bluuebunny/crossref_metadata_2025_split huggingface dataset:
The comparative immunogenicity of human and porcine factor VIII in haemophilia A mice
Authors: Healey John F. , Parker Ernest T. , Barrow Rachel T. , Langley Travis J. , Church William R. , Lollar Pete 
Published: April 2009

SummaryInhibitory antibodies to factor VIII (FVIII inhibitors) are the most significant complication in the management of haemophilia A. The immunogenicity of FVIII may be driven in part by structural determinants within the FVIII molecule itself. Regions of nonidentity between human and porcine FVIII possibly could drive differential immune responses. The goal of this study was to compare the overall antibody response and levels of antibodies to the individual FVIII domains in naïve haemophilia A mice immunised with human or porcine FVIII. Haemophilia A mice were immunised with human or porcine FVIII using a protocol that mimics human clinical use. Inhibitor and total anti-FVIII antibody titers were measured and the domain-specificity of antibodies from 1,759 anti-FVIII hybridomas was determined. The overall immunogenicity of human and porcine FVIII was similar but significant differences in domain recognition were discovered. Anti-A2 and anti-C2 antibodies constituted the majority of inhibitors in both the human and porcine FVIII groups, similar to inhibitors that develop in humans.The proportions of anti-A2 or anti-C2 antibodies were not significantly different between the two groups. However, the specific inhibitory activity of anti-A2 antibodies was higher in the human FVIII group. Additionally, proportion of anti-C1 antibodies was significantly higher in the human FVIII group. In contrast, anti-A3 antibodies were more common in the porcine FVIII group.The differential immune response to human and porcine FVIII suggests that it may be possible to reduce the immunogenicity of FVIII by mutagenesis of the A2, A3 and C1 domains.
Prescription of fondaparinux in hospitalised patients
Authors: Labreche Matthew , Niles Matthew , Fanikos John , Goldhaber Samuel , Baroletti Steven 
Published: April 2009

SummaryFondaparinux is an antithrombotic agent with unique properties that may offer benefit to patients beyond the current approved indications. To explore the off-label use versus approved use of fondaparinux, we initiated a single-center registry of fondaparinux use. During the 25-month study period, 219 patients were prescribed fondaparinux: 157 (71.7%) for prophylaxis and 62 (28.3%) patients for the treatment of thrombosis. When fondaparinux was used for prophylaxis in our registry, 94% of patients had documentation of heparin-induced thrombocytopenia (HIT). Fondaparinux warrants further evaluation in patients with HIT or suspected HIT. In the meantime, its off-label use may exceed its use for FDA-approved indications.
Bridging of oral anticoagulation with low-molecular-weight heparin: Experience in 373 patients with renal insufficiency undergoing invasive procedures
Authors: Hammerstingl Christoph , Omran Heyder ,   for the Bonn Registry of Alternative Anticoagulation to Prevent Vascular Events
Published: April 2009

SummaryIf surgery or another intervention is planned, current guidelines recommend bridging oral anticoagulation (OAC) with heparins in patients at elevated thromboembolic (TE) risk. While patients with renal impairment have a higher risk of bleeding and dosing of heparins is more difficult, there are no specific recommendations for bridging the latter patients. Hence, we aimed to investigate the efficacy and tolerability of using reduced low-molecular-weight heparin (enoxaparin) dosages for bridging of OAC. Three hundred twenty-two hospitalised and 51 ambulatory adult patients at moderate to high TE risk were enrolled. Patients with renal insufficiency (n=274 with creatinine clearance [CrCl] 30–50 ml/min and n=99 with CrCl 20–29 ml/min) received after discontinuation of OAC therapy enoxaparin 1mg/ kg once daily. Surgery was performed at international normalised ratio (INR) <1.5. Mean time between the last enoxaparin dose and procedure was 26.8 ± 2.7 hours. Within 30 days of individual follow-up, no case of TE was observed (0 %; 95 % confidence interval [CI] 0– 0.9). A total of 30 bleeding events (8.0 %; CI 5.5–11.3) occurred (3 major [0.8 %; CI 0.2–2.3] and 27 minor [7.2 %; CI 4.8–10.4]). Bleeding events occurred in 6.5% (CI 3.9–10.2) of patients with CrCl 30–50 ml/min and in 12.1% (CI 6.4–20.2) of patients with CrCl 20–29 ml/min (p between groups =0.08). Logistic regression analysis identified the CHADS2 score as the only independent haemorrhagic risk factor (p= 0.03). No heparin-induced thrombocytopenia (HIT-II) was reported. Bridging therapy could be performed in 51 (13.7%) ambulatory patients. In renally impaired patients undergoing bridging of OAC, the use of a priori reduced dosage of enoxaparin was not compromised by any TE events. It appeared well tolerated as the rate of major bleeds was low.
The effects of community-based rehabilitation on stroke patients in China: a single-blind, randomized controlled multicentre trial
Authors: JianJun Yu  , YongShan Hu  , Wu Yi , WenHua Chen  , YuLian Zhu  , Xiao Cui  , WeiBo Lu  , Qi Qi  , PeiYu Qu  , XiaoHua Shen  
Published: April 2009

