bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease-specific training in Parkinson’s disease for care assistants: a comparison of interactive and self-study methods
Authors: Axelrod Lesley , Bryan Karen , Gage Heather , Kaye Julie , Ting Sharlene , Williams Peter , Trend Patrick , Wade Derick 
Published: December 2011

Objective: To compare two approaches to providing training to care assistants in Parkinson’s disease. Design: Pragmatic parallel arm controlled trial. Setting: Training either by an interactive training day at a local medical education establishment or self study. Subjects: Care assistants recruited from local health and social care providers. Interventions: The content of both interventions was similar, covering causes, symptoms, diagnosis of Parkinson’s disease, multidisciplinary management, mobility, communication, swallowing, and involving 5 hours of study time. Main measures: Knowledge about Parkinson’s (assessed by true/false quizzes and identifying ‘four facts’ about Parkinson’s) immediately post training and six weeks later; views on training methods of care assistants and employers/managers. Results: Thirty-seven employers nominated 100 care staff who were allocated to interactive training (49) and self study (51). Training completion rates (retained to six-week follow-up) were lower for self study (42.1% vs. 83.7% training day). There were no significant differences between groups on quiz or ‘four facts’ scores at baseline or six-week follow-up. Immediately post training, the self-study group (with access to written materials) had significantly higher quiz scores than the training day group (no access to materials at test). Within-group comparisons showed improvements post training. Although interactive training may be preferred, obtaining release from duties can be problematic. Conclusions: Both approaches have similar effects on knowledge of care assistants without prior specific training. Providing a variety of approaches will cater for all preferences. The findings may be generalizable to training the care workforce for other specific roles.
Ultrasonic measurement of self-loosening in bolted joints
Authors: Marshall MB , Lewis R , Howard T , Brunskill H 
Published: December 2011

Self-loosening of bolted joints in response to vibration can lead to the catastrophic failure of a range of engineering components and structures. Many techniques employed to study this phenomenon focus on directly measuring the pre-load remaining in the bolt itself, and offer little insight into the behaviour of the clamped interface. In this study, a non-intrusive ultrasonic reflection-based technique is used to first characterize interface pressure in the joint, and then determine the rate at which relaxation occurs. A key advantage of the technique is that it does not require the modification of the contact conditions, and rather utilizes the spring-like behaviour of a rough surface interface when subject to ultrasonic excitation. A series of different bolt torques were investigated, along with the inclusion of both plain and spring washers under the bolt head. All test samples were subjected to an oscillating fixed–displacement vibration cycle. An initial rapid reduction in interface clamping pressure was observed, followed by a more steady-state period. Increasing bolt torque was seen to enhance joint integrity, whereas both the plain and spring washers showed little improvement. The spring washer was observed to extend the secondary steady-state phase of loosening, though as the majority of pre-load was removed prior to this period any change was largely unbeneficial.
Phagocytosis by macrophages and endothelial cells inhibits procoagulant and fibrinolytic activity of acute promyelocytic leukemia cells
Authors: Xie Rui , Gao Chunyan , Li Wen , Zhu Jiuxin , Novakovic Valerie , Wang Jing , Ma Ruishuang , Zhou Jin , Gilbert Gary E. , Shi Jialan 
Published: December 2011

