bluuebunny/crossref_metadata_2025_split huggingface dataset:
RUNX1 regulates phosphoinositide 3-kinase/AKT pathway: role in chemotherapy sensitivity in acute megakaryocytic leukemia
Authors: Edwards Holly , Xie Chengzhi , LaFiura Katherine M. , Dombkowski Alan A. , Buck Steven A. , Boerner Julie L. , Taub Jeffrey W. , Matherly Larry H. , Ge Yubin 
Published: July 2009

Abstract
RUNX1 (AML1) encodes the core binding factor α subunit of a heterodimeric transcription factor complex which plays critical roles in normal hematopoiesis. Translocations or down-regulation of RUNX1 have been linked to favorable clinical outcomes in acute leukemias, suggesting that RUNX1 may also play critical roles in chemotherapy responses in acute leukemias; however, the molecular mechanisms remain unclear. The median level of RUNX1b transcripts in Down syndrome (DS) children with acute megakaryocytic leukemia (AMkL) were 4.4-fold (P < .001) lower than that in non-DS AMkL cases. Short hairpin RNA knockdown of RUNX1 in a non-DS AMkL cell line, Meg-01, resulted in significantly increased sensitivity to cytosine arabinoside, accompanied by significantly decreased expression of PIK3CD, which encodes the δ catalytic subunit of the survival kinase, phosphoinositide 3 (PI3)–kinase. Transcriptional regulation of PIK3CD by RUNX1 was further confirmed by chromatin immunoprecipitation and promoter reporter gene assays. Further, a PI3-kinase inhibitor, LY294002, and cytosine arabinoside synergized in antileukemia effects on Meg-01 and primary pediatric AMkL cells. Our results suggest that RUNX1 may play a critical role in chemotherapy response in AMkL by regulating the PI3-kinase/Akt pathway. Thus, the treatment of AMkL may be improved by integrating PI3-kinase or Akt inhibitors into the chemotherapy of this disease.
A prospective study of serum soluble CD30 concentration and risk of non-Hodgkin lymphoma
Authors: Purdue Mark P. , Lan Qing , Martinez-Maza Otoniel , Oken Martin M. , Hocking William , Huang Wen-Yi , Baris Dalsu , Conde Betty , Rothman Nathaniel 
Published: July 2009

AbstractPrediagnostic serum concentration of soluble CD30 (sCD30), a marker for chronic B-cell stimulation, has been associated with increased risk of developing AIDS-related non-Hodgkin lymphoma (NHL) in a recent study of HIV+ patients. To investigate among healthy persons whether serum sCD30 is associated with NHL risk, we carried out a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. There was a strong dose-response relationship between prediagnostic sCD30 concentration and NHL risk among 234 cases and 234 individually matched controls (odds ratio [95% confidence interval] for second, third, and fourth quartiles vs first quartile: 1.4 [0.8-2.6], 2.2 [1.2-4.1], 4.1 [2.2-7.8]; Ptrend < .001), which persisted among cases diagnosed 6 to 10 years after providing a blood sample. Given that a similar relationship has been observed among HIV+ patients, our findings suggest that chronic B-cell stimulation may be an important mechanism involved in B-cell lymphomagenesis among severely immunocompromised and healthy populations alike.
How I treat ADA deficiency
Authors: Gaspar H. Bobby , Aiuti Alessandro , Porta Fulvio , Candotti Fabio , Hershfield Michael S. , Notarangelo Luigi D. 
Published: July 2009

AbstractAdenosine deaminase deficiency is a disorder of purine metabolism leading to severe combined immunodeficiency (ADA-SCID). Without treatment, the condition is fatal and requires early intervention. Haematopoietic stem cell transplantation is the major treatment for ADA-SCID, although survival following different donor sources varies considerably. Unlike other SCID forms, 2 other options are available for ADA-SCID: enzyme replacement therapy (ERT) with pegylated bovine ADA, and autologous haematopoietic stem cell gene therapy (GT). Due to the rarity of the condition, the lack of large scale outcome studies, and availability of different treatments, guidance on treatment strategies is limited. We have reviewed the currently available evidence and together with our experience of managing this condition propose a consensus management strategy. Matched sibling donor transplants represent a successful treatment option with high survival rates and excellent immune recovery. Mismatched parental donor transplants have a poor survival outcome and should be avoided unless other treatments are unavailable. ERT and GT both show excellent survival, and therefore the choice between ERT, MUD transplant, or GT is difficult and dependent on several factors, including accessibility to the different modalities, response of patients to long-term ERT, and the attitudes of physicians and parents to the short- and potential long-term risks associated with different treatments.
CLEAN: CLustering Enrichment ANalysis
Authors: Freudenberg Johannes M , Joshi Vineet K , Hu Zhen , Medvedovic Mario 
Published: July 2009

