bluuebunny/crossref_metadata_2025_split huggingface dataset:
An educational package that supports laycarers to safely manage breakthrough subcutaneous injections for home-based palliative care patients: Development and evaluation of a service quality improvement
Authors: Healy Sue , Israel Fiona , Charles Margaret A , Reymond Liz 
Published: November 2012

Background: Palliative care services strive to support people to live and die well in their chosen environment, with optimal symptom control and a pattern of care supportive of laycarers. The likelihood of patients remaining at home often depends upon laycarers, who may be required to manage subcutaneous medications. Aim and Design: This study reports the development, trial and evaluation of a package that teaches laycarers to manage subcutaneous medications used for symptom control in home-based patients. The package was developed by palliative care stakeholders and comprises an educational session, delivered by nurses, and a range of demonstrative, audiovisual and written resources. Settings/Participants: The package was trialled across 24 sites and was evaluated by 76 laycarers (pre- and post-use) and 53 nurses (at study completion). Results: Outcomes of primary interest were perceived global usefulness of the package and rated relevance of components. Laycarers and nurses rated the usefulness and relevance of the package highly – all means were above 5 on a 7-point scale. Also, laycarers were invited to comment on the package, and three focus groups for 26 nurses explored post hoc issues following package implementation. Conclusions: In terms of the palliative patient’s illness trajectory, consensus was that the time for package introduction depended upon each particular clinical situation and laycarer. Nursing opinion was divided concerning whether it is safe and appropriate for laycarers to manage subcutaneous injections. Nevertheless, this study demonstrates that the package supports laycarers to manage subcutaneous medications. This has important implications for families, services and health-care systems.
Multiple sclerosis risk genotypes correlate with an elevated cerebrospinal fluid level of the suggested prognostic marker CXCL13
Authors: Lindén M , Khademi M , Lima Bomfim I , Piehl F , Jagodic M , Kockum I , Olsson T 
Published: November 2012

Background: The mechanisms of multiple sclerosis (MS) pathogenesis are still largely unknown. The heterogeneity of disease manifestations make the prediction of prognosis and choice of appropriate treatment protocols challenging. Recently, increased cerebrospinal fluid (CSF) levels of the B-cell chemokine CXCL13 was proposed as a possible marker for a more severe disease course and conversion from clinically isolated syndrome (CIS) to relapsing–remitting MS (RRMS). Objective: To investigate whether there are genetic susceptibility variants in MS that correlate with the levels of CXCL13 present in the CSF of MS patients. Methods: We genotyped the human leukocyte antigens HLA-DRB1 and HLA-A, plus a panel of single nucleotide polymorphisms (SNPs) that have been associated with susceptibility to MS and then correlated the genotypes with the levels of CXCL13, as measured with ELISA in the CSF of a total of 663 patients with MS, CIS, other neurological diseases (OND) or OND with an inflammatory component (iOND). Results: Presence of the HLA-DRB1*15 and the MS risk genotypes for SNPs in the RGS1, IRF5 and OLIG3/TNFAIP3 gene regions correlated significantly with increased levels of CXCL13. Conclusion: Our results pointed towards a genetic predisposition for increased CXCL13 levels, which in MS patients correlates with the severity of the disease course. These findings encourage further investigation and replication, in an independent patient cohort.
Clinical drug resistance linked to interconvertible phenotypic and functional states of tumor-propagating cells in multiple myeloma
Authors: Chaidos Aristeidis , Barnes Chris P. , Cowan Gillian , May Philippa C. , Melo Valeria , Hatjiharissi Evdoxia , Papaioannou Maria , Harrington Heather , Doolittle Helen , Terpos Evangelos , Dimopoulos Meletios , Abdalla Saad , Yarranton Helen , Naresh Kikkeri , Foroni Letizia , Reid Alistair , Rahemtulla Amin , Stumpf Michael , Roberts Irene , Karadimitris Anastasios 
Published: November 2012