Abstract
The coagulopathy of acute promyelocytic leukemia (APL) is mainly related to procoagulant substances and fibrinolytic activators of APL blasts, but the fate of these leukemic cells is unknown. The aim of this study was to investigate the removal of APL blasts by macrophages and endothelial cells in vitro and consequent procoagulant and fibrinolytic activity of APL cells. We found that human umbilical vein endothelial cells as well as THP-1 and monocyte-derived macrophages bound, engulfed, and subsequently degraded immortalized APL cell line NB4 and primary APL cells. Lactadherin promoted phagocytosis of APL cells in a time-dependent fashion. Furthermore, factor Xa and prothrombinase activity of phosphatidylserine-exposed target APL cells was time-dependently decreased after incubation with phagocytes (THP-1–derived macrophages or HUVECs). Thrombin production on target APL cells was reduced by 40%-45% after 2 hours of coincubation with phagocytes and 80% by a combination of lactadherin and phagocytes. Moreover, plasmin generation of target APL cells was inhibited 30% by 2 hours of phagocytosis and ∼ 50% by lactadherin-mediated engulfment. These results suggest that engulfment by macrophages and endothelial cells reduce procoagulant and fibrinolytic activity of APL blasts. Lactadherin and phagocytosis could cooperatively ameliorate the clotting disorders in APL.
Functional characterization of CD4+ T cells in aplastic anemia
Authors: Kordasti Shahram , Marsh Judith , Al-Khan Sufyan , Jiang Jie , Smith Alexander , Mohamedali Azim , Abellan Pilar Perez , Veen Caroline , Costantini Benedetta , Kulasekararaj Austin G. , Benson-Quarm Nana , Seidl Thomas , Mian Syed A. , Farzaneh Farzin , Mufti Ghulam J. 
Published: December 2011

AbstractThe role of CD4+ T cells in the pathogenesis of aplastic anemia (AA) is not well characterized. We investigate CD4+ T-cell subsets in AA. Sixty-three patients with acquired AA were studied. Th1 and Th2 cells were significantly higher in AA patients than in healthy donors (HDs; P = .03 and P = .006). Tregs were significantly lower in patients with severe AA than in HDs (P < .001) and patients with non-severe AA (P = .01). Th17 cells were increased in severe AA (P = .02) but normal in non-severe AA. Activated and resting Tregs were reduced in AA (P = .004; P = .01), whereas cytokine-secreting non-Tregs were increased (P = .003). Tregs from AA patients were unable to suppress normal effector T cells. In contrast, AA effector T cells were suppressible by Tregs from HDs. Th1 clonality in AA, investigated by high-throughput sequencing, was greater than in HDs (P = .03). Our results confirm that Th1 and Th2 cells are expanded and Tregs are functionally abnormal in AA. The clonally restricted expansion of Th1 cells is most likely to be antigen-driven, and induces an inflammatory environment, that exacerbate the functional impairment of Tregs, which are reduced in number.
AAV-mediated gene transfer in the perinatal period results in expression of FVII at levels that protect against fatal spontaneous hemorrhage
Authors: Binny Christopher , McIntosh Jenny , Della Peruta Marco , Kymalainen Hanna , Tuddenham Edward G. D. , Buckley Suzanne M. K. , Waddington Simon N. , McVey John H. , Spence Yunyu , Morton Christopher L. , Thrasher Adrian J. , Gray John T. , Castellino Francis J. , Tarantal Alice F. , Davidoff Andrew M. , Nathwani Amit C. 
Published: December 2011

Abstract
We explored adeno-associated viral vector (AAV)–mediated gene transfer in the perinatal period in animal models of severe congenital factor VII (FVII) deficiency, a disease associated with early postnatal life-threatening hemorrhage. In young adult mice with plasma FVII < 1% of normal, a single tail vein administration of AAV (1 × 1013 vector genomes [vg]/kg) resulted in expression of murine FVII at 266% ± 34% of normal for ≥ 67 days, which mediated protection against fatal hemorrhage and significantly improved survival. Codon optimization of human FVII (hFVIIcoop) improved AAV transgene expression by 37-fold compared with the wild-type hFVII cDNA. In adult macaques, a single peripheral vein injection of 2 × 1011 vg/kg of the hFVIIcoop AAV vector resulted in therapeutic levels of hFVII expression that were equivalent in males (10.7% ± 3.1%) and females (12.3% ± 0.8%). In utero delivery of this vector in the third trimester to fetal monkeys conferred expression of hFVII at birth of 20.4% ± 3.7%, with a gradual decline to > 1% by 7 weeks. Re-administration of an alternative serotype at 12 months postnatal age increased hFVII levels to 165% ± 6.2% of normal, which remained at therapeutic levels for a further 28 weeks without toxicity. Thus, perinatal AAV-mediated gene transfer shows promise for disorders with onset of pathology early after birth.
Comparison of lists of genes based on functional profiles
Authors: Salicrú Miquel , Ocaña Jordi , Sánchez-Pla Alex 
Published: December 2011

