bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem cell transplantation can provide durable disease control in blastic plasmacytoid dendritic cell neoplasm: a retrospective study from the European Group for Blood and Marrow Transplantation
Authors: Roos-Weil Damien , Dietrich Sascha , Boumendil Ariane , Polge Emmanuelle , Bron Dominique , Carreras Enric , Iriondo Atienza Arturo , Arcese William , Beelen Dietrich W. , Cornelissen Jan J. , Kröger Nicolaus , Milone Giuseppe , Rossi Giuseppe , Jardin Fabrice , Peters Christina , Rocha Vanderson , Sureda Anna , Mohty Mohamad , Dreger Peter 
Published: December 2012

Abstract
Patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) have a poor prognosis with conventional chemotherapy. In the present study, we retrospectively analyzed the outcome of patients with BPDCN who underwent allogeneic stem cell transplantation (allo-SCT) or autologous stem cell transplantation (auto-SCT). A total of 39 patients (allo-SCT, n = 34; auto-SCT, n = 5) were identified in the European Group for Blood and Marrow Transplantation registry. The 34 allo-SCT patients had a median age of 41 years (range, 10-70) and received transplantations from sibling (n = 11) or unrelated donors (n = 23) between 2003 and 2009. MAC was used in 74% of patients. Nineteen allo-SCT patients (56%) received transplantations in first complete remission. The 3-year cumulative incidence of relapse, disease-free survival, and overall survival was 32%, 33%, and 41%, respectively. By univariate comparison, being in first remission at allo-SCT favorably influenced survival, whereas age, donor source, and chronic GVHD had no significant impact. We conclude that high-dose therapy followed by allo-SCT from related or unrelated donors can provide durable remission even in elderly patients with BPDCN. However, it remains to be shown if graft-versus-malignancy effects can contribute significantly to BPDCN control after allo-SCT.
In vitro substrate phosphorylation by Ca2+/calmodulin-dependent protein kinase kinase using guanosine-5′-triphosphate as a phosphate donor
Authors: Yurimoto Saki , Fujimoto Tomohito , Magari Masaki , Kanayama Naoki , Kobayashi Ryoji , Tokumitsu Hiroshi 
Published: December 2012

Abstract

Background
Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) phosphorylates and activates particular downstream protein kinases — including CaMKI, CaMKIV, and AMPK— to stimulate multiple Ca2+-signal transduction pathways. To identify previously unidentified CaMKK substrates, we used various nucleotides as phosphate donors to develop and characterize an in vitro phosphorylation assay for CaMKK.

Results
Here, we found that the recombinant CaMKK isoforms were capable of utilizing Mg-GTP as a phosphate donor to phosphorylate the Thr residue in the activation-loop of CaMKIα (Thr177) and of AMPK (Thr172) in vitro. Kinetic analysis indicated that the K
m values of CaMKK isoforms for GTP (400-500 μM) were significantly higher than those for ATP (~15 μM), and a 2- to 4-fold decrease in V
max was observed with GTP. We also confirmed that an ATP competitive CaMKK inhibitor, STO-609, also competes with GTP to inhibit the activities of CaMKK isoforms. In addition, to detect enhanced CaMKI phosphorylation in brain extracts with Mg-GTP and recombinant CaMKKs, we found potential CaMKK substrates of ~45 kDa and ~35 kDa whose Ca2+/CaM-induced phosphorylation was inhibited by STO-609.

Conclusions
These results indicated that screens that use STO-609 as a CaMKK inhibitor and Mg-GTP as a CaMKK-dependent phosphate donor might be useful to identify previously unidentified downstream target substrates of CaMKK.
Uninformative polymorphisms bias genome scans for signatures of selection
Authors: Roesti Marius , Salzburger Walter , Berner Daniel 
Published: December 2012

Abstract

Background
With the establishment of high-throughput sequencing technologies and new methods for rapid and extensive single nucleotide (SNP) discovery, marker-based genome scans in search of signatures of divergent selection between populations occupying ecologically distinct environments are becoming increasingly popular.