Objective: To evaluate the effects of community-based rehabilitation therapy on neurological function deficit in stroke patients. Design: Prospective, single-blind, randomized controlled multicentre trial. Setting: At home, in Shanghai, China. Subjects: A total of 737 stroke patients in the community. Intervention: The rehabilitation group received additional standardized community-based rehabilitation therapy at home for five months. Main outcome measures: Patients were evaluated using the Clinical Neurological Function Deficit Scale before intervention and at the end of two and five months. Results: Although both the rehabilitation group and the control group improved over time, the rehabilitation group showed a greater improvement in Clinical Neurological Function Deficit Scale scores. The differences between the groups were significant. After five months, the Clinical Neurological Function Deficit Scale scores of the cerebral infarction rehabilitation group improved by 6.77; the haemorrhage rehabilitation group by 7.99; the total rehabilitation group by 7.03. In comparison, the Clinical Neurological Function Deficit Scale scores of the cerebral infarction control group improved by 1.57; the haemorrhage control group by 5.34; the total control group by 2.43. This implies a difference in improvement of 5.2 in the cerebral infarction group, 2.65 in the haemorrhage group, and 4.6 in the total group in favour of the rehabilitation group between groups. Conclusion: Standardized community-based rehabilitation therapy may help stroke patients to improve their neurological function.
An evaluation of two decision-making scales for children with life-limiting illnesses
Authors: Knapp C , Huang IC , Madden V , Vadaparampil S , Quinn G , Shenkman E 
Published: April 2009

Purpose Annually, about 500,000 children are coping with life-limiting illnesses. Many of these children could benefit from pediatric palliative care which provides supportive services. These services can also aid parents in decision making. In order to measure the effect of pediatric palliative care programs on decision making, a valid and reliable tool must be identified. This study aims to validate the psychometric properties of the Decisional Conflict Scale (DCS) and the COMRADE instruments for children with life-limiting illnesses. Methods Analyses were conducted using survey data collected from 266 parents whose Medicaid enrolled children have life-limiting illnesses. Results Results of the analyses suggest that the DCS has better psychometric properties for measuring decision making within the population of children with life-limiting illnesses than the COMRADE. Conclusion Pediatric palliative care programs should use the DCS to measure the effectiveness of services aimed at supporting families with high levels of decisional conflict.
A Combined Technique for Distal Biceps Repair Using a Soft Tissue Button and Biotenodesis Interference Screw
Authors: Heinzelmann Andrew D. , Savoie Felix H. , Randall Ramsey J. , Field Larry D. , Mazzocca Augustus D. 
Published: April 2009

Background There are many techniques described to repair acute distal biceps tendon ruptures. The authors’ objective is to report the results of a single-incision technique using a combination of a soft tissue button and biotenodesis interference screw with accelerated rehabilitation. Hypothesis Dual fixation of a distal biceps rupture will allow for early return to function. Study Design Case series; Level of evidence, 4. Methods From February 2004 to July 2007, 41 elbows in 40 patients had repair of an acute distal biceps tendon rupture (<6 weeks) through an anterior incision using a soft tissue button and interference screw combined technique. The patients were evaluated pre- and postoperatively with a physical examination, radiographs, and the Andrews-Carson elbow score. Nine patients were unavailable for follow-up. The remaining 31 patients (32 elbows) were contacted for a telephone interview at an average of 24 months postoperatively. Results The preoperative Andrews-Carson score averaged 168 and the postoperative Andrews-Carson score averaged 196 points at final clinical follow-up. There was a statistically significant difference between the pre- and postoperative Andrews-Carson scores (P < .001). One patient had heterotopic ossification associated with decreased pronation and supination. Two superficial radial nerve palsies completely resolved by final follow-up. The average postoperative time to resume normal activities or return to work was 6.5 weeks. Conclusion Repair of acute distal biceps tendon ruptures using a soft tissue button and interference screw technique through a limited anterior incision can allow for accelerated rehabilitation and early return to function.
Gfi1 integrates progenitor versus granulocytic transcriptional programming
Authors: Horman Shane R. , Velu Chinavenmeni S. , Chaubey Aditya , Bourdeau Tristan , Zhu Jinfang , Paul William E. , Gebelein Brian , Grimes H. Leighton 
Published: April 2009

