bluuebunny/crossref_metadata_2025_split huggingface dataset:
A three-year longitudinal evaluation of the forearm bone density of users of etonogestrel- and levonorgestrel-releasing contraceptive implants
Authors: Monteiro-Dantas Cecilia , Espejo-Arce Ximena , Lui-Filho Jeffrey F , Fernandes Arlete M , Monteiro Ilza , Bahamondes Luis 
Published: November 2007

Abstract

Background
The aim of this study was to evaluate bone mineral density (BMD) at baseline and at 18 and 36 months of use of etonogestrel (ENG)-and levonorgestrel (LNG)-releasing contraceptive implants. This is a continuation of a previous study in which BMD was evaluated at baseline and at 18 months of use.

Methods
A total of 111 women, 19–43 years of age, wererandomly allocated to use one of the two implants. At 36 months of follow-up, only 36 and 39 women were still using the ENG- and LNG-releasing implants, respectively. BMD was evaluated at the distal and at the ultra-distal radius of the non-dominant forearm using dual-energy X-ray absorptiometry.

Results
There was no difference in the BMD of users of either implant at 18 and at 36 months. BMD was significantly lower at 18 and at 36 months at the distal radius in both groups of users compared to pre-insertion values; however, no difference was found at the ultra-distal radius.

Conclusion
Women 19–43 years of age using either one of these two contraceptive implants for 36 months had lower BMD values at the distal radius compared to pre-insertion values; however, no difference was found at the ultra-distal radius.
Recurrent laryngeal nerve palsy due to impacted dental plate in the thoracic oesophagus: case report
Authors: Sutcliffe Robert P , Rohatgi Ashish , Forshaw Matthew J , Mason Robert C 
Published: November 2007

Abstract

Background
Retained oesophageal foreign bodies must be urgently removed to prevent potentially serious complications. Recurrent laryngeal nerve palsy is rare and has not been reported in association with a foreign body in the thoracic oesophagus.

Case presentation
We present a case of a dental plate in the thoracic oesophagus that caused high dysphagia. Delayed diagnosis led to a recurrent laryngeal nerve palsy, which persisted despite successful surgical removal of the foreign body.

Conclusion
Oesophagoscopy is essential to fully assess patients with persistent symptoms after foreign body ingestion, irrespective of the level of dysphagia. Recurrent laryngeal nerve palsy may indicate impending perforation and should prompt urgent evaluation and treatment.
Tissue interactions in the developing chick diencephalon
Authors: Guinazu Maria Flavia , Chambers David , Lumsden Andrew , Kiecker Clemens 
Published: November 2007

Abstract
Background
The developing vertebrate brain is patterned first by global signalling gradients that define crude anteroposterior and dorsoventral coordinates, and subsequently by local signalling centres (organisers) that refine cell fate assignment within pre-patterned regions. The interface between the prethalamus and the thalamus, the zona limitans intrathalamica (ZLI), is one such local signalling centre that is essential for the establishment of these major diencephalic subdivisions by secreting the signalling factor Sonic hedgehog. Various models for ZLI formation have been proposed, but a thorough understanding of how this important local organiser is established is lacking.

Results
Here, we describe tissue explant experiments in chick embryos aimed at characterising the roles of different forebrain areas in ZLI formation. We found that: the ZLI becomes specified unexpectedly early; flanking regions are required for its characteristic morphogenesis; ZLI induction can occur independently from ventral tissues; interaction between any prechordal and epichordal neuroepithelial tissue anterior to the midbrain-hindbrain boundary is able to generate a ZLI; and signals from the dorsal diencephalon antagonise ZLI formation. We further show that a localised source of retinoic acid in the dorsal diencephalon is a likely candidate to mediate this inhibitory signal.

