bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving knowledge and changing behavior towards guideline based decisions in diabetes care: a controlled intervention study of a team-based learning approach for continuous professional development of physicians
Authors: Kühne-Eversmann Lisa , Fischer Martin R 
Published: January 2013

Abstract

Background
Continuing Professional Development (CPD) courses should ideally improve a physician’s knowledge and change their professional behavior in daily practice towards a best clinical practice reference model and guideline adherence. Interactive methods such as team-based learning and case-based learning, as compared to lectures, can impart sustainable knowledge and lead to high satisfaction among participants. We designed an interactive case-based CPD-seminar on diabetes care using a team-based learning approach to evaluate whether it leads to an improvement of short-term knowledge and changing of behavior towards guideline based decisions and how this learning approach is perceived by participants.

Methods
Questionnaires and an electronic voting system were used to evaluate motivation, acceptance and knowledge of voluntary participants. Furthermore, we analyzed data on index diagnostic tests and referrals of patients with diabetes of participating physicians over a period of six months before and after the course in comparison with a matched control group in a quasi-experimental design.

Results
Participants (n=103) rated the interactivity and team-based discussions as the main reasons for enhanced learning. They also expected that the course would change their professional behavior. Participants scored a mean of 43.9% right answers before and 62.6% after the course (p<0.001). The referral to diabetes specialists increased by 30.8% (p<0.001). Referral for fundoscopy also increased (8.5%, n.s.) while it dropped in the control group. Furthermore, the participating physicians tested their patients more often for microalbuminuria (7.1%, n.s.).

Conclusions
Our team-based learning CPD-approach was highly accepted and resulted in an increase of short-term knowledge. It significantly increased the referral to diabetes specialists in daily practice whereas all other key professional behavior indicators did change but not significantly.
TFPIα and TFPIβ are expressed at the surface of breast cancer cells and inhibit TF-FVIIa activity
Authors: Stavik Benedicte , Tinholt Mari , Sletten Marit , Skretting Grethe , Sandset Per Morten , Iversen Nina 
Published: January 2013

AbstractBackgroundTissue factor (TF) pathway inhibitor-1 (TFPI) is expressed in several malignant tissues- and cell lines and we recently reported that it possesses anti-tumor effects in breast cancer cells, indicating a biological role of TFPI in cancer. The two main splice variants of TFPI; TFPIα and TFPIβ, are both able to inhibit TF-factor VIIa (FVIIa) activity in normal cells, but only TFPIα circulates in plasma. The functional importance of TFPIβ is therefore largely unknown, especially in cancer cells. We aimed to characterize the expression and function of TFPIα, TFPIβ, and TF in a panel of tumor derived breast cancer cell lines in comparison to normal endothelial cells.MethodsTFPIα, TFPIβ, and TF mRNA and protein measurements were conducted using qRT-PCR and ELISA, respectively. Cell-associated TFPI was detected after phosphatidylinositol-phospholipase C (PI-PLC) and heparin treatment by flow cytometry, immunofluorescence, and Western blotting. The potential anticoagulant activity of cell surface TFPI was determined in a factor Xa activity assay.ResultsThe expression of both isoforms of TFPI varied considerably among the breast cancer cell lines tested, from no expression in Sum149 cells to levels above or in the same range as normal endothelial cells in Sum102 and MDA-MB-231 cells. PI-PLC treatment released both TFPIα and TFPIβ from the breast cancer cell membrane and increased TF activity on the cell surface, showing TF-FVIIa inhibitory activity of the glycosylphosphatidylinositol- (GPI-) anchored TFPI. Heparin treatment released TFPIα without decreasing the cell surface levels, thus indicating the presence of intracellular storage pools of TFPIα in the breast cancer cells.ConclusionGPI-attached TFPI located at the surface of breast cancer cells inhibited TF activity and could possibly reduce TF signaling and breast cancer cell growth locally, indicating a therapeutic potential of the TFPIβ isoform.
Development of an observational instrument to determine variations in the patient care process and patient flow among emergency physicians and internists at the emergency department
Authors: Koks Daisy Roxanna Johanna Christina , Zonderland Maartje Elisabeth , Heringhaus Christian 
Published: January 2013

Abstract

Background
The increasing demand for acute care and restructuring of hospitals resulting in emergency department (ED) closures and fewer inpatient beds are reasons to improve ED efficiency. The approach towards the patient care process varies among doctors. The objective of this study was to determine variations in the patient care process and patient flow among emergency physicians (EP’s) and internists at the ED of Leiden University Medical Centre (LUMC), the Netherlands.

