bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia
Authors: Farrar Jason E. , Nater Michelle , Caywood Emi , McDevitt Michael A. , Kowalski Jeanne , Takemoto Clifford M. , Talbot C. Conover , Meltzer Paul , Esposito Diane , Beggs Alan H. , Schneider Hal E. , Grabowska Agnieszka , Ball Sarah E. , Niewiadomska Edyta , Sieff Colin A. , Vlachos Adrianna , Atsidaftos Eva , Ellis Steven R. , Lipton Jeffrey M. , Gazda Hanna T. , Arceci Robert J. 
Published: June 2008

AbstractDiamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, congenital abnormalities, and cancer predisposition. Small ribosomal subunit genes RPS19, RPS24, and RPS17 are mutated in approximately one-third of patients. We used a candidate gene strategy combining high-resolution genomic mapping and gene expression microarray in the analysis of 2 DBA patients with chromosome 3q deletions to identify RPL35A as a potential DBA gene. Sequence analysis of a cohort of DBA probands confirmed involvement RPL35A in DBA. shRNA inhibition shows that Rpl35a is essential for maturation of 28S and 5.8S rRNAs, 60S subunit biogenesis, normal proliferation, and cell survival. Analysis of pre-rRNA processing in primary DBA lymphoblastoid cell lines demonstrated similar alterations of large ribosomal subunit rRNA in both RPL35A-mutated and some RPL35A wild-type patients, suggesting additional large ribosomal subunit gene defects are likely present in some cases of DBA. These data demonstrate that alterations of large ribosomal subunit proteins cause DBA and support the hypothesis that DBA is primarily the result of altered ribosomal function. The results also establish that haploinsufficiency of large ribosomal subunit proteins contributes to bone marrow failure and potentially cancer predisposition.
Differences across health care systems in outcome and cost-utility of surgical and conservative treatment of chronic low back pain: a study protocol
Authors: Melloh Markus , Röder Christoph , Elfering Achim , Theis Jean-Claude , Müller Urs , Staub Lukas P , Aghayev Emin , Zweig Thomas , Barz Thomas , Kohlmann Thomas , Wieser Simon , Jüni Peter , Zwahlen Marcel 
Published: June 2008

Abstract

Background
There is little evidence on differences across health care systems in choice and outcome of the treatment of chronic low back pain (CLBP) with spinal surgery and conservative treatment as the main options. At least six randomised controlled trials comparing these two options have been performed; they show conflicting results without clear-cut evidence for superior effectiveness of any of the evaluated interventions and could not address whether treatment effect varied across patient subgroups. Cost-utility analyses display inconsistent results when comparing surgical and conservative treatment of CLBP. Due to its higher feasibility, we chose to conduct a prospective observational cohort study.

Methods
This study aims to examine if
1. Differences across health care systems result in different treatment outcomes of surgical and conservative treatment of CLBP
2. Patient characteristics (work-related, psychological factors, etc.) and co-interventions (physiotherapy, cognitive behavioural therapy, return-to-work programs, etc.) modify the outcome of treatment for CLBP
3. Cost-utility in terms of quality-adjusted life years differs between surgical and conservative treatment of CLBP.
This study will recruit 1000 patients from orthopaedic spine units, rehabilitation centres, and pain clinics in Switzerland and New Zealand. Effectiveness will be measured by the Oswestry Disability Index (ODI) at baseline and after six months. The change in ODI will be the primary endpoint of this study.
Multiple linear regression models will be used, with the change in ODI from baseline to six months as the dependent variable and the type of health care system, type of treatment, patient characteristics, and co-interventions as independent variables. Interactions will be incorporated between type of treatment and different co-interventions and patient characteristics. Cost-utility will be measured with an index based on EQol-5D in combination with cost data.