Conclusion
Our results are consistent with a model where planar, rather than vertical, signals position the ZLI at early stages of neural development and they implicate retinoic acid as a novel molecular cue that determines its dorsoventral extent.
Receptor downregulation and desensitization enhance the information processing ability of signalling receptors
Authors: Shankaran Harish , Wiley H Steven , Resat Haluk 
Published: November 2007

AbstractBackgroundIn addition to initiating signaling events, the activation of cell surface receptors also triggers regulatory processes that restrict the duration of signaling. Acute attenuation of signaling can be accomplished either via ligand-induced internalization of receptors (endocytic downregulation) or via ligand-inducedreceptor desensitization. These phenomena have traditionally been viewed in the context ofadaptationwherein the receptor system enters a refractory state in the presence of sustained ligand stimuli and thereby prevents the cell from over-responding to the ligand. Here we use the epidermal growth factor receptor (EGFR) and G-protein coupled receptors (GPCR) as model systems to respectively examine the effects of downregulation and desensitization on the ability of signaling receptors to decode time-varying ligand stimuli.ResultsUsing a mathematical model, we show that downregulation and desensitization mechanisms can lead to tight and efficient input-output coupling thereby ensuring synchronous processing of ligand inputs. Frequency response analysis indicates that upstream elements of the EGFR and GPCR networks behave like low-pass filters with the system being able to faithfully transduce inputs below a critical frequency. Receptor downregulation and desensitization increase the filter bandwidth thereby enabling the receptor systems to decode inputs in a wider frequency range. Further, system-theoretic analysis reveals that the receptor systems are analogous to classical mechanical over-damped systems. This analogy enables us to metaphorically describe downregulation and desensitization as phenomena that make the systems more resilient in responding to ligand perturbations thereby improving the stability of the system resting state.ConclusionOur findings suggest that in addition to serving as mechanisms for adaptation, receptor downregulation and desensitization can play a critical role in temporal information processing. Furthermore, engineering metaphors such as the ones described here could prove to be invaluable in understanding the design principles of biological systems.
A fatal case of recurrent amiodarone-induced thyrotoxicosis after percutaneous tracheotomy: a case report
Authors: Papaioannou Vasilios , Terzi Irene , Dragoumanis Christos , Konstantonis Dimitrios , Theodorou Vassiliki , Pneumatikos Ioannis 
Published: November 2007

AbstractBackgroundAmiodarone is a widely used antiarrythmic drug, which may produce secondary effects on the thyroid. In 14–18% of amiodarone-treated patients, there is overt thyroid dysfunction, usually in the form of amiodarone-induced thyrotoxicosis, which can be difficult to manage with standard medical treatment.Case presentationPresented is the case of a 65-year-old man, under chronic treatment of atrial fibrillation with amiodarone, who was admitted to the Intensive Care Unit with acute cardio-respiratory failure and fever. He was recently hospitalized with respiratory distress, attributed to amiodarone-induced pulmonary fibrosis. Clinical and laboratory investigation revealed thyrotoxicosis due to amiodarone treatment. He was begun on thionamide, prednisone and beta-blockers. After a short term improvement of his clinical status the patient underwent percutaneous tracheotomy due to weaning failure from mechanical ventilation, which led to the development of recurrent thyrotoxicosis, unresponsive to medical treatment. Finally, the patient developed multiple organ failure and died, seven days later.ConclusionWe suggest that percutaneous tracheotomy could precipitate a thyrotoxic crisis, particularly in non-euthyroid patients suffering from concurrent severe illness and should be performed only in parallel with emergency thyroid surgery, when indicated.
Signal transducer and activator of transcription 5b: a new target of breast tumor kinase/protein tyrosine kinase 6
Authors: Weaver Amanda M , Silva Corinne M 
Published: November 2007

Abstract
Introduction
Signal transducers and activators of transcription (STATs) are mediators of cytokine and growth factor signaling. In recent years, STAT5b has emerged as a key regulator of tumorigenesis. STAT5b phosphorylation and activation is mediated by several kinases known to be overexpressed in breast cancer, such as epidermal growth factor receptor, HER2, and c-Src. Breast tumor kinase (Brk), also known as protein tyrosine kinase 6, is a nonreceptor tyrosine kinase expressed in more than 60% of breast cancers. Only a few substrates of the Brk tyrosine kinase have been identified, the most recent being STAT3. In the present article we investigate the potential role of Brk in the phosphorylation and activation STAT5b.

Methods
To determine whether Brk can phosphorylate STAT5b, transient transfection and in vitro kinase assays were performed. Luciferase reporter assays were used to measure Brk-induced STAT5b transcriptional activity. siRNA technology was utilized to investigate the biological significance of Brk-induced activation of STAT5b in breast cancer cell models.