AbstractThe phenotype and function of cells enriched in tumor-propagating activity and their relationship to the phenotypic architecture in multiple myeloma (MM) are controversial. Here, in a cohort of 30 patients, we show that MM composes 4 hierarchically organized, clonally related subpopulations, which, although phenotypically distinct, share the same oncogenic chromosomal abnormalities as well as immunoglobulin heavy chain complementarity region 3 area sequence. Assessed in xenograft assays, myeloma-propagating activity is the exclusive property of a population characterized by its ability for bidirectional transition between the dominant CD19−CD138+ plasma cell (PC) and a low frequency CD19−CD138− subpopulation (termed Pre-PC); in addition, Pre-PCs are more quiescent and unlike PCs, are primarily localized at extramedullary sites. As shown by gene expression profiling, compared with PCs, Pre-PCs are enriched in epigenetic regulators, suggesting that epigenetic plasticity underpins the phenotypic diversification of myeloma-propagating cells. Prospective assessment in paired, pretreatment, and posttreatment bone marrow samples shows that Pre-PCs are up to 300-fold more drug-resistant than PCs. Thus, clinical drug resistance in MM is linked to reversible, bidirectional phenotypic transition of myeloma-propagating cells. These novel biologic insights have important clinical implications in relation to assessment of minimal residual disease and development of alternative therapeutic strategies in MM.
Structural framework of c-Src activation by integrin β3
Authors: Xiao Run , Xi Xiao-Dong , Chen Zhu , Chen Sai-Juan , Meng Guoyu 
Published: November 2012

AbstractThe integrin β3-mediated c-Src priming and activation, via the SH3 domain, is consistently associated with diseases, such as the formation of thrombosis and the migration of tumor cells. Conventionally, activation of c-Src is often induced by the binding of proline-rich sequences to its SH3 domain. Instead, integrin β3 uses R760GT762 for priming and activation. Because of the lack of structural information, it is not clear where RGT will bind to SH3, and under what mechanism this interaction can prime/activate c-Src. In this study, we present a 2.0-Å x-ray crystal structure in which SH3 is complexed with the RGT peptide. The binding site lies in the “N”-Src loop of the SH3 domain. Structure-based site-directed mutagenesis showed that perturbation on the “N”-Src loop disrupts the interaction between the SH3 domain and the RGT peptide. Furthermore, the simulated c-Src:β3 complex based on the crystal structure of SH3:RGT suggests that the binding of the RGT peptide might disrupt the intramolecular interaction between the SH3 and linker domains, leading to the disengagement of Trp260:“C”-helix and further activation of c-Src.
Small RNA and transcriptome deep sequencing proffers insight into floral gene regulation in Rosa cultivars
Authors: Kim Jungeun , Park June Hyun , Lim Chan Ju , Lim Jae Yun , Ryu Jee-Youn , Lee Bong-Woo , Choi Jae-Pil , Kim Woong Bom , Lee Ha Yeon , Choi Yourim , Kim Donghyun , Hur Cheol-Goo , Kim Sukweon , Noh Yoo-Sun , Shin Chanseok , Kwon Suk-Yoon 
Published: November 2012

Abstract

Background
Roses (Rosa sp.), which belong to the family Rosaceae, are the most economically important ornamental plants—making up 30% of the floriculture market. However, given high demand for roses, rose breeding programs are limited in molecular resources which can greatly enhance and speed breeding efforts. A better understanding of important genes that contribute to important floral development and desired phenotypes will lead to improved rose cultivars. For this study, we analyzed rose miRNAs and the rose flower transcriptome in order to generate a database to expound upon current knowledge regarding regulation of important floral characteristics. A rose genetic database will enable comprehensive analysis of gene expression and regulation via miRNA among different Rosa cultivars.

Results
We produced more than 0.5 million reads from expressed sequences, totalling more than 110 million bp. From these, we generated 35,657, 31,434, 34,725, and 39,722 flower unigenes from Rosa hybrid: ‘Vital’, ‘Maroussia’, and ‘Sympathy’ and Rosa rugosa Thunb. , respectively. The unigenes were assigned functional annotations, domains, metabolic pathways, Gene Ontology (GO) terms, Plant Ontology (PO) terms, and MIPS Functional Catalogue (FunCat) terms. Rose flower transcripts were compared with genes from whole genome sequences of Rosaceae members (apple, strawberry, and peach) and grape. We also produced approximately 40 million small RNA reads from flower tissue for Rosa, representing 267 unique miRNA tags. Among identified miRNAs, 25 of them were novel and 242 of them were conserved miRNAs. Statistical analyses of miRNA profiles revealed both shared and species-specific miRNAs, which presumably effect flower development and phenotypes.

