bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia
Authors: Nachman James B. , Heerema Nyla A. , Sather Harland , Camitta Bruce , Forestier Erik , Harrison Christine J. , Dastugue Nicole , Schrappe Martin , Pui Ching-Hon , Basso Giuseppe , Silverman Lewis B. , Janka-Schaub Gritta E. 
Published: May 2007

Abstract
One-hundred thirty-nine patients with acute lymphoblastic leukemia (ALL) and hypodiploidy (fewer than 45 chromosomes) were collected from 10 different national ALL study groups and single institutions. Patients were stratified by modal chromosome number into 4 groups: 24 to 29 (N = 46); 33 to 39 (N = 26); 40 to 43 (N = 13); and 44 (N = 54) chromosomes. Nine patients were Philadelphia chromosome (Ph) positive (4 cases: 44 chromosomes; 5 cases: 40-43 chromosomes) and were not considered further. Event-free survival (EFS) and overall survival (OS) of the remaining 130 patients were 38.5% ± 4.4% and 49.8% ± 4.2% at 8 years, respectively. There were no significant differences in outcome between patients with 24 to 29, 33 to 39, or 40 to 43 chromosomes. Compared with patients with fewer than 44 chromosomes, patients with 44 chromosomes had a significantly better EFS (P = .01; 8-year estimate, 52.2% vs 30.1%) and OS (P = .017; 69% vs 37.5%). For patients with 44 chromosomes, monosomy 7, the presence of a dicentric chromosome, or both predicted a worse EFS but similar OS. Doubling of the hypodiploid clone occurred in 32 patients (24-29 chromosomes [n = 25] and 33-39 chromosomes [n = 7]) and had no prognostic implication. Children and adolescents with ALL and hypodiploidy with fewer than 44 chromosomes have a poor outcome despite contemporary therapy.
Gene-expression profiling identifies distinct subclasses of core binding factor acute myeloid leukemia
Authors: Bullinger Lars , Rücker Frank G. , Kurz Stephan , Du Juan , Scholl Claudia , Sander Sandrine , Corbacioglu Andrea , Lottaz Claudio , Krauter Jürgen , Fröhling Stefan , Ganser Arnold , Schlenk Richard F. , Döhner Konstanze , Pollack Jonathan R. , Döhner Hartmut 
Published: May 2007

Abstract
Core binding factor (CBF) leukemias, characterized by either inv(16)/t(16;16) or t(8;21), constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, there exists substantial biologic and clinical heterogeneity within these cytogenetic groups that is not fully reflected by the current classification system. To improve the molecular characterization we profiled gene expression in a large series (n = 93) of AML patients with CBF leukemia [(inv (16), n = 55; t(8;21), n = 38)]. By unsupervised hierarchical clustering we were able to define a subgroup of CBF cases (n = 35) characterized by shorter overall survival times (P = .03). While there was no obvious correlation with fusion gene transcript levels, FLT3 tyrosine kinase domain, KIT, and NRAS mutations, the newly defined inv(16)/t(8;21) subgroup was associated with elevated white blood cell counts and FLT3 internal tandem duplications (P = .011 and P = .026, respectively). Supervised analyses of gene expression suggested alternative cooperating pathways leading to transformation. In the “favorable” CBF leukemias, antiapoptotic mechanisms and deregulated mTOR signaling and, in the newly defined “unfavorable” subgroup, aberrant MAPK signaling and chemotherapy-resistance mechanisms might play a role. While the leukemogenic relevance of these signatures remains to be validated, their existence nevertheless supports a prognostically relevant biologic basis for the heterogeneity observed in CBF leukemia.
Mapping of possible prion protein self-interaction domains using peptide arrays
Authors: Rigter Alan , Langeveld Jan PM , Timmers-Parohi Drophatie , Jacobs Jorg G , Moonen Peter LJM , Bossers Alex 
Published: May 2007