Results
Phosphospecific antibodies, mutational analysis, and in vitro kinase assays demonstrated that Brk specifically mediated STAT5b phosphorylation at the activating tyrosine, Y699. Transient transfection of Brk into the Brk-negative BT-549 breast cancer cell line enhanced STAT5b transcriptional activity, as measured by a STAT5-specific luciferase reporter. Furthermore, overexpression of kinase active c-Src enhanced Brk-induced STAT5b transcriptional activity. In Brk-positive breast cancer cell lines BT-20 and SKBr3, knockdown of Brk protein or of STAT5b protein using siRNA methodology resulted in a decrease in DNA synthesis. Knockdown of Brk and STAT5b together did not further decrease DNA synthesis compared with each alone, suggesting that Brk and STAT5b converge on the same pathway, ultimately leading to cellular proliferation.

Conclusion
Our studies demonstrate that Brk phosphorylates STAT5b on Y699, leading to increased STAT5b transcriptional activity. Furthermore, analysis of DNA synthesis suggests that STAT5b and Brk are converging upon the same proproliferative signaling pathway in breast cancer cells. We propose that Brk, like other tyrosine kinases, signals downstream to STAT5b to mediate proliferation of breast cancer cells. These results further establish STAT5b as well as Brk as potential targets for breast cancer therapy.
GeneChip analysis of human embryonic stem cell differentiation into hemangioblasts: an in silicodissection of mixed phenotypes
Authors: Lu Shi-Jiang , Hipp Jennifer A , Feng Qiang , Hipp Jason D , Lanza Robert , Atala Anthony 
Published: November 2007

Abstract
Background
Microarrays are being used to understand human embryonic stem cell (hESC) differentiation. Most differentiation protocols use a multi-stage approach that induces commitment along a particular lineage. Therefore, each stage represents a more mature and less heterogeneous phenotype. Thus, characterizing the heterogeneous progenitor populations upon differentiation are of increasing importance. Here we describe a novel method of data analysis using a recently developed differentiation protocol involving the formation of functional hemangioblasts from hESCs. Blast cells are multipotent and can differentiate into multiple lineages of hematopoeitic cells (erythroid, granulocyte and macrophage), endothelial and smooth muscle cells.

Results
Large-scale transcriptional analysis was performed at distinct time points of hESC differentiation (undifferentiated hESCs, embryoid bodies, and blast cells, the last of which generates both hematopoietic and endothelial progenies). Identifying genes enriched in blast cells relative to hESCs revealed a genetic signature indicative of erythroblasts, suggesting that erythroblasts are the predominant cell type in the blast cell population. Because of the heterogeneity of blast cells, numerous comparisons were made to publicly available data sets in silico, some of which blast cells are capable of differentiating into, to assess and characterize the blast cell population. Biologically relevant comparisons masked particular genetic signatures within the heterogeneous population and identified genetic signatures indicating the presence of endothelia, cardiomyocytes, and hematopoietic lineages in the blast cell population.

Conclusion
The significance of this microarray study is in its ability to assess and identify cellular populations within a heterogeneous population through biologically relevant in silico comparisons of publicly available data sets. In conclusion, multiple in silico comparisons were necessary to characterize tissue-specific genetic signatures within a heterogeneous hemangioblast population.
Combined treatment of CpG-oligodeoxynucleotide with Nutlin-3 induces strong immune stimulation coupled to cytotoxicity in B-chronic lymphocytic leukemic (B-CLL) cells
Authors: Secchiero Paola , Melloni Elisabetta , Tiribelli Mario , Gonelli Arianna , Zauli Giorgio 
Published: November 2007

AbstractWe have investigated the effect of combined treatment with CpG-oligodeoxynucleotide (CpG-ODN) plus Nutlin-3, a small molecule inhibitor of the murine double minute 2/p53 interaction, on the immune activation, cell cycle progression, and apoptosis of peripheral blood B chronic lymphocytic leukemia (B-CLL) cells. CpG-ODN induced a robust up-regulation of immune activation markers (CD54, CD69, CD80, CD86, MHC-II) in Zap70high and Zap70low B-CLL samples. Although cotreatment of B-CLL cells with CpG-ODN + Nutlin-3 did not interfere with such immune activation, CpG-ODN potentiated the Nutlin-3-mediated induction of the death receptors CD95 and TRAIL receptor 2. Importantly, treatment with CpG-ODN did not interfere with the ability of Nutlin-3 to inhibit cell cycle progression and to induce apoptosis. Thus, a therapeutic regimen including CpG-ODN plus Nutlin-3 might have the advantage to preserve the immune activation of B-CLL cells while restraining the prosurvival/proliferative potential of CpG-ODN treatment.
IL-17 receptor signaling influences virus-induced corneal inflammation
Authors: Molesworth-Kenyon Sara J , Yin Rong , Oakes John E , Lausch Robert N 
Published: November 2007