Abstract

Background
How to compare studies on the basis of their biological significance is a problem of central importance in high-throughput genomics. Many methods for performing such comparisons are based on the information in databases of functional annotation, such as those that form the Gene Ontology (GO). Typically, they consist of analyzing gene annotation frequencies in some pre-specified GO classes, in a class-by-class way, followed by p-value adjustment for multiple testing. Enrichment analysis, where a list of genes is compared against a wider universe of genes, is the most common example.

Results
A new global testing procedure and a method incorporating it are presented. Instead of testing separately for each GO class, a single global test for all classes under consideration is performed. The test is based on the distance between the functional profiles, defined as the joint frequencies of annotation in a given set of GO classes. These classes may be chosen at one or more GO levels. The new global test is more powerful and accurate with respect to type I errors than the usual class-by-class approach. When applied to some real datasets, the results suggest that the method may also provide useful information that complements the tests performed using a class-by-class approach if gene counts are sparse in some classes. An R library, goProfiles, implements these methods and is available from Bioconductor, http://bioconductor.org/packages/release/bioc/html/goProfiles.html.

Conclusions
The method provides an inferential basis for deciding whether two lists are functionally different. For global comparisons it is preferable to the global chi-square test of homogeneity. Furthermore, it may provide additional information if used in conjunction with class-by-class methods.
Desert hedgehogis a mammal-specific gene expressed during testicular and ovarian development in a marsupial
Authors: O'Hara William A , Azar Walid J , Behringer Richard R , Renfree Marilyn B , Pask Andrew J 
Published: December 2011

Abstract

Background

Desert hedgehog (DHH) belongs to the hedgehog gene family that act as secreted intercellular signal transducers. DHH is an essential morphogen for normal testicular development and function in both mice and humans but is not present in the avian lineage. Like other hedgehog proteins, DHH signals through the patched (PTCH) receptors 1 and 2. Here we examine the expression and protein distribution of DHH, PTCH1 and PTCH2 in the developing testes of a marsupial mammal (the tammar wallaby) to determine whether DHH signalling is a conserved factor in gonadal development in all therian mammals.

Results

DHH, PTCH1 and PTCH2 were present in the marsupial genome and highly conserved with their eutherian orthologues. Phylogenetic analyses indicate that DHH has recently evolved and is a mammal-specific hedgehog orthologue. The marsupial PTCH2 receptor had an additional exon (exon 21a) not annotated in eutherian PTCH2 proteins. Interestingly we found evidence of this exon in humans and show that its translation would result in a truncated protein with functions similar to PTCH1. We also show that DHH expression was not restricted to the testes during gonadal development (as in mice), but was also expressed in the developing ovary. Expression of DHH, PTCH1 and PTCH2 in the adult tammar testis and ovary was consistent with findings in the adult mouse.

Conclusions
These data suggest that there is a highly conserved role for DHH signalling in the differentiation and function of the mammalian testis and that DHH may be necessary for marsupial ovarian development. The receptors PTCH1 and PTCH2 are highly conserved mediators of hedgehog signalling in both the developing and adult marsupial gonads. Together these findings indicate DHH is an essential therian mammal-specific morphogen in gonadal development and gametogenesis.
AluScan: a method for genome-wide scanning of sequence and structure variations in the human genome
Authors: Mei Lingling , Ding Xiaofan , Tsang Shui-Ying , Pun Frank W , Ng Siu-Kin , Yang Jianfeng , Zhao Cunyou , Li Dezhi , Wan Weiqing , Yu Chi-Hung , Tan Tze-Ching , Poon Wai-Sang , Leung Gilberto Ka-Kit , Ng Ho-Keung , Zhang Liwei , Xue Hong 
Published: December 2011

Abstract

Background
To complement next-generation sequencing technologies, there is a pressing need for efficient pre-sequencing capture methods with reduced costs and DNA requirement. The Alu family of short interspersed nucleotide elements is the most abundant type of transposable elements in the human genome and a recognized source of genome instability. With over one million Alu elements distributed throughout the genome, they are well positioned to facilitate genome-wide sequence amplification and capture of regions likely to harbor genetic variation hotspots of biological relevance.

