bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for the Osteoporosis Choice trial. A pilot randomized trial of a decision aid in primary care practice
Authors: Pencille Laurie J , Campbell Megan E , Van Houten Holly K , Shah Nilay D , Mullan Rebecca J , Swiglo Brian A , Breslin Maggie , Kesman Rebecca L , Tulledge-Scheitel Sidna M , Jaeger Thomas M , Johnson Ruth E , Bartel Gregory A , Wermers Robert A , Melton L Joseph , Montori Victor M 
Published: December 2009

Abstract

Background
Bisphosphonates can reduce fracture risk in patients with osteoporosis, but many at-risk patients do not start or adhere to these medications. The aims of this study are to: (1) preliminarily evaluate the effect of an individualized 10-year osteoporotic fracture risk calculator and decision aid (O

STEOPOROSIS CHOICE
) for postmenopausal women at risk for osteoporotic fractures; and (2) assess the feasibility and validity (i.e., absence of contamination) of patient-level randomization (vs. cluster randomization) in pilot trials of decision aid efficacy.

Methods/Design
This is a protocol for a parallel, 2-arm, randomized trial to compare an intervention group receiving O

STEOPOROSIS CHOICE
to a control group receiving usual primary care. Postmenopausal women with bone mineral density T-scores of <-1.0, not receiving bisphosphonate therapy, and receiving care at participating primary care practices in and around Rochester, Minnesota, USA will be eligible to participate in the trial. We will measure the effect of OSTEOPOROSIS CHOICE on five outcomes: (a) patient knowledge regarding osteoporosis risk factors and treatment; (b) quality of the decision-making process for both the patient and clinician; (c) patient and clinician acceptability and satisfaction with the decision aid; (d) rate of bisphosphonate use and adherence, and (e) trial processes (e.g., ability to recruit participants, collect patient outcomes). To capture these outcomes, we will use patient and clinician surveys following each visit and video recordings of the clinical encounters. These video recordings will also allow us to determine the extent to which clinicians previously exposed to the decision aid were able to recreate elements of the decision aid with control patients (i.e., contamination). Pharmacy prescription profiles and follow-up phone interviews will assess medication start and adherence at 6 months.

Discussion
This pilot trial will provide evidence of feasibility, validity of patient randomization, and preliminary efficacy of a novel approach -- decision aids -- to improving medication adherence for postmenopausal women at risk of osteoporotic fractures. The results will inform the design of a larger trial that could provide more precise estimates of the efficacy of the decision aid.

Trial registration
Clinical Trials.gov Identifier: NCT00578981
In silico approaches to study mass and energy flows in microbial consortia: a syntrophic case study
Authors: Taffs Reed , Aston John E , Brileya Kristen , Jay Zackary , Klatt Christian G , McGlynn Shawn , Mallette Natasha , Montross Scott , Gerlach Robin , Inskeep William P , Ward David M , Carlson Ross P 
Published: December 2009

Abstract

Background
Three methods were developed for the application of stoichiometry-based network analysis approaches including elementary mode analysis to the study of mass and energy flows in microbial communities. Each has distinct advantages and disadvantages suitable for analyzing systems with different degrees of complexity and a priori knowledge. These approaches were tested and compared using data from the thermophilic, phototrophic mat communities from Octopus and Mushroom Springs in Yellowstone National Park (USA). The models were based on three distinct microbial guilds: oxygenic phototrophs, filamentous anoxygenic phototrophs, and sulfate-reducing bacteria. Two phases, day and night, were modeled to account for differences in the sources of mass and energy and the routes available for their exchange.

Results
The in silico models were used to explore fundamental questions in ecology including the prediction of and explanation for measured relative abundances of primary producers in the mat, theoretical tradeoffs between overall productivity and the generation of toxic by-products, and the relative robustness of various guild interactions.