AbstractBackgroundIntegration of biological knowledge encoded in various lists of functionally related genes has become one of the most important aspects of analyzing genome-wide functional genomics data. In the context of cluster analysis, functional coherence of clusters established through such analyses have been used to identify biologically meaningful clusters, compare clustering algorithms and identify biological pathways associated with the biological process under investigation.ResultsWe developed a computational framework for analytically and visually integrating knowledge-based functional categories with the cluster analysis of genomics data. The framework is based on the simple, conceptually appealing, and biologically interpretable gene-specific functional coherence score (CLEAN score). The score is derived by correlating the clustering structure as a whole with functional categories of interest. We directly demonstrate that integrating biological knowledge in this way improves the reproducibility of conclusions derived from cluster analysis. The CLEAN score differentiates between the levels of functional coherence for genes within the same cluster based on their membership in enriched functional categories. We show that this aspect results in higher reproducibility across independent datasets and produces more informative genes for distinguishing different sample types than the scores based on the traditional cluster-wide analysis. We also demonstrate the utility of the CLEAN framework in comparing clusterings produced by different algorithms. CLEAN was implemented as an add-on R package and can be downloaded athttp://Clusteranalysis.org. The package integrates routines for calculating gene specific functional coherence scores and the open source interactive Java-based viewer Functional TreeView (FTreeView).ConclusionOur results indicate that using the gene-specific functional coherence score improves the reproducibility of the conclusions made about clusters of co-expressed genes over using the traditional cluster-wide scores. Using gene-specific coherence scores also simplifies the comparisons of clusterings produced by different clustering algorithms and provides a simple tool for selecting genes with a "functionally coherent" expression profile.
All-trans retinoic acid promotes neural lineage entry by pluripotent embryonic stem cells via multiple pathways
Authors: Lu Jianfeng , Tan Li , Li Ping , Gao Hui , Fang Bo , Ye Shoudong , Geng Zhe , Zheng Ping , Song Houyan 
Published: July 2009

Abstract

Background
All-trans retinoic acid (RA) is one of the most important morphogens with pleiotropic actions. Its embryonic distribution correlates with neural differentiation in the developing central nervous system. To explore the precise effects of RA on neural differentiation of mouse embryonic stem cells (ESCs), we detected expression of RA nuclear receptors and RA-metabolizing enzymes in mouse ESCs and investigated the roles of RA in adherent monolayer culture.

Results
Upon addition of RA, cell differentiation was directed rapidly and exclusively into the neural lineage. Conversely, pharmacological interference with RA signaling suppressed this neural differentiation. Inhibition of fibroblast growth factor (FGF) signaling did not suppress significantly neural differentiation in RA-treated cultures. Pharmacological interference with extracellular signal-regulated kinase (ERK) pathway or activation of Wnt pathway effectively blocked the RA-promoted neural specification. ERK phosphorylation was enhanced in RA-treated cultures at the early stage of differentiation.

Conclusion
RA can promote neural lineage entry by ESCs in adherent monolayer culture systems. This effect depends on RA signaling and its crosstalk with the ERK and Wnt pathways.
Differential expression of three galaxin-related genes during settlement and metamorphosis in the scleractinian coral Acropora millepora
Authors: Reyes-Bermudez Alejandro , Lin Zhiyi , Hayward David C , Miller David J , Ball Eldon E 
Published: July 2009