Conclusion
This study will provide evidence if differences across health care systems in the outcome of treatment of CLBP exist. It will classify patients with CLBP into different clinical subgroups and help to identify specific target groups who might benefit from specific surgical or conservative interventions. Furthermore, cost-utility differences will be identified for different groups of patients with CLBP. Main results of this study should be replicated in future studies on CLBP.
Are cultural dimensions relevant for explaining cross-national differences in antibiotic use in Europe?
Authors: Deschepper Reginald , Grigoryan Larissa , Lundborg Cecilia Stålsby , Hofstede Geert , Cohen Joachim , Kelen Greta Van Der , Deliens Luc , Haaijer-Ruskamp Flora M 
Published: June 2008

Abstract

Background
Antibiotics are widely-used medicines for which a more prudent use has been advocated to minimize development of resistance. There are considerable cross-national differences that can only partially be explained by epidemiological difference and variations in health care structure. The aim of this study was to explore whether cross-national differences in use of antibiotics (prescribed and non-prescribed) are associated with differences between national cultures as described in Hofstede's model of cultural dimensions (Power Distance, Individualism, Masculinity, Uncertainty Avoidance and Long-Term Orientation).

Methods
Country-level data of prescribed antibiotic use and self-medication with antibiotics were correlated to country-specific scores of cultural dimensions obtained from Hofstede. Data on use of antibiotics were provided by three European studies, based on different methods and/or countries: Self-medication with Antibiotics and Resistance in Europe (SAR), based on a survey in 2003 on reported use of antibiotics in 19 countries, the European Surveillance on Antimicrobial Consumption, based on distribution and reimbursement of antibiotics in ambulatory care (1997–2002), and the 2002 interview-based Eurobarometer study, asking whether respondents had taken antibiotics in the previous 12 months. These studies provided data on antibiotics use for 27 European countries in total, for which scores of cultural dimensions were also available. The SAR-study differentiated between prescribed antibiotics and self-medication with antibiotics.

Results
Significant positive correlations were found for Power Distance Index with use of prescribed antibiotics in the three studies (rho between 0.59 and 0.62) and with self-medication (rho = 0.54) in the SAR study. Positive significant correlations were found for the Uncertainty Avoidance Index with the use of antibiotics as reported in two studies (rho between 0.57 and 0.59; for the SAR study the correlations were insignificant). Masculinity was not significantly correlated, except in one study after controlling for GDP (r = 0.81). For Individualism and Long-Term Orientation no significant correlations were found.

Conclusion
Power Distance is a cultural aspect associated with antibiotic use, suggesting that the culture-specific way people deal with authority is an important factor in explaining cross-national differences in antibiotic use. There are indications that Uncertainty Avoidance also plays a role but further research is needed to better understand the complex effect of cultural dimensions.
Identification of glycosaminoglycan binding regions in the Plasmodium falciparum encoded placental sequestration ligand, VAR2CSA
Authors: Resende Mafalda , Nielsen Morten A , Dahlbäck Madeleine , Ditlev Sisse B , Andersen Pernille , Sander Adam F , Ndam Nicaise T , Theander Thor G , Salanti Ali 
Published: June 2008

Abstract

Background
Pregnancy malaria is caused by Plasmodium falciparum-infected erythrocytes binding the placental receptor chondroitin sulfate A (CSA). This results in accumulation of parasites in the placenta with severe clinical consequences for the mother and her unborn child. Women become resistant to placental malaria as antibodies are acquired which specifically target the surface of infected erythrocytes binding in the placenta. VAR2CSA is most likely the parasite-encoded protein which mediates binding to the placental receptor CSA. Several domains have been shown to bind CSA in vitro; and it is apparent that a VAR2CSA-based vaccine cannot accommodate all the CSA binding domains and serovariants. It is thus of high priority to define minimal ligand binding regions throughout the VAR2CSA molecule.

Methods
To define minimal CSA-binding regions/peptides of VAR2CSA, a phage display library based on the entire var2csa coding region was constructed. This library was screened on immobilized CSA and cells expressing CSA resulting in a limited number of CSA-binding phages. Antibodies against these peptides were affinity purified and tested for reactivity against CSA-binding infected erythrocytes.

Results
The most frequently identified phages expressed peptides residing in the parts of VAR2CSA previously defined as CSA binding. In addition, most of the binding regions mapped to surface-exposed parts of VAR2CSA. The binding of a DBL2X peptide to CSA was confirmed with a synthetic peptide. Antibodies against a CSA-binding DBL2X peptide reacted with the surface of infected erythrocytes indicating that this epitope is accessible for antibodies on native VAR2CSA on infected erythrocytes.