Conclusion
The three modeling approaches represent a flexible toolbox for creating cellular metabolic networks to study microbial communities on scales ranging from cells to ecosystems. A comparison of the three methods highlights considerations for selecting the one most appropriate for a given microbial system. For instance, communities represented only by metagenomic data can be modeled using the pooled method which analyzes a community's total metabolic potential without attempting to partition enzymes to different organisms. Systems with extensive a priori information on microbial guilds can be represented using the compartmentalized technique, employing distinct control volumes to separate guild-appropriate enzymes and metabolites. If the complexity of a compartmentalized network creates an unacceptable computational burden, the nested analysis approach permits greater scalability at the cost of more user intervention through multiple rounds of pathway analysis.
Inhibition of trypsin expression in Lutzomyia longipalpis using RNAi enhances the survival of Leishmania
Authors: Sant'Anna Mauricio RV , Diaz-Albiter Hector , Mubaraki Murad , Dillon Rod J , Bates Paul A 
Published: December 2009

Abstract

Background

Leishmania parasites must overcome several barriers to achieve transmission by their sand fly vectors. One of the earliest threats is exposure to enzymes during blood meal digestion. Trypsin-like enzymes appear to be detrimental to parasite survival during the very early phase of development as amastigotes transform into promastigote stages. Here, we investigate whether parasites can affect trypsin secretion by the sand fly midgut epithelium and if inhibition of this process is of survival value to the parasites.

Results
Infections of Lutzomyia longipalpis with Leishmania mexicana were studied and these showed that infected sand flies produced less trypsin-like enzyme activity during blood meal digestion when compared to uninfected controls. RNA interference was used to inhibit trypsin 1 gene expression by micro-injection into the thorax, as trypsin 1 is the major blood meal induced trypsin activity in the sand fly midgut. Injection of specific double stranded RNA reduced trypsin 1 expression as assessed by RT-PCR and enzyme assays, and also led to increased numbers of parasites in comparison with mock-injected controls. Injection by itself was observed to have an inhibitory effect on the level of infection, possibly through stimulation of a wound repair or immune response by the sand fly.

Conclusion

Leishmania mexicana was shown to be able to modulate trypsin secretion by Lutzomyia longipalpis to its own advantage, and direct inhibition of trypsin gene expression led to increased parasite numbers in the midguts of infected flies. Successful application of RNA interference methodology to Leishmania-infected sand flies now opens up the use of this technique to study a wide range of sand fly genes and their role in the parasite-vector interaction.
Carotid body tumors: radioguided surgical approach
Authors: Martinelli Ombretta , Irace Luigi , Massa Rita , Savelli Sara , Giannoni Fabrizia , Gattuso Roberto , Gossetti Bruno , Benedetti-Valentini Fabrizio , Izzo Luciano 
Published: December 2009

Abstract

Background
Carotid body tumours (CBTs) are very rare lesions which should be treated as soon as possible even when benign since small tumour size permits easier removal and lower incidence of perioperative complications and recurrence. Malignant forms are rare and they can be identified by lymph node invasion and metastases in distant locations. The need of reliable and effective diagnostic modalities for both primary CBTs and its metastases or recurrence is evident.
The present study reviews our experience and attempt to define the role of colour coded ultrasound (CCU) and Somatostatin receptor scintigraphy (SRS) with Indium-111-DTPA-pentetretide (Octreoscan®) using both planar and single photon emission tomography (SPECT) technique in the diagnosis and follow-up of these uncommon lesions within a multidisciplinary approach.

Methods
From 1997 to 2008, 12 patients suffering from 16 CBTs (4 bilateral) were investigated by CCU and SRS-SPECT before and after surgery. All tumours were grouped according to Shamblin's classification in order to assess the technical difficulties and morbidity of surgical resection on the ground of their size and relationship with the carotid arteries. Intraoperative radiocaptation by Octreoscan®) was also carried out in all cases to evaluate the radicality of surgery. All perioperative scans were evaluated by the same nuclear medicine physician.

Results
Preoperatively CCU showed CBTs (four were not palpable) with a sensitivity of 100%. Radioisotope imaging identified the CBTs as chemodectomas in 15 cases while no radioisotopic uptake was detected in 1 vagus nerve neurinoma. No evidence of metastasis or multicentricity were seen by total body radioisotopic scans. Combined data from CCU and SRS-SPECT allowed to determine tumour size in order to select 7 larger tumours which were submitted to selective preoperative embolization.
Intraoperatively Octreoscan demonstrated microscopic tumour leftovers promptly removed in 1 case and an unresectable remnant at the base of the skull in another case.
During follow-up CCI and radioisotope scans showed no recurrence in 14 cases and a slightly enlargement of the intracranial residual as detected during surgery in 1 patient.