Methods and Results
On the basis of genome-wide SNP marker data generated by RAD sequencing of lake and stream stickleback populations, we show that the outcome of such studies can be systematically biased if markers with a low minor allele frequency are included in the analysis. The reason is that these ‘uninformative’ polymorphisms lack the adequate potential to capture signatures of drift and hitchhiking, the focal processes in ecological genome scans. Bias associated with uninformative polymorphisms is not eliminated by just avoiding technical artifacts in the data (PCR and sequencing errors), as a high proportion of SNPs with a low minor allele frequency is a general biological feature of natural populations.

Conclusions
We suggest that uninformative markers should be excluded from genome scans based on empirical criteria derived from careful inspection of the data, and that these criteria should be reported explicitly. Together, this should increase the quality and comparability of genome scans, and hence promote our understanding of the processes driving genomic differentiation.
The Corynebacterium pseudotuberculosis in silico predicted pan-exoproteome
Authors: Santos Anderson R , Carneiro Adriana , Gala-García Alfonso , Pinto Anne , Barh Debmalya , Barbosa Eudes , Aburjaile Flávia , Dorella Fernanda , Rocha Flávia , Guimarães Luis , Zurita-Turk Meritxell , Ramos Rommel , Almeida Sintia , Soares Siomar , Pereira Ulisses , Abreu Vinícius C , Silva Artur , Miyoshi Anderson , Azevedo Vasco 
Published: December 2012

AbstractBackgroundPan-genomic studies aim, for instance, at defining the core, dispensable and unique genes within a species. A pan-genomics study for vaccine design tries to assess the best candidates for a vaccine against a specific pathogen. In this context, rather than studying genes predicted to be exported in a single genome, with pan-genomics it is possible to study genes present in different strains within the same species, such as virulence factors. The target organism of this pan-genomic work here presented isCorynebacterium pseudotuberculosis, the etiologic agent of caseous lymphadenitis (CLA) in goat and sheep, which causes significant economic losses in those herds around the world. Currently, only a few antigens against CLA are known as being the basis of commercial and still ineffective vaccines. In this regard, the here presented work analyses,in silico, fiveC. pseudotuberculosisgenomes and gathers data to predict common exported proteins in all five genomes. These candidates were also compared to two recentC. pseudotuberculosis in vitroexoproteome results.ResultsThe complete genome of fiveC. pseudotuberculosisstrains (1002, C231, I19, FRC41 and PAT10) were submitted to pan-genomics analysis, yielding 306, 59 and 12 gene sets, respectively, representing the core, dispensable and uniquein silicopredicted exported pan-genomes. These sets bear 150 genes classified as secreted (SEC) and 227 as potentially surface exposed (PSE). Our findings suggest that the mainC. pseudotuberculosis in vitroexoproteome could be greater, appended by a fraction of the 35 proteins formerly predicted as making part of the variantin vitroexoproteome. These genomes were manually curated for correct methionine initiation and redeposited with a total of 1885 homogenized genes.ConclusionsThein silicoprediction of exported proteins has allowed to define a list of putative vaccine candidate genes present in all five completeC. pseudotuberculosisgenomes. Moreover, it has also been possible to define thein silicopredicted dispensable and uniqueC. pseudotuberculosisexported proteins. These results providein silicoevidence to further guide experiments in the areas of vaccines, diagnosis and drugs. The work here presented is the first wholeC. pseudotuberculosis in silicopredicted pan-exoproteome completed till today.
Methods for high-throughput MethylCap-Seq data analysis
Authors: Rodriguez Benjamin AT , Frankhouser David , Murphy Mark , Trimarchi Michael , Tam Hok-Hei , Curfman John , Huang Rita , Chan Michael WY , Lai Hung-Cheng , Parikh Deval , Ball Bryan , Schwind Sebastian , Blum William , Marcucci Guido , Yan Pearlly , Bundschuh Ralf 
Published: December 2012

Abstract

Background
Advances in whole genome profiling have revolutionized the cancer research field, but at the same time have raised new bioinformatics challenges. For next generation sequencing (NGS), these include data storage, computational costs, sequence processing and alignment, delineating appropriate statistical measures, and data visualization. Currently there is a lack of workflows for efficient analysis of large, MethylCap-seq datasets containing multiple sample groups.