AbstractIL-17 has been associated with selected inflammatory and autoimmune diseases. We characterized the expression of this proinflammatory cytokine following HSV-1 corneal infection and investigated whether IL-17R signaling modulated the host response to the viral pathogen at early time-points postinfection. IL-17 was elevated in the murine cornea 24 h after high-dose virus infection and subsequently persisted at low levels during the first week. Immunofluorescent studies showed that the IL-17R was expressed by cultured mouse corneal fibroblasts. Exposure of corneal cells to IL-17 led to production of IL-6 and MIP-2 in vitro and in vivo, indicating that the IL-17R was functional. Mice lacking IL-17R displayed significantly reduced neutrophil infiltration and corneal opacity. However, this effect was transient, as corneal pathology and neutrophil influx resembled that of wild-type (WT) hosts 4 days postinfection. HSV-1 growth and clearance in IL-17R−/− hosts were similar to that of the WT controls. Infection of IFN-γ gene knockout mice was associated with elevated IL-17 levels and accelerated corneal opacity, suggesting that IFN-γ negatively regulated IL-17 expression. Collectively, our results establish that IL-17 is rapidly produced in the cornea after HSV-1 infection and is regulated at least in part by IFN-γ. The absence of IL-17 signaling results in a transient decrease in the expression of proinflammatory mediators, neutrophil migration, and corneal pathology, but control of virus growth in the cornea and trigeminal ganglia is not compromised. Thus, IL-17 actively influences early virus-induced corneal inflammation.
Cardiovascular Adverse Events During Adjuvant Endocrine Therapy for Early Breast Cancer Using Letrozole or Tamoxifen: Safety Analysis of BIG 1-98 Trial
Authors: Mouridsen Henning , Keshaviah Aparna , Coates Alan S. , Rabaglio Manuela , Castiglione-Gertsch Monica , Sun Zhuoxin , Thürlimann Beat , Mauriac Louis , Forbes John F. , Paridaens Robert , Gelber Richard D. , Colleoni Marco , Smith Ian , Price Karen N. , Goldhirsch Aron 
Published: November 2007

Purpose Previous analyses of adjuvant studies of aromatase inhibitors versus tamoxifen, including the Breast International Group (BIG) 1-98 study, have suggested a small numerical excess of cardiac adverse events (AEs) on aromatase inhibitors, a reduction in the incidence of hypercholesterolemia on tamoxifen, and significantly higher incidence of thromboembolic AEs on tamoxifen. The purpose of the present study is to provide detailed updated information on these AEs in BIG 1-98. Patients and Methods Eight thousand twenty-eight postmenopausal women with receptor-positive early breast cancer were randomly assigned (double-blind) between March 1998 and May 2003 to receive 5 years of adjuvant endocrine therapy with letrozole, tamoxifen, or a sequence of these agents. Seven thousand nine hundred sixty-three patients who actually received therapy are included in this safety analysis, which focuses on cardiovascular events. AE recording ceased 30 days after therapy completion (or after switch on the sequential arms). Results Baseline comorbidities were balanced. At a median follow-up time of 30.1 months, we observed similar overall incidence of cardiac AEs (letrozole, 4.8%; tamoxifen, 4.7%), more grade 3 to 5 cardiac AEs on letrozole (letrozole, 2.4%; tamoxifen, 1.4%; P = .001)—an excess only partially attributable to prior hypercholesterolemia—and more overall (tamoxifen, 3.9%; letrozole, 1.7%; P < .001) and grade 3 to 5 thromboembolic AEs on tamoxifen (tamoxifen, 2.3%; letrozole, 0.9%; P < .001). There was no significant difference between tamoxifen and letrozole in incidence of hypertension or cerebrovascular events. Conclusion The present safety analysis, limited to cardiovascular AEs in BIG 1-98, documents a low overall incidence of cardiovascular AEs, which differed between treatment arms.
Intermittent model predictive control
Authors: Gawthrop P. J. , Wang L 
Published: November 2007

