bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymptomatic Saddle Pulmonary Embolism: Case Report and Literature Review
Authors: Musani Muzammil H. 
Published: March 2010

Saddle pulmonary embolism is defined as a visible thromboembolus straddling the bifurcation of the main pulmonary artery trunk. Patient with saddle pulmonary embolism have a 2-week mortality of 5.8%. 46 years old, hypertensive male, presented with right leg swelling and pain, with no evidence of cardiopulmonary distress. CTA showed a large saddle pulmonary embolus. Doppler ultrasound of right lower extremity, revealed a large filling defect extending from the common femoral vein distally involving the deep femoral vein, femoral vein and popliteal vein on the right. Diagnosis of saddle embolus on its own is not associated with an unfavorable outcome, therefore should not influence management of PE. Echocardiography done within 48hours in-patient with symptomatic saddle pulmonary embolism reveals mild to moderate right ventricular enlargement in 90% and mild to severe right ventricular dysfunction in 80%. Emerging evidence suggest that primary therapy with thrombolytics and embolectomy, should be used in PE patients who presents with hypotension plus moderate to severe right ventricular dysfunction on echo cardiogram. Patients with saddle pulmonary embolism can have normal cardiopulmonary reserve; these patients can be managed with conventional treatment for pulmonary embolism in hospital settings, in order to deal with any complications developed during management. Aggressive management should be reserved for patients who are hemodynamically unstable as well as those with echocardiographic evidence of severe right ventricular strain. Physicians should decrease their threshold for suspicion of pulmonary embolism in patients with deep venous thrombosis in the hope of revealing more and more hidden cases of pulmonary embolism.
Pegylated interferon-α, ribavirin, and rituximab combined therapy of hepatitis C virus–related mixed cryoglobulinemia: a long-term study
Authors: Dammacco Franco , Tucci Felicia Anna , Lauletta Gianfranco , Gatti Pietro , De Re Valli , Conteduca Vincenza , Sansonno Silvia , Russi Sabino , Mariggiò Maria Addolorata , Chironna Maria , Sansonno Domenico 
Published: March 2010

AbstractThis study illustrates the use and efficacy of a combination of pegylated interferon-α (Peg-IFN-α) and ribavirin (RBV), with or without rituximab (RTX), in hepatitis C virus (HCV)–related mixed cryoglobulinemia (MC). Twenty-two patients with HCV-related MC received Peg-IFN-α (2a: 180 μg or 2b: 1.5 μg/kg) weekly plus RBV (1000 or 1200 mg) daily for 48 weeks, and RTX (375 mg/m2) once a week for 1 month followed by two 5-monthly infusions (termed PIRR). Fifteen additional patients received Peg-IFN-α/RBV with the same modalities as the PIRR schedule. Complete response was achieved in 54.5% (12/22) and in 33.3% (5/15) of patients who received PIRR and Peg-IFN-α/RBV, respectively (P < .05). Clearance of HCV RNA and conversion of B-cell populations from oligoclonal to polyclonal in liver, bone marrow, and peripheral blood was maintained for up to 3 years in 10 of 12 (83.3%) and in 2 of 5 (40%) patients receiving PIRR and Peg-IFN-α/RBV, respectively (P < .01). Cryoproteins in 22.7% (5/22) of patients with PIRR and in 33.3% (5/15) with Peg-IFN-α/RBV persisted despite sustained HCV RNA clearance. No response occurred in remaining 5 patients of both groups. PIRR therapy is well tolerated and more effective than Peg-IFN-α/RBV combination in HCV-related MC. Its effect may last for more than 3 years.
Cross-presentation by dendritic cells from live cells induces protective immune responses in vivo
Authors: Matheoud Diana , Perié Leila , Hoeffel Guillaume , Vimeux Lene , Parent Isabelle , Marañón Concepción , Bourdoncle Pierre , Renia Laurent , Prevost-Blondel Armelle , Lucas Bruno , Feuillet Vincent , Hosmalin Anne 
Published: March 2010