Conclusion
Short continuous regions of VAR2CSA with affinity for multiple types of CSA were defined. A number of these regions localize to CSA-binding domains and to surface-exposed regions within these domains and a synthetic peptide corresponding to a peptide sequence in DBL2 was shown to bind to CSA and not to CSC. It is likely that some of these epitopes are involved in native parasite CSA adhesion. However, antibodies directed against single epitopes did not inhibit parasite adhesion. This study supports phage display as a technique to identify CSA-binding regions of large proteins such as VAR2CSA.
Pectoralis major inverse plasty for functional reconstruction in patients with anterolateral deltoid deficiency
Authors: Resch H. , Povacz P. , Maurer H. , Koller H. , Tauber M. 
Published: June 2008

After establishing anatomical feasibility, functional reconstruction to replace the anterolateral part of the deltoid was performed in 20 consecutive patients with irreversible deltoid paralysis using the sternoclavicular portion of the pectoralis major muscle. The indication for reconstruction was deltoid deficiency combined with massive rotator cuff tear in 11 patients, brachial plexus palsy in seven, and an isolated axillary nerve lesion in two. All patients were followed clinically and radiologically for a mean of 70 months (24 to 125). The mean gender-adjusted Constant score increased from 28% (15% to 54%) to 51% (19% to 83%). Forward elevation improved by a mean of 37°, abduction by 30° and external rotation by 9°. The pectoralis inverse plasty may be used as a salvage procedure in irreversible deltoid deficiency, providing subjectively satisfying results. Active forward elevation and abduction can be significantly improved.
Limb-sparing surgery preserves more function than amputation
Authors: Aksnes L. H. , Bauer H. C. F. , Jebsen N. L. , Foller̊s G. , Allert C. , Haugen G. S. , Hall K. S. 
Published: June 2008

We evaluated the long-term functional outcome in 118 patients treated for osteosarcoma or Ewing’s sarcoma in the extremities a minimum of five years after treatment. We also examined if impaired function influenced their quality of life and ability to work.The function was evaluated according to the Musculoskeletal Tumor Society (MSTS) score and the Toronto Extremity Salvage Score (TESS). Quality of life was assessed by using the Short Form-36 (SF-36).The mean age at follow-up was 31 years (15 to 57) and the mean follow-up was for 13 years (6 to 22). A total of 67 patients (57%) initially had limb-sparing surgery, but four had a secondary amputation. The median MSTS score was 70% (17% to 100%) and the median TESS was 89% (43% to 100%). The amputees had a significantly lower MSTS score than those with limb-sparing surgery (p < 0.001), but there was no difference for the TESS. Tumour localisation above knee level resulted in significantly lower MSTS scores and TESS (p = 0.003 and p = 0.02, respectively).There were no significant differences in quality of life between amputees and those with limb-sparing surgery except in physical functioning. Of the patients 11% (13) did not work or study. In multivariate analysis, amputation, tumour location above the knee and having muscular pain were associated with low physical function.We conclude that most of the bone tumour survivors managed well after adjustment to their physical limitations. A total of 105 are able to work and have an overall good quality of life.
IFATS Collection: In Vivo Therapeutic Potential of Human Adipose Tissue Mesenchymal Stem Cells After Transplantation into Mice with Liver Injury
Authors: Banas Agnieszka , Teratani Takumi , Yamamoto Yusuke , Tokuhara Makoto , Takeshita Fumitaka , Osaki Mitsuhiko , Kawamata Masaki , Kato Takashi , Okochi Hitoshi , Ochiya Takahiro 
Published: June 2008