Intermittent control, where a sequence of open-loop trajectories is punctuated by intermittent feedback, is described, and a number of design methods are presented. A generalized hold representation is derived and shown to be useful for both implementation and analysis. The relationship between predictive control of a time delay system and intermittent control is examined, and it is shown that a simplified predictor can be used in the latter case. The applicability of intermittent control to the implementation of model-based predictive control (MPC) is discussed and illustrated by the control of a difficult mechanical system - a self-balancing seesaw.
Bio-Inspired Membranes for Advanced Polymer Electrolyte Fuel Cells. Anhydrous Proton-Conducting Membrane via Molecular Self-Assembly
Authors: Honma Itaru , Yamada Masanori 
Published: November 2007

Abstract
Bio-inspired materials or natural biopolymers have attracted much attention for industrial applications as biocompatible materials. Although these materials have been discarded as industrial waste around the world, there is an increasing interest in environmental, engineering, and electrical applications of the biomaterials because of their well-controlled structures and superior conducting properties. The controlled structures of the hydrogen-bonding network in biomolecules, such as bioenergetic proteins, are essential for efficient energy transduction in living systems and application of a biomolecular mechanism could make it possible to prepare efficient electrolytes with superior conducting properties. We report here a recent investigation on the new class and new concept of electrolyte materials with bio-inspired molecular architectures of acid–base pairs for anhydrous proton conduction and its application in intermediate temperature (100–200 °C) polymer electrolyte fuel cells (PEFC). Although some membranes were composed from entirely biomolecular materials, they showed large anhydrous proton conductivities from room temperature to 160 °C, and fuel cells employing biomembranes as a polymer electrolyte produced electrical power under non-humidified H2/O2 condition at 160 °C. These bio-inspired materials may have many potential applications not only because of its superior ion conducting properties, in particular, under anhydrous (water-free) or extremely low-humidity conditions, but also because of its biocompatibility.
Kinetic Stability of Gold Fullerenes and the 2(N+1)2 Rule
Authors: Ishida Toshimasa , Kanno Hideaki , Aihara Jun-ichi 
Published: November 2007

Abstract
Gold fullerenes conform to the 2(N+1)2 skeletal electron counting rule, namely, they attain the maximum degree of kinetic stability when they have 2(N+1)2 mobile electrons. Icosahedral Au32 (N=3) is predicted to possess the highest kinetic stability with the largest minimum bond resonance energy. Thus, gold fullerenes are much less sensitive to local ring structure than carbon fullerenes. In such a situation, the 2(N+1)2 rule works as a rule of kinetic stability rather than as that of spherical aromaticity.
New Steroids from the Soft Coral Nephthea chabrolii
Authors: Su Jui-Hsin , Lin Fang-Yee , Dai Chang-Feng , Wu Yang-Chang , Hsu Chi-Hsin , Sheu Jyh-Horng 
Published: November 2007

Abstract
Six new steroids, chabrolosteroids D–I (1–6), were isolated from the organic extract of a Taiwanese soft coral Nephthea chabrolii. The structures of these metabolites were determined on the basis of extensive spectroscopic analysis. Metabolite 6 was found to exhibit weak cytotoxicity against the growth of Hep 3B and A-549 cell lines.
New and Direct Approach to Hypervalent Iodine Compounds from Arenes and Iodine. Straightforward Synthesis of (Diacetoxyiodo)arenes and Diaryliodonium Salts Using Potassium μ-Peroxo-hexaoxodisulfate
Authors: Hossain Md Delwar , Kitamura Tsugio 
Published: November 2007

Abstract
The reaction of arenes with elemental iodine, acetic acid, and potassium μ-peroxo-hexaoxodisulfate (K2S2O8) in the presence of concentrated sulfuric acid, efficiently generated the corresponding (diacetoxyiodo)arenes in good yields. Diaryliodonium triflates were directly synthesized by reaction of arenes with elemental iodine in good yields by using K2S2O8, AcOH, and TfOH. Diaryliodonium tosylates were also prepared from arenes and elemental iodine by using K2S2O8, AcOH, H2SO4, and TsOH. The procedure involved mild conditions and a straightforward one-pot synthesis.