bluuebunny/crossref_metadata_2025_split huggingface dataset:
MELD score to predict outcome in adult patients with non‐acetaminophen‐induced acute liver failure
Authors: Katoonizadeh Aezam , Decaestecker Jochen , Wilmer Alexander , Aerts Raymond , Verslype Chris , Vansteenbergen Werner , Yap Paul , Fevery Johan , Roskams Tania , Pirenne Jacques , Nevens Frederik 
Published: January 2007

AbstractAims/Background: A model for end stage liver disease (MELD) score >30 was proposed as an excellent predictor of mortality in patients with non‐acetaminophen‐induced acute liver failure (ALF). We analyzed the prognostic value of MELD score in our patients with ALF who were prospectively registered in our database since 1990.Methods: Overall, 106 patients met the criteria of ALF. Excluding seven patients with acetaminophen etiology, 99 patients (42±15 years, 40M/59F) were studied.Results: Causes were cryptogenic (n=38), viral (n=29), drugs (n=20) and miscellaneous (n=12). Of these, 37% (n=37) survived with medical management alone (group I), 16% (n=16) died (group II) and 46% (n=46) underwent liver transplantation (group III). The strongest predictors of poor outcome were advanced encephalopathy, cryptogenic/drug‐induced/hepatitis B etiology and a high MELD score. At the time of diagnosis, King's College Hospital criteria and MELD score >30 had similar high negative predictive value (92% and 91%, respectively) and low positive predictive value (52% and 56%, respectively). The predictive values improved only slightly during follow‐up. The best cut‐off point for MELD score to discriminate between survivors and nonsurvivors was >35, with a sensitivity and specificity of 86% and 75%, respectively.Conclusions: MELD score, which mostly takes into consideration the degree of liver impairment, has a similar prognostic value as King's College Hospital criteria to predict outcome in adult patients with nonacetaminophen‐induced ALF. Overall, all current scores miss accuracy and therefore there is a clear need for factors that can better predict the regeneration of the liver in this setting.
The multifocal electroretinogram (mfERG) in the pig
Authors: Voss Kyhn Maria , Kiilgaard Jens F. , Lopez Ana Garcia , Scherfig Erik , Prause Jan U. , La Cour Morten 
Published: January 2007

Abstract.Purpose:  To establish a method allowing multifocal electroretinography (mfERG) recording with simultaneous fundus monitoring on anaesthetized pigs. In addition we characterize the peaks of the porcine mfERG trace, and compare the visual streak area with the optic nerve head, a known non‐response area. Finally we illustrate the feasibility of the method by performing mfERG after an induced laser burn in the visual streak.Methods:  Fifteen pigs underwent mfERG recordings at baseline, and after 1 and 6 weeks of observation. One pig was evaluated before and after retinal diode laser treatment in the visual streak.Results:  The porcine mfERG trace appears similar to the human mfERG trace, and can be described by three peaks named N1, P1 and N2. Significantly faster implicit time was found in the visual streak regarding N1 (P < 0.001) than in areas outside the visual streak. Amplitudes of all three peaks were increased in the visual streak (P < 0.005). The laser‐treated area was characterized by a response similar to what is found at the location of the optic nerve head.Conclusion:  Porcine mfERG is similar in appearance to the human response and can be described by the same three peaks. Significantly higher amplitudes of all three peaks are found in the visual streak when compared to the optic nerve head and inferior retina. We have detected the functional deficit caused by a laser burn at the size of 3 × 3 mm.
Lupus‐like reaction to interferon at the injection site: report of five cases
Authors: Arrue Itziar , Saiz Ana , Ortiz‐Romero Pablo Luis , Rodríguez‐Peralto José Luis 
Published: January 2007