AbstractMesenchymal stem cells (MSCs), largely present in the adult human body, represent an attractive tool for the establishment of a stem cell-based therapy for liver diseases. Recently, the therapeutic potential and immunomodulatory activity of MSCs have been revealed. Adipose tissue-derived mesenchymal stem cells (AT-MSCs), so-called adipose-derived stem cells or adipose stromal cells, because of their high accessibility with minimal invasiveness, are especially attractive in the context of future clinical applications. The goal of the present study was to evaluate the therapeutic potential of AT-MSCs by their transplantation into nude mice with CCl4-caused liver injury. We observed that after transplantation, AT-MSCs can improve liver functions, which we verified by changes in the levels of biochemical parameters. Ammonia, uric acid, glutamic-pyruvic transaminase, and glutamic-oxaloacetic transaminase concentrations returned to a nearly normal level after AT-MSC transplantation. These results raised the question of how AT-MSCs can achieve this. To discover the possible mechanisms involved in this therapeutic ability of AT-MSCs, in vitro production of cytokines and growth factors was analyzed and compared with MSCs from bone marrow (BM-MSCs) and normal human dermal fibroblasts (NHDFs). As a result we observed that AT-MSCs secrete interleukin 1 receptor α (IL-1Rα), IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein 1, nerve growth factor, and hepatocyte growth factor in a volume higher than both BM-MSCs and NHDFs. Thus, our findings suggest that AT-MSCs may account for their broad therapeutic efficacy in animal models of liver diseases and in the clinical settings for liver disease treatment.Disclosure of potential conflicts of interest is found at the end of this article.
Olfactory Mucosa Is a Potential Source for Autologous Stem Cell Therapy for Parkinson's Disease
Authors: Murrell Wayne , Wetzig Andrew , Donnellan Michael , Féron François , Burne Tom , Meedeniya Adrian , Kesby James , Bianco John , Perry Chris , Silburn Peter , Mackay-Sim Alan 
Published: June 2008

AbstractParkinson's disease is a complex disorder characterized by degeneration of dopaminergic neurons in the substantia nigra in the brain. Stem cell transplantation is aimed at replacing dopaminergic neurons because the most successful drug therapies affect these neurons and their synaptic targets. We show here that neural progenitors can be grown from the olfactory organ of humans, including those with Parkinson's disease. These neural progenitors proliferated and generated dopaminergic cells in vitro. They also generated dopaminergic cells when transplanted into the brain and reduced the behavioral asymmetry induced by ablation of the dopaminergic neurons in the rat model of Parkinson's disease. Our results indicate that Parkinson's patients could provide their own source of neuronal progenitors for cell transplantation therapies and for direct investigation of the biology and treatments of Parkinson's disease.Disclosure of potential conflicts of interest is found at the end of this article.
Embryonic Stem Cells and Their Differentiated Derivatives Have a Fragile Immune Privilege but Still Represent Novel Targets of Immune Attack
Authors: Wu Douglas C. , Boyd Ashleigh Susan , Wood Kathryn J. 
Published: June 2008

Abstract
Embryonic stem cells (ESCs) offer an attractive potential in cell replacement therapy and regenerative medicine because of their inherent plasticity and ability to self-renew. However, the immunological response against transplanted ESC-derived allografts requires further evaluation. In this study, we showed that ESCs expressing the major histocompatibility complex class I molecule H2Kb escape immune recognition by H2Kb-reactive CD8+ T cells, irrespective of H2Kb expression levels. In the face of more robust immunological challenge, however, evidence of ESC allograft rejection becomes apparent. We further assessed the adaptive immune response against terminally differentiated insulin-producing tissue derived from an ESC source to examine the potential future applicability of this tissue as a β-cell replacement therapy for type 1 diabetes mellitus. The functional ESC-derived insulin-producing tissue was infiltrated by alloreactive T cells and rejected in immunocompetent hosts. Hence, although ESCs and their terminally differentiated derivatives may possess a fragile immune privilege, they still represent novel targets of attack by elements of the immune system and are rejected. These findings provide insight into the mechanisms of adaptive immunity toward ESCs and their derivatives.
Disclosure of potential conflicts of interest is found at the end of this article.
G9a and Jhdm2a Regulate Embryonic Stem Cell Fusion-Induced Reprogramming of Adult Neural Stem Cells
Authors: Ma Dengke K. , Chiang Cheng-Hsuan J. , Ponnusamy Karthikeyan , Ming Guo-li , Song Hongjun 
Published: June 2008