Abstract

Background
The common event in transmissible spongiform encephalopathies (TSEs) or prion diseases is the conversion of host-encoded protease sensitive cellular prion protein (PrPC) into strain dependent isoforms of scrapie associated protease resistant isoform (PrPSc) of prion protein (PrP). These processes are determined by similarities as well as strain dependent variations in the PrP structure. Selective self-interaction between PrP molecules is the most probable basis for initiation of these processes, potentially influenced by chaperone molecules, however the mechanisms behind these processes are far from understood. We previously determined that polymorphisms do not affect initial PrPC to PrPSc binding but rather modulate a subsequent step in the conversion process. Determining possible sites of self-interaction could elucidate which amino acid(s) or amino acid sequences contribute to binding and further conversion into other isoforms. To this end, ovine – and bovine PrP peptide-arrays consisting of 15-mer overlapping peptides were probed with recombinant sheep PrPC fused to maltose binding protein (MBP-PrP).

Results
The peptide-arrays revealed two distinct high binding areas as well as some regions of lower affinity in PrPC resulting in total in 7 distinct amino acid sequences (AAs). The first high binding area comprises sheep-PrP peptides 43–102 (AA 43–116), including the N-terminal octarepeats. The second high binding area of sheep-PrP peptides 134–177 (AA 134–191), encompasses most of the scrapie susceptibility-associated polymorphisms in sheep. This concurs with previous studies showing that scrapie associated-polymorphisms do not modulate the initial binding of PrPC to PrPSc. Comparison of ovine – and bovine peptide-array binding patterns revealed that amino acid specific differences can influence the MBP-PrP binding pattern. PrP-specific antibodies were capable to completely block interaction between the peptide-array and MBP-PrP. MBP-PrP was also capable to specifically bind to PrP in a Western blot approach. The octarepeat region of PrP seems primarily important for this interaction because proteinase K pre-treatment of PrPSc completely abolished binding.

Conclusion
Binding of MBP-PrP to PrP-specific sequences indicate that several specific self-interactions between individual PrP molecules can occur and suggest that an array of interactions between PrPC-PrPC as well as PrPC-PrPSc may be possible, which ultimately lead to variations in species barrier and strain differences.
Non-coding sequence retrieval system for comparative genomic analysis of gene regulatory elements
Authors: Doh Sung Tae , Zhang Yunyu , Temple Matthew H , Cai Li 
Published: May 2007

AbstractBackgroundCompletion of the human genome sequence along with other species allows for greater understanding of the biochemical mechanisms and processes that govern healthy as well as diseased states. The large size of the genome sequences has made them difficult to study using traditional methods. There are many studies focusing on the protein coding sequences, however, not much is known about the function of non-coding regions of the genome. It has been demonstrated that parts of the non-coding region play a critical role as gene regulatory elements. Enhancers that regulate transcription processes have been found in intergenic regions. Furthermore, it is observed that regulatory elements found in non-coding regions are highly conserved across different species. However, the analysis of these regulatory elements is not as straightforward as it may first seem. The development of a centralized resource that allows for the quick and easy retrieval of non-coding sequences from multiple species and is capable of handing multi-gene queries is critical for the analysis of non-coding sequences. Here we describe the development of a web-based non-coding sequence retrieval system.ResultsThis paper presents a Non-Coding Sequences Retrieval System (NCSRS). The NCSRS is a web-based bioinformatics tool that performs fast and convenient retrieval of non-coding and coding sequences from multiple species related to a specific gene or set of genes. This tool has compiled resources from multiple sources into one easy to use and convenient web based interface. With no software installation necessary, the user needs only internet access to use this tool.ConclusionThe unique features of this tool will be very helpful for those studying gene regulatory elements that exist in non-coding regions. The web based application can be accessed on the internet at:http://cell.rutgers.edu/ncsrs/.
Evolutionary hierarchies of conserved blocks in 5'-noncoding sequences of dicot rbcS genes
Authors: Weeks Katie E , Chuzhanova Nadia A , Donnison Iain S , Scott Ian M 
Published: May 2007

