastases and with normal liver function (cohort 1) and for patients with liver metastases and normal or mildly abnormal liver function (cohort 2). Doses were given daily for 5 days, with cycles repeating every 3 weeks. Assessments included adverse events (AEs), laboratory tests, pharmacokinetics, and imaging to evaluate antitumor activity.ResultsSeventy-one patients received a mean of 18.3 doses; seven patients completed all eight treatment cycles. The AE profile of rhApo2L/TRAIL was similar in cohorts 1 and 2. The most common AEs were fatigue (38%), nausea (28%), vomiting (23%), fever (23%), anemia (18%), and constipation (18%). Liver enzyme elevations were concurrent with progressive metastatic liver disease. Two patients with sarcoma (synovial and undifferentiated) experienced serious AEs associated with rapid tumor necrosis. Two patients with chondrosarcoma experienced durable partial responses to rhApo2L/TRAIL.ConclusionAt the tested schedule and dose range, rhApo2L/TRAIL was safe and well tolerated. Dose escalation achieved peak rhApo2L/TRAIL serum concentrations equivalent to those associated with preclinical antitumor efficacy.
Pregnancy Outcome After Treatment for Wilms Tumor: A Report From the National Wilms Tumor Long-Term Follow-Up Study
Authors: Green Daniel M. , Lange Jane M. , Peabody Eve M. , Grigorieva Natalia N. , Peterson Susan M. , Kalapurakal John A. , Breslow Norman E. 
Published: May 2010

Purpose This study was undertaken to evaluate the effect of prior treatment with radiation therapy or chemotherapy for unilateral Wilms tumor (WT) diagnosed during childhood on pregnancy complications, birth weight, and the frequency of congenital malformations in live-born offspring. Patients and Methods We reviewed pregnancy outcomes among female survivors and partners of male survivors of WT treated on National Wilms Tumor Studies 1, 2, 3, and 4 by using a maternal questionnaire and a review of both maternal and offspring medical records. Results We received reports of 1,021 pregnancies with duration of 20 weeks or longer, including 955 live-born singletons, for whom 700 sets of maternal and offspring medical records were reviewed. Rates of hypertension complicating pregnancy (International Classification of Diseases [ICD] code 642), early or threatened labor (ICD-644) and malposition of the fetus (ICD-652) increased with increasing radiation dose in female patients. The percentages of offspring weighing less than 2,500 g at birth and of those having less than 37 weeks of gestation also increased with dose. There was no significant trend with radiation dose in the number of congenital anomalies recorded in offspring of female patients. Conclusion Women who receive flank radiation therapy as part of the treatment for unilateral WT are at increased risk of hypertension complicating pregnancy, fetal malposition, and premature labor. The offspring of these women are at risk for low birth weight and premature (ie, < 37 weeks gestation) birth. These risks must be considered in the obstetrical management of female survivors of WT.
Chemotherapy Patients' Perceptions of Drug Administration Safety
Authors: Schwappach David L.B. , Wernli Martin 
Published: May 2010

Purpose To explore chemotherapy patients' experiences of drug administration safety and to investigate the relationship between perceptions of risk and harm from error, staff safety practices, and patients' engagement in error prevention strategies. Patients and Methods Four hundred seventy-nine chemotherapy patients treated at the oncology/hematology department of a large regional hospital in Switzerland completed a self-administered survey (53% response rate). Results Sixteen percent of patients reported having experienced an error in their care, and 11% were currently very concerned about errors. Patients perceived the risk of four detailed errors as rather low, whereas the mean rating of potential harm from error was substantial. Relative to other errors, patients seem to underestimate the harm associated with drug overdosing. Seventy-seven percent of responders agreed that patients can help to prevent errors. Although patients perceived staff as being committed to providing safe care, ratings related to patient involvement in safety were considerably lower. More than one quarter of patients disagreed that staff instructed them to watch for and report errors. Patients engaged in safety behaviors, particularly in those behaviors that are compatible with traditional patient-provider relations. Risk of error perceptions, affirmative attitudes toward patient preventability, and error experience were positively linked to safety-related behaviors, whereas higher levels of global trust in staff safety practices were inconsistently associated with lower frequency of engagement in safety strategies. Conclusion Chemotherapy safety is a considerable concern for patients. Many patients are prepared to be involved in error prevention. The results highlight areas for improvement in communication and cooperation for safety between patients and providers.
Service Robotics as an Application for the Grand Challenges in Computer Enginering
Authors: Maehle Erik 
Published: May 2010