Conclusions
In this study, we constructed a Rose miRNA and transcriptome database, and we analyzed the miRNAs and transcriptome generated from the flower tissues of four Rosa cultivars. The database provides a comprehensive genetic resource which can be used to better understand rose flower development and to identify candidate genes for important phenotypes.
Concerted suppression of all starch branching enzyme genes in barley produces amylose-only starch granules
Authors: Carciofi Massimiliano , Blennow Andreas , Jensen Susanne L , Shaik Shahnoor S , Henriksen Anette , Buléon Alain , Holm Preben B , Hebelstrup Kim H 
Published: November 2012

Abstract

Background
Starch is stored in higher plants as granules composed of semi-crystalline amylopectin and amorphous amylose. Starch granules provide energy for the plant during dark periods and for germination of seeds and tubers. Dietary starch is also a highly glycemic carbohydrate being degraded to glucose and rapidly absorbed in the small intestine. But a portion of dietary starch, termed “resistant starch” (RS) escapes digestion and reaches the large intestine, where it is fermented by colonic bacteria producing short chain fatty acids (SCFA) which are linked to several health benefits. The RS is preferentially derived from amylose, which can be increased by suppressing amylopectin synthesis by silencing of starch branching enzymes (SBEs). However all the previous works attempting the production of high RS crops resulted in only partly increased amylose-content and/or significant yield loss.

Results
In this study we invented a new method for silencing of multiple genes. Using a chimeric RNAi hairpin we simultaneously suppressed all genes coding for starch branching enzymes (SBE I, SBE IIa, SBE IIb) in barley (Hordeum vulgare L.), resulting in production of amylose-only starch granules in the endosperm. This trait was segregating 3:1. Amylose-only starch granules were irregularly shaped and showed peculiar thermal properties and crystallinity. Transgenic lines retained high-yield possibly due to a pleiotropic upregualtion of other starch biosynthetic genes compensating the SBEs loss. For gelatinized starch, a very high content of RS (65 %) was observed, which is 2.2-fold higher than control (29%). The amylose-only grains germinated with same frequency as control grains. However, initial growth was delayed in young plants.

Conclusions
This is the first time that pure amylose has been generated with high yield in a living organism. This was achieved by a new method of simultaneous suppression of the entire complement of genes encoding starch branching enzymes. We demonstrate that amylopectin is not essential for starch granule crystallinity and integrity. However the slower initial growth of shoots from amylose-only grains may be due to an important physiological role played by amylopectin ordered crystallinity for rapid starch remobilization explaining the broad conservation in the plant kingdom of the amylopectin structure.
Green tea consumption and risk of esophageal cancer: a meta-analysis of epidemiologic studies
Authors: Zheng Ping , Zheng Hai-ming , Deng Xing-ming , Zhang Yang-de 
Published: November 2012

Abstract

Background
Green tea has shown the role of chemoprevention for cancer. Recently, several studies suggested that green tea intake may have effect on esophageal cancer risk, whereas the results were inconsistent.

Methods
We performed a meta-analysis of all English and Chinese language studies of green tea consumption and esophageal cancer risk indexed in Medline, Embase, the Science Citation Index, the Chinese Biomedical Database and Wanfang Data from 1980 to June 2012. After reviewing each study, extracting data, and evaluating heterogeneity (Chi-square-based Q test and Ι2) and publication bias (Begg and Egger test), a meta-analysis was performed to evaluate the association between high/medium/low green tea consumption and non-drinking esophageal cancer risk. Pooled relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs) were calculated using the fixed- or random-effect models.