AbstractBackgroundEvolutionary processes in gene regulatory regions are major determinants of organismal evolution, but exceptionally challenging to study. We explored the possibilities of evolutionary analysis of phylogenetic footprints in 5'-noncoding sequences (NCS) from 27 ribulose-1,5-bisphosphate carboxylase small subunit (rbcS) genes, from three dicot families (Brassicaceae, Fabaceae and Solanaceae).ResultsSequences of up to 400 bp encompassing proximal promoter and 5'-untranslated regions were analyzed. We conducted phylogenetic footprinting by several alternative methods: generalized Lempel-Ziv complexity (CLZ), multiple alignments with DIALIGN and ALIGN-M, and the MOTIF SAMPLER Gibbs sampling algorithm. These tools collectively defined 36 conserved blocks of mean length 12.8 bp. On average, 12.5 blocks were found in each 5'-NCS. The blocks occurred in arrays whose relative order was absolutely conserved, confirming the existence of 'conserved modular arrays' in promoters. Identities of half of the blocks confirmed pastrbcSresearch, including versions of the I-box, G-box, and GT-1 sites such as Box II. Over 90% of blocks overlapped DNase-protected regions in tomato 5'-NCS. Regions characterized by lowCLZin sliding-window analyses were also frequently associated with DNase-protection. Blocks could be assigned to evolutionary hierarchies based on taxonomic distribution and estimated age. Lineage divergence dates implied that 13 blocks found in all three plant families were of Cretaceous antiquity, while other family-specific blocks were much younger. Blocks were also dated by formation of multigene families, using genome and coding sequence information. Dendrograms of evolutionary relations of the 5'-NCS were produced by several methods, including: cluster analysis using pairwiseCLZvalues; evolutionary trees of DIALIGN sequence alignments; and cladistic analysis of conserved blocks.ConclusionDicot 5'-NCS contain conserved modular arrays of recurrent sequence blocks, which are coincident with functional elements. These blocks are amenable to evolutionary interpretation as hierarchies in which ancient, taxonomically widespread blocks can be distinguished from more recent, taxon-specific ones.
Gene function in early mouse embryonic stem cell differentiation
Authors: Sene Kagnew Hailesellasse , Porter Christopher J , Palidwor Gareth , Perez-Iratxeta Carolina , Muro Enrique M , Campbell Pearl A , Rudnicki Michael A , Andrade-Navarro Miguel A 
Published: May 2007

AbstractBackgroundLittle is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC) differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5) undergoing undirected differentiation into embryoid bodies (EBs) over a period of two weeks.ResultsWe identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g.Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1), our analysis points to others (such as transcription factorPhf21a, extracellular matrix relatedLama1andCyr61, or endoplasmic reticulum relatedSc4molandScd2) that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set.ConclusionOur analysis profiles for the first time gene expression at a very early stage of mESC differentiation, and identifies a functional and phylogenetic signature for the genes involved. The data generated constitute a valuable resource for further studies. All DNA microarray data used in this study are available in the StemBase database of stem cell gene expression data [1] and in the NCBI's GEO database.
Patient risk profiles and practice variation in nonadherence to antidepressants, antihypertensives and oral hypoglycemics
Authors: van Dijk Liset , Heerdink Eibert R , Somai Dinesh , van Dulmen Sandra , Sluijs Emmy M , de Ridder Denise T , Griens Anna MGF , Bensing Jozien M 
Published: May 2007

Abstract
Background
Many patients experience difficulties in following treatment recommendations. This study's objective is to identify nonadherence risk profiles regarding medication (antidepressants, antihypertensives, and oral hypoglycemics) from a combination of patients' socio-demographic characteristics, morbidity presented within general practice and medication characteristics. An additional objective is to explore differences in nonadherence among patients from different general practices.

Methods
Data were obtained by linkage of a Dutch general practice registration database to a dispensing registration database from the year 2001. Subjects included in the analyses were users of antidepressants (n = 4,877), antihypertensives (n = 14,219), or oral hypoglycemics (n = 2,428) and their GPs. Outcome variables were: 1) early dropout i.e., a maximum of two prescriptions and 2) refill nonadherence (in patients with 3+ prescriptions); refill adherence < 80% was considered as nonadherence. Multilevel modeling was used for analyses.