AbstractCross-presentation is an essential mechanism that allows dendritic cells (DCs) to efficiently present exogenous antigens to CD8+ T cells. Among cellular antigen sources, apoptotic cells are commonly considered as the best for cross-presentation by DCs. However, the potential of live cells as a source of antigen has been overlooked. Here we explored whether DCs were able to capture and cross-present antigens from live cells. DCs internalized cytosolic and membrane material into vesicles from metabolically labeled live cells. Using time-lapse confocal microscopy in whole spleens, we showed that DCs internalized material from live cells in vivo. After ovalbumin uptake from live cells, DCs cross-primed ovalbumin-specific naive OT-I CD8+ T cells in vitro. Injected into mice previously transferred with naive OT-I T cells, they also cross-primed in vivo, even in the absence of endogenous DCs able to present the epitope in the recipient mice. Interestingly, DCs induced stronger natural CD8+ T-cell responses and protection against a lethal tumor challenge after capture of antigens from live melanoma cells than from apoptotic melanoma cells. The potential for cross-presentation from live cells uncovers a new type of cellular intercommunication and must be taken into account for induction of tolerance or immunity against self, tumors, grafts, or pathogens.
How I treat hemochromatosis
Authors: Adams Paul C. , Barton James C. 
Published: March 2010

AbstractHemochromatosis is a common genetic disorder in which iron may progressively accumulate in the liver, heart, and other organs. The primary goal of therapy is iron depletion to normalize body iron stores and to prevent or decrease organ dysfunction. The primary therapy to normalize iron stores is phlebotomy. In this opinion article, we discuss the indications for and monitoring of phlebotomy therapy to achieve iron depletion, maintenance therapy, dietary and pharmacologic maneuvers that could reduce iron absorption, and the role of voluntary blood donation.
Improving pairwise sequence alignment accuracy using near-optimal protein sequence alignments
Authors: Sierk Michael L , Smoot Michael E , Bass Ellen J , Pearson William R 
Published: March 2010

Abstract

Background
While the pairwise alignments produced by sequence similarity searches are a powerful tool for identifying homologous proteins - proteins that share a common ancestor and a similar structure; pairwise sequence alignments often fail to represent accurately the structural alignments inferred from three-dimensional coordinates. Since sequence alignment algorithms produce optimal alignments, the best structural alignments must reflect suboptimal sequence alignment scores. Thus, we have examined a range of suboptimal sequence alignments and a range of scoring parameters to understand better which sequence alignments are likely to be more structurally accurate.

Results
We compared near-optimal protein sequence alignments produced by the Zuker algorithm and a set of probabilistic alignments produced by the probA program with structural alignments produced by four different structure alignment algorithms. There is significant overlap between the solution spaces of structural alignments and both the near-optimal sequence alignments produced by commonly used scoring parameters for sequences that share significant sequence similarity (E-values < 10-5) and the ensemble of probA alignments. We constructed a logistic regression model incorporating three input variables derived from sets of near-optimal alignments: robustness, edge frequency, and maximum bits-per-position. A ROC analysis shows that this model more accurately classifies amino acid pairs (edges in the alignment path graph) according to the likelihood of appearance in structural alignments than the robustness score alone. We investigated various trimming protocols for removing incorrect edges from the optimal sequence alignment; the most effective protocol is to remove matches from the semi-global optimal alignment that are outside the boundaries of the local alignment, although trimming according to the model-generated probabilities achieves a similar level of improvement. The model can also be used to generate novel alignments by using the probabilities in lieu of a scoring matrix. These alignments are typically better than the optimal sequence alignment, and include novel correct structural edges. We find that the probA alignments sample a larger variety of alignments than the Zuker set, which more frequently results in alignments that are closer to the structural alignments, but that using the probA alignments as input to the regression model does not increase performance.