Results
Ten eligible epidemiologic studies including 33731 participants and 3557 cases for esophageal cancer were included. Eight of which were case–control studies, and two were cohort studies. Overall, there were no association between high/medium/low green tea consumption and non-drinking risk of esophageal cancer (High: highest vs non-drinker: RR/OR = 0.76, 95% CI: 0.49 to 1.02. Medium: drinker vs non-drinker: RR/OR = 0.86, 95% CI: 0.70 to 1.03. Low: lowest vs non-drinker: RR/OR = 0.83, 95% CI: 0.58 to 1.08). When stratified analyses according to study design (case–control and cohort studies), country (China and Japan), participates source (population-based and hospital-based case–control), and gender (female and male), there were significant association between high/medium/low green tea consumption and non-drinking risk of esophageal cancer among female (High: RR/OR = 0.32, 95% CI: 0.10 to 0.54. Medium: RR/OR = 0.43, 95% CI: 0.21 to 0.66. Low: RR/OR = 0.45, 95% CI: 0.10 to 0.79), but not the others.

Conclusions
We did not found significant association between green tea consumption and non-drinking esophageal cancer risk, but an evidence of protective effect was observed among female.
Renal AA-amyloidosis in intravenous drug users – a role for HIV-infection?
Authors: Jung Oliver , Haack Hans Stefan , Buettner Maike , Betz Christoph , Stephan Christoph , Gruetzmacher Peter , Amann Kerstin , Bickel Markus 
Published: November 2012

Abstract

Background
Chronic renal disease is a serious complication of long-term intravenous drug use (IVDU). Recent reports have postulated a changing pattern of underlying nephropathy over the last decades.

Methods
Retrospective investigation including all patients with prior or present IVDU that underwent renal biopsy because of chronic kidney disease between 01.04.2002 and 31.03.2012 in the city of Frankfurt/Main, Germany.

Results
Twenty four patients with IVDU underwent renal biopsy because of progressive chronic kidney disease or proteinuria. Renal AA-amyloidosis was the predominant cause of renal failure in 50% of patients. Membranoproliferative glomerulonephritis (GN) was the second most common cause found in 21%. Patients with AA-amyloidosis were more likely to be HIV infected (67 vs.17%; p=0.036) and tended to have a higher rate of repeated systemic infections (92 vs. 50%; p=0.069). Patients with AA-amyloidosis presented with progressive renal disease and nephrotic-range proteinuria but most patients had no peripheral edema or systemic hypertension. Development of proteinuria preceded the decline of GFR for approximately 1–2 years.

Conclusions
AA-amyloidosis was the predominant cause of progressive renal disease in the last 10 years in patients with IVDU. The highest rate of AA-amyloidosis observed was seen in HIV infected patients with IVDU. We speculate that chronic HIV-infection as well as the associated immunosuppression might promote development of AA-amyloidosis by increasing frequency and duration of infections acquired by IVDU.
Acute symptomatic hypoglycaemia mimicking ischaemic stroke on imaging: a systemic review
Authors: Yong Ai Wain , Morris Zoe , Shuler Kirsten , Smith Colin , Wardlaw Joanna 
Published: November 2012

Abstract

Background
Acute symptomatic hypoglycaemia is a differential diagnosis in patients presenting with stroke-like neurological impairment, but few textbooks describe the full brain imaging appearances. We systematically reviewed the literature to identify how often hypoglycaemia may mimic ischaemic stroke on imaging, common patterns and relationships with hypoglycaemia severity, duration, clinical outcome and add two new cases.

Methods
We searched EMBASE and Medline databases for papers reporting imaging in adults with symptomatic hypoglycaemia. We analysed the clinical presentation, outcome, brain imaging findings, duration and severity of hypoglycaemia, time course of lesion appearance, including two new cases.

Results
We found 42 papers describing computed tomography or magnetic resonance imaging in 65 patients, plus our two cases with symptomatic hypoglycaemia. Imaging abnormalities on computed tomography and magnetic resonance were uni or bilateral, cortical or sub-cortical. Thirteen (20%) mimicked cortical or lacunar stroke. Acute lesions had restricted diffusion on magnetic resonance or low attenuation on computed tomography, plus swelling; older lesions showed focal atrophy or disappeared, as with ischaemic stroke. The association between the depth or duration of hypoglycaemia, the severity or extent of neurological deficit, and the imaging abnormalities, was weak.