AbstractIn patients with severe congenital neutropenia (SCN) and mice with growth factor independent-1 (Gfi1) loss of function, arrested myeloid progenitors accumulate, whereas terminal granulopoiesis is blocked. One might assume that Gfi-null progenitors accumulate because they lack the ability to differentiate. Instead, our data indicate that Gfi1 loss of function deregulates 2 separable transcriptional programs, one of which controls the accumulation and lineage specification of myeloid progenitors, but not terminal granulopoiesis. We demonstrate that Gfi1 directly represses HoxA9, Pbx1, and Meis1 during normal myelopoiesis. Gfi1−/− progenitors exhibit elevated levels of HoxA9, Pbx1 and Meis1, exaggerated HoxA9-Pbx1-Meis1 activity, and progenitor transformation in collaboration with oncogenic K-Ras. Limiting HoxA9 alleles corrects, in a dose-dependent manner, in vivo and in vitro phenotypes observed with loss of Gfi1 in myeloid progenitor cells but did not rescue Gfi1−/− blocked granulopoiesis. Thus, Gfi1 integrates 2 events during normal myeloid differentiation; the suppression of a HoxA9-Pbx1-Meis1 progenitor program and the induction of a granulopoietic transcription program.
The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8
Authors: Cheranov Sergey Y. , Wang Dong , Kundumani-Sridharan Venkatesh , Karpurapu Manjula , Zhang Qiuhua , Chava Koteswara R. , Rao Gadiparthi N. 
Published: April 2009

AbstractTo understand the molecular basis underlying 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE)–induced angiogenesis, we have studied the role of the Janus kinase-signal transducer and activator of transcription (Jak-STAT) signaling. The 15(S)-HETE stimulated tyrosine phosphorylation of Jak2 in a time-dependent manner in human retinal microvascular endothelial cells (HRMVECs). Inhibition of Jak2 activation via adenovirus-mediated expression of its dominant-negative mutant attenuated 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Similarly, 15(S)-HETE activated tyrosine phosphorylation of STAT-5B in a time-dependent manner. Dominant-negative mutant-mediated interference of STAT-5B activation suppressed 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. The 15(S)-HETE induced interleukin-8 (IL-8) expression in Jak2-STAT-5B–dependent manner in HRMVECs. In addition, neutralizing anti–IL-8 antibodies reduced 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Cloning and Transfac analysis of IL-8 promoter revealed the presence of 1 putative STAT-binding sequence at −476 nt, and electrophoretic mobility shift assay and chromatin immunoprecipitation analysis showed the binding of STAT-5B to this site in response to 15(S)-HETE. Mutational analysis showed that STAT binding site is essential for 15(S)-HETE–induced IL-8 promoter activity. Together, these observations suggest that 15(S)-HETE–induced angiogenesis requires Jak2-STAT-5B–dependent expression of IL-8.
Ligand of scavenger receptor class A indirectly induces maturation of human blood dendritic cells via production of tumor necrosis factor-α
Authors: Jin Jun-O , Park Hae-Young , Xu Qi , Park Joo-In , Zvyagintseva Tatyana , Stonik Valentin A. , Kwak Jong-Young 
Published: April 2009

