bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of cerebrospinal fluid and cerebrospinal fluid cells from patients with multiple sclerosis for detection of JC virus DNA
Authors: Iacobaeus E , Ryschkewitsch C , Gravell M , Khademi M , Wallstrom E , Olsson T , Brundin L , Major EO 
Published: September 2008

Objective 1) To determine whether JC virus (JCV) DNA was present in the cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) in comparison with controls and 2) to find out if our clinical material, based on presence of JCV DNA, included any patient at risk for progressive multifocal leukoencephalopathy (PML). Methods The prevalence of JCV DNA was analyzed in CSF and plasma from 217 patients with MS, 86 patients with clinically isolated syndrome (CIS), and 212 patients with other neurological diseases (OND). In addition, we analyzed CSF cells, the first report of JCV DNA in CSF cells in a single sample, and peripheral blood cells in a subgroup of MS ( n = 49), CIS ( n = 14) and OND ( n = 53). Results A low copy number of JCV DNA was detected in one MS cell free CSF sample and in one MS CSF cell samples. None of these had any signs of PML or developed this disease during follow-up. In addition, two OND plasma samples were JCV DNA positive, whereas all the other samples had no detectable virus. Conclusion A low copy number of JCV DNA may occasionally be observed both in MS and other diseases and may occur as part of the normal biology of JC virus in humans. This study does not support the hypothesis that patients with MS would be at increased risk to develop PML, and consequently screening of CSF as a measurable risk for PML is not useful.
Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation
Authors: Fagius J , Lundgren J , Öberg G 
Published: September 2008

Background During the last 15 years, high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) has globally been performed for severe multiple sclerosis (MS). Most patients have been in progressive phase with long disease duration. As a rule, treatment effect has been minor or moderate. Patients Since 2004, we have performed HSCT in nine young patients with “malignant” relapsing–remitting MS. Criteria for treatment were short duration of disease; very frequent, severe relapses; recent improvement periods indicating potential for recovery after strong immunosuppression. Findings Median age at treatment was 27 (range 9–34) years, MS duration 26 (4–100) months, and annualized relapse rate 10 (4–12). Median Disability Status Scale (extended disability status scale, EDSS) at HSCT was 7.0 (3.5–8.0). Median follow-up time April 2008 is 29 (23–47) months. Median EDSS improvement is 3.5 (1.0–7.0), clearly surpassing most previous reports. One patient relapsed mildly with rapid recovery 7 months after HSCT. All patients are otherwise stable, median EDSS being 2.0 (0–6.0). Before HSCT, 61 relapses occurred in 82 patient months; during follow-up, one relapse in 289 patient months. Conclusion This small series of patients with “malignant” relapsing–remitting MS suggests HSCT to be an effective treatment option for this relatively rare disease course. It further suggests that future criteria for HSCT in MS should be close to the present ones.
Interferon-β bioactivity measurement in multiple sclerosis: feasibility for routine clinical practice
Authors: van der Voort LF , Kok A ,   A Visser, Oudejans CBM , Caldano M , Gilli F , Bertolotto A , Polman CH , Killestein J 
Published: September 2008

