bluuebunny/crossref_metadata_2025_split huggingface dataset:
A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425
Authors: Schwartz Cindy L. , Constine Louis S. , Villaluna Doojduen , London Wendy B. , Hutchison Robert E. , Sposto Richard , Lipshultz Steven E. , Turner Charles S. , deAlarcon Pedro A. , Chauvenet Allen 
Published: July 2009

Abstract
Current treatment strategies for Hodgkin lymphoma result in excellent survival but often confer significant long-term toxicity. We designed ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide) to (1) enhance treatment efficacy by dose-dense drug delivery and (2) reduce risk of long-term sequelae by response-based reduction of cumulative chemotherapy. Efficient induction of early response by dose-dense drug delivery supported an early-response–adapted therapeutic paradigm. The 216 eligible patients were younger than 22 years with intermediate- or high-risk Hodgkin lymphoma. ABVE-PC was administered every 21 days. Rapid early responders (RERs) to 3 ABVE-PC cycles received 21 Gy radiation to involved regions; RER was documented in 63% of patients. Slow early responders received 2 additional ABVE-PC cycles before 21 Gy radiation. Five-year event-free-survival was 84%: 86% for the RER and 83% for the slow early responders (P = .85). Only 1% of patients had progressive disease. Five-year overall survival was 95%. With this regimen, cumulative doses of alkylators, anthracyclines, and epipodophyllotoxins are below thresholds usually associated with significant long-term toxicity. ABVE-PC is a dose-dense regimen that provides outstanding event-free survival/overall survival with short duration, early-response–adapted therapy. This trial was registered at www.clinicaltrials.gov as #NCT00005578.
miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53
Authors: Navarro Francisco , Gutman David , Meire Eti , Cáceres Mario , Rigoutsos Isidore , Bentwich Zvi , Lieberman Judy 
Published: July 2009

AbstractThe role of miRNAs in regulating megakaryocyte differentiation was examined using bipotent K562 human leukemia cells. miR-34a is strongly up-regulated during phorbol ester–induced megakaryocyte differentiation, but not during hemin-induced erythrocyte differentiation. Enforced expression of miR-34a in K562 cells inhibits cell proliferation, induces cell-cycle arrest in G1 phase, and promotes megakaryocyte differentiation as measured by CD41 induction. miR-34a expression is also up-regulated during thrombopoietin-induced differentiation of CD34+ hematopoietic precursors, and its enforced expression in these cells significantly increases the number of megakaryocyte colonies. miR-34a directly regulates expression of MYB, facilitating megakaryocyte differentiation, and of CDK4 and CDK6, to inhibit the G1/S transition. However, these miR-34a target genes are down-regulated rapidly after inducing megakaryocyte differentiation before miR-34a is induced. This suggests that miR-34a is not responsible for the initial down-regulation but may contribute to maintaining their suppression later on. Previous studies have implicated miR-34a as a tumor suppressor gene whose transcription is activated by p53. However, in p53-null K562 cells, phorbol esters induce miR-34a expression independently of p53 by activating an alternative phorbol ester-responsive promoter to produce a longer pri-miR-34a transcript.
Minimal residual disease levels assessed by NPM1 mutation–specific RQ-PCR provide important prognostic information in AML
Authors: Schnittger Susanne , Kern Wolfgang , Tschulik Claudia , Weiss Tamara , Dicker Frank , Falini Brunangelo , Haferlach Claudia , Haferlach Torsten 
Published: July 2009