Abstract
Service robots have a very high potential for the future and are already today employed in a number of important applications. For exploiting this potential successfully progress has to be made in many disciplines. This article focuses on robot control architectures in hardware and software. Taking today existing robots as examples typical current control architectures are presented and the contribution of the Grand Challenges in Computer Science to their further development is discussed.
Intragenic Suppression of a Trafficking-Defective Brassinosteroid Receptor Mutant in Arabidopsis
Authors: Belkhadir Youssef , Durbak Amanda , Wierzba Michael , Schmitz Robert J , Aguirre Andrea , Michel Rene , Rowe Scott , Fujioka Shozo , Tax Frans E 
Published: May 2010

Abstract
The cell surface receptor kinase BRASSINOSTEROID-INSENSITIVE-1 (BRI1) is the major receptor for steroid hormones in Arabidopsis. Plants homozygous for loss-of-function mutations in BRI1 display a reduction in the size of vegetative organs, resulting in dwarfism. The recessive bri1-5 mutation produces receptors that do not accumulate to wild-type levels and are retained mainly in the endoplasmic reticulum. We have isolated a dominant suppressor of the dwarf phenotype of bri1-5 plants. We show that this suppression is caused by a second-site mutation in BRI1, bri1-5R1. The bri1-5R1 mutation partially rescues the phenotypes of bri1-5 in many tissues and enhances bri1-5 phenotypes above wild-type levels in several other tissues. We demonstrate that the phenotypes of bri1-5R1 plants are due to both increased cell expansion and increased cell division. To test the mechanism of bri1-5 suppression, we assessed whether the phenotypic suppression in bri1-5R1 was dependent on ligand availability and the integrity of the signaling pathway. Our results indicate that the suppression of the dwarf phenotypes associated with bri1-5R1 requires both BR biosynthesis and the receptor kinase BRI1-ASSOCIATED KINASE-1 (BAK1). Finally, we show that bri1-5R1 partially restores the accumulation and plasma membrane localization of BRI1. Collectively, our results point toward a model in which bri1-R1 compensates for the protein-folding abnormalities caused by bri1-5, restoring accumulation of the receptor and its delivery to the cell surface.
The Next Generation of Molecular Markers From Massively Parallel Sequencing of Pooled DNA Samples
Authors: Futschik Andreas , Schlötterer Christian 
Published: May 2010

AbstractNext generation sequencing (NGS) is about to revolutionize genetic analysis. Currently NGS techniques are mainly used to sequence individual genomes. Due to the high sequence coverage required, the costs for population-scale analyses are still too high to allow an extension to nonmodel organisms. Here, we show that NGS of pools of individuals is often more effective in SNP discovery and provides more accurate allele frequency estimates, even when taking sequencing errors into account. We modify the population genetic estimators Tajima's π and Watterson's θ to obtain unbiased estimates from NGS pooling data. Given the same sequencing effort, the resulting estimators often show a better performance than those obtained from individual sequencing. Although our analysis also shows that NGS of pools of individuals will not be preferable under all circumstances, it provides a cost-effective approach to estimate allele frequencies on a genome-wide scale.
Some Consequences of Demographic Stochasticity in Population Genetics
Authors: Parsons Todd L , Quince Christopher , Plotkin Joshua B 
Published: May 2010

Abstract
Much of population genetics is based on the diffusion limit of the Wright–Fisher model, which assumes a fixed population size. This assumption is violated in most natural populations, particularly for microbes. Here we study a more realistic model that decouples birth and death events and allows for a stochastically varying population size. Under this model, classical quantities such as the probability of and time before fixation of a mutant allele can differ dramatically from their Wright–Fisher expectations. Moreover, inferences about natural selection based on Wright–Fisher assumptions can yield erroneous and even contradictory conclusions: at small population densities one allele will appear superior, whereas at large densities the other allele will dominate. Consequently, competition assays in laboratory conditions may not reflect the outcome of long-term evolution in the field. These results highlight the importance of incorporating demographic stochasticity into basic models of population genetics.