bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discontinuing prophylactic transfusions increases the risk of silent brain infarction in children with sickle cell disease: data from STOP II
Authors: Abboud Miguel R. , Yim Eunsil , Musallam Khaled M. , Adams Robert J. ,   for the STOP II Study Investigators
Published: June 2011

AbstractIn the STOP II trial, discontinuation of prophylactic transfusions in high risk children with sickle cell disease (SCD) resulted in a high rate of reversion to abnormal blood-flow velocities on transcranial Doppler (TCD) ultrasonography and strokes. We analyzed data from STOP II to determine the effect of discontinuing transfusions on the development or progression of silent brain infarcts on magnetic resonance imaging (MRI). At study entry, 21 of 79 (27%) patients had evidence of silent infarcts. There were no statistically significant differences in baseline characteristics between patients with normal brain MRI or silent infarcts at study entry. At study end, 3 of 37 (8.1%) patients in the continued-transfusion group developed new brain MRI lesions compared with 11 of 40 (27.5%) in the transfusion-halted group (P = .03). The total number of lesions remained essentially unchanged decreasing from 25 to 24 in the continued-transfusion group while increasing from 27 to 45 in transfusion-halted patients. Thus, discontinuation of transfusions in children with SCD and abnormal TCD who revert to low-risk increases the risk of silent brain infarction. Together with data from STOP, these findings demonstrate that transfusions prevent the development of silent infarcts in patients with SCD and abnormal TCD but normal MRA.
Influence of immunosuppressive treatment on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation
Authors: Inamoto Yoshihiro , Flowers Mary E. D. , Lee Stephanie J. , Carpenter Paul A. , Warren Edus H. , Deeg H. Joachim , Storb Rainer F. , Appelbaum Frederick R. , Storer Barry E. , Martin Paul J. 
Published: June 2011

AbstractThis study was conducted to elucidate the influence of immunosuppressive treatment (IST) and GVHD on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation (HCT). The study cohort included 2656 patients who received allogeneic HCT after high-intensity conditioning regimens for treatment of hematologic malignancies. Rates and hazard ratios of relapse and mortality were analyzed according to GVHD and IST as time-varying covariates. Adjusted Cox analyses showed that acute and chronic GVHD were both associated with statistically similar reductions in risk of relapse beyond 18 months after HCT but not during the first 18 months. In patients with GVHD, resolution of GVHD followed by withdrawal of IST was not associated with a subsequent increase in risk of relapse. In patients without GVHD, withdrawal of IST was associated with a reduced risk of relapse during the first 18 months, but the risk of subsequent relapse remained considerably higher than in patients with GVHD. In summary, the association of GVHD with risk of relapse changes over time after HCT. In patients without GVHD, early withdrawal of IST might help to prevent relapse during the first 18 months, but other interventions would be needed to prevent relapse at later time points.
Steroid-refractory GVHD: T-cell attack within a vulnerable endothelial system
Authors: Luft Thomas , Dietrich Sascha , Falk Christine , Conzelmann Michael , Hess Michael , Benner Axel , Neumann Frank , Isermann Berend , Hegenbart Ute , Ho Anthony D. , Dreger Peter 
Published: June 2011

Abstract
Acute graft-versus-host disease (GVHD) is a major complication of allogeneic stem cell transplantation (SCT) and can be readily controlled by systemic high-dose steroids in many patients. However, patients whose GVHD is refractory to this therapy have a poor prognosis. Refractory patients have ongoing end-organ damage despite effective immunosuppression with second-line regimens, suggesting pathomechanisms independent from the initiating T-cell attack. To explore whether endothelial damage might contribute to GVHD refractoriness and to study the role of angiopoietin-2 (ANG2) in this process, we have compared kinetics of T-cell activation markers and markers of endothelial dysfunction in the serum of patients with sensitive (n = 23) and refractory GVHD (n = 25). Longitudinal measurements of soluble FAS ligand along with other immune markers demonstrate that refractory patients are not exposed to an overwhelming or unresponsive T-cell attack. However, in contrast to sensitive GVHD, refractory GVHD was associated with rising thrombomodulin levels and high ANG2/ vascular endothelial-derived growth factor ratios. Patients with refractory GVHD showed significantly increased ANG2 levels already before SCT. These results suggest that endothelial cell vulnerability and dysfunction, rather than refractory T-cell activity, drives treatment refractoriness of GVHD and opens new avenues for prediction and control of this devastating condition.
A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura
Authors: Scully Marie , McDonald Vickie , Cavenagh Jamie , Hunt Beverley J. , Longair Ian , Cohen Hannah , Machin Samuel J. 
Published: June 2011