Results
Here we report on the use of inter-Alu PCR with an enhanced range of amplicons in conjunction with next-generation sequencing to generate an Alu-anchored scan, or 'AluScan', of DNA sequences between Alu transposons, where Alu consensus sequence-based 'H-type' PCR primers that elongate outward from the head of an Alu element are combined with 'T-type' primers elongating from the poly-A containing tail to achieve huge amplicon range. To illustrate the method, glioma DNA was compared with white blood cell control DNA of the same patient by means of AluScan. The over 10 Mb sequences obtained, derived from more than 8,000 genes spread over all the chromosomes, revealed a highly reproducible capture of genomic sequences enriched in genic sequences and cancer candidate gene regions. Requiring only sub-micrograms of sample DNA, the power of AluScan as a discovery tool for genetic variations was demonstrated by the identification of 357 instances of loss of heterozygosity, 341 somatic indels, 274 somatic SNVs, and seven potential somatic SNV hotspots between control and glioma DNA.

Conclusions
AluScan, implemented with just a small number of H-type and T-type inter-Alu PCR primers, provides an effective capture of a diversity of genome-wide sequences for analysis. The method, by enabling an examination of gene-enriched regions containing exons, introns, and intergenic sequences with modest capture and sequencing costs, computation workload and DNA sample requirement is particularly well suited for accelerating the discovery of somatic mutations, as well as analysis of disease-predisposing germline polymorphisms, by making possible the comparative genome-wide scanning of DNA sequences from large human cohorts.
Evaluation of the NOD/SCID xenograft model for glucocorticoid-regulated gene expression in childhood B-cell precursor acute lymphoblastic leukemia
Authors: Bhadri Vivek A , Cowley Mark J , Kaplan Warren , Trahair Toby N , Lock Richard B 
Published: December 2011

Abstract

Background
Glucocorticoids such as prednisolone and dexamethasone are critical drugs used in multi-agent chemotherapy protocols used to treat acute lymphoblastic leukemia (ALL), and response to glucocorticoids is highly predictive of outcome. The NOD/SCID xenograft mouse model of ALL is a clinically relevant model in which the mice develop a systemic leukemia which retains the fundamental biological characteristics of the original disease. Here we report a study evaluating the NOD/SCID xenograft mouse model to investigate glucocorticoid-induced gene expression. Cells from a glucocorticoid-sensitive xenograft derived from a child with B-cell precursor ALL were inoculated into NOD/SCID mice. When highly engrafted the mice were randomized into groups of 4 to receive dexamethasone 15 mg/kg by intraperitoneal injection or vehicle control. Leukemia cells were harvested from mice spleens at 0, 8, 24 or 48 hours thereafter, and gene expression analyzed on Illumina WG-6_V3 chips, comparing all groups to time 0 hours.

Results
The 8 hour dexamethasone-treated timepoint had the highest number of significantly differentially expressed genes, with fewer observed at the 24 and 48 hour timepoints, and with minimal changes seen across the time-matched controls. When compared to publicly available datasets of glucocorticoid-induced gene expression from an in vitro cell line study and from an in vivo study of patients with ALL, at the level of pathways, expression changes in the 8 hour xenograft samples showed a similar response to patients treated with glucocorticoids. Replicate analysis revealed that at the 8 hour timepoint, a dataset with high signal and differential expression, using data from 3 replicates instead of 4 resulted in excellent recovery scores of > 0.9. However at other timepoints with less signal very poor recovery scores were obtained with 3 replicates.