Methods
An observational instrument was developed during a pilot study at the LUMC ED, following observations of activities performed by EP’s and internists. The instrument divides all different types of activities a clinician can perform on the ED into eight categories. Using the observational instrument, their activities were observed and registered for 10 separate days. Primary outcomes were defined as the time spend on the eight separate activity categories, the total length of stay (LOS) and the number of patients seen during an interval. Secondary outcomes were general observations of working routine features that determine patient flow at the ED. The obtained data were analyzed into SPSS.

Results
Ten doctors were observed during a total of ± 36 hours in which 42 patients were seen. Although EP’s were observed for a shorter period of time than internists (13:48 vs. 22:10 hrs, -38%), they saw more patients (26 vs. 16, +62%). EP’s tended to spend a higher proportion of their time on patient contact than internists (27.2% vs. 17.3%, p = 0.06). Both groups dedicated the highest proportion of their time to documentation (31.5% and 33.4%, p = 0.75) and had little communication with ED nurses (3.7% and 2.4% p = 0.57). The average LOS of internal patients was higher than that of EP’s patients (5.25 ± sd 1:33 and 2.26 ± sd 1:32 hours). Internists occupied more treatment rooms at the same time (2.41 vs. 2.08, p < 0.00) and followed a more sequential working routine.

Conclusions
This paper describes the determination of variations in the ED care process and patient flow among EP’s and internists by an observational instrument. A pilot study with the instrument showed variations in the patient care process and patient flow among the two groups at the LUMC ED.
Peripapillary choroidal neovascularization in pars planitis
Authors: Mehta Sonia , Hariharan Luxme , Ho Allen C , Kempen John H 
Published: January 2013

AbstractBackgroundChoroidal neovascularization (CNV) is a rare complication of intermediate uveitis. Risk factors are not well-characterized. Here, we describe a case of peripapillary CNV in a patient with intermediate uveitis and explore the pathophysiology and treatment of this condition. This study is a case report and review of the literature.ResultsA 15-year-old boy with intermediate uveitis - suppressed for the preceding year on immunosuppressive therapy and low-dose corticosteroids - and chronic disc swelling presented with unilateral metamorphopsia, peripapillary subretinal hemorrhage, and subretinal fluid. Fluorescein angiogram confirmed the presence of an active choroidal neovascular membrane. Treatment with intravitreal bevacizumab 1.25 mg every 4 weeks for 4 months resulted in resolution of subretinal fluid, subretinal hemorrhage, and regression of the CNV. The patient's intermediate uveitis remained inactive throughout this time.ConclusionReview of the existing literature and pathophysiologic consideration suggests that chronic disc edema may be a risk factor for this condition. Peripapillary CNV in the context of intermediate uveitis appears to respond well to VEGF-inhibitor therapy.
Public‐private partnerships as driving forces in the quest for innovative medicines
Authors: Goldman Michel , Compton Carolyn , Mittleman Barbara B 
Published: January 2013

AbstractBackgroundDespite progress in translational research, we are still falling short in developing the innovative medicines required to address major public health needs. Furthermore, the failure rate, time, and cost required for registration of a new drug are pushing the economics of the industry to the breaking point. New models of drug development based on collaborative endeavours are badly needed to improve this dire situation.FindingsIn 2004, the US Food and Drug Administration (FDA) introduced the Critical Path Initiative with the intent of modernizing drug development by implementing public‐private partnerships (PPP) to share data, expertise, and resources. In response to FDA's initiative, in the following year the non‐profit Critical Path Institute (C‐Path) was formed. At the same time, the National Institutes of Health (NIH) Public‐Private Partnership program was established. In Europe, the Innovative Medicines Initiative (IMI) supported jointly by the European Union and the European Federation of Pharmaceutical Industries and Associations was launched in 2008. These independent efforts have a common long‐term objective, namely to facilitate the emergence of innovative medicines by developing new tools for drug discovery, new indicators for drug efficacy or safety, and new approaches for patient stratification. Herein, we present evidence that PPP already exert a positive impact on the drug development process.ConclusionsPublic‐private partnerships represent attractive means to leverage resources dispersed across industry, academia, and voluntary health organizations in order to address multiple challenges of drug development in an era of constrained resources and increased regulatory pressure.
Association of the AIRE gene with susceptibility to rheumatoid arthritis in a European population: a case control study
Authors: García-Lozano José-Raúl , Torres-Agrela Belén , Montes-Cano Marco-Antonio , Ortiz-Fernández Lourdes , Conde-Jaldón Marta , Teruel María , García Alicia , Núñez-Roldán Antonio , Martín Javier , González-Escribano María-Francisca 
Published: January 2013

Abstract
Introduction
AIRE is a transcriptional regulator playing a functional role in thymocyte education and negative selection by controlling the expression of peripheral antigens in the thymus. Recently, the AIRE gene was identified as a genetic risk factor for rheumatoid arthritis (RA) in genome wide association (GWA) studies performed in the Japanese population. According to the available data this association is restricted to the Asian population. However, different facts could influence the lack of association in Caucasian populations. The aim of this study was to further investigate the possible role of the AIRE gene in susceptibility to RA in a Caucasian population.