Abstract
Nucleophosmin (NPM1)–mutated acute myeloid leukemia (AML), which is recognized as a provisional entity in the World Health Organization 2008 classification of myeloid neoplasms, accounts for 30% of AML. We analyzed 1227 diagnostic and follow-up samples in 252 NPM1-mutated AML patients with 17 different NPM1 mutation–specific real-time quantitative polymerase chain reaction (RQ-PCR) assays. Paired diagnostic/relapse samples of 84 patients revealed stable NPM1 mutations in all cases, suggesting that they are pathogenetically early events and thus applicable for minimal residual disease detection. A total of 47 relapses were predictable because of an NPM1 mutation level (%NPM1/ABL1) increase of at least 1 log or in 15 cases because of NPM1 mutation levels not decreasing less than 3 log ranges. A high prognostic value of NPM1 levels was shown for 4 different intervals after therapy was initiated. Furthermore, thresholds of 0.1 and 0.01%NPM1/ABL1 during/after treatment discriminated between prognostic subgroups. Univariate analyses, including age, white blood cell count, blast count, CD34 positivity, FLT3 mutations status, FAB type, karyotype, NPM1 mutation type, and pretreatment NPM1 mutational level, showed that, besides NPM1 mutation level, only age and FLT3-LM mutation status were prognostically significant for EFS. Multivariate analysis, including age, FLT3-LM status, and NPM1 mutation level at different time points, demonstrated that NPM1 level was the most relevant prognostic factor during first-line treatment. Similar results were obtained in patients undergoing second-line chemotherapy or allogeneic stem cell transplantation.
Tricyclic pyrone compounds prevent aggregation and reverse cellular phenotypes caused by expression of mutant huntingtin protein in striatal neurons
Authors: Trushina Eugenia , Rana Sandeep , McMurray Cynthia T , Hua Duy H 
Published: July 2009

Abstract

Background
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion mutation in the coding region of a novel gene. The mechanism of HD is unknown. Most data suggest that polyglutamine-mediated aggregation associated with expression of mutant huntingtin protein (mhtt) contributes to the pathology. However, recent studies have identified early cellular dysfunctions that preclude aggregate formation. Suppression of aggregation is accepted as one of the markers of successful therapeutic approaches. Previously, we demonstrated that tricyclic pyrone (TP) compounds efficiently inhibited formation of amyloid-β (Aβ) aggregates in cell and mouse models representing Alzheimer's Disease (AD). In the present study, we aimed to determine whether TP compounds could prevent aggregation and restore early cellular defects in primary embryonic striatal neurons from animal model representing HD.

Results
TP compounds effectively inhibit aggregation caused by mhtt in neurons and glial cells. Treatment with TP compounds also alleviated cholesterol accumulation and restored clathrin-independent endocytosis in HD neurons.

Conclusion
We have found that TP compounds not only blocked mhtt-induced aggregation, but also alleviated early cellular dysfunctions that preclude aggregate formation. Our data suggest TP molecules may be used as lead compounds for prevention or treatment of multiple neurodegenerative diseases including HD and AD.
Optimising corticosteroid injection for lateral epicondylalgia with the addition of physiotherapy: A protocol for a randomised control trial with placebo comparison
Authors: Coombes Brooke K , Bisset Leanne , Connelly Luke B , Brooks Peter , Vicenzino Bill 
Published: July 2009

AbstractBackgroundCorticosteroid injection and physiotherapy are two commonly prescribed interventions for management of lateral epicondylalgia. Corticosteroid injections are the most clinically efficacious in the short term but are associated with high recurrence rates and delayed recovery, while physiotherapy is similar to injections at 6 weeks but with significantly lower recurrence rates. Whilst practitioners frequently recommend combining physiotherapy and injection to overcome harmful effects and improve outcomes, study of the benefits of this combination of treatments is lacking. Clinicians are also faced with the paradox that the powerful anti-inflammatory corticosteroid injections work well, albeit in the short term, for a non-inflammatory condition like lateral epicondylalgia. Surprisingly, these injections have not been rigorously tested against placebo injections. This study primarily addresses both of these issues.MethodsA randomised placebo-controlled clinical trial with a 2 × 2 factorial design will evaluate the clinical efficacy, cost-effectiveness and recurrence rates of adding physiotherapy to an injection. In addition, the clinical efficacy and adverse effects of corticosteroid injection beyond that of a placebo saline injection will be studied. 132 participants with a diagnosis of lateral epicondylalgia will be randomly assigned by concealed allocation to one of four treatment groups – corticosteroid injection, saline injection, corticosteroid injection with physiotherapy or saline injection with physiotherapy. Physiotherapy will comprise 8 sessions of elbow manipulation and exercise over an 8 week period. Blinded follow-up assessments will be conducted at baseline, 4, 8, 12, 26 and 52 weeks after randomisation. The primary outcome will be a participant rating of global improvement, from which measures of success and recurrence will be derived. Analyses will be conducted on an intention-to-treat basis using linear mixed and logistic regression models. Healthcare costs will be collected from a societal perspective, and along with willingness-to-pay and quality of life data will facilitate cost-effectiveness and cost-benefit analyses.ConclusionThis trial will utilise high quality trial methodologies in accordance with CONSORT guidelines. Findings from this study will assist in the development of evidence based practice recommendations and potentially the optimisation of resource allocation for rehabilitating lateral epicondylalgia.Trial registrationAustralian New Zealand Clinical Trials Register ACTRN12609000051246
Comparison of different methods to obtain and store liver biopsies for molecular and histological research
Authors: Hoffmann Gaby , Ijzer Jooske , Brinkhof Bas , Schotanus Baukje A , van den Ingh Ted SGAM , Penning Louis C , Rothuizen Jan 
Published: July 2009