Conclusions
The pool of suboptimal pairwise protein sequence alignments substantially overlaps structure-based alignments for pairs with statistically significant similarity, and a regression model based on information contained in this alignment pool improves the accuracy of pairwise alignments with respect to structure-based alignments.
Correcting for intra-experiment variation in Illumina BeadChip data is necessary to generate robust gene-expression profiles
Authors: Kitchen Robert R , Sabine Vicky S , Sims Andrew H , Macaskill E Jane , Renshaw Lorna , Thomas Jeremy S , van Hemert Jano I , Dixon J Michael , Bartlett John MS 
Published: March 2010

Abstract

Background
Microarray technology is a popular means of producing whole genome transcriptional profiles, however high cost and scarcity of mRNA has led many studies to be conducted based on the analysis of single samples. We exploit the design of the Illumina platform, specifically multiple arrays on each chip, to evaluate intra-experiment technical variation using repeated hybridisations of universal human reference RNA (UHRR) and duplicate hybridisations of primary breast tumour samples from a clinical study.

Results
A clear batch-specific bias was detected in the measured expressions of both the UHRR and clinical samples. This bias was found to persist following standard microarray normalisation techniques. However, when mean-centering or empirical Bayes batch-correction methods (ComBat) were applied to the data, inter-batch variation in the UHRR and clinical samples were greatly reduced. Correlation between replicate UHRR samples improved by two orders of magnitude following batch-correction using ComBat (ranging from 0.9833-0.9991 to 0.9997-0.9999) and increased the consistency of the gene-lists from the duplicate clinical samples, from 11.6% in quantile normalised data to 66.4% in batch-corrected data. The use of UHRR as an inter-batch calibrator provided a small additional benefit when used in conjunction with ComBat, further increasing the agreement between the two gene-lists, up to 74.1%.

Conclusion
In the interests of practicalities and cost, these results suggest that single samples can generate reliable data, but only after careful compensation for technical bias in the experiment. We recommend that investigators appreciate the propensity for such variation in the design stages of a microarray experiment and that the use of suitable correction methods become routine during the statistical analysis of the data.
Evidence of perturbations of cell cycle and DNA repair pathways as a consequence of human and murine NF1-haploinsufficiency
Authors: Pemov Alexander , Park Caroline , Reilly Karlyne M , Stewart Douglas R 
Published: March 2010

Abstract

Background
Neurofibromatosis type 1 (NF1) is a common monogenic tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Haploinsufficiency of NF1 fosters a permissive tumorigenic environment through changes in signalling between cells, however the intracellular mechanisms for this tumor-promoting effect are less clear. Most primary human NF1
+/- cells are a challenge to obtain, however lymphoblastoid cell lines (LCLs) have been collected from large NF1 kindreds. We hypothesized that the genetic effects of NF1-haploinsufficiency may be discerned by comparison of genome-wide transcriptional profiling in somatic, non-tumor cells (LCLs) from NF1-affected and -unaffected individuals. As a cross-species filter for heterogeneity, we compared the results from two human kindreds to whole-genome transcriptional profiling in spleen-derived B lymphocytes from age- and gender-matched Nf1
+/- and wild-type mice, and used gene set enrichment analysis (GSEA), Onto-Express, Pathway-Express and MetaCore tools to identify genes perturbed in NF1-haploinsufficiency.

Results
We observed moderate expression of NF1 in human LCLs and of Nf1 in CD19+ mouse B lymphocytes. Using the t test to evaluate individual transcripts, we observed modest expression differences in the transcriptome in NF1-haploinsufficient LCLs and Nf1-haploinsuffiicient mouse B lymphocytes. However, GSEA, Onto-Express, Pathway-Express and MetaCore analyses identified genes that control cell cycle, DNA replication and repair, transcription and translation, and immune response as the most perturbed in NF1-haploinsufficient conditions in both human and mouse.