AbstractThe safety and efficacy of weekly rituximab 375 mg/m2 (×4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n = 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated. Before the second rituximab infusion, 68% of cases had a platelet count > 50 × 109/L and 38% > 150 × 109/L. Fewer PEX were required in whites compared to nonwhite in the rituximab group (mean 14 vs 21, P = .0095). Inpatient stay was reduced by 7 days in the non-ICU trial cases compared to historical controls (P = .04), especially in whites, with a mean reduction of 7 days (P = .05). Ten percent of trial cases relapsed, median, 27 months (17-31 months), compared to 57% in historical controls, median 18 months (3-60 months; P = .0011). There were no excess infections or serious adverse events with rituximab. In conclusion, rituximab appears a safe and effective therapy. Inpatient stay and relapse are significantly reduced in the rituximab cohort. Rituximab should be considered in conjunction with standard therapy on acute presentation of TTP. This study was registered at www.clinicaltrials.gov as NCT009-3713.
Rap1 promotes VEGFR2 activation and angiogenesis by a mechanism involving integrin αvβ3
Authors: Lakshmikanthan Sribalaji , Sobczak Magdalena , Chun Changzoon , Henschel Angela , Dargatz Jillian , Ramchandran Ramani , Chrzanowska-Wodnicka Magdalena 
Published: June 2011

AbstractVascular endothelial growth factor (VEGF) acting through VEGF receptor 2 (VEGFR2) on endothelial cells (ECs) is a key regulator of angiogenesis, a process essential for wound healing and tumor metastasis. Rap1a and Rap1b, 2 highly homologous small G proteins, are both required for angiogenesis in vivo and for normal EC responses to VEGF. Here we sought to determine the mechanism through which Rap1 promotes VEGF-mediated angiogenesis. Using lineage-restricted Rap1-knockout mice we show that Rap1-deficiency in endothelium leads to defective angiogenesis in vivo, in a dose-dependent manner. Using ECs obtained from Rap1-deficient mice we demonstrate that Rap1b promotes VEGF-VEGFR2 kinase activation and regulates integrin activation. Importantly, the Rap1b-dependent VEGF-VEGFR2 activation is in part mediated via integrin αvβ3. Furthermore, in an in vivo model of zebrafish angiogenesis, we demonstrate that Rap1b is essential for the sprouting of intersomitic vessels, a process known to be dependent on VEGF signaling. Using 2 distinct pharmacologic VEGFR2 inhibitors we show that Rap1b and VEGFR2 act additively to control angiogenesis in vivo. We conclude that Rap1b promotes VEGF-mediated angiogenesis by promoting VEGFR2 activation in ECs via integrin αvβ3. These results provide a novel insight into the role of Rap1 in VEGF signaling in ECs.
A single vaccination of commercial broilers does not reduce transmission of H5N1 highly pathogenic avian influenza
Authors: Poetri Okti , Bouma Annemarie , Claassen Ivo , Koch Guus , Soejoedono Retno , Stegeman Arjan , van Boven Michiel 
Published: June 2011