Abstract

Background
To minimize the necessary number of biopsies for molecular and histological research we evaluated different sampling techniques, fixation methods, and storage procedures for canine liver tissue. For addressing the aim, three biopsy techniques (wedge biopsy, Menghini, True-cut), four storage methods for retrieval of RNA (snap freezing, RNAlater, Boonfix, RLT-buffer), two RNA isolation procedures (Trizol and RNAeasy), and three different fixation protocols for histological studies (10% buffered formalin, RNAlater, Boonfix) were compared. Histological evaluation was based on hematoxylin-eosin (HE) and reticulin (fibrogenesis) staining, and rubeanic acid and rhodanine stains for copper. Immunohistochemical evaluation was performed for cytokeratin-7 (K-7), multidrug resistance binding protein-2 (MRP-2) and Hepar-1.

Results
RNA quality was best guaranteed by the combination of a Menghini biopsy with NaCl, followed by RNAlater preservation and RNAeasy mini kit extraction. These results were confirmed by quantitative RT-PCR testing. Reliable histological assessment for copper proved only possible in formalin fixed liver tissue. Short formalin fixation (1–4 hrs) improved immunohistochemical reactivity and preservation of good morphology in small liver biopsies.

Conclusion
At least two biopsies (RNAlater and formalin) are needed. Since human and canine liver diseases are highly comparable, it is conceivable that the protocols described here can be easily translated into the human biomedical field.
Erythropoietin improves operant conditioning and stability of cognitive performance in mice
Authors: El-Kordi Ahmed , Radyushkin Konstantin , Ehrenreich Hannelore 
Published: July 2009

Abstract

Background

Executive functions, learning and attention are imperative facets of cognitive performance, affected in many neuropsychiatric disorders. Recently, we have shown that recombinant human erythropoietin improves cognitive functions in patients with chronic schizophrenia, and that it leads in healthy mice to enhanced hippocampal long-term potentiation, an electrophysiological correlate of learning and memory. To create an experimental basis for further mechanistic insight into erythropoietin-modulated cognitive processes, we employed the Five Choice Serial Reaction Time Task. This procedure allows the study of the effects of erythropoietin on discrete processes of learning and attention in a sequential fashion.

Results

Male mice were treated for 3 weeks with erythropoietin (5,000 IU/kg) versus placebo intraperitoneally every other day, beginning at postnatal day 28. After termination of treatment, mice were started on the Five Choice Serial Reaction Time Task, with daily training and testing extending to about 3 months.
Overall, a significantly higher proportion of erythropoietin-treated mice finished the task, that is, reached the criteria of adequately reacting to a 1.0 sec flash light out of five arbitrarily appearing choices. During acquisition of this capability, that is, over almost all sequential training phases, learning readouts (magazine training, operant and discriminant learning, stability of performance) were superior in erythropoietin-treated versus control mice.

Conclusion

Early erythropoietin treatment leads to lasting improvement of cognitive performance in healthy mice. This finding should be exploited in novel treatment strategies for brain diseases.
Improvement of a real-time RT-PCR assay for the detection of enterovirus RNA
Authors: Piqueur Marian AC , Verstrepen Walter A , Bruynseels Peggy , Mertens An H 
Published: July 2009

Abstract
We describe an improvement of an earlier reported real-time RT-PCR assay for the detection of enterovirus RNA, based on the 5' exonuclease digestion of a dual-labeled fluorogenic probe by Taq DNA polymerase. A different extraction method, real-time RT-PCR instrument and primer set were evaluated. Our data show that the optimized assay yields a higher sensitivity and reproducibility and resulted in a significant reduced hands-on time per sample.
Morphogen-defined patterning of Escherichia coli enabled by an externally tunable band-pass filter
Authors: Sohka Takayuki , Heins Richard A , Ostermeier Marc 
Published: July 2009

Abstract

Background
Gradients of morphogens pattern cell fate – a phenomenon that is especially important during development. A simple model system for studying how morphogens pattern cell behavior would overcome difficulties inherent in the study of natural morphogens in vivo. A synthetic biology approach to building such a system is attractive.