Background Neutralising antibodies (NAb) to interferon beta (IFNβ) are associated with a reduced bioactivity and efficacy of IFNβ in multiple sclerosis (MS). Unclear is how to apply IFNβ bioactivity measurements (quantification of Myxovirus resistance protein A (MxA) mRNA) in clinical practice. Objectives To evaluate value and feasibility of IFNβ bioactivity measurement with a single MxA mRNA measurement for screening and a second measurement before and after IFNβ administration for definite confirmation of IFNβ bioactivity status. Methods In 79 MS patients MxA mRNA expression was determined 4 hours after IFNβ administration. If inadequate, MxA mRNA expression testing was repeated 3 months afterwards, comparing post- and pre injection samples to determine whether IFNb bioactivity was persistently lacking. MxA mRNA expression was compared to NAβ titres, determined by the cytopathic effect assay (CPE). Results NAb titres correlated significantly with MxA mRNA expression and MxA mRNA induction. Of all screened patients, only one patient had adequate MxA mRNA expression and high NAb titres simultaneously. Of the biological non-responders at second measurement (21/55), 17 (81%) were high-titre NAb positive, 1 (5%) was low-titre NAb positive and 3 (14%) were NAb negative. Without considering the pre-injection measurement, two more NAb negative patients would have tested negative for IFNβ bioactivity, emphasizing the need of a pre-injection sample. Conclusions Our data suggest that for IFNβ bioactivity screening a single post-injection measurement seems reasonable. However, MxA induction measurement based on both pre- and post-IFNβ injection samples at second measurement is somewhat more precise in determining ultimate IFNβ bioactivity status.
Differential diagnosis of suspected multiple sclerosis: a consensus approach
Authors: Miller DH , Weinshenker BG , Filippi M , Banwell BL , Cohen JA , Freedman MS , Galetta SL , Hutchinson M , Johnson RT , Kappos L , Kira J , Lublin FD , McFarland HF , Montalban X , Panitch H , Richert JR , Reingold SC , Polman CH 
Published: September 2008

Background and objectives Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. Methods Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. Results We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of “clinically isolated syndromes” (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. Conclusions Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.
Potential side effect of high-dose corticosteroid relapse treatment: acute generalized exanthematous pustulosis (AGEP)
Authors: Ziemssen T , Bauer A , Bär M 
Published: September 2008

Introduction High-dose glucocorticosteroids (GC) are the treatment of choice for acute relapses in patients with multiple sclerosis as proven by several controlled clinical trials. The common adverse effects of GC are well known Case Presentation In this study, we report on the exceptional case of a young female treated with intravenous high-dose prednisolone for optic neuritis who developed acute generalized exanthematous pustulosis (AGEP). AGEP is a rare cutaneous adverse reaction induced most frequently by antimicrobial or antihypertensive drugs and viral infections. It is characterized by a febrile erythematous and pustular rash and blood granulocytosis. Conclusion In our patient, switching to dexamethasone for the next relapse was tolerated well and is an option for treatment. AGEP is a rare adverse effect of carticosteroid treatment.
NF-κB1 and c-Rel cooperate to promote the survival of TLR4-activated B cells by neutralizing Bim via distinct mechanisms
Authors: Banerjee Ashish , Grumont Raelene , Gugasyan Raffi , White Christine , Strasser Andreas , Gerondakis Steve 
Published: September 2008

AbstractThe nuclear factor-κB (NF-κB) pathway is crucial for the survival of B cells stimulated through Toll-like receptors (TLRs). Here, we show that the heightened death of TLR4-activated nfkb1−/− B cells is the result of a failure of the Tpl2/MEK/ERK pathway to phosphorylate the proapo-ptotic BH3-only protein Bim and target it for degradation. ERK inactivation of Bim after TLR4 stimulation is accompanied by an increase in A1/Bim and Bcl-xL/Bim complexes that we propose represents a c-Rel–dependent mechanism for neutralizing Bim. Together these findings establish that optimal survival of TLR4-activated B cells depends on the NF-κB pathway neutralizing Bim through a combination of Bcl-2 prosurvival protein induction and Tpl2/ERK-dependent Bim phosphorylation and degradation.
Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping
Authors: Johnson David C. , Corthals Sophie , Ramos Christine , Hoering Antje , Cocks Kim , Dickens Nicholas J. , Haessler Jeff , Goldschmidt Harmut , Child J. Anthony , Bell Sue E. , Jackson Graham , Baris Dalsu , Rajkumar S. Vincent , Davies Faith E. , Durie Brian G. M. , Crowley John , Sonneveld Pieter , Van Ness Brian , Morgan Gareth J. 
Published: September 2008