Abstract
Vaccination of chickens has become routine practice in Asian countries in which H5N1 highly pathogenic avian influenza (HPAI) is endemically present. This mainly applies to layer and breeder flocks, but broilers are usually left unvaccinated. Here we investigate whether vaccination is able to reduce HPAI H5N1 virus transmission among broiler chickens. Four sets of experiments were carried out, each consisting of 22 replicate trials containing a pair of birds. Experiments 1-3 were carried out with four-week-old birds that were unvaccinated, and vaccinated at day 1 or at day 10 of age. Experiment 4 was carried out with unvaccinated day-old broiler chicks. One chicken in each trial was inoculated with H5N1 HPAI virus. One chicken in each trial was inoculated with virus. The course of the infection chain was monitored by serological analysis, and by virus isolation performed on tracheal and cloacal swabs. The analyses were based on a stochastic SEIR model using a Bayesian inferential framework. When inoculation was carried out at the 28th day of life, transmission was efficient in unvaccinated birds, and in birds vaccinated at first or tenth day of life. In these experiments estimates of the latent period (~1.0 day), infectious period (~3.3 days), and transmission rate parameter (~1.4 per day) were similar, as were estimates of the reproduction number (~4) and generation interval (~1.4 day). Transmission was significantly less efficient in unvaccinated chickens when inoculation was carried out on the first day of life. These results show that vaccination of broiler chickens does not reduce transmission, and suggest that this may be due to the interference of maternal immunity.
Extensive production of Neospora caninum tissue cysts in a carnivorous marsupial succumbing to experimental neosporosis
Authors: King Jessica S , McAllan Bronwyn , Spielman Derek S , Lindsay Scott A , Hůrková-Hofmannová Lada , Hartigan Ashlie , Al-Qassab Sarwat E , Ellis John T , Šlapeta Jan 
Published: June 2011

Abstract
Experimental infections of Sminthopsis crassicaudata, the fat-tailed dunnart, a carnivorous marsupial widely distributed throughout the arid and semi-arid zones of Australia, show that this species can act as an intermediate host for Neospora caninum. In contrast to existing models that develop relatively few N. caninum tissue cysts, dunnarts offer a new animal model in which active neosporosis is dominated by tissue cyst production. The results provide evidence for a sylvatic life cycle of N. caninum in Australia between marsupials and wild dogs. It establishes the foundation for an investigation of the impact and costs of neosporosis to wildlife.
Binding Site Prediction for Protein-Protein Interactions and Novel Motif Discovery using Re-occurring Polypeptide Sequences
Authors: Amos-Binks Adam , Patulea Catalin , Pitre Sylvain , Schoenrock Andrew , Gui Yuan , Green James R , Golshani Ashkan , Dehne Frank 
Published: June 2011

Abstract

Background
While there are many methods for predicting protein-protein interaction, very few can determine the specific site of interaction on each protein. Characterization of the specific sequence regions mediating interaction (binding sites) is crucial for an understanding of cellular pathways. Experimental methods often report false binding sites due to experimental limitations, while computational methods tend to require data which is not available at the proteome-scale. Here we present PIPE-Sites, a novel method of protein specific binding site prediction based on pairs of re-occurring polypeptide sequences, which have been previously shown to accurately predict protein-protein interactions. PIPE-Sites operates at high specificity and requires only the sequences of query proteins and a database of known binary interactions with no binding site data, making it applicable to binding site prediction at the proteome-scale.

Results
PIPE-Sites was evaluated using a dataset of 265 yeast and 423 human interacting proteins pairs with experimentally-determined binding sites. We found that PIPE-Sites predictions were closer to the confirmed binding site than those of two existing binding site prediction methods based on domain-domain interactions, when applied to the same dataset. Finally, we applied PIPE-Sites to two datasets of 2347 yeast and 14,438 human novel interacting protein pairs predicted to interact with high confidence. An analysis of the predicted interaction sites revealed a number of protein subsequences which are highly re-occurring in binding sites and which may represent novel binding motifs.

Conclusions
PIPE-Sites is an accurate method for predicting protein binding sites and is applicable to the proteome-scale. Thus, PIPE-Sites could be useful for exhaustive analysis of protein binding patterns in whole proteomes as well as discovery of novel binding motifs. PIPE-Sites is available online at http://pipe-sites.cgmlab.org/.
The CDK9/Cyclin T1 subunits of P-TEFb in mouse oocytes and preimplantation embryos: A possible role in embryonic genome activation
Authors: Oqani Reza K , Kim Hong R , Diao Yun F , Park Chang S , Jin Dong I 
Published: June 2011

Abstract

Background
Two stages of genome activation have been identified in the mouse embryo. Specifically, minor transcriptional activation is evident at the one-cell stage and a second major episode of activation occurs at the two-cell stage. Nuclear translocation of RNA polymerase II and phosphorylation of the C-terminal domain (CTD) of the largest enzyme subunit are major determinants of embryonic genome activation. P-TEFb, the Pol II CTD kinase, regulates transcriptional elongation via phosphorylation of the serine 2 residues of the CTD.

