bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimony-Resistant Clinical Isolates of Leishmania donovani Are Susceptible to Paromomycin and Sitamaquine
Authors: Kulshrestha Arpita , Singh Ruchi , Kumar Dhiraj , Negi Narender Singh , Salotra Poonam 
Published: April 2011

ABSTRACT

Widespread antimonial resistance in anthroponotic visceral leishmaniasis (VL) makes it critical to monitor the susceptibility of prevailing field isolates to upcoming antileishmanials in order to frame the right treatment policies to protect these drugs against development of resistance. We aimed to generate the baseline data on natural
in vitro
susceptibility to paromomycin and sitamaquine in
Leishmania donovani
field isolates from VL patients (
n
= 20) coming from zones of varying sodium antimony gluconate (SAG) resistance. We further monitored nitric oxide (NO) release in infected macrophages treated with these drugs. Field isolates exhibited variable sensitivity to paromomycin and sitamaquine with respective mean 50% effective dose (ED
50
) values ± standard error of the mean (SEM) of 3.9 ± 0.3 μM and 2.1 ± 0.2 μM at the intracellular amastigote stage and 29.8 ± 2.5 μM and 17.7 ± 1.0 μM at the promastigote stage. Susceptibilities at the two parasite stages did not correlate for either drug. Isolates from high SAG resistance zones exhibited significantly lower susceptibility to sitamaquine than those from low SAG resistance zones, while isolates from different zones showed similar susceptibilities to paromomycin. NO release was promoted in
L. donovani
-infected macrophages upon treatment with paromomycin/sitamaquine. NO inhibitors significantly compromised amastigote killing by sitamaquine, but not by paromomycin. In conclusion, SAG-resistant/sensitive VL isolates were susceptible to both paromomycin and sitamaquine. Paromomycin, exhibiting higher efficacy against SAG-resistant parasites and having a distinct mechanism of action, appears to be a promising drug for combination therapy.
Very High Concentrations of Active Intracellular Phosphorylated Emtricitabine in Neonates (ANRS 12109 Trial, Step 2)
Authors: Hirt Déborah , Pruvost Alain , Ekouévi Didier K. , Urien Saïk , Arrivé Elise , Kone Mamourou , Nerrienet Eric , Nyati Mandisa , Gray Glenda , Kruy Leang Sim , Blanche Stéphane , Dabis François , Tréluyer Jean-Marc 
Published: April 2011

ABSTRACTOur objective was to investigate neonatal emtricitabine (FTC) plasma and intracellular pharmacokinetics. The study was designed as a phase I/II prospective trial in two sequential steps evaluating the combination of tenofovir disoproxil fumarate (TDF) and FTC for the prevention of mother-to-child-transmission (PMTCT) of HIV. HIV-1-infected pregnant women received two tablets of TDF (300 mg) and FTC (200 mg) at onset of labor and then one tablet daily for 7 days postpartum. Based on the data obtained in the first part of the Tenofovir/Emtricitabine in Africa and Asia (TEmAA) Study, single doses of 2 mg/kg of FTC and 13 mg/kg of TDF were given to the neonates within 12 h after birth. A total of 540 FTC plasma concentrations and 44 active intracellular phosphorylated metabolite FTC-TP concentrations were taken from the 36 enrolled women and their neonates. Concentrations were measured by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and analyzed by a population approach. The proposed dose obtained by simulations based on plasma drug concentrations was confirmed. However, median FTC-TP exposures were, respectively, 5.9 and 6.8 times higher in the fetus and the neonate than in the adult. High FTC-TP concentrations were observed in the four children who had serious adverse events (SAEs), but the link between FTC-TP concentrations and SAEs in children was not formally identified. The exposure to the active form of FTC was high in neonates despite plasma drug concentrations equivalent to those in adults. Our results are similar to those obtained with zidovudine or lamivudine.
Antimicrobial Resistance in Fecal Escherichia coli Isolates from Healthy Urban Children of Two Age Groups in Relation to Their Antibiotic Therapy
Authors: Literak Ivan , Petro Radim , Dolejska Monika , Gruberova Erika , Dobiasova Hana , Petr Jan , Cizek Alois 
Published: April 2011

ABSTRACTThe study was performed in the Czech Republic during 2007 to 2009. OfEscherichia coliisolates from 275 children aged 6 weeks, 36% (n= 177) were resistant to 1 to 7 antibiotics. Of isolates from 253 children aged 6 to 17 years, 24% (n= 205) were resistant to 1 to 5 antibiotics. There was no significant difference in the prevalences of antibiotic-resistantE. coliisolates between these groups of children, even though the consumptions of antibiotics were quite different.
Plasmodium falciparum-Infected Erythrocytes and β-Hematin Induce Partial Maturation of Human Dendritic Cells and Increase Their Migratory Ability in Response to Lymphoid Chemokines
Authors: Giusti Pablo , Urban Britta C. , Frascaroli Giada , Albrecht Letusa , Tinti Anna , Troye-Blomberg Marita , Varani Stefania 
Published: April 2011