AbstractA venous thromboembolism (VTE) with the subsequent risk of pulmonary embolism is a major concern in the treatment of patients with multiple myeloma with thalidomide. The susceptibility to developing a VTE in response to thalidomide therapy is likely to be influenced by both genetic and environmental factors. To test genetic variation associated with treatment related VTE in patient peripheral blood DNA, we used a custom-built molecular inversion probe (MIP)–based single nucleotide polymorphism (SNP) chip containing 3404 SNPs. SNPs on the chip were selected in “functional regions” within 964 genes spanning 67 molecular pathways thought to be involved in the pathogenesis, treatment response, and side effects associated with myeloma therapy. Patients and controls were taken from 3 large clinical trials: Medical Research Council (MRC) Myeloma IX, Hovon-50, and Eastern Cooperative Oncology Group (ECOG) EA100, which compared conventional treatments with thalidomide in patients with myeloma. Our analysis showed that the set of SNPs associated with thalidomide-related VTE were enriched in genes and pathways important in drug transport/metabolism, DNA repair, and cytokine balance. The effects of the SNPs associated with thalidomide-related VTE may be functional at the level of the tumor cell, the tumor-related microenvironment, and the endothelium. The clinical trials described in this paper have been registered as follows: MRC Myeloma IX: ISRCTN68454111; Hovon-50: NCT00028886; and ECOG EA100: NCT00033332.
Dendritic cell microvilli: a novel membrane structure associated with the multifocal synapse and T-cell clustering
Authors: Fisher Phyllis J. , Bulur Peggy A. , Vuk-Pavlovic Stanimir , Prendergast Franklyn G. , Dietz Allan B. 
Published: September 2008

Abstract
Polarizing effects of productive dendritic cell (DC)–T-cell interactions on DC cytoskeleton have been known in some detail, but the effects on DC membrane have been studied to a lesser extent. We found that T-cell incubation led to DC elongation and segregation of characteristic DC veils to the broader pole of the cell. On the opposite DC pole, we observed a novel membrane feature in the form of bundled microvilli. Each villus was approximately 100 nm in diameter and 600 to 1200 nm long. Microvilli exhibited high density of antigen-presenting molecules and costimulatory molecules and provided the physical basis for the multifocal immune synapse we observed during human DC and T-cell interactions. T cells preferentially bound to this site in clusters often contained both CD4+ and CD8+ T cells.
Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients
Authors: Federici Augusto B. , Mannucci Pier M. , Castaman Giancarlo , Baronciani Luciano , Bucciarelli Paolo , Canciani Maria T. , Pecci Alessandro , Lenting Peter J. , De Groot Philip G. 
Published: September 2008

AbstractType 2B von Willebrand disease (VWD2B) is caused by an abnormal von Willebrand factor (VWF) with increased affinity for the platelet receptor glycoprotein Ib-α (GPIb-α) that may result in moderate to severe thrombocytopenia. We evaluated the prevalence and clinical and molecular predictors of thrombocytopenia in a cohort of 67 VWD2B patients from 38 unrelated families characterized by VWF mutations. Platelet count, mean platelet volume, and morphologic evaluations of blood smear were obtained at baseline and during physiologic (pregnancy) or pathologic (infections, surgeries) stress conditions. Thrombocytopenia was found in 20 patients (30%) at baseline and in 38 (57%) after stress conditions, whereas platelet counts were always normal in 16 patients (24%) from 5 families carrying the P1266L/Q or R1308L mutations. VWF in its GPIb-α–binding conformation (VWF–GPIb-α/BC) was higher than normal in all except the 16 cases without thrombocytopenia (values up to 6-fold higher than controls). The risk of bleeding was higher in patients with thrombocytopenia (adjusted hazard ratio = 4.57; 95% confidence interval, 1.17-17.90) and in those with the highest tertile of bleeding severity score (5.66; 95% confidence interval, 1.03-31.07). Prediction of possible thrombocytopenia in VWD2B by measuring VWF–GPIb-α/BC is important because a low platelet count is an independent risk factor for bleeding.
Endoglin expression in blood and endothelium is differentially regulated by modular assembly of the Ets/Gata hemangioblast code
Authors: Pimanda John E. , Chan Wan Y. I. , Wilson Nicola K. , Smith Aileen M. , Kinston Sarah , Knezevic Kathy , Janes Mary E. , Landry Josette-Renée , Kolb-Kokocinski Anja , Frampton Jonathan , Tannahill David , Ottersbach Katrin , Follows George A. , Lacaud Georges , Kouskoff Valerie , Göttgens Berthold 
Published: September 2008