Results
Here, we show that the CDK9 and cyclin T1 subunits of P-TEFb are present in mouse oocytes and preimplantation embryos. Both proteins translocate to pronuclei at the late one-cell stage and are predominantly localized in nuclei at the two-cell stage. We additionally examine the effects of the CDK9-specific inhibitor, flavopiridol, on mouse preimplantation development. Our data show that treatment with the drug results in mislocalization of CDK9, cyclin T1, and phosphorylated Pol II, as well as developmental arrest at the two-cell stage.

Conclusions
A change in CDK9 localization from the cytoplasm to the pronucleus occurs at the time of minor embryonic genome activation, and CDK9 accumulation at the two-cell stage is evident, concomitant with major transcriptional activation of the embryonic genome. Moreover, CDK9 inhibition triggers a developmental block at the two-cell stage. Our findings clearly indicate that CDK9 is essential for embryonic genome activation in the mouse.
A novel class of heat-responsive small RNAs derived from the chloroplast genome of Chinese cabbage (Brassica rapa)
Authors: Wang Lu , Yu Xiang , Wang Han , Lu Yi-Zhen , de Ruiter Marjo , Prins Marcel , He Yu-Ke 
Published: June 2011

Abstract

Background
Non-coding small RNAs play critical roles in various cellular processes in a wide spectrum of eukaryotic organisms. Their responses to abiotic stress have become a popular topic of economic and scientific importance in biological research. Several studies in recent years have reported a small number of non-coding small RNAs that map to chloroplast genomes. However, it remains uncertain whether small RNAs are generated from chloroplast genome and how they respond to environmental stress, such as high temperature. Chinese cabbage is an important vegetable crop, and heat stress usually causes great losses in yields and quality. Under heat stress, the leaves become etiolated due to the disruption and disassembly of chloroplasts. In an attempt to determine the heat-responsive small RNAs in chloroplast genome of Chinese cabbage, we carried out deep sequencing, using heat-treated samples, and analysed the proportion of small RNAs that were matched to chloroplast genome.

Results
Deep sequencing provided evidence that a novel subset of small RNAs were derived from the chloroplast genome of Chinese cabbage. The c hloroplast s mall RNAs (csRNAs) include those derived from mRNA, rRNA, tRNA and intergenic RNA. The rRNA-derived csRNAs were preferentially located at the 3'-ends of the rRNAs, while the tRNA-derived csRNAs were mainly located at 5'-termini of the tRNAs. After heat treatment, the abundance of csRNAs decreased in seedlings, except those of 24 nt in length. The novel heat-responsive csRNAs and their locations in the chloroplast were verified by Northern blotting. The regulation of some csRNAs to the putative target genes were identified by real-time PCR. Our results reveal that high temperature suppresses the production of some csRNAs, which have potential roles in transcriptional or post-transcriptional regulation.

Conclusions
In addition to nucleus, the chloroplast is another important organelle that generates a number of small RNAs. Many members of csRNA families are highly sensitive to heat stress. Some csRNAs respond to heat stress by silencing target genes. We suggest that proper temperature is important for production of chloroplast small RNAs, which are associated with plant resistance to abiotic stress.
Retraction Note: Molecular characterization of Legionella pneumophila-induced interleukin-8 expression in T cells
Authors: Takamatsu Reika , Teruya Hiromitsu , Takeshima Eriko , Ishikawa Chie , Matsumoto Kunihiro , Mukaida Naofumi , Li Jian-Dong , Heuner Klaus , Higa Futoshi , Fujita Jiro , Mori Naoki 
Published: June 2011

Abstract
Article Retracted
Retraction Note: NF-κB activation by Helicobacter pylorirequires Akt-mediated phosphorylation of p65
Authors: Takeshima Eriko , Tomimori Koh , Kawakami Hirochika , Ishikawa Chie , Sawada Shigeki , Tomita Mariko , Senba Masachika , Kinjo Fukunori , Mimuro Hitomi , Sasakawa Chihiro , Fujita Jiro , Mori Naoki 
Published: June 2011