Conclusion
CCU may allow an early and noninvasive detection of CBTs and hence safer operations. The combined use of CCU and SRS-SPECT provide useful data to identify those tumours and to evaluate their extent and carotid arteries infiltration. Radioisotope imaging is a sensitive modality to detect metastases and lymph node involvement that are markers of CBT malignancy. After surgery CCU and SRS-SPECT can be accurate modalities for surveillance for an early detection of CBTs recurrence.
Comparison of linear discriminant analysis methods for the classification of cancer based on gene expression data
Authors: Huang Desheng , Quan Yu , He Miao , Zhou Baosen 
Published: December 2009

AbstractBackgroundMore studies based on gene expression data have been reported in great detail, however, one major challenge for the methodologists is the choice of classification methods. The main purpose of this research was to compare the performance of linear discriminant analysis (LDA) and its modification methods for the classification of cancer based on gene expression data.MethodsThe classification performance of linear discriminant analysis (LDA) and its modification methods was evaluated by applying these methods to six public cancer gene expression datasets. These methods included linear discriminant analysis (LDA), prediction analysis for microarrays (PAM), shrinkage centroid regularized discriminant analysis (SCRDA), shrinkage linear discriminant analysis (SLDA) and shrinkage diagonal discriminant analysis (SDDA). The procedures were performed by software R 2.80.ResultsPAM picked out fewer feature genes than other methods from most datasets except from Brain dataset. For the two methods of shrinkage discriminant analysis, SLDA selected more genes than SDDA from most datasets except from 2-class lung cancer dataset. When comparing SLDA with SCRDA, SLDA selected more genes than SCRDA from 2-class lung cancer, SRBCT and Brain dataset, the result was opposite for the rest datasets. The average test error of LDA modification methods was lower than LDA method.ConclusionsThe classification performance of LDA modification methods was superior to that of traditional LDA with respect to the average error and there was no significant difference between theses modification methods.
Comparative, double-blind, controlled study of intra-articular hyaluronic acid (Hyalubrix®) injections versus local anesthetic in osteoarthritis of the hip
Authors: Migliore Alberto , Massafra Umberto , Bizzi Emanuele , Vacca Francesca , Martin-Martin Severino , Granata Mauro , Alimonti Andrea , Tormenta Sandro 
Published: December 2009

Abstract
Introduction
Comparison of intra-articular bacterial-derived hyaluronic acid (Hyalubrix®) (HA) with local analgesia (mepivacaine) for osteoarthritis (OA) of the hip.

Methods
A pilot prospective, double-blind, 6-month randomized trial of 42 patients with hip OA. HA or mepivacaine was administered twice (once a month) under ultrasound guidance. Efficacy measurements included the Lequesne's algofunctional index, a visual analog scale for pain, concomitant use of analgesia, patient and physician global measurement, and safety.

Results
Patients in the HA group exhibited a significantly reduced Lequesne's algofunctional index 3 and 6 months after treatment (P < 0.001) and significantly reduced visual analog scale pain scores 3 and 6 months after treatment (P < 0.05) compared with the local anesthetic group. All primary and secondary measures were significantly improved versus baseline, but other than the above were not different from each other at 3 or 6 months. Adverse effects were minimal.

Conclusions
This comparative study suggests a beneficial effect and safety of intra-articular HA in the management of hip OA.