Abstract
Dendritic cells (DCs) are the most potent antigen-presenting cells for naive T cells. In this study, scavenger receptor class A type I and type II (SR-A) were shown to be expressed by peripheral blood DCs (PBDCs) and monocyte-derived DCs (MDDCs). In addition, the binding of anti–SR-A antibody to these cells was lower in the presence of fucoidan, an SR-A agonist. Treatment of these DCs with fucoidan or anti–SR-A antibody markedly increased the surface expression of costimulatory molecules CD83 and major histocompatibility complex class II on the CD11chighCD123low myeloid subset of PBDCs. Furthermore, fucoidan-treated PBDCs produced tumor necrosis factor-α (TNF-α) but not IL-12p70. In addition, fucoidan-induced maturation was eliminated by pretreatment with TNF-α–neutralizing antibody. Finally, interferon-γ secretion and T-cell proliferation were enhanced by coculture of T cells with fucoidan-matured PBDCs. Specific inhibitors of p38 MAPK and glycogen synthase kinase 3 suppressed TNF-α production and maturation of fucoidan-treated PBDCs. Moreover, MDDCs lacking SR-A failed to up-regulate CD83 expression, TNF-α production, and phosphorylation of p38 MAPK and glycogen synthase kinase 3-β in the presence of fucoidan. Taken together, these results suggest that ligation of SR-A leads to induction of TNF-α, which subsequently induces PBDC maturation, thereby leading to enhanced T-cell stimulatory capacity.
Analysis of human α globin gene mutations that impair binding to the α hemoglobin stabilizing protein
Authors: Yu Xiang , Mollan Todd L. , Butler Andrew , Gow Andrew J. , Olson John S. , Weiss Mitchell J. 
Published: April 2009

AbstractAlpha hemoglobin stabilizing protein (AHSP) reversibly binds nascent α globin to maintain its native structure and facilitate its incorporation into hemoglobin A. Previous studies indicate that some naturally occurring human α globin mutations may destabilize the protein by inhibiting its interactions with AHSP. However, these mutations could also affect hemoglobin A production through AHSP-independent effects, including reduced binding to β globin. We analyzed 6 human α globin variants with altered AHSP contact surfaces. Alpha globin amino acid substitutions H103Y, H103R, F117S, and P119S impaired interactions with both AHSP and β globin. These mutations are destabilizing in biochemical assays and are associated with microcytosis and anemia in humans. By contrast, K99E and K99N α globins bind β globin normally but exhibit attenuated binding to AHSP. These mutations impair protein folding and expression in vitro and appear to be mildly destabilizing in vivo. In Escherichia coli and erythroid cells, α globin K99E stability is rescued on coexpression with AHSP mutants in which binding to the abnormal globin chain is restored. Our results better define the biochemical properties of some α globin variants and support the hypothesis that AHSP promotes α globin chain stability during human erythropoiesis.
GLOSSI: a method to assess the association of genetic loci-sets with complex diseases
Authors: Chai High-Seng , Sicotte Hugues , Bailey Kent R , Turner Stephen T , Asmann Yan W , Kocher Jean-Pierre A 
Published: April 2009

Abstract

Background
The developments of high-throughput genotyping technologies, which enable the simultaneous genotyping of hundreds of thousands of single nucleotide polymorphisms (SNP) have the potential to increase the benefits of genetic epidemiology studies. Although the enhanced resolution of these platforms increases the chance of interrogating functional SNPs that are themselves causative or in linkage disequilibrium with causal SNPs, commonly used single SNP-association approaches suffer from serious multiple hypothesis testing problems and provide limited insights into combinations of loci that may contribute to complex diseases. Drawing inspiration from Gene Set Enrichment Analysis developed for gene expression data, we have developed a method, named GLOSSI (G ene-lo ci S et Analysi s), that integrates prior biological knowledge into the statistical analysis of genotyping data to test the association of a group of SNPs (loci-set) with complex disease phenotypes. The most significant loci-sets can be used to formulate hypotheses from a functional viewpoint that can be validated experimentally.

Results
In a simulation study, GLOSSI showed sufficient power to detect loci-sets with less than 10% of SNPs having moderate-to-large effect sizes and intermediate minor allele frequency values. When applied to a biological dataset where no single SNP-association was found in a previous study, GLOSSI was able to identify several loci-sets that are significantly related to blood pressure response to an antihypertensive drug.