Abstract
Article retracted
Premature ventricular contractions originating from the left ventricular septum: Results of Radiofrequency Catheter Ablation in twenty patients
Authors: Jia Li , Yue-Chun Li , Kang-Ting Ji , Na-Dan Zhou , Jia-Xuan Lin , Wen-Wu Zhang , Peng-Lin Yang , Ji-Fei Tang , Jia-Feng Lin 
Published: June 2011

Abstract

Background
RFCA has been established as an effective and curative therapy for severely symptomatic PVC from the outflow tract in structurally normal hearts. However, it is unknown whether PVCs originating from the left ventricular septum, are effectively eliminated by RFCA. This study aimed to investigate electrophysiologic characteristics and effects of Radiofrequency catheter ablation (RFCA) for patients with symptomatic premature ventricular contraction (PVC) originating from the left ventricular septum without including fascicular PVCs.

Methods
Characteristics of body surface electrocardiogram (ECG) and electrophysiologic recordings endocardiogram in a successful RFCA target were analyzed in 20 patients with symptomatic PVCs originating from the left ventricular septum. RFCA was performed using pace mapping and activation mapping.

Results
The QRS morphology of PVCs originating from the left ventricular septum is similar to that seen in fascicular tachycardia. Most of the PVCs originated from the left septum appears in the form of ventricular parasystole. The incidence of ventricular parasystole was 70%. Sustained ventricular tachycardia was not inducible by electrical stimulation and isoproterenol infusion in all 20 patients, ablation at the site recording the earliest Purkinje potential was not effective in all 20 patients, and Purkinje potentials were not identified at successful sites during point mapping. Sixteen patients were successful with RFCA using pace mapping and activation mapping, 3 failed, and 1 recurrent.

Conclusion
Although the ECG characteristics of the PVCs arising from the left ventricular septum are similar to that seen in fascicular tachycardia, the electrophysiologic characteristics are different between the two types of PVCs. The distinguishing characteristic of the PVCs is that Purkinje potentials were not present at the site of successful ablation, suggesting a myocardial as opposed to fascicular substrate. RFCA is an effective curative therapy for symptomatic PVCs originating from the left ventricular septum (not from the left anterior and posterior fascicle).
Untapped ethical resources for neurodegeneration research
Authors: Robillard Julie M , Federico Carole A , Tairyan Kate , Ivinson Adrian J , Illes Judy 
Published: June 2011

Abstract

Background
The research community has a mandate to discover effective treatments for neurodegenerative disorders. The ethics landscape surrounding this mandate is in a constant state of flux, and ongoing challenges place ever greater demands on investigators to be accountable to the public and to answer questions about the implications of their work for health care, society, and policy.

Methods
We surveyed US-based investigators involved in neurodegenerative diseases research about how they value ethics-related issues, what motivates them to give consideration to those issues, and the barriers to doing so. Using the NIH CRISP database we identified 1,034 researchers with relevant, active grants and invited them to complete an online questionnaire. We received 193 responses. We used exploratory factor analysis to transform individual survey questions into a smaller set of factors, and linear regression to understand the effect of key variables of interest on the factor scores.

Results
Ethics-related issues clustered into two groups: research ethics and external influences. Heads of research groups viewed issues of research ethics to be more important than the other respondents. Concern about external influences was related to overall interest in ethics. Motivators clustered into five groups: ensuring public understanding, external forces, requirements, values, and press and public. Heads of research groups were more motivated to ensure public understanding of research than the other respondents. Barriers clustered into four groups: lack of resources, administrative burden, relevance to the research, and lack of interest. Perceived lack of ethics resources was a particular barrier for investigators working in drug discovery.

Conclusions
The data suggest that senior level neuroscientists working in the field of neurodegeneration (ND), and drug discovery specifically, are motivated to consider ethics issues related to their work, but the perceived lack of ethics resources thwarts their efforts. With bioethics centres at more than 50% of the institutions at which these respondents reside, the neuroscience and bioethics communities appear to be disconnected. Dedicated ethical, legal and social implications (ELSI) programs, such as those fully integrated into genetics and regenerative medicine, provide models for achieving meaningful partnerships not yet adequately realized for scholars and trainees interested in drug discovery for ND.