AbstractEndoglin is an accessory receptor for TGF-β signaling and is required for normal hemangioblast, early hematopoietic, and vascular development. We have previously shown that an upstream enhancer, Eng −8, together with the promoter region, mediates robust endothelial expression yet is inactive in blood. To identify hematopoietic regulatory elements, we used array-based methods to determine chromatin accessibility across the entire locus. Subsequent transgenic analysis of candidate elements showed that an endothelial enhancer at Eng +9 when combined with an element at Eng +7 functions as a strong hemato-endothelial enhancer. Chromatin immunoprecipitation (ChIP)–chip analysis demonstrated specific binding of Ets factors to the promoter as well as to the −8, +7+9 enhancers in both blood and endothelial cells. By contrast Pu.1, an Ets factor specific to the blood lineage, and Gata2 binding was only detected in blood. Gata2 was bound only at +7 and GATA motifs were required for hematopoietic activity. This modular assembly of regulators gives blood and endothelial cells the regulatory freedom to independently fine-tune gene expression and emphasizes the role of regulatory divergence in driving functional divergence.
POEM, A 3-dimensional exon taxonomy and patterns in untranslated exons
Authors: Knapp Keith , Chonka Ashley , Chen Yi-Ping Phoebe 
Published: September 2008

Abstract

Background
The existence of exons and introns has been known for thirty years. Despite this knowledge, there is a lack of formal research into the categorization of exons. Exon taxonomies used by researchers tend to be selected ad hoc or based on an information poor de-facto standard. Exons have been shown to have specific properties and functions based on among other things their location and order. These factors should play a role in the naming to increase specificity about which exon type(s) are in question.

Results
POEM (Protein Oriented Exon Monikers) is a new taxonomy focused on protein proximal exons. It integrates three dimensions of information (Global Position, Regional Position and Region), thus its exon categories are based on known statistical exon features. POEM is applied to two congruent untranslated exon datasets resulting in the following statistical properties. Using the POEM taxonomy previous wide ranging estimates of initial 5' untranslated region exons are resolved. According to our datasets, 29–36% of genes have wholly untranslated first exons. Untranslated exon containing sequences are shown to have consistently up to 6 times more 5' untranslated exons than 3' untranslated exons. Finally, three exon patterns are determined which account for 70% of untranslated exon genes.

Conclusion
We describe a thorough three-dimensional exon taxonomy called POEM, which is biologically and statistically relevant. No previous taxonomy provides such fine grained information and yet still includes all valid information dimensions. The use of POEM will improve the accuracy of genefinder comparisons and analysis by means of a common taxonomy. It will also facilitate unambiguous communication due to its fine granularity
Analysis of the goldfish Carassius auratus olfactory epithelium transcriptome reveals the presence of numerous non-olfactory GPCR and putative receptors for progestin pheromones
Authors: Kolmakov Nikolay N , Kube Michael , Reinhardt Richard , Canario Adelino VM 
Published: September 2008