Conclusions
The NOD/SCID xenograft mouse model provides a reproducible experimental system in which to investigate clinically-relevant mechanisms of drug-induced gene regulation in ALL; the 8 hour timepoint provides the highest number of significantly differentially expressed genes; time-matched controls are redundant and excellent recovery scores can be obtained with 3 replicates.
Relative impact of key sources of systematic noise in Affymetrix and Illumina gene-expression microarray experiments
Authors: Kitchen Robert R , Sabine Vicky S , Simen Arthur A , Dixon J Michael , Bartlett John MS , Sims Andrew H 
Published: December 2011

Abstract

Background
Systematic processing noise, which includes batch effects, is very common in microarray experiments but is often ignored despite its potential to confound or compromise experimental results. Compromised results are most likely when re-analysing or integrating datasets from public repositories due to the different conditions under which each dataset is generated. To better understand the relative noise-contributions of various factors in experimental-design, we assessed several Illumina and Affymetrix datasets for technical variation between replicate hybridisations of Universal Human Reference (UHRR) and individual or pooled breast-tumour RNA.

Results
A varying degree of systematic noise was observed in each of the datasets, however in all cases the relative amount of variation between standard control RNA replicates was found to be greatest at earlier points in the sample-preparation workflow. For example, 40.6% of the total variation in reported expressions were attributed to replicate extractions, compared to 13.9% due to amplification/labelling and 10.8% between replicate hybridisations. Deliberate probe-wise batch-correction methods were effective in reducing the magnitude of this variation, although the level of improvement was dependent on the sources of noise included in the model. Systematic noise introduced at the chip, run, and experiment levels of a combined Illumina dataset were found to be highly dependant upon the experimental design. Both UHRR and pools of RNA, which were derived from the samples of interest, modelled technical variation well although the pools were significantly better correlated (4% average improvement) and better emulated the effects of systematic noise, over all probes, than the UHRRs. The effect of this noise was not uniform over all probes, with low GC-content probes found to be more vulnerable to batch variation than probes with a higher GC-content.

Conclusions
The magnitude of systematic processing noise in a microarray experiment is variable across probes and experiments, however it is generally the case that procedures earlier in the sample-preparation workflow are liable to introduce the most noise. Careful experimental design is important to protect against noise, detailed meta-data should always be provided, and diagnostic procedures should be routinely performed prior to downstream analyses for the detection of bias in microarray studies.
Revealing the missing expressed genes beyond the human reference genome by RNA-Seq
Authors: Chen Geng , Li Ruiyuan , Shi Leming , Qi Junyi , Hu Pengzhan , Luo Jian , Liu Mingyao , Shi Tieliu 
Published: December 2011

Abstract

Background
The complete and accurate human reference genome is important for functional genomics researches. Therefore, the incomplete reference genome and individual specific sequences have significant effects on various studies.

Results
we used two RNA-Seq datasets from human brain tissues and 10 mixed cell lines to investigate the completeness of human reference genome. First, we demonstrated that in previously identified ~5 Mb Asian and ~5 Mb African novel sequences that are absent from the human reference genome of NCBI build 36, ~211 kb and ~201 kb of them could be transcribed, respectively. Our results suggest that many of those transcribed regions are not specific to Asian and African, but also present in Caucasian. Then, we found that the expressions of 104 RefSeq genes that are unalignable to NCBI build 37 in brain and cell lines are higher than 0.1 RPKM. 55 of them are conserved across human, chimpanzee and macaque, suggesting that there are still a significant number of functional human genes absent from the human reference genome. Moreover, we identified hundreds of novel transcript contigs that cannot be aligned to NCBI build 37, RefSeq genes and EST sequences. Some of those novel transcript contigs are also conserved among human, chimpanzee and macaque. By positioning those contigs onto the human genome, we identified several large deletions in the reference genome. Several conserved novel transcript contigs were further validated by RT-PCR.

Conclusion
Our findings demonstrate that a significant number of genes are still absent from the incomplete human reference genome, highlighting the importance of further refining the human reference genome and curating those missing genes. Our study also shows the importance of de novo transcriptome assembly. The comparative approach between reference genome and other related human genomes based on the transcriptome provides an alternative way to refine the human reference genome.