Results
Using an externally-tunable band-pass filter paradigm, we engineered Escherichia coli cells to function as a model system for the study of how multiple morphogens can pattern cell behavior. We demonstrate how our system exhibits behavior such as morphogen crosstalk and how the cells' growth and fluorescence can be patterned in a number of complex patterns. We extend our cell patterning from 2D cultures on the surface of plates to 3D cultures in soft agarose medium.

Conclusion
Our system offers a convenient, well-defined model system for fundamental studies on how multiple morphogen gradients can affect cell fate and lead to pattern formation. Our design principles could be applied to eukaryotic cells to develop other models systems for studying development or for enabling the patterning of cells for applications such as tissue engineering and biomaterials.
Negative association of the chemokine receptor CCR5 d32 polymorphism with systemic inflammatory response, extra-articular symptoms and joint erosion in rheumatoid arthritis
Authors: Rossol Manuela , Pierer Matthias , Arnold Sybille , Keyßer Gernot , Burkhardt Harald , Baerwald Christoph , Wagner Ulf 
Published: July 2009

Abstract
Introduction
Chemokines and their receptors control immune cell migration during infections as well as in autoimmune responses. A 32 bp deletion in the gene of the chemokine receptor CCR5 confers protection against HIV infection, but has also been reported to decrease susceptibility to rheumatoid arthritis (RA). The influence of this deletion variant on the clinical course of this autoimmune disease was investigated.

Methods
Genotyping for CCR5d32 was performed by PCR and subsequent electrophoretic fragment length determination. For the clinical analysis, the following extra-articular manifestations of RA were documented by the rheumatologist following the patient: presence of rheumatoid nodules, major organ vasculitis, pulmonary fibrosis, serositis or a Raynaud's syndrome. All documented CRP levels were analyzed retrospectively, and the last available hand and feet radiographs were analyzed with regards to the presence or absence of erosive disease.

Results
Analysis of the CCR5 polymorphism in 503 RA patients and in 459 age-matched healthy controls revealed a significantly decreased disease susceptibility for carriers of the CCR5d32 deletion (Odds ratio 0.67, P = 0.0437). Within the RA patient cohort, CCR5d32 was significantly less frequent in patients with extra-articular manifestations compared with those with limited, articular disease (13.2% versus 22.8%, P = 0.0374). In addition, the deletion was associated with significantly lower average CRP levels over time (median 8.85 vs. median 14.1, P = 0.0041) and had a protective effect against the development of erosive disease (OR = 0.40, P = 0.0047). Intriguingly, homozygosity for the RA associated DNASE2 -1066 G allele had an additive effect on the disease susceptibility conferred by the wt allele of CCR5 (OR = 2.24, P = 0.0051 for carrier of both RA associated alleles)

Conclusions
The presence of CCR5d32 significantly influenced disease susceptibility to and clinical course of RA in a German study population. The protective effect of this deletion, which has been described to lead to a decreased receptor expression in heterozygous patients, underlines the importance of chemokines in the pathogenesis of RA.
Non-invasive stroke volume measurement and passive leg raising predict volume responsiveness in medical ICU patients: an observational cohort study
Authors: Thiel Steven W , Kollef Marin H , Isakow Warren 
Published: July 2009

Abstract
Introduction
The assessment of volume responsiveness and the decision to administer a fluid bolus is a common dilemma facing physicians caring for critically ill patients. Static markers of cardiac preload are poor predictors of volume responsiveness, and dynamic markers are often limited by the presence of spontaneous respirations or cardiac arrhythmias. Passive leg raising (PLR) represents an endogenous volume challenge that can be used to predict fluid responsiveness.

Methods
Medical intensive care unit (ICU) patients requiring volume expansion were eligible for enrollment. Non-invasive measurements of stroke volume (SV) were obtained before and during PLR using a transthoracic Doppler ultrasound device prior to volume expansion. Measurements were then repeated following volume challenge to classify patients as either volume responders or non-responders based on their hemodynamic response to volume expansion. The change in SV from baseline during PLR was then compared with the change in SV with volume expansion to determine the ability of PLR in conjunction with SV measurement to predict volume responsiveness.