Conclusions
Haploinsufficiency arises when loss of one allele of a gene is sufficient to give rise to disease. Haploinsufficiency has traditionally been viewed as a passive state. Our observations of perturbed, up-regulated cell cycle and DNA repair pathways may functionally contribute to NF1-haploinsufficiency as an "active state" that ultimately promotes the loss of the wild-type allele.
CoBaltDB: Complete bacterial and archaeal orfeomes subcellular localization database and associated resources
Authors: Goudenège David , Avner Stéphane , Lucchetti-Miganeh Céline , Barloy-Hubler Frédérique 
Published: March 2010

AbstractBackgroundThe functions of proteins are strongly related to their localization in cell compartments (for example the cytoplasm or membranes) but the experimental determination of the sub-cellular localization of proteomes is laborious and expensive. A fast and low-cost alternative approach isin silicoprediction, based on features of the protein primary sequences. However, biologists are confronted with a very large number of computational tools that use different methods that address various localization features with diverse specificities and sensitivities. As a result, exploiting these computer resources to predict protein localization accurately involves querying all tools and comparing every prediction output; this is a painstaking task. Therefore, we developed a comprehensive database, called CoBaltDB, that gathers all prediction outputs concerning complete prokaryotic proteomes.DescriptionThe current version of CoBaltDB integrates the results of 43 localization predictors for 784 complete bacterial and archaeal proteomes (2.548.292 proteins in total). CoBaltDB supplies a simple user-friendly interface for retrieving and exploring relevant information about predicted features (such as signal peptide cleavage sites and transmembrane segments). Data are organized into three work-sets ("specialized tools", "meta-tools" and "additional tools"). The database can be queried using the organism name, a locus tag or a list of locus tags and may be browsed using numerous graphical and text displays.ConclusionsWith its new functionalities, CoBaltDB is a novel powerful platform that provides easy access to the results of multiple localization tools and support for predicting prokaryotic protein localizations with higher confidence than previously possible. CoBaltDB is available athttp://www.umr6026.univ-rennes1.fr/english/home/research/basic/software/cobalten.
Symbiotic functioning and bradyrhizobial biodiversity of cowpea (Vigna unguiculataL. Walp.) in Africa
Authors: Pule-Meulenberg Flora , Belane Alphonsus K , Krasova-Wade Tatiana , Dakora Felix D 
Published: March 2010

Abstract

Background
Cowpea is the most important food grain legume in Sub-Saharan Africa. However, no study has so far assessed rhizobial biodiversity and/or nodule functioning in relation to strain IGS types at the continent level. In this study, 9 cowpea genotypes were planted in field experiments in Botswana, South Africa and Ghana with the aim of i) trapping indigenous cowpea root-nodule bacteria (cowpea "rhizobia") in the 3 countries for isolation, molecular characterisation using PCR-RFLP analysis, and sequencing of the 16S - 23S rDNA IGS gene, ii) quantifying N-fixed in the cowpea genotypes using the 15N natural abundance technique, and iii) relating the levels of nodule functioning (i.e. N-fixed) to the IGS types found inside nodules.

Results
Field measurements of N2 fixation revealed significant differences in plant growth, δ15N values, %Ndfa and amounts of N-fixed between and among the 9 cowpea genotypes in Ghana and South Africa. Following DNA analysis of 270 nodules from the 9 genotypes, 18 strain IGS types were found. Relating nodule function to the 18 IGS types revealed significant differences in IGS type N2-fixing efficiencies. Sequencing the 16S - 23S rDNA gene also revealed 4 clusters, with cluster 2 forming a distinct group that may be a new Bradyrhizobium species. Taken together, our data indicated greater biodiversity of cowpea bradyrhizobia in South Africa relative to Botswana and Ghana.

Conclusions
We have shown that cowpea is strongly dependant on N2 fixation for its N nutrition in both South Africa and Ghana. Strain IGS type symbiotic efficiency was assessed for the first time in this study, and a positive correlation was discernible where there was sole nodule occupancy. The differences in IGS type diversity and symbiotic efficiency probably accounts for the genotype × environment interaction that makes it difficult to select superior genotypes for use across Africa. The root-nodule bacteria nodulating cowpea in this study all belonged to the genus Bradyrhizobium. Some strains from Southern Africa were phylogenetically very distinct, suggesting a new Bradyrhizobium species.
Reference gene alternatives to Gapdh in rodent and human heart failure gene expression studies
Authors: Brattelid Trond , Winer Lisbeth H , Levy Finn Olav , Liestøl Knut , Sejersted Ole M , Andersson Kristin B 
Published: March 2010