Trial registration number
ISRCTN39397064.
A combination of methotrexate and zoledronic acid prevents bone erosions and systemic bone mass loss in collagen induced arthritis
Authors: Le Goff Benoit , Soltner Elise , Charrier Céline , Maugars Yves , Rédini Françoise , Heymann Dominique , Berthelot Jean-Marie 
Published: December 2009

Abstract
Introduction
Osteoclasts play a key role in the pathogenesis of bone erosion and systemic bone mass loss during rheumatoid arthritis (RA). In this study, we aimed to determine the effect of methotrexate (MTX) and zoledronic acid (ZA), used alone or in combination, on osteoclast-mediated bone erosions and systemic bone mass loss in a rat model of collagen induced arthritis (CIA). We hypothesized that MTX and ZA could have an additive effect to prevent both bone erosion and systemic bone loss.

Methods
Arthritis was induced in 64 female Sprague-Dawley rats. After the clinical onset of CIA, rats were assigned to treatment with MTX (1 mg/kg/week), ZA (100 μg/kg twice weekly), both treatments at the same regimens, or vehicle. Arthritis score and paw thickness were recorded twice weekly. The rats were sacrificed on D28 and hind paws were removed for radiographic, histological and immunohistochemical analysis. The effects of treatments on osteoclastogenesis were determined by Tartrate resistant acid phosphatase (TRAP) staining. Micro-CT of the tibia was carried out for histomorphometric analysis. Bone mass density was evaluated by densitometry.

Results
MTX significantly decreased the severity of CIA, whereas ZA slightly exacerbated it. When these two drugs were used in combination, MTX prevented the pro-inflammatory effect of ZA. The combination of ZA with MTX was more effective than MTX alone for reducing structural joint damage with a dramatic decrease of osteoclasts' number in the eroded joints. However, MTX alone also significantly reduced the number of osteoclasts and the number of CD68+ mononuclear cells. ZA alone, or ZA with MTX, significantly increased the systemic bone mass density measured by densitometry and bone volume on histomorphometric analysis.

Conclusions
A combination of MTX and ZA prevented both bone erosion and systemic bone loss in a rat model of arthritis. Both treatments independently decreased the number of osteoclasts in the eroded joint. However, while MTX probably acts mainly through a decrease of inflammation, ZA has a direct effect on osteoclasts, allowing a dramatic down-regulation of these cells in inflamed joints. These two different mechanisms of action provide support for the use of a combination of these two drugs to improve the prevention of structural joint damage in RA.
Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast
Authors: Maia Ana-Teresa , Spiteri Inmaculada , Lee Alvin JX , O'Reilly Martin , Jones Linda , Caldas Carlos , Ponder Bruce AJ 
Published: December 2009

Abstract
Introduction
Normal gene expression variation is thought to play a central role in inter-individual variation and susceptibility to disease. Regulatory polymorphisms in cis-acting elements result in the unequal expression of alleles. Differential allelic expression (DAE) in heterozygote individuals could be used to develop a new approach to discover regulatory breast cancer susceptibility loci. As access to large numbers of fresh breast tissue to perform such studies is difficult, a suitable surrogate test tissue must be identified for future studies.

Methods
We measured differential allelic expression of 12 candidate genes possibly related to breast cancer susceptibility (BRCA1, BRCA2, C1qA, CCND3, EMSY, GPX1, GPX4, MLH3, MTHFR, NBS1, TP53 and TRXR2) in breast tissue (n = 40) and fresh blood (n = 170) of healthy individuals and EBV-transformed lymphoblastoid cells (n = 19). Differential allelic expression ratios were determined by Taqman assay. Ratio distributions were compared using t-test and Wilcoxon rank sum test, for mean ratios and variances respectively.

Results
We show that differential allelic expression is common among these 12 candidate genes and is comparable between breast and blood (fresh and transformed lymphoblasts) in a significant proportion of them. We found that eight out of nine genes with DAE in breast and fresh blood were comparable, as were 10 out of 11 genes between breast and transformed lymphoblasts.