AbstractBackgroundThe coral skeleton consists of CaCO3deposited upon an organic matrix primarily as aragonite. Currently galaxin, fromGalaxea fascicularis, is the only soluble protein component of the organic matrix that has been characterized from a coral. Three genes related togalaxinwere identified in the coralAcropora millepora.ResultsOne of theAcroporagenes (Amgalaxin) encodes a clear galaxin ortholog, while the others (Amgalaxin-like 1andAmgalaxin-like 2) encode larger and more divergent proteins. All three proteins are predicted to be extracellular and share common structural features, most notably the presence of repetitive motifs containing dicysteine residues. In situ hybridization reveals distinct, but partially overlapping, spatial expression of the genes in patterns consistent with distinct roles in calcification. Both of theAmgalaxin-likegenes are expressed exclusively in the early stages of calcification, whileAmgalaxincontinues to be expressed in the adult, consistent with the situation in the coralGalaxea.ConclusionComparisons with molluscs suggest functional convergence in the two groups; lustrin A/pearlin proteins may be the mollusc counterparts of galaxin, whereas the galaxin-like proteins combine characteristics of two distinct proteins involved in mollusc calcification. Database searches indicate that, although sequences with high similarity to the galaxins are restricted to the Scleractinia, more divergent members of this protein family are present in other cnidarians and some other metazoans. We suggest that ancestral galaxins may have been secondarily recruited to roles in calcification in the Triassic, when the Scleractinia first appeared. Understanding the evolution of the broader galaxin family will require wider sampling and expression analysis in a range of cnidarians and other animals.
A stochastic model for identifying differential gene pair co-expression patterns in prostate cancer progression
Authors: Mo Wen Juan , Fu Xu Ping , Han Xiao Tian , Yang Guang Yuan , Zhang Ji Gang , Guo Feng Hua , Huang Yan , Mao Yu Min , Li Yao , Xie Yi 
Published: July 2009

AbstractBackgroundThe identification of gene differential co-expression patterns between cancer stages is a newly developing method to reveal the underlying molecular mechanisms of carcinogenesis. Most researches of this subject lack an algorithm useful for performing a statistical significance assessment involving cancer progression. Lacking this specific algorithm is apparently absent in identifying precise gene pairs correlating to cancer progression.ResultsIn this investigation we studied gene pair co-expression change by using a stochastic process model for approximating the underlying dynamic procedure of the co-expression change during cancer progression. Also, we presented a novel analytical method named 'Stochastic process model for Identifying differentially co-expressed Gene pair' (SIG method). This method has been applied to two well known prostate cancer data sets: hormone sensitive versus hormone resistant, and healthy versus cancerous. From these data sets, 428,582 gene pairs and 303,992 gene pairs were identified respectively. Afterwards, we used two different current statistical methods to the same data sets, which were developed to identify gene pair differential co-expression and did not consider cancer progression in algorithm. We then compared these results from three different perspectives: progression analysis, gene pair identification effectiveness analysis, and pathway enrichment analysis. Statistical methods were used to quantify the quality and performance of these different perspectives. They included: Re-identification Scale (RS) and Progression Score (PS) in progression analysis, True Positive Rate (TPR) in gene pair analysis, and Pathway Enrichment Score (PES) in pathway analysis. Our results show small values of RS and large values of PS, TPR, and PES; thus, suggesting that gene pairs identified by the SIG method are highly correlated with cancer progression, and highly enriched in disease-specific pathways. From this research, several gene interaction networks inferred could provide clues for the mechanism of prostate cancer progression.ConclusionThe SIG method reliably identifies cancer progression correlated gene pairs, and performs well both in gene pair ontology analysis and in pathway enrichment analysis. This method provides an effective means of understanding the molecular mechanism of carcinogenesis by appropriately tracking down the process of cancer progression.
Unstable housing and hepatitis C incidence among injection drug users in a Canadian setting
Authors: Kim Christina , Kerr Thomas , Li Kathy , Zhang Ruth , Tyndall Mark W , Montaner Julio SG , Wood Evan 
Published: July 2009

Abstract

Background
There has emerged growing recognition of the link between housing and health. Since Vancouver, Canada has had increasing concerns with homelessness brought about by urban renewal in the lead-up to the 2010 Winter Olympic Games, we evaluated hepatitis C virus (HCV) incidence among injection drug users (IDU) with and without stable housing.

Methods
Data were derived from a collaboration between two prospective cohort studies of IDU in Vancouver, Canada. Using Cox Proportional Hazards regression, we compared HCV incidence among participants with and without stable housing, and determined independent predictors of HCV incidence.