Conclusion
Imaging abnormalities in patients with hypoglycaemia are uncommon but very variable, weakly associated with neurological deficit, and about a fifth mimic acute ischaemic stroke. Blood glucose testing should be routine in all patients with acute neurological impairment and hypoglycaemia should be included in the differential diagnosis of imaging appearances in patients presenting with acute stroke.
Minocycline-associated rimmed vacuolar myopathy in a patient with rheumatoid arthritis
Authors: Bokuda Kota , Sugaya Keizo , Tamura Shunichiro , Miyamoto Kazuhito , Matsubara Shiro , Komori Takashi 
Published: November 2012

Abstract

Background
The autophagic vacuolar myopathies (AVM) are a group of inherited myopathies defined by the presence of autophagic vacuoles in pathological muscle specimens. AVM can be categorized into three groups: acid maltase deficiency, myopathies characterized by autophagic vacuoles with unique sarcolemmal features, and rimmed vacuolar myopathies (RVM). While the pathogeneses of these conditions are still being elucidated, some drugs (e.g., chloroquine, its analog, hydroxychloroquine, and colchicine) can also cause AVM. Minocycline is a disease-modifying anti-rheumatic drug that may be used in the treatment of rheumatoid arthritis (RA). Here, we describe the first case of minocycline-associated AVM with rimmed vacuole formation.

Case presentation
A 75-year-old woman suffering from RA has been continuously treated with minocycline (200 mg/day) for the past 7 years. During this time, she developed a myopathy that predominantly affected her lower limbs. Histological studies of biopsied muscle revealed scattered atrophic myofibers with rimmed vacuoles that contained pigment granules. Histochemical staining revealed that the pigment comprised both iron and melanin, which is consistent with type II minocycline-induced cutaneous pigmentation. Under electron microscopy, autophagic vacuoles were consistently observed in association with numerous collections of pigment granules.

Conclusions
This is the first report of minocycline-induced pigmentation in skeletal muscle. The strong association between autophagic vacuoles and the accumulation of minocycline-induced pigments suggest that long-term minocycline treatment induced pigment accumulation, leading to elevation of autophagic activity and RVM. It might also be possible that minocycline directly activated autophagy, as the observed pigments are known to form complexes containing minocycline and/or its metabolites. As long-term minocycline treatment is expected to be used more widely in the future, we must draw attention to this adverse effect.
The effects of a rhythm and music-based therapy program and therapeutic riding in late recovery phase following stroke: a study protocol for a three-armed randomized controlled trial
Authors: Bunketorp Käll Lina , Lundgren-Nilsson Åsa , Blomstrand Christian , Pekna Marcela , Pekny Milos , Nilsson Michael 
Published: November 2012

Abstract

Background
Stroke represents one of the most costly and long-term disabling conditions in adulthood worldwide and there is a need to determine the effectiveness of rehabilitation programs in the late phase after stroke. Limited scientific support exists for training incorporating rhythm and music as well as therapeutic riding and well-designed trials to determine the effectiveness of these treatment modalities are warranted.

Methods/Design
A single blinded three-armed randomized controlled trial is described with the aim to evaluate whether it is possible to improve the overall health status and functioning of individuals in the late phase of stroke (1-5 years after stroke) through a rhythm and music-based therapy program or therapeutic riding. About 120 individuals will be consecutively and randomly allocated to one of three groups: (T1) rhythm and music-based therapy program; (T2) therapeutic riding; or (T3) control group receiving the T1 training program a year later. Evaluation is conducted prior to and after the 12-week long intervention as well as three and six months later. The evaluation comprises a comprehensive functional and cognitive assessment (both qualitative and quantitative), and questionnaires. Based on the International classification of functioning, disability, and health (ICF), the outcome measures are classified into six comprehensive domains, with participation as the primary outcome measure assessed by the Stroke Impact Scale (SIS, version 2.0.). The secondary outcome measures are grouped within the following domains: body function, activity, environmental factors and personal factors. Life satisfaction and health related quality of life constitute an additional domain.

Current status
A total of 84 participants were randomised and have completed the intervention. Recruitment proceeds and follow-up is on-going, trial results are expected in early 2014.

Discussion
This study will ascertain whether any of the two intervention programs can improve overall health status and functioning in the late phase of stroke. A positive outcome would increase the scientific basis for the use of such interventions in the late phase after stroke.

Trial registration
Clinical Trials.gov Identifier: NCT01372059