Abstract
Somatic nuclei can be reprogrammed to pluripotency through fusion with embryonic stem cells (ESCs). The underlying mechanism is largely unknown, primarily because of a lack of effective approaches to monitor and quantitatively analyze transient, early reprogramming events. The transcription factor Oct4 is expressed specifically in pluripotent stem cells, and its reactivation from somatic cell genome constitutes a hallmark for effective reprogramming. Here we developed a double fluorescent reporter system using engineered ESCs and adult neural stem cells/progenitors (NSCs) to simultaneously and independently monitor cell fusion and reprogramming-induced reactivation of transgenic Oct4-enhanced green fluorescent protein (EGFP) expression. We demonstrate that knockdown of a histone methyltransferase, G9a, or overexpression of a histone demethylase, Jhdm2a, promotes ESC fusion-induced Oct4-EGFP reactivation from adult NSCs. In addition, coexpression of Nanog and Jhdm2a further enhances the ESC-induced Oct4-EGFP reactivation. Interestingly, knockdown of G9a alone in adult NSCs leads to demethylation of the Oct4 promoter and partial reactivation of the endogenous Oct4 expression from adult NSCs. Our results suggest that ESC-induced reprogramming of somatic cells occurs with coordinated actions between erasure of somatic epigenome and transcriptional resetting to restore pluripotency. These mechanistic findings may guide more efficient reprogramming for future therapeutic applications of stem cells.
Disclosure of potential conflicts of interest is found at the end of this article.
Sex Differences in Diabetes Risk and the Effect of Intensive Lifestyle Modification in the Diabetes Prevention Program
Authors: Perreault Leigh , Ma Yong , Dagogo-Jack Sam , Horton Edward , Marrero David , Crandall Jill , Barrett-Connor Elizabeth ,   for the Diabetes Prevention Program
Published: June 2008

OBJECTIVE—In participants of the Diabetes Prevention Program (DPP) randomized to intensive lifestyle modification (ILS), meeting ILS goals strongly correlated with prevention of diabetes in the group as a whole. Men met significantly more ILS goals than women but had a similar incidence of diabetes. Therefore, we explored sex differences in risk factors for diabetes and the effect of ILS on risk factors.
RESEARCH DESIGN AND METHODS—Baseline risk factors for diabetes and percent change in risk factors over the first year in men versus women were compared using Wilcoxon's rank-sum tests.
RESULTS—At baseline, men were older and had a larger waist circumference; higher fasting plasma glucose concentration, caloric intake, and blood pressure; and lower HDL cholesterol and corrected insulin response than women, who were less physically active and had a higher BMI (P &lt; 0.01 for all comparisons). Over the first year of the DPP, no sex difference in risk factors for diabetes was observed for those who lost &lt;3% body weight. Weight loss of 3–7% body weight yielded greater decreases in 2-h glucose (P &lt; 0.01), insulin concentration (P &lt; 0.04), and insulin resistance (P &lt; 0.03) in men than in women. Weight loss of &gt;7% body weight resulted in greater decreases in 2-h glucose (P &lt; 0.01), triglyceride level (P &lt; 0.01), and A1C (P &lt; 0.03) in men than in women.
CONCLUSIONS—Weight loss &gt;3% body weight yielded greater reduction in risk factors for diabetes in men than in women. Despite the more favorable effects of ILS in men, baseline risk factors were more numerous in men and likely obscured any sex difference in incident diabetes.
The massage in the medium: Transfer of connotative meaning from typeface to names and products
Authors: Doyle John R. , Bottomley Paul A. 
Published: June 2008

AbstractAll text must be written in some particular style of lettering, known as its typeface or font. If it is once accepted that different typefaces generate their own connotations then every written word originates two meanings. Three experiments demonstrate that people who are asked to evaluate names and products are affected by transfer of meaning from the typeface in which they are presented. The meaning of the word is pulled towards the meaning of the typeface (assimilation), rather than pushed away from it (contrast). Copyright © 2008 John Wiley & Sons, Ltd.