Background:  Interferon therapy at the injection sites has been related to different cutaneous lesions including erythema and induration as the most frequent ones. While the glycoprotein induces fatigue, fever and is even believed to precipitate autoimmune disorders such as type I diabetes, thyroid disease and systemic lupus erythematosus, a lupus erythematosus‐like histologic reaction at the interferon injection site has never been reported. To our knowledge, a microscopic self‐resolving lesion mimicking lupus erythematosus at the injection site of interferon has not been described.Results:  We report five cases of cutaneous lesions at the inoculation site of interferon with a histopathologic lupus erythematosus‐like pattern. Three of them were receiving interferon alfa therapy because of a malignant melanoma and the other two patients were receiving interferon beta‐1b for multiple sclerosis. Biopsy specimens taken from different lesions showed similar microscopic findings consisting of dermal mucin deposits and dense lymphocytic infiltrates along hair follicles with hydropic degeneration of follicular basal layer.Conclusions:  Multiple cutaneous lesions related to interferon at the injection site have been reported, but none of them with a histologic lupus‐like presentation. In this study we describe five cases in which interferon therapy has induced a resolutive cutaneous lesion mimicking lupus erythematous. This peculiar microscopic pattern has been previously described once before, but interpreted as cutaneous mucinosis.
Tuberculids as sentinel lesions of tuberculous epididymo‐orchitis
Authors: Ramdial Pratistadevi K. , Calonje Eduardo , Sydney Clive , Subrayen Sumeshini , Meyiwa Phumlani S. , Aboobaker Jamila 
Published: January 2007

Background:  Tuberculids are rarely associated with male genital tract tuberculosis (TB). Tuberculous epididymo‐orchitis (TBEO) has been associated rarely with papulonecrotic tuberculid (PNT) but not with erythema induratum (EI) or the simultaneous occurrence of different tuberculids.Methods:  A retrospective assessment of tuberculids that occurred with underlying TBEO was carried out.Results:  Five patients, four with one and one with two skin biopsies, with clinical diagnoses of PNT (two), EI (one), impetigo (two) and calf ulcer (one), formed the study cohort. Histopathological evaluation confirmed PNT and EI in four and two skin biopsies, respectively. Two patients who returned for follow‐up were commenced on anti‐tuberculous therapy. All patients sought medical attention 3–34 months later for tender right‐sided (two) and left‐sided (three) testicular masses. Orchidectomy was undertaken following a poor clinical response to empirical treatment with trimethoprim sulfamethoxazole. Pathological examination of the testis and epididymis confirmed TBEO. The patients were initiated on anti‐tuberculous therapy. There was dramatic healing of the skin lesions.Conclusion:  Tuberculids are a sentinel cutaneous manifestation of visceral TB and a valuable external audit of treatment compliance and response. Heightened recognition of and more rigorous genitourinary tract investigation are necessary to identify occult or asymptomatic TBEO as the underlying cause of tuberculids.
Development of a Semiquantitative Degenerate Real-Time PCR-Based Assay for Estimation of Numbers of Butyryl-Coenzyme A (CoA) CoA Transferase Genes in Complex Bacterial Samples
Authors: Louis Petra , Flint Harry J. 
Published: January 2007

ABSTRACT
We describe a new degenerate real-time PCR approach to simultaneously quantify phylogenetically different butyrate-producing bacteria based on the detection of butyryl-coenzyme A (CoA) CoA transferase genes. This pathway is present in numerically important groups of butyrate producers within the human colon, and thus this assay estimates the butyrate-producing ability of the microbiota.
ICRAD: AN INTEGRATED PROCESS FOR THE SOLUTION OF REQUIREMENTS CONFLICTS AND ARCHITECTURAL DESIGN
Authors: HERRMANN ANDREA , PAECH BARBARA , PLAZA DAMIAN 
Published: January 2007

In order to solve requirements conflicts when developing or enhancing an IT system, it is essential to understand its architecture. Frequently, the costs for the realization of certain requirements are a decision criterion. Requirements negotiation and architectural design must be treated together, as conflicts cannot be solved before the architecture has been designed. So far, no integrated process exists which clearly defines input and output among these activities, and which takes into account a variety of different types of dependencies among requirements and between requirements and architecture. In this paper, we develop a detailed iterative process named ICRAD (Integrated Conflict Resolution and Architectural Design). ICRAD integrates requirements negotiation and architectural design and takes into account nine types of dependencies. We define three types of requirements conflicts. We also present a case study.
Programmed Cell Death-4 Tumor Suppressor Protein Contributes to Retinoic Acid–Induced Terminal Granulocytic Differentiation of Human Myeloid Leukemia Cells
Authors: Ozpolat Bulent , Akar Ugur , Steiner Michael , Zorrilla-Calancha Isabel , Tirado-Gomez Maribel , Colburn Nancy , Danilenko Michael , Kornblau Steven , Lopez Berestein Gabriel 
Published: January 2007