AbstractBackgroundThe goldfish (Carassius auratus) uses steroids and prostaglandins as pheromone cues at different stages of the reproductive cycle to facilitate spawning synchronization. Steroid progestin pheromone binding has been detected in goldfish olfactory membranes but the receptors responsible for this specific binding remain unknown. In order to shed some light on the olfactory epithelium transcriptome and search for possible receptor candidates a large set of EST from this tissue were analysed and compared to and combined with a similar zebrafish (Danio rerio) resource.ResultsWe generated 4,797 high quality sequences from a normalized cDNA library of the goldfish olfactory epithelium, which were clustered in 3,879 unique sequences, grouped in 668 contigs and 3,211 singletons. BLASTX searches produced 3,243 significant (E-value < e-10) hits and Gene Ontology (GO) analysis annotated a further 1,223 of these genes (37.7%). Comparative analysis with zebrafish olfactory epithelium ESTs revealed 1,088 identical unigenes. The transcriptome size of both species was estimated at about 16,400 unigenes, based on the proportion of genes identified involved in Glucose Metabolic Process. Of 124 G-protein coupled receptors identified in the olfactory epithelium of both species, 56 were olfactory receptors. Beta and gamma membrane progestin receptors were also isolated by subcloning of RT-PCR products from both species and an olfactory epithelium specific splice form identified.ConclusionThe high similarity between the goldfish and zebrafish olfactory systems allowed the creation of a 'cyprinid' olfactory epithelium library estimated to represent circa 70% of the transcriptome. These results are an important resource for the identification of components of signalling pathways involved in olfaction as well as putative targets for pharmacological and histochemical studies. The possible function of the receptors identified in the olfactory system is described. Moreover, the role of olfactory epithelium specific isoforms of classical membrane progestin receptor genes as candidates for preovulatory pheromone sensing is discussed.
A pilot study of rivastigmine in the treatment of delirium after stroke: A safe alternative
Authors: Oldenbeuving Annemarie W , de Kort Paul LM , Jansen Ben PW , Kappelle L Jaap , Roks Gerwin 
Published: September 2008

Abstract

Background
Delirium is a common disorder in the early phase of stroke. Given the presumed cholinergic deficiency in delirium, we tested treatment with the acetylcholinesterase inhibitor rivastigmine.

Methods
This pilot study was performed within an epidemiological study. In 527 consecutive stroke patients presence of delirium was assessed during the first week with the confusion assessment method. Severity was scored with the delirium rating scale (DRS). Sixty-two patients developed a delirium in the acute phase of stroke. Only patients with a severe and persistent delirium (defined as a DRS of 12 or more for more than 24 hours) were enrolled in the present study. In total 26 fulfilled these criteria of whom 17 were treated with orally administered rivastigmine with a total dose between 3 and 12 mg a day. Eight patients could not be treated because of dysphagia and one because of early discharge.

Results
No major side effects were recorded. In 16 patients there was a considerable decrease in severity of delirium. The mean DRS declined from 14.8 on day one to 8.5 after therapy and 5.6 after tapering. The mean duration of delirium was 6.7 days (range; 2–17).

Conclusion
Rivastigmine is safe in stroke patients with delirium even after rapid titration. In the majority of patients the delirium improved after treatment. A randomized controlled trial is needed to establish the usefulness of rivastigmine in delirium after stroke.

Trial registration
Nederlands Trial Register NTR1395
Menopausal hormone therapy in relation to breast cancer characteristics and prognosis: a cohort study
Authors: Rosenberg Lena U , Granath Fredrik , Dickman Paul W , Einarsdóttir Kristjana , Wedrén Sara , Persson Ingemar , Hall Per 
Published: September 2008

Abstract
Introduction
Menopausal hormone therapy has been reported to increase the risk of certain subtypes of breast cancer and to be associated with a favorable survival. These associations could either be due to an increased mammographic surveillance or to a biological effect. We assessed these associations in a Swedish cohort of postmenopausal breast cancer patients holding information on mammographic examinations, menopausal hormone therapy use, other breast cancer risk factors, and cancer treatment.

Methods
We analyzed 2,660 postmenopausal women aged 50 to 74 years, diagnosed with invasive breast cancer in 1993 to 1995 and followed until the end of 2003 (median follow-up, 9 years and 3 months). We assessed the influence of hormone therapy before diagnosis on tumor characteristics and breast cancer-specific survival. We analyzed hormone therapy before diagnosis by regimen (estrogen–progestin therapy or estrogen alone therapy), recency (current or past), and duration of use (<5 years or ≥ 5 years).

Results
Current use, but not past use, compared with never use of hormone therapy before diagnosis seemed to be associated with tumors of low grade and with improved breast cancer-specific survival. The associations were stronger with longer duration, but did not vary significantly by regimen. The favorable survival among current users of hormone therapy was only partly explained by differences in available tumor characteristics and mammographic surveillance.

Conclusions
We conclude that current menopausal hormone therapy, especially long term, is associated with favorable tumor characteristics and survival.