Methods
A total of 472 Spanish Caucasian RA patients and 475 ethnically matched controls were included in the study. Three single-nucleotide polymorphisms (SNPs) (rs2776377, rs878081 and rs1055311) with a minor allele frequency >0.05 in the Caucasian population which were not included in the high-throughput platforms used in the GWA studies performed in susceptibility to RA, and two SNPs (rs2075876 and rs1800520) associated with RA in the Japanese population, were selected and genotyped using TaqMan assays.

Results
No significant differences in the distribution of the alleles of rs2776377, rs2075876, rs1055311 and rs1800520 SNPs between RA patients and controls were observed. Nevertheless, the frequency of the C allele of rs878081 was significantly higher among RA patients (80.5% vs. 74.6% in the control group, pc = 0.012, OR = 1.41, 95%CI 1.13-1.75). Regarding the distribution of the rs878081 genotypes, a higher frequency of CC homozygous individuals was found in the RA patient group (65.56% vs. 56.47% in the control group, pc = 0.013, OR = 1.47, 95%CI 1.12-1.93). The in silico analysis predicted lower affinity to the binding-site of a motif of the transcription NF-κB family and lower transcription levels of AIRE gene for the rs878081C risk variant

Conclusions
Our findings suggest that the AIRE gene is associated with susceptibility to RA in the Spanish population. Probably, this association has not been detected in the European population in the GWA studies because the earliest high-throughput platforms did not include SNP suitable markers (e.g. rs878081).
The spectrum of renal thrombotic microangiopathy in lupus nephritis
Authors: Song Di , Wu Li-hua , Wang Feng-mei , Yang Xiao-wei , Zhu Di , Chen Min , Yu Feng , Liu Gang , Zhao Ming-hui 
Published: January 2013

Abstract
Introduction
Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China.

Methods
Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed.

Results
In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with the non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09 ± 4.64 vs. 4.75 ± 3.13 g/24h, P = 0.007) and serum creatinine (159, 86 to 215 vs. 81, 68 to 112 μmol/l, P <0.001), higher scores of total activity indices (AI) (P <0.001), endocapillary hypercellularity (P <0.001), subendothelial hyaline deposits (P = 0.003), interstitial inflammation (P = 0.005), glomerular leukocyte infiltration (P = 0.006), total chronicity indices (CI) (P = 0.033), tubular atrophy (P = 0.004) and interstitial fibrosis (P = 0.018). Patients with renal TMA presented with poorer renal outcome (P = 0.005) compared with the non-TMA group. Renal TMA (hazard ratio (HR): 2.772, 95% confidence interval: 1.009 to 7.617, P = 0.048) was an independent risk factor for renal outcome in patients with lupus nephritis. The renal outcome was poorer for those with both C4d deposition and decreased serum complement factor H in the TMA group (P = 0.007).

Conclusions
There were various causes of renal TMA in lupus nephritis. Complement over-activation via both classical and alternative pathways might play an important role in the pathogenesis of renal TMA in lupus nephritis.
Promoter hypermethylation of the tumor-suppressor genes ITIH5, DKK3, and RASSF1A as novel biomarkers for blood-based breast cancer screening
Authors: Kloten Vera , Becker Birte , Winner Kirsten , Schrauder Michael G , Fasching Peter A , Anzeneder Tobias , Veeck Jürgen , Hartmann Arndt , Knüchel Ruth , Dahl Edgar 
Published: January 2013

Abstract
Introduction
For early detection of breast cancer, the development of robust blood-based biomarkers that accurately reflect the host tumor is mandatory. We investigated DNA methylation in circulating free DNA (cfDNA) from blood of breast cancer patients and matched controls to establish a biomarker panel potentially useful for early detection of breast cancer.

Methods
We examined promoter methylation of seven putative tumor-suppressor genes (SFRP1, SFRP2, SFRP5, ITIH5, WIF1, DKK3, and RASSF1A) in cfDNA extracted from serum. Clinical performance was first determined in a test set (n = 261 sera). In an independent validation set (n = 343 sera), we validated the most promising genes for further use in early breast cancer detection. Sera from 59 benign breast disease and 58 colon cancer patients were included for additional specificity testing.

Results
Based on the test set, we determined ITIH5 and DKK3 promoter methylation as candidate biomarkers with the best sensitivity and specificity. In both the test and validation set combined, ITIH5 and DKK3 methylation achieved 41% sensitivity with a specificity of 93% and 100% in healthy and benign disease controls, respectively. Combination of these genes with RASSF1A methylation increased the sensitivity to 67% with a specificity of 69% and 82% in healthy controls and benign disease controls, respectively.