Methods
The NGS application MethylCap-seq involves the in vitro capture of methylated DNA and subsequent analysis of enriched fragments by massively parallel sequencing. The workflow we describe performs MethylCap-seq experimental Quality Control (QC), sequence file processing and alignment, differential methylation analysis of multiple biological groups, hierarchical clustering, assessment of genome-wide methylation patterns, and preparation of files for data visualization.

Results
Here, we present a scalable, flexible workflow for MethylCap-seq QC, secondary data analysis, tertiary analysis of multiple experimental groups, and data visualization. We demonstrate the experimental QC procedure with results from a large ovarian cancer study dataset and propose parameters which can identify problematic experiments. Promoter methylation profiling and hierarchical clustering analyses are demonstrated for four groups of acute myeloid leukemia (AML) patients. We propose a Global Methylation Indicator (GMI) function to assess genome-wide changes in methylation patterns between experimental groups. We also show how the workflow facilitates data visualization in a web browser with the application Anno-J.

Conclusions
This workflow and its suite of features will assist biologists in conducting methylation profiling projects and facilitate meaningful biological interpretation.
The experience of puberty in Iranian adolescent girls: a qualitative content analysis
Authors: Golchin Nayereh Azam Hagikhani , Hamzehgardeshi Zeinab , Fakhri Moloud , Hamzehgardeshi Leila 
Published: December 2012

Abstract

Background
Adolescence is an important stage in human life span. Physiologic changes associated with puberty manifest themselves in often complex and bizarre ways to which girls show different reactions. This study aims to explore to puberty experiences in adolescent girls who live in the city of Sari in Iran.

Methods
The present study is a qualitative study of content analysis. Sampling took place in the city of Sari, Iran and was objective focused in accordance with qualitative studies. Participants were 38 girls of 12–20 years old who had at least experienced 3 menstrual cycles. Data was collected by means of focus group and in-depth interviews.

Results
As follows, Seven main themes were extracted from the interviews are follows: Menarche as the most unpleasant event in puberty, getting nervous about and ashamed of bodily changes, psychological changes, discordance with parents, sexual orientation and the need for education on this issue, scholastic dysfunction and religious considerations.

Conclusion
The results showed that for the majority of the participants puberty was an unpleasant experience. Most of them were in need of education on how to go about the issues surrounding puberty. The society, families and of course the adolescents themselves are responsible to work together in order to create an atmosphere in which correct information on puberty and the associated issues are readily accessible.
Early outcomes of colon laparoscopic resection in the elderly patients compared with the younger
Authors: Bottino Vincenzo , Esposito Maria Grazia , Mottola Arianna , Marte Giampaolo , Di Maio Vittorio , Sciascia Valerio , Nunziante Marco , Fregola Giovanni , Cuzzovaglia Salvatore , Galante Francesco , Andreoli Federica , Breglia Alfredo , Giuliano Maria Elena , Papaleo Domenico , Della Rocca Paola , Maida Pietro 
Published: December 2012

Abstract

Background
The aim of this study was to define any benefits in terms of early outcome for laparoscopic colectomy in patients over 75 years old (OP) compared with the outcomes of a younger populations (YP).

Methods
Forty elderly patients undergoing laparoscopic colectomy for colorectal cancer between 2007-2011 were studied, the patients are divided for gender, age, year of surgery, site of cancer, and comorbidity on admission and compared with 40 younger patients.