Conclusion
GLOSSI is valuable for association of SNPs at multiple genetic loci with complex disease phenotypes. In contrast to methods based on the Kolmogorov-Smirnov statistic, the approach is parametric and only utilizes information from within the interrogated loci-set. It properly accounts for dependency among SNPs and allows the testing of loci-sets of any size.
Automics: an integrated platform for NMR-based metabonomics spectral processing and data analysis
Authors: Wang Tao , Shao Kang , Chu Qinying , Ren Yanfei , Mu Yiming , Qu Lijia , He Jie , Jin Changwen , Xia Bin 
Published: April 2009

Abstract

Background
Spectral processing and post-experimental data analysis are the major tasks in NMR-based metabonomics studies. While there are commercial and free licensed software tools available to assist these tasks, researchers usually have to use multiple software packages for their studies because software packages generally focus on specific tasks. It would be beneficial to have a highly integrated platform, in which these tasks can be completed within one package. Moreover, with open source architecture, newly proposed algorithms or methods for spectral processing and data analysis can be implemented much more easily and accessed freely by the public.

Results
In this paper, we report an open source software tool, Automics, which is specifically designed for NMR-based metabonomics studies. Automics is a highly integrated platform that provides functions covering almost all the stages of NMR-based metabonomics studies. Automics provides high throughput automatic modules with most recently proposed algorithms and powerful manual modules for 1D NMR spectral processing. In addition to spectral processing functions, powerful features for data organization, data pre-processing, and data analysis have been implemented. Nine statistical methods can be applied to analyses including: feature selection (Fisher's criterion), data reduction (PCA, LDA, ULDA), unsupervised clustering (K-Mean) and supervised regression and classification (PLS/PLS-DA, KNN, SIMCA, SVM). Moreover, Automics has a user-friendly graphical interface for visualizing NMR spectra and data analysis results. The functional ability of Automics is demonstrated with an analysis of a type 2 diabetes metabolic profile.

Conclusion
Automics facilitates high throughput 1D NMR spectral processing and high dimensional data analysis for NMR-based metabonomics applications. Using Automics, users can complete spectral processing and data analysis within one software package in most cases. Moreover, with its open source architecture, interested researchers can further develop and extend this software based on the existing infrastructure.
Modular evolution of glutathione peroxidase genes in association with different biochemical properties of their encoded proteins in invertebrate animals
Authors: Bae Young-An , Cai Guo-Bin , Kim Seon-Hee , Zo Young-Gun , Kong Yoon 
Published: April 2009

Abstract

Background
Phospholipid hydroperoxide glutathione peroxidases (PHGPx), the most abundant isoforms of GPx families, interfere directly with hydroperoxidation of lipids. Biochemical properties of these proteins vary along with their donor organisms, which has complicated the phylogenetic classification of diverse PHGPx-like proteins. Despite efforts for comprehensive analyses, the evolutionary aspects of GPx genes in invertebrates remain largely unknown.

Results
We isolated GPx homologs via in silico screening of genomic and/or expressed sequence tag databases of eukaryotic organisms including protostomian species. Genes showing strong similarity to the mammalian PHGPx genes were commonly found in all genomes examined. GPx3- and GPx7-like genes were additionally detected from nematodes and platyhelminths, respectively. The overall distribution of the PHGPx-like proteins with different biochemical properties was biased across taxa; selenium- and glutathione (GSH)-dependent proteins were exclusively detected in platyhelminth and deuterostomian species, whereas selenium-independent and thioredoxin (Trx)-dependent enzymes were isolated in the other taxa. In comparison of genomic organization, the GSH-dependent PHGPx genes showed a conserved architectural pattern, while their Trx-dependent counterparts displayed complex exon-intron structures. A codon for the resolving Cys engaged in reductant binding was found to be substituted in a series of genes. Selection pressure to maintain the selenocysteine codon in GSH-dependent genes also appeared to be relaxed during their evolution. With the dichotomized fashion in genomic organizations, a highly polytomic topology of their phylogenetic trees implied that the GPx genes have multiple evolutionary intermediate forms.

Conclusion
Comparative analysis of invertebrate GPx genes provides informative evidence to support the modular pathways of GPx evolution, which have been accompanied with sporadic expansion/deletion and exon-intron remodeling. The differentiated enzymatic properties might be acquired by the evolutionary relaxation of selection pressure and/or biochemical adaptation to the acting environments. Our present study would be beneficial to get detailed insights into the complex GPx evolution, and to understand the molecular basis of the specialized physiological implications of this antioxidant system in their respective donor organisms.