Results
Overall, 3074 individuals were recruited between May 1996 and July 2007, among whom 2541 (82.7%) were baseline HCV-infected. Among the 533 (17.3%) individuals who were not HCV-infected at baseline, 147 tested HCV antibody-positive during follow-up, for an incidence density of 16.89 (95% confidence interval: 14.76 – 19.32) per 100 person-years. In a multivariate Cox regression model, unstable housing remained independently associated with HCV infection (relative hazard = 1.47 (1.02 – 2.13).

Conclusion
HCV prevalence and incidence are high in this setting and were associated with unstable housing. Efforts to protect existing low-income housing and improve access to housing may help to reduce HCV incidence.
A computational approach identifies two regions of Hepatitis C Virus E1 protein as interacting domains involved in viral fusion process
Authors: Bruni Roberto , Costantino Angela , Tritarelli Elena , Marcantonio Cinzia , Ciccozzi Massimo , Rapicetta Maria , El Sawaf Gamal , Giuliani Alessandro , Ciccaglione Anna Rita 
Published: July 2009

Abstract

Background
The E1 protein of Hepatitis C Virus (HCV) can be dissected into two distinct hydrophobic regions: a central domain containing an hypothetical fusion peptide (FP), and a C-terminal domain (CT) comprising two segments, a pre-anchor and a trans-membrane (TM) region. In the currently accepted model of the viral fusion process, the FP and the TM regions are considered to be closely juxtaposed in the post-fusion structure and their physical interaction cannot be excluded. In the present study, we took advantage of the natural sequence variability present among HCV strains to test, by purely sequence-based computational tools, the hypothesis that in this virus the fusion process involves the physical interaction of the FP and CT regions of E1.

Results
Two computational approaches were applied. The first one is based on the co-evolution paradigm of interacting peptides and consequently on the correlation between the distance matrices generated by the sequence alignment method applied to FP and CT primary structures, respectively. In spite of the relatively low random genetic drift between genotypes, co-evolution analysis of sequences from five HCV genotypes revealed a greater correlation between the FP and CT domains than respect to a control HCV sequence from Core protein, so giving a clear, albeit still inconclusive, support to the physical interaction hypothesis.
The second approach relies upon a non-linear signal analysis method widely used in protein science called Recurrence Quantification Analysis (RQA). This method allows for a direct comparison of domains for the presence of common hydrophobicity patterns, on which the physical interaction is based upon. RQA greatly strengthened the reliability of the hypothesis by the scoring of a lot of cross-recurrences between FP and CT peptides hydrophobicity patterning largely outnumbering chance expectations and pointing to putative interaction sites. Intriguingly, mutations in the CT region of E1, reducing the fusion process in vitro, strongly reduced the amount of cross-recurrence further supporting interaction between this region and FP.

Conclusion
Our results support a fusion model for HCV in which the FP and the C-terminal region of E1 are juxtaposed and interact in the post-fusion structure. These findings have general implications for viruses, as any visualization of the post-fusion FP-TM complex has been precluded by the impossibility to obtain crystallised viral fusion proteins containing the trans-membrane region. This limitation gives to sequence based modelling efforts a crucial role in the sketching of a molecular interpretation of the fusion process. Moreover, our data also have a more general relevance for cell biology as the mechanism of intracellular fusion showed remarkable similarities with viral fusion
Treatment of malaria from monotherapy to artemisinin-based combination therapy by health professionals in urban health facilities in Yaoundé, central province, Cameroon
Authors: Sayang Collins , Gausseres Mathieu , Vernazza-Licht Nicole , Malvy Denis , Bley Daniel , Millet Pascal 
Published: July 2009