ABSTRACTAcute and chronicPlasmodium falciparuminfections alter the immune competence of the host possibly through changes in dendritic cell (DC) functionality. DCs are the most potent activators of T cells, and migration is integral to their function. Mature DCs express lymphoid chemokine receptors (CCRs), expression of which enables them to migrate to the lymph nodes, where they encounter naïve T cells. The present study aimed to investigate the impact of the synthetic analog to malaria parasite pigment hemozoin, i.e., β-hematin, or infected erythrocytes (iRBCs) on the activation status of human monocyte-derived DCs and on their expression of CCRs. Human monocyte-derived DCs partially matured upon incubation with β-hematin as indicated by an increased expression of CD80 and CD83. Both β-hematin and iRBCs provoked the release of proinflammatory and anti-inflammatory cytokines, such as interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha, but not IL-12, and induced upregulation of the lymphoid chemokine receptor CXCR4, which was coupled to an increased migration to lymphoid ligands. Taken together, these results suggest that the partial and transient maturation of human myeloid DCs upon stimulation with malaria parasite-derived products and the increased IL-10 but lack of IL-12 secretion may lead to suboptimal activation of T cells. This may in turn lead to impaired adaptive immune responses and therefore insufficient clearance of the parasites.
Mortality Associated With Atrial Fibrillation in Patients With Myocardial Infarction
Authors: Jabre Patricia , Roger Véronique L. , Murad Mohammad H. , Chamberlain Alanna M. , Prokop Larry , Adnet Frédéric , Jouven Xavier 
Published: April 2011

Background—
Atrial fibrillation (AF) is a common finding in patients with myocardial infarction (MI). Atrial fibrillation is not generally perceived by clinicians as a critical event during the acute phase of MI; however, its prognostic influence in MI remains controversial. Furthermore, contradictory data exist concerning the risk of death according to AF timing. This article, a systematic review and first meta-analysis, aims to quantify the mortality risk associated with AF in MI patients and its timing.

Methods and Results—

A comprehensive search of several electronic databases (1970 to 2010; adults, any language) identified MI studies that evaluated mortality related to AF. Evidence was reviewed by 2 blinded reviewers with a formal assessment of the methodological quality of the studies. Adjusted odds ratios were pooled across studies using the random-effects model. The I
2
statistic was used to assess heterogeneity. In the 43 included studies (278 854 subjects), the mortality odds ratio associated with AF was 1.46 (95% confidence interval, 1.35 to 1.58; I
2
=76%; 23 studies). This worse prognosis persisted regardless of the timing of AF; the odds ratio of mortality for new AF with no prior history of AF was 1.37 (95% confidence interval, 1.26 to 1.49), I
2
=28%, 9 studies), and for prior AF was 1.28 (95% confidence interval, 1.16 to 1.40; I
2
=24%; 4 studies). The sensitivity analysis of new AF studies adjusting for confounding factors did not show a decrease in risk of death.

Conclusions—
Atrial fibrillation is associated with increased risk of mortality in MI patients. New AF with no history of AF before MI remained associated with an increased risk of mortality even after adjustment for several important AF risk factors. These subsequent increases in mortality suggest that AF can no longer be considered a nonsevere event during MI.
Prognostic value of demographic factors, pre-test probability scoring, exercise test diagnosis, and inability to exercise in patients with recent onset suspected cardiac chest pain
Authors: Khattar Rajdeep S , Nair Satheesh B , Hamid Tahir , Chacko Sanoj , Mamas Mamas , Turkie Wajdi , Arumugam Parthiban 
Published: April 2011

Aims: To assess the prognostic value of an inconclusive exercise test or inability to exercise in patients with recent onset suspected cardiac chest pain and to determine the independent predictors of events in these patients. Methods: This was an observational follow-up study of patients presenting to a rapid access chest pain clinic with a history of recent-onset suspected cardiac chest pain as referred by the family practitioner. The main outcome measure was a composite endpoint of death and acute coronary syndrome hospital admission. Results: The study cohort consisted of 1851 patients in whom a total of 147 events were recorded during a mean follow-up period of 4.1 ± 1.1 years. Those with events were significantly older (65.1 ± 12.5 years versus 56.4 ± 13.2 years, p < 0.001), had higher mean pre-test probability of coronary artery disease (CAD), and had higher prevalence of diabetes (18.4% vs. 13.6%, p < 0.001), hypertension (55.8% vs. 38.7%, p < 0.001), and smoking (36.7% vs. 25.4%, p = 0.03) than those without events. These patients were also more likely to have a positive exercise electrocardiogram (ECG) (15.6% vs. 8.6%, p < 0.001) or not have a diagnostic exercise test because of an inconclusive result or inability to exercise (60.5% vs. 28.6%, p < 0.001). Cox multivariate regression analysis showed that age (hazard ratio, HR 1.03, p < 0.001), pre-test probability of CAD (HR 1.08, p = 0.04), positive exercise ECG (HR 2.94, p < 0.001), and an inconclusive test or inability to exercise (HR 3.45, p < 0.001) were independent predictors of events. Conclusions: In patients with recent onset suspected cardiac chest pain, not having a diagnostic exercise ECG because of an inconclusive test or inability to exercise is an independent predictor of events and has similar prognostic implications to a positive exercise ECG. In addition, pre-test probability estimation at baseline is a robust indicator of clinical outcome. Future models of care need to incorporate early and increased access to non-exercise cardiac imaging techniques in order to meet the needs of this high-risk subgroup of patients.
Residues within a lipid-associated segment of the PECAM-1 cytoplasmic domain are susceptible to inducible, sequential phosphorylation
Authors: Paddock Cathy , Lytle Betsy L. , Peterson Francis C. , Holyst