Conclusions
Our findings support the use of differential allelic expression in blood as a surrogate for breast tissue in future studies on predisposition to breast cancer.
Towards accurate imputation of quantitative genetic interactions
Authors: Ulitsky Igor , Krogan Nevan J , Shamir Ron 
Published: December 2009

AbstractRecent technological breakthroughs have enabled high-throughput quantitative measurements of hundreds of thousands of genetic interactions among hundreds of genes in Saccharomyces cerevisiae. However, these assays often fail to measure the genetic interactions among up to 40% of the studied gene pairs. Here we present a novel method, which combines genetic interaction data together with diverse genomic data, to quantitatively impute these missing interactions. We also present data on almost 190,000 novel interactions.
Reduced T cell expansion by a superantigen as a result of impaired B cell development in mice deficient for the p85α regulatory subunit of PI3K
Authors: Arimura Yutaka , Ezaki Taichi , Koyanagi Madoka , Uchiyama Takehiko , Koyasu Shigeo , Yagi Junji 
Published: December 2009

Abstract
PI3K p85α subunit alters the superantigen presentation capacity of B cells and indirectly modulates the magnitude of the T cell response.
PI3K plays crucial roles in the immune system. Mice deficient for p85α, a major regulatory subunit of class IA PI3K, show various defects and alterations in B cells, mast cells, macrophages, and DCs, and peripheral T cells are reportedly normal, at least in vitro. In normal mice, long-term exposure to a SAg, SEA, in vivo induced a high level of the protracted expansion of SEA-reactive Vβ3+CD4+ T cells, whereas the same treatment induced T cell expansion in p85α-deficient mice but to a much lesser extent than in normal mice. However, mixed bone marrow chimera mice, which have normal and p85α-deficient T and B cells, demonstrated equal responses of both T cells following stimulation with a SEA pump. In reciprocal cotransfer experiments of T and B cells from normal and p85α-deficient mice into Rag2-deficient mice, followed by SEA stimulation, p85α-deficient T cells revealed much higher proliferative capacity in the presence of normal B cells than did normal T cells with p85α-deficient B cells. Histologically, a marked B cell reduction was observed in the follicles and MZ of the spleen, and DCs accumulated in the MZ. In addition, p85α-deficient B cells had a low level of MHC class II expression. Collectively, these data suggested that the PI3K p85α subunit alters the SAg presentation capacity of B cells and indirectly modulates the magnitude of the T cell response, which may affect the protection against SEA-containing bacteria.
A GMCSF-neuroantigen fusion protein is a potent tolerogen in experimental autoimmune encephalomyelitis (EAE) that is associated with efficient targeting of neuroantigen to APC
Authors: Blanchfield J Lori , Mannie Mark D 
Published: December 2009

Abstract
This study shows that a DC-targeting, antigen-specific therapeutic is capable of inhibiting an ongoing inflammatory autoimmune disease.
Cytokine-NAg fusion proteins represent an emerging platform for specific targeting of self-antigen to particular APC subsets as a means to achieve antigen-specific immunological tolerance. This study focused on cytokine-NAg fusion proteins that targeted NAg to myeloid APC. Fusion proteins contained GM-CSF or the soluble extracellular domain of M-CSF as the N-terminal domain and the encephalitogenic 69–87 peptide of MBP as the C-terminal domain. GMCSF-NAg and MCSF-NAg fusion proteins were ∼1000-fold and 32-fold more potent than NAg in stimulating antigenic proliferation of MBP-specific T cells, respectively. The potentiated antigenic responses required cytokine-NAg covalent linkage and receptor-mediated uptake. That is, the respective cytokines did not potentiate antigenic responses when cytokine and NAg were added as separate molecules, and the potentiated responses were inhibited specifically by the respective free cytokine. Cytokine-dependent targeting of NAg was specific for particular subsets of APC. GMCSF-NAg and MCSF-NAg targeted NAg to DC and macrophages; conversely, IL4-NAg and IL2-NAg fusion proteins, respectively, induced an ∼1000-fold enhancement in NAg reactivity in the presence of B cell and T cell APC. GMCSF-NAg significantly attenuated severity of EAE when treatment was completed before encephalitogenic challenge or alternatively, when treatment was initiated after onset of EAE. MCSF-NAg also had significant tolerogenic activity, but GMCSF-NAg was substantially more efficacious as a tolerogen. Covalent GMCSF-NAg linkage was required for prevention and treatment of EAE. In conclusion, GMCSF-NAg was highly effective for targeting NAg to myeloid APC and was a potent, antigen-specific tolerogen in EAE.