Results and discussion
Mean (standard deviation) age was 81.3 in OP and 68.3 YP Conversion rate was the same between the two groups. There was no difference in operative mean time . The overall mortality rate was 0% percent. The surgical morbidity rate was the same but there was an increased in cardiologic e bronchopneumonia complications in older population. Patients treated with laparoscopic approach had a faster recovery of bowel function and a significant reduction of the mean length of hospital stay not age related. Laparoscopy allowed a better preservation of postoperative independence status.

Conclusions
Laparoscopic colectomy for cancer in elderly patients is safe and beneficial including preservation of postoperative independence and a reduction of length of hospital stay.
Student perceptions of evaluation in undergraduate medical education: A qualitative study from one medical school
Authors: Schiekirka Sarah , Reinhardt Deborah , Heim Susanne , Fabry Götz , Pukrop Tobias , Anders Sven , Raupach Tobias 
Published: December 2012

Abstract

Background
Evaluation is an integral part of medical education. Despite a wide use of various evaluation tools, little is known about student perceptions regarding the purpose and desired consequences of evaluation. Such knowledge is important to facilitate interpretation of evaluation results. The aims of this study were to elicit student views on the purpose of evaluation, indicators of teaching quality, evaluation tools and possible consequences drawn from evaluation data.

Methods
This qualitative study involved 17 undergraduate medical students in Years 3 and 4 participating in 3 focus group interviews. Content analysis was conducted by two different researchers.

Results
Evaluation was viewed as a means to facilitate improvements within medical education. Teaching quality was believed to be dependent on content, process, teacher and student characteristics as well as learning outcome, with an emphasis on the latter. Students preferred online evaluations over paper-and-pencil forms and suggested circulating results among all faculty and students. Students strongly favoured the allocation of rewards and incentives for good teaching to individual teachers.

Conclusions
In addition to assessing structural aspects of teaching, evaluation tools need to adequately address learning outcome. The use of reliable and valid evaluation methods is a prerequisite for resource allocation to individual teachers based on evaluation results.
Development of a decision aid to inform patients’ and families’ renal replacement therapy selection decisions
Authors: Ameling Jessica M , Auguste Priscilla , Ephraim Patti L , Lewis-Boyer LaPricia , DePasquale Nicole , Greer Raquel C , Crews Deidra C , Powe Neil R , Rabb Hamid , Boulware L Ebony 
Published: December 2012

Abstract

Background
Few educational resources have been developed to inform patients’ renal replacement therapy (RRT) selection decisions. Patients progressing toward end stage renal disease (ESRD) must decide among multiple treatment options with varying characteristics. Complex information about treatments must be adequately conveyed to patients with different educational backgrounds and informational needs. Decisions about treatment options also require family input, as families often participate in patients’ treatment and support patients’ decisions. We describe the development, design, and preliminary evaluation of an informational, evidence-based, and patient-and family-centered decision aid for patients with ESRD and varying levels of health literacy, health numeracy, and cognitive function.

Methods
We designed a decision aid comprising a complementary video and informational handbook. We based our development process on data previously obtained from qualitative focus groups and systematic literature reviews. We simultaneously developed the video and handbook in “stages.” For the video, stages included (1) directed interviews with culturally appropriate patients and families and preliminary script development, (2) video production, and (3) screening the video with patients and their families. For the handbook, stages comprised (1) preliminary content design, (2) a mixed-methods pilot study among diverse patients to assess comprehension of handbook material, and (3) screening the handbook with patients and their families.

Results
The video and handbook both addressed potential benefits and trade-offs of treatment selections. The 50-minute video consisted of demographically diverse patients and their families describing their positive and negative experiences with selecting a treatment option. The video also incorporated health professionals’ testimonials regarding various considerations that might influence patients’ and families’ treatment selections. The handbook was comprised of written words, pictures of patients and health care providers, and diagrams describing the findings and quality of scientific studies comparing treatments. The handbook text was written at a 4th to 6th grade reading level. Pilot study results demonstrated that a majority of patients could understand information presented in the handbook. Patient and families screening the nearly completed video and handbook reviewed the materials favorably.