Results
Both early dropout and refill nonadherence were highest for antidepressants, followed by antihypertensives. Risk factors appeared medication specific and included: 1) non-western immigrants being more vulnerable for nonadherence to antihypertensives and antidepressants; 2) type of medication influencing nonadherence in both antihypertensives and antidepressants, 3) GP consultations contributing positively to adherence to antihypertensives and 4) somatic co-morbidity influencing adherence to antidepressants negatively. There was a considerable range between general practices in the proportion of patients who were nonadherent.

Conclusion
No clear risk profiles for nonadherence could be constructed. Characteristics that are correlated with nonadherence vary across different types of medication. Moreover, both patient and prescriber influence adherence. Especially non-western immigrants need more attention with regard to nonadherence, for example by better monitoring or communication. Since it is not clear which prescriber characteristics influence adherence levels of their patients, there is need for further research into the role of the prescriber.
Diagnosis and treatment of malaria in peripheral health facilities in Uganda: findings from an area of low transmission in south-western Uganda
Authors: Ndyomugyenyi Richard , Magnussen Pascal , Clarke Siân 
Published: May 2007

Abstract

Background
Early recognition of symptoms and signs perceived as malaria are important for effective case management, as few laboratories are available at peripheral health facilities. The validity and reliability of clinical signs and symptoms used by health workers to diagnose malaria were assessed in an area of low transmission in south-western Uganda.

Methods
The study had two components: 1) passive case detection where all patients attending the out patient clininc with a febrile illness were included and 2) a longitudinal active malaria case detection survey was conducted in selected villages. A malaria case was defined as any slide-confirmed parasitaemia in a person with an axillary temperature ≥ 37.5°C or a history of fever within the last 24 hrs and no signs suggestive of other diseases.

Results
Cases of malaria were significantly more likely to report joint pains, headache, vomiting and abdominal pains. However, due to the low prevalence of malaria, the predictive values of these individual signs alone, or in combination, were poor. Only 24.8% of 1627 patients had malaria according to case definition and > 75% of patients were unnecessarily treated for malaria and few slide negative cases received alternative treatment.

Conclusion
In low-transmission areas, more attention needs to be paid to differential diagnosis of febrile illnesses In view of suggested changes in anti-malarial drug policy, introducing costly artemisinin combination therapy accurate, rapid diagnostic tools are necessary to target treatment to people in need.
Some facts and thoughts: p73 as a tumor suppressor gene in the network of tumor suppressors
Authors: Boominathan Lakshmanane 
Published: May 2007

Abstract
The question of whether p73 is a tumor suppressor gene, is not yet answered with full confidence. The lack of spontaneous tumor formation in p73 null mice and infrequent p73 mutations seen in a variety of cancers analyzed would straightaway negate its role as a primary tumor suppressor gene. However, accumulating evidence suggest that p73 gene and its target genes are hypermethylated in the cancer of lymphoid origin. Here I discuss some facts and thoughts that support the idea that p73 could still be a tumor suppressor gene. The tumor suppressor network in which p73 appears to be a participant involves E2F1, JunB, INK4a/p16, ARF/p19, p57kip2 and BRCA1. Knock out of each gene in E2F-1-p73-JunB-p16INK4a network of tumor suppressor proteins result in lymphoma/leukemia formation. Further, I tried to explain why lymphomas are not seen in p73 null mice and why p73 gene is not prone to frequent mutation.
Tumor-specific T cells signal tumor destruction via the lymphotoxin β receptor
Authors: Winter Hauke , van den Engel Natasja K , Poehlein Christian H , Hatz Rudolf A , Fox Bernard A , Hu Hong-Ming 
Published: May 2007