Results
A total of 102 fluid challenges in 89 patients were evaluated. In 47 of the 102 fluid challenges (46.1%), SV increased by ≥15% after volume infusion (responders). A SV increase induced by PLR of ≥15% predicted volume responsiveness with a sensitivity of 81%, specificity of 93%, positive predictive value of 91% and negative predictive value of 85%.

Conclusions
Non-invasive SV measurement and PLR can predict fluid responsiveness in a broad population of medical ICU patients. Less than 50% of ICU patients given fluid boluses were volume responsive.
Electrochemiluminescence Devices Consisting of ZnO Nanorods Vertically Grown on Substrate
Authors: Tanaka Tomohito , Takishita Hiroshi , Sagawa Takashi , Yoshikawa Susumu , Hayase Shuzi 
Published: July 2009

Abstract
Unique behaviors of electrochemiluminescence from a device consisting of ZnO nanorod (Cell-1) are reported. Cell-1 emitted more intense electrochemiluminescence than cell consisting of two flat electrodes (Cell-2). The onset potential at which the emission starts was 1.5 V for Cell-1, which was lower than 2.5 V for Cell-2. The unique behaviors were explained by asymmetric collision modes of emitting species (RuI and RuIII) in the nanospace among ZnO nanorods and were characteristic to the ZnO nanorod array.
Synthesis of Hollow Nanospheres Consisting of Amphiphilic Block Copolymers
Authors: Matsune Hideki , Sakurai Daisuke , Takenaka Sakae , Kishida Masahiro 
Published: July 2009

Abstract
Hollow polymeric nanospheres with shells consisting of inner hydrophilic and outer hydrophobic polymer chains are prepared by a surface-initiated living radical polymerization of 2-trimethylsilyloxyethyl acrylate and methyl methacrylate from initiator-modified silica nanoparticles; these nanospheres are subsequently prepared by intraparticle cross-linking and by dissolution of silica matrices with HF. The translation behavior of hydrophilic substrates from an aqueous phase to an oil phase through the nanocapsules is investigated.
Stability of Boronic Esters to Hydrolysis: A Comparative Study
Authors: Bernardini Raffaella , Oliva Ambrogio , Paganelli Alessandro , Menta Ernesto , Grugni Mario , Munari Sergio De , Goldoni Luca 
Published: July 2009

Abstract
Boronic esters are key intermediates in the synthesis of biologically active compounds such as thrombin and proteasome inhibitors. However, they have low hydrolytic stability both during synthetic reactions and in biological media. We report the preparation of several boronic esters and a comparative study of their stability to hydrolysis vs. the corresponding pinanediol boronic esters, which are among the most hydrolytically stable. We discovered that the boronic esters derived from (1,1′-bicyclohexyl)-1,1′-diol are the most stable among those examined.
Epoxidized Natural Rubber Bionanocomposite: A Model Case of Bionanocomposite Using Nanofibrous Chitosan and Its Consequent Functional Properties
Authors: Lertwattanaseri Tipparat , Ichikawa Naoya , Mizoguchi Tetuo , Tanaka Yasuyuki , Chirachanchai Suwabun 
Published: July 2009

Abstract
A bionanocomposite of epoxidized natural rubber (ENR) with nanofibrous chitosan is proposed. The bionanocomposite is formed under the reaction between epoxy groups of ENR and amino and hydroxy groups of chitosan as confirmed by qualitative and quantitative FTIR techniques. The nanofibrous chitosan induces stiffness at nanoscale as observed by AFM and tensile strength at microscale to the ENR–chitosan nanocomposite system. The nanocomposite also shows the copper ion absorptivity as investigated by SEM metal ion mapping mode.
Surface Accumulable Coreactant for Bright Electrogenerated Chemiluminescence at Trace Level Concentrations
Authors: Kurita Ryoji , Nakamoto Kohei , Kato Dai , Niwa Osamu 
Published: July 2009

Abstract
We applied trimethylammonioethanethiol as an electrogenerated chemiluminescence coreactant for obtaining bright emission in a low concentration region. This is because trimethylammoniomethanethiol has the bifunctional properties of luminescence acceleration and surface accumulation on a gold electrode surface.