AbstractProgrammed cell death-4 (PDCD4) is a recently discovered tumor suppressor protein that inhibits protein synthesis by suppression of translation initiation. We investigated the role and the regulation of PDCD4 in the terminal differentiation of acute myeloid leukemia (AML) cells. Expression of PDCD4 was markedly up-regulated during all-trans retinoic acid (ATRA)–induced granulocytic differentiation in NB4 and HL60 AML cell lines and in primary human promyelocytic leukemia (AML-M3) and CD34+ hematopoietic progenitor cells but not in differentiation-resistant NB4.R1 and HL60R cells. Induction of PDCD4 expression was associated with nuclear translocation of PDCD4 in NB4 cells undergoing granulocytic differentiation but not in NB4.R1 cells. Other granulocytic differentiation inducers such as DMSO and arsenic trioxide also induced PDCD4 expression in NB4 cells. In contrast, PDCD4 was not up-regulated during monocytic/macrophagic differentiation induced by 1,25-dihydroxyvitamin D3 or 12-O-tetradecanoyl-phorbol-13-acetate in NB4 cells or by ATRA in THP1 myelomonoblastic cells. Knockdown of PDCD4 by RNA interference (siRNA) inhibited ATRA-induced granulocytic differentiation and reduced expression of key proteins known to be regulated by ATRA, including p27Kip1 and DAP5/p97, and induced c-myc and Wilms' tumor 1, but did not alter expression of c-jun, p21Waf1/Cip1, and tissue transglutaminase (TG2). Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was found to regulate PDCD4 expression because inhibition of PI3K by LY294002 and wortmannin or of mTOR by rapamycin induced PDCD4 protein and mRNA expression. In conclusion, our data suggest that PDCD4 expression contributes to ATRA-induced granulocytic but not monocytic/macrophagic differentiation. The PI3K/Akt/mTOR pathway constitutively represses PDCD4 expression in AML, and ATRA induces PDCD4 through inhibition of this pathway. (Mol Cancer Res 2007;5(1):95–108)
Regulation of IκB Kinase ε Expression by the Androgen Receptor and the Nuclear Factor-κB Transcription Factor in Prostate Cancer
Authors: Péant Benjamin , Diallo Jean-Simon , Lessard Laurent , Delvoye Nathalie , Le Page Cécile , Saad Fred , Mes-Masson Anne-Marie 
Published: January 2007

Abstract
Although several genes have been associated with prostate cancer progression, it is clear that we are far from understanding all the molecular events implicated in the initiation and progression of the disease to a hormone-refractory state. The androgen receptor is a central player in the initiation and proliferation of prostate cancer and its response to hormone therapy. Nuclear factor-κB has important proliferative and antiapoptotic activities that could contribute to the development and progression of cancer cells as well as resistance to therapy. In this study, we report that IκB kinase ε (IKKε), which is controlled by nuclear factor-κB in human chondrocytes, is expressed in human prostate cancer cells. We show that IKKε gene expression is stimulated by tumor necrosis factor-α treatment in LNCaP cells and is inhibited by transfection of a dominant-negative form of IκBα, which prevents the nuclear translocation of p65. Furthermore, we found that tumor necrosis factor-α–induced IKKε expression is inhibited by an androgen analogue (R1881) in androgen-sensitive prostate cancer cells and that this inhibition correlates with the modulation of IκBα expression by R1881. We also noted constitutive IKKε expression in androgen-independent PC-3 and DU145 cells. To our knowledge, this is the first report of an IκB kinase family member whose expression is modulated by androgen and deregulated in androgen receptor–negative cells. (Mol Cancer Res 2007;5(1):87–94)
Roles of Aurora Kinases in Mitosis and Tumorigenesis
Authors: Fu Jingyan , Bian Minglei , Jiang Qing , Zhang Chuanmao 
Published: January 2007

Abstract
Aurora kinases, which have been implicated in several vital events in mitosis, represent a protein kinase family highly conserved during evolution. The activity of Aurora kinases is delicately regulated, mainly by phosphorylation and degradation. Deregulation of Aurora kinase activity can result in mitotic abnormality and genetic instability, leading to defects in centrosome function, spindle assembly, chromosome alignment, and cytokinesis. Both the expression level and the kinase activity of Aurora kinases are found to be up-regulated in many human cancers, indicating that these kinases might serve as useful targets for the development of anticancer drugs. This review focuses on recent progress on the roles of Aurora kinases in mitosis and tumorigenesis. (Mol Cancer Res 2007;5(1):1–10)
Estrogen-Related Receptor α1 Transcriptional Activities Are Regulated in Part via the ErbB2/HER2 Signaling Pathway
Authors: Ariazi Eric A. , Kraus Richard J. , Farrell Michael L. , Jordan V. Craig , Mertz Janet E. 
Published: January 2007