Abstract

Background
Quantitative real-time RT-PCR (RT-qPCR) is a highly sensitive method for mRNA quantification, but requires invariant expression of the chosen reference gene(s). In pathological myocardium, there is limited information on suitable reference genes other than the commonly used Gapdh mRNA and 18S ribosomal RNA. Our aim was to evaluate and identify suitable reference genes in human failing myocardium, in rat and mouse post-myocardial infarction (post-MI) heart failure and across developmental stages in fetal and neonatal rat myocardium.

Results
The abundance of Arbp, Rpl32, Rpl4, Tbp, Polr2a, Hprt1, Pgk1, Ppia and Gapdh mRNA and 18S ribosomal RNA in myocardial samples was quantified by RT-qPCR. The expression variability of these transcripts was evaluated by the geNorm and Normfinder algorithms and by a variance component analysis method. Biological variability was a greater contributor to sample variability than either repeated reverse transcription or PCR reactions.

Conclusions
The most stable reference genes were Rpl32, Gapdh and Polr2a in mouse post-infarction heart failure, Polr2a, Rpl32 and Tbp in rat post-infarction heart failure and Rpl32 and Pgk1 in human heart failure (ischemic disease and cardiomyopathy). The overall most stable reference genes across all three species was Rpl32 and Polr2a. In rat myocardium, all reference genes tested showed substantial variation with developmental stage, with Rpl4 as was most stable among the tested genes.
The expression of TRMT2A, a novel cell cycle regulated protein, identifies a subset of breast cancer patients with HER2 over-expression that are at an increased risk of recurrence
Authors: Hicks David G , Janarthanan Bagi R , Vardarajan Ramya , Kulkarni Swati A , Khoury Thaer , Dim Daniel , Budd G Thomas , Yoder Brian J , Tubbs Raymond , Schreeder Marshall T , Estopinal Noel C , Beck Rodney A , Wang Yanling , Ring Brian Z , Seitz Robert S , Ross Douglas T 
Published: March 2010

Abstract

Background
Over-expression of HER2 in a subset of breast cancers (HER2+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of HER2+ patients to both adjuvant cytotoxic chemotherapy and targeted therapy (e.g. trastuzumab) suggests that unrecognized biologic and clinical diversity is confounding treatment strategies. Furthermore, the small but established risk of cardiac morbidity with trastuzumab therapy compels efforts towards the identification of biomarkers that might help stratify patients.

Methods
A single institution tissue array cohort assembled at the Clearview Cancer Institute of Huntsville (CCIH) was screened by immunohistochemistry staining using a large number of novel and commercially available antibodies to identify those with a univariate association with clinical outcome in HER2+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in HER2+ patients. This association with outcome was tested in two independent validation cohorts; an existing staining dataset derived from tissue assembled at the Cleveland Clinic Foundation (CCF), and in a new retrospective study performed by staining archived paraffin blocks available at the Roswell Park Cancer Institute (RPCI).

Results
TRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 HER2+ patients from the CCIH discovery cohort (HR 7.0; 95% CI 2.4 to 20.1, p < 0.0004). This association with outcome was confirmed using 75 HER2+ patients from the CCF cohort (HR 3.6; 95% CI 1.3 to 10.2, p < 0.02) and 64 patients from the RPCI cohort (HR 3.4; 95% CI 1.3-8.9, p < 0.02). In bivariable analysis the association with outcome was independent of grade, tumor size, nodal status and the administration of conventional adjuvant chemotherapy in the CCIH and RPCI cohorts.

Conclusions
Studies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in HER2+ breast cancer patients. These results suggest that TRMT2A expression should be further studied in the clinical trial setting to explore its predictive power for response to adjuvant cytotoxic chemotherapy in combination with HER2 targeted therapy.