AbstractBackgroundPreviously, we reported that adoptively transferred perforin k/o (PKO), and IFN-γ k/o (GKO), or perforin/IFN-γ double k/o (PKO/GKO) effector T cells mediated regression of B16BL6-D5 (D5) pulmonary metastases and showed that TNF receptor signaling played a critical role in mediating tumor regression. In this report we investigated the role of lymphotoxin-α (LT-α) as a potential effector molecules of tumor-specific effector T cells.MethodsEffector T cells were generated from tumor vaccine-draining lymph node (TVDLN) of wt, GKO, LT-α deficient (LKO), or PKO/GKO mice and tested for their ability to mediate regression of D5 pulmonary metastases in the presence or absence of LT-βR-Fc fusion protein or anti-IFN-γ antibody. Chemokine production by D5 tumor cells was determined by ELISA, RT-PCR and Chemotaxis assays.ResultsStimulated effector T cells from wt, GKO, or PKO/GKO mice expressed ligands for LT-β receptor (LT-βR). D5 tumor cells were found to constitutively express the LT-βR. Administration of LT-βR-Fc fusion protein completely abrogated the therapeutic efficacy of GKO or PKO/GKO but not wt effector T cells (p < 0.05). Consistent with this observation, therapeutic efficacy of effector T cells deficient in LT-α, was greatly reduced when IFN-γ production was neutralized. While recombinant LT-α1β2 did not induce apoptosis of D5 tumor cells in vitro, it induced secretion of chemokines by D5 that promoted migration of macrophages.ConclusionThe contribution of LT-α expression by effector T cells to anti-tumor activity in vivo was not discernable when wt effector T cells were studied. However, the contribution of LT-β R signaling was identified for GKO or PKO/GKO effector T cells. Since LT-α does not directly induce killing of D5 tumor cells in vitro, but does stimulate D5 tumor cells to secrete chemokines, these data suggest a model where LT-α expression by tumor-specific effector T cells interacts via cross-linking of the LT-βR on tumor cells to induce secretion of chemokines that are chemotactic for macrophages. While the contribution of macrophages to tumor elimination in our system requires additional study, this model provides a possible explanation for the infiltration of inate effector cells that is seen coincident with tumor regression.
A focus reduction neutralization assay for hepatitis C virus neutralizing antibodies
Authors: Fournier Carole , Duverlie Gilles , François Catherine , Schnuriger Aurelie , Dedeurwaerder Sarah , Brochot Etienne , Capron Dominique , Wychowski Czeslaw , Thibault Vincent , Castelain Sandrine 
Published: May 2007

Abstract

Background/Aim
The role of humoral immunity in hepatitis C virus (HCV) infection is poorly understood. Nevertheless, there is increasing interest in characterizing the neutralizing antibodies in the serum of HCV-infected patients. Focus reduction assays have been widely used to evaluate neutralizing antibody responses against a range of non-cytopathic viruses. Based on the recent development of a HCV cell culture system using the genotype 2 JFH-1-strain, we developed a focus reduction assay for HCV-neutralizing antibodies.

Methods
The focus reduction assay was based on a standard microneutralization assay in which immunostained foci on tissue culture plates are counted. The neutralizing anti-HCV antibodies titers of purified serum immunoglobulin samples from seventy-seven individuals were determined using a 50% focus reduction neutralization assay. Each titer was determined as the log value of the reciprocal antibody dilution that reduced the number of viral foci by 50%. IgG antibodies were first purified from each serum in order to avoid the facilitating effect of HDL on HCV entry.

Results
The assay's cut-off using an ELISA and RNA HCV-negative samples was found to be 1.25 log, corresponding to a dilution of 1:18. The assay was compared with a commercial HCV ELISA and exhibited specificity and sensitivity values of 100% and 96.5%, respectively, and good reproducibility (with intra-assay and inter-assay coefficients of variation of 6.7% and 12.6%, respectively). The assay did not show any cross-reactivity with anti-HIV, anti-HBs or heterophile antibody-positive samples. The neutralizing antibodies titers were 2.13 log (1:134) for homologous samples from HCV genotype 2 infected patients harboring the same genotype as JFH-1 and 1.93 log (1:85) for heterologous samples from patients infected by genotypes other than type 2. These results confirm the presence of broadly cross-neutralizing antibodies already reported using the HCV pseudoparticles system.

Conclusion
This study presents a simple, specific and reproducible cell culture-based assay for determination of HCV-neutralizing antibodies in human sera. The assay should be an important tool for gauging the relationship between the neutralizing antibodies response and viral load kinetics in acutely or chronically infected patients and for investigating the possible eradication or prevention of HCV infection by neutralizing antibodies.