Abstract
We previously showed that (a) estrogen-related receptor α1 (ERRα1) down-modulates estrogen receptor (ER)–stimulated transcription in low ErbB2–expressing MCF-7 mammary carcinoma cells, and (b) ERRα and ErbB2 mRNA levels positively correlate in clinical breast tumors. We show here that ERRα1 represses ERα-mediated activation in MCF-7 cells because it failed to recruit the coactivator glucocorticoid receptor interacting protein 1 (GRIP1) when bound to an estrogen response element. In contrast, ERRα1 activated estrogen response element– and ERR response element–mediated transcription in ERα-positive, high ErbB2–expressing BT-474 mammary carcinoma cells, activation that was enhanced by overexpression of GRIP1. Likewise, regulation of the endogenous genes pS2, progesterone receptor, and ErbB2 by ERRα1 reflected the cell type–specific differences observed with our reporter plasmids. Importantly, overexpression of activated ErbB2 in MCF-7 cells led to transcriptional activation, rather than repression, by ERRα1. Two-dimensional PAGE of radiophosphate-labeled ERRα1 indicated that it was hyperphosphorylated in BT-474 relative to MCF-7 cells; incubation of these cells with anti-ErbB2 antibody led to reduction in the extent of ERRα1 phosphorylation. Additionally, mitogen-activated protein kinases (MAPK) and Akts, components of the ErbB2 pathway, phosphorylated ERRα1 in vitro. ERRα1-activated transcription in BT-474 cells was inhibited by disruption of ErbB2/epidermal growth factor receptor signaling with trastuzumab or gefitinib or inactivation of downstream components of this signaling, MAPK kinase/MAPK, and phosphatidylinositol-3-OH kinase/Akt, with U0126 or LY294002, respectively. Thus, ERRα1 activities are regulated, in part, via ErbB2 signaling, with ERRα1 likely positively feedback-regulating ErbB2 expression. Taken together, we conclude that ERRα1 phosphorylation status shows potential as a biomarker of clinical course and antihormonal- and ErbB2-based treatment options, with ERRα1 serving as a novel target for drug development. (Mol Cancer Res 2007;5(1):71–86)
Functional Characterization of a Novel BRCA1-Null Ovarian Cancer Cell Line in Response to Ionizing Radiation
Authors: DelloRusso Christiana , Welcsh Piri L. , Wang Weixin , Garcia Rochelle L. , King Mary-Claire , Swisher Elizabeth M. 
Published: January 2007

Abstract
The breast and ovarian cancer susceptibility gene BRCA1 plays a major role in the DNA damage response pathway. The lack of well-characterized human BRCA1-null cell lines has limited the investigation of BRCA1 function, particularly with regard to its role in ovarian cancer. We propagated a novel BRCA1-null human ovarian cancer cell line UWB1.289 from a tumor of papillary serous histology, the most common form of ovarian carcinoma. UWB1.289 carries a germline BRCA1 mutation within exon 11 and has a deletion of the wild-type allele. UWB1.289 is estrogen and progesterone receptor negative and has an acquired somatic mutation in p53, similar to the commonly used BRCA1-null breast cancer cell line HCC1937. We used ionizing radiation to induce DNA damage in both UWB1.289 and in a stable UWB1.289 line in which wild-type BRCA1 was restored. We examined several responses to DNA damage in these cell lines, including sensitivity to radiation, cell cycle checkpoint function, and changes in gene expression using microarray analysis. We observed that UWB1.289 is sensitive to ionizing radiation and lacks cell cycle checkpoint functions that are a normal part of the DNA damage response. Restoration of wild-type BRCA1 function in these cells partially restores DNA damage responses. Expression array analysis not only supports this partial functional correction but also reveals interesting new information regarding BRCA1-positive regulation of the expression of claudin 6 and other metastasis-associated genes and negative regulation of multiple IFN-inducible genes. (Mol Cancer Res 2007;5(1):35–45)
Low Plasma RANTES Levels Are an Independent Predictor of Cardiac Mortality in Patients Referred for Coronary Angiography
Authors: Cavusoglu Erdal , Eng Calvin , Chopra Vineet , Clark Luther T. , Pinsky David J. , Marmur Jonathan D. 
Published: January 2007