AbstractBackgroundAfter adoption of artesunate-amodiaquine (AS/AQ) as first-line therapy for the treatment of uncomplicated malaria by the malaria control programme, this study was designed to assess the availability of anti-malarial drugs, treatment practices and acceptability of the new protocol by health professionals, in the urban health facilities and drugstores of Yaoundé city, Cameroon.MethodsBetween April and August 2005, retrospective and current information was collected by consulting registers and interviewing health practitioners in urban health facilities using a structured questionnaire.ResultsIn 2005, twenty-seven trade-named drugs have been identified in drugstores; quinine tablets (300 mg) were the most affordable anti-malarial drugs. Chloroquine was restricted to food market places and no generic artemisinin derivative was available in public health centres. In public health facilities, 13.6% of health professionals were informed about the new guidelines; 73.5% supported the use of AS-AQ as first-line therapy. However, 38.6% apprehended its use due to adverse events attributed to amodiaquine. Malaria treatment was mainly based on the diagnosis of fever. Quinine (300 mg tablets) was the most commonly prescribed first-line anti-malarial drug in adults (44.5%) and pregnant women (52.5%). Artequin®was the most cited artemsinin-based combination therapy (ACT) (9.9%). Medical sales representatives were the main sources of information on anti-malarials.ConclusionThe use of AS/AQ was not implemented in 2005 in Yaoundé, despite the wide range of anti-malarials and trade-named artemisinin derivatives available. Nevertheless, medical practitioners will support the use of this combination, when it is available in a paediatric formulation, at an affordable price. Training, information and participation of health professionals in decision-making is one of the key elements to improve adherence to new protocol guidelines. This baseline information will be useful to monitor progress in ACT implementation in Cameroon.
Lipoprotein lipase expression, serum lipid and tissue lipid deposition in orally-administered glycyrrhizic acid-treated rats
Authors: Lim Wai Yen Alfred , Chia Yoke Yin , Liong Shih Yeen , Ton So Ha , Kadir Khalid Abdul , Syed Husain Sharifah Noor Akmal 
Published: July 2009

Abstract

Background
The metabolic syndrome (MetS) is a cluster of metabolic abnormalities comprising visceral obesity, dyslipidaemia and insulin resistance (IR). With the onset of IR, the expression of lipoprotein lipase (LPL), a key regulator of lipoprotein metabolism, is reduced. Increased activation of glucocorticoid receptors results in MetS symptoms and is thus speculated to have a role in the pathophysiology of the MetS. Glycyrrhizic acid (GA), the bioactive constituent of licorice roots (Glycyrrhiza glabra) inhibits 11β-hydroxysteroid dehydrogenase type 1 that catalyzes the activation of glucocorticoids. Thus, oral administration of GA is postulated to ameliorate the MetS.

Results
In this study, daily oral administration of 50 mg/kg of GA for one week led to significant increase in LPL expression in the quadriceps femoris (p < 0.05) but non-significant increase in the abdominal muscle, kidney, liver, heart and the subcutaneous and visceral adipose tissues (p > 0.05) of the GA-treated rats compared to the control. Decrease in adipocyte size (p > 0.05) in both the visceral and subcutaneous adipose tissue depots accompanies such selective induction of LPL expression. Consistent improvement in serum lipid parameters was also observed, with decrease in serum free fatty acid, triacylglycerol, total cholesterol and LDL-cholesterol but elevated HDL-cholesterol (p > 0.05). Histological analysis using tissue lipid staining with Oil Red O showed significant decrease in lipid deposition in the abdominal muscle and quadriceps femoris (p < 0.05) but non-significant decrease in the heart, kidney and liver (p > 0.05).

Conclusion
Results from this study may imply that GA could counteract the development of visceral obesity and improve dyslipidaemia via selective induction of tissue LPL expression and a positive shift in serum lipid parameters respectively, and retard the development of IR associated with tissue steatosis.
Harm reduction in hospitals: is it time?
Authors: Rachlis Beth S , Kerr Thomas , Montaner Julio SG , Wood Evan 
Published: July 2009

Abstract
Among persons who inject drugs (IDU), illicit drug use often occurs in hospitals and contributes to patient expulsion and/or high rates of leaving against medical advice (AMA) when withdrawal is inadequately managed. Resultant disruptions in medical care may increase the likelihood of several harms including drug resistance to antibiotics as well as costly readmissions and increased patient morbidity. In this context, there remains a clear need for the evaluation of harm reduction strategies versus abstinence-based strategies with respect to addressing ongoing issues related to substance use among addicted hospitalized patients. While hospitalization can be used to stabilize addicted patients as they recover from their acute illness and help them to achieve abstinence, patients unable to maintain abstinence should not be penalized for failing to do so at the expense of their health. This article describes harm reduction activities within hospitals and areas for future investigation.