Conclusions
This rigorously designed decision aid may help patients and families make informed decisions about their treatment options for RRT that are well aligned with their values.
Cost comparison of MRSA screening and management – a decision tree analysis
Authors: Tübbicke Andrea , Hübner Claudia , Hübner Nils-Olaf , Wegner Christian , Kramer Axel , Fleßa Steffen 
Published: December 2012

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a serious challenge for health-care institutions. Rapid and precise identification of MRSA carriers can help to reduce both nosocomial transmissions and unnecessary isolations and associated costs. The practical details of MRSA screenings (who, how, when and where to screen) remain a controversial issue.

Methods
Aim of this study was to determine which MRSA screening and management strategy causes the lowest expected cost for a hospital. For this cost analysis a decision analytic cost model was developed, primary based on data from peer-reviewed literature. Single and multiplex sensitivity analyses of the parameters “costs per MRSA case per day”, “costs for pre-emptive isolation per day”, “MRSA rate of transmission not in isolation per day” and “MRSA prevalence” were conducted.

Results
The omission of MRSA screening was identified as the alternative with the highest risk for the hospital. Universal MRSA screening strategies are by far more cost-intensive than targeted screening approaches. Culture confirmation of positive PCR results in combination with pre-emptive isolation generates the lowest costs for a hospital. This strategy minimizes the chance of false-positive results as well as the possibility of MRSA cross transmissions and therefore contains the costs for the hospital. These results were confirmed by multiplex and single sensitivity analyses. Single sensitivity analyses have shown that the parameters “MRSA prevalence” and the “rate of MRSA of transmission per day of non-isolated patients” exert the greatest influence on the choice of the favorite screening strategy.

Conclusions
It was shown that universal MRSA screening strategies are far more cost-intensive than the targeted screening approaches. In addition, it was demonstrated that all targeted screening strategies produce lower costs than not performing a screening at all.
Lyn is involved in CD24-induced ERK1/2 activation in colorectal cancer
Authors: Su Ning , Peng Liang , Xia Bingqing , Zhao Yingying , Xu Angao , Wang Jing , Wang Xinying , Jiang Bo 
Published: December 2012

AbstractBackground and aimCD24 expression is associated with human colorectal cancer (CRC). Our previous data indicated that CD24 promoted the proliferation and invasion of colorectal cancer cells through the activation of ERK1/2. Since Src family kinases are frequently deregulated in CRC and closely related to the MAPK signaling pathway, we investigated the impact of Lyn, an important member of SFKs, on CD24-induced ERK1/2 activation in CRC.Methods and ResultsThe interaction of CD24 and Lyn was identified by co-immunoprecipitation (Co-IP) and ectopic expression of CD24-induced Lyn activation. Inhibition of Lyn activation by phosphatase PP2 in SW480CD24cells abrogated CD24-induced invasion. The results of the Co-IP and immunofluorescence assay revealed that overexpression of CD24 enhanced the interaction of Lyn and ERK1/2 and induced the nuclear translocation of Lyn. However, inhibition of Lyn activity attenuated CD24-induced ERK1/2 activation, and depletion of CD24 disrupted Lyn-ERK1/2 interaction. Immunohistochemistry analysis for 202 cases of CRC showed that the expression of both CD24 and Lyn was positively correlated with tumor grade, stage, lymph node and distant metastasis. Patients with lower expression of CD24 or Lyn had a higher survival rate. The Cox multivariate analysis showed that CD24 expression, but not Lyn expression, was an independent prognostic factor of CRC.ConclusionsOur results suggest that Lyn is involved in CD24-induced ERK1/2 activation in CRC. The expression of CD24 is associated with activation of Lyn and ERK1/2, which might be a novel mechanism related to CD24-mediated regulation of CRC development.