Objective—Our objective was to evaluate the prognostic value of baseline plasma RANTES levels in patients with known or suspected coronary artery disease. RANTES is a chemokine produced by a variety of cell types including platelets that has been implicated in atherosclerosis.Methods and Results—Baseline plasma RANTES levels were measured in 389 male patients undergoing coronary angiography at a Veterans Affairs Medical Center. The patients were followed-up prospectively for the occurrence of cardiac mortality and myocardial infarction. Follow-up data at 24 months were available for 97% of patients. In the entire cohort of patients, low baseline RANTES levels were an independent predictor of cardiac mortality. For cardiac death at 24 months, the survival rate was 87.3% in the lowest tertile of RANTES values, compared with 94% in the upper 2 tertiles combined (P=0.0298 by log rank test). Furthermore, when patients were risk-stratified into those with and without an acute coronary syndrome, RANTES was an independent predictor of both cardiac mortality and myocardial infarction in those without an acute coronary syndrome. Finally, RANTES was also an independent predictor of cardiac mortality in the diabetic subset.Conclusions—In a cohort of male patients undergoing coronary angiography, low baseline plasma RANTES levels are an independent predictor of cardiac mortality.
Critical Role for Casein Kinase 2 and Phosphoinositide-3-Kinase in the Interferon-γ–Induced Expression of Monocyte Chemoattractant Protein-1 and Other Key Genes Implicated in Atherosclerosis
Authors: Harvey Elizabeth J. , Li Na , Ramji Dipak P. 
Published: January 2007

Objective—The interferon-γ (IFN-γ)–mediated regulation of macrophage gene expression is of crucial importance in the pathogenesis of atherosclerosis. The mechanisms underlying the actions of IFN-γ signaling in macrophages were investigated using monocyte chemoattractant protein (MCP)-1 as a model gene.Methods and Results—The IFN-γ–induced expression of MCP-1 in macrophages was attenuated by inhibitors of phosphoinositide-3-kinase (PI3K), casein kinase 2 (CK2), and Janus kinase (JAK)-2. AKT was the downstream target for PI3K action. Electrophoretic mobility shift assays and chromatin immunoprecipitation showed that signal transducer and activator of transcription (STAT)-1 interacted with IFN-γ responsive elements in the MCP-1 gene promoter. The IFN-γ–induced activity of the MCP-1 gene promoter and an artificial promoter containing STAT1 responsive elements was inhibited by expression of dominant negative forms of JAK-1 and -2, STAT1, CK2, and AKT. The action of CK2 and AKT on STAT1 activation was mediated, at least in part, through the regulation of serine 727 phosphorylation. Analysis of a number of other genes regulated by this cytokine and implicated in atherosclerosis revealed a gene-specific action for PI3K/AKT in IFN-γ signaling.Conclusions—These studies provide novel insights into the role of PI3K/AKT and CK2 in IFN-γ signaling relevant to changes in macrophage gene expression during atherosclerosis.
The Tension between Fire Risk and Carbon Storage: Evaluating U.S. Carbon and Fire Management Strategies through Ecosystem Models
Authors: Girod C. M. , Hurtt G. C. , Frolking S. , Aber J. D. , King A. W. 
Published: January 2007

AbstractFire risk and carbon storage are related environmental issues because fire reduction results in carbon storage through the buildup of woody vegetation, and stored carbon is a fuel for fires. The sustainability of the U.S. carbon sink and the extent of fire activity in the next 100 yr depend in part on the type and effectiveness of fire reduction employed. Previous studies have bracketed the range of dynamics from continued fire reduction to the complete failure of fire reduction activities. To improve these estimates, it is necessary to explicitly account for fire reduction in terrestrial models. A new fire reduction submodel that estimates the spatiotemporal pattern of reduction across the United States was developed using gridded data on biomass, climate, land-use, population, and economic factors. To the authors’ knowledge, it is the first large-scale, gridded fire model that explicitly accounts for fire reduction. The model was calibrated to 1° × 1° burned area statistics [Global Burnt Area 2000 Project (GBA-2000)] and compared favorably to three important diagnostics. The model was then implemented in a spatially explicit ecosystem model and used to analyze 1620 scenarios of future fire risk and fire reduction strategies. Under scenarios of climate change and urbanization, burned area and carbon emissions both increased in scenarios where fire reduction efforts were not adjusted to match new patterns of fire risk. Fuel reducing management strategies reduced burned area and fire risk, but also limited carbon storage. These results suggest that to promote carbon storage and minimize fire risk in the future, fire reduction efforts will need to be increased and spatially adjusted and will need to employ a mixture of fuel-reducing and non-fuel-reducing strategies.