Conclusions
Tumor-specific methylation of the three-gene panel (ITIH5, DKK3, and RASSF1A) might be a valuable biomarker for the early detection of breast cancer.
MetAMOS: a modular and open source metagenomic assembly and analysis pipeline
Authors: Treangen Todd J , Koren Sergey , Sommer Daniel D , Liu Bo , Astrovskaya Irina , Ondov Brian , Darling Aaron E , Phillippy Adam M , Pop Mihai 
Published: January 2013

AbstractWe describe MetAMOS, an open source and modular metagenomic assembly and analysis pipeline. MetAMOS represents an important step towards fully automated metagenomic analysis, starting with next-generation sequencing reads and producing genomic scaffolds, open-reading frames and taxonomic or functional annotations. MetAMOS can aid in reducing assembly errors, commonly encountered when assembling metagenomic samples, and improves taxonomic assignment accuracy while also reducing computational cost. MetAMOS can be downloaded from: https://github.com/treangen/MetAMOS.
Improved Outcome in Pediatric Relapsed Acute Myeloid Leukemia: Results of a Randomized Trial on Liposomal Daunorubicin by the International BFM Study Group
Authors: Kaspers Gertjan J.L. , Zimmermann Martin , Reinhardt Dirk , Gibson Brenda E.S. , Tamminga Rienk Y.J. , Aleinikova Olga , Armendariz Hortensia , Dworzak Michael , Ha Shau-Yin , Hasle Henrik , Hovi Liisa , Maschan Alexei , Bertrand Yves , Leverger Guy G. , Razzouk Bassem I. , Rizzari Carmelo , Smisek Petr , Smith Owen , Stark Batia , Creutzig Ursula 
Published: January 2013

Purpose In pediatric relapsed acute myeloid leukemia (AML), optimal reinduction therapy is unknown. Studies suggest that liposomal daunorubicin (DNX; DaunoXome; Galen, Craigavon, United Kingdom) is effective and less cardiotoxic, which is important in this setting. These considerations led to a randomized phase III study by the International Berlin-Frankfurt-Münster Study Group. Patients and Methods Patients with relapsed or primary refractory non–French-American-British type M3 AML who were younger than 21 years of age were eligible. Patients were randomly assigned to fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG) or to FLAG plus DNX in the first reinduction course. The primary end point was status of the bone marrow (BM) sampled shortly before the second course of chemotherapy (the day 28 BM). Data are presented according to intention-to-treat for all 394 randomly assigned patients (median follow-up, 4.0 years). Results The complete remission (CR) rate was 64%, and the 4-year probability of survival (pOS) was 38% (SE, 3%). The day 28 BM status (available in 359 patients) was good (≤ 20% leukemic blasts) in 80% of patients randomly assigned to FLAG/DNX and 70% for patients randomly assigned to FLAG (P = .04). Concerning secondary end points, the CR rate was 69% with FLAG/DNX and 59% with FLAG (P = .07), but overall survival was similar. However, core-binding factor (CBF) AML treated with FLAG/DNX resulted in pOS of 82% versus 58% with FLAG (P = .04). Grade 3 to 4 toxicity was essentially similar in both groups. Conclusion DNX added to FLAG improves early treatment response in pediatric relapsed AML. Overall long-term survival was similar, but CBF-AML showed an improved survival with FLAG/DNX. International collaboration proved feasible and resulted in the best outcome for pediatric relapsed AML reported thus far.
Chromosome Instability Accounts for Reverse Metastatic Outcomes of Pediatric and Adult Synovial Sarcomas
Authors: Lagarde Pauline , Przybyl Joanna , Brulard Céline , Pérot Gaëlle , Pierron Gaelle , Delattre Olivier , Sciot Raf , Wozniak Agnieszka , Schöffski Patrick , Terrier Philippe , Neuville Agnès , Coindre Jean-Michel , Italiano Antoine , Orbach Daniel , Debiec-Rychter Maria , Chibon Frédéric 
Published: January 2013

Purpose Synovial sarcoma (SS) occurs in both children and adults, although metastatic events are much more common in adults. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC; Complexity Index in Sarcoma) and Genomic Index prognostic signatures related to chromosome integrity in sarcomas and GI stromal tumors. Here we investigate whether these signatures can also predict outcomes in SS. Patients and Methods One hundred patients who had primary untreated SS tumors were selected for expression and genomic profiling in a training/validation approach. Results CINSARC and Genomic Index have strong independent and validated prognostic values (P < .001). By comparing expression profiles of tumors with or without metastasis, 14 genes that are common to the CINSARC signature were identified, and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult versus pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis. Conclusion Metastasis development in SS is strongly associated with chromosome complexity, and CINSARC and Genomic Index are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. Genomic Index is potentially the best overall biomarker and clearly the most clinically relevant, considering that genome profiling from formalin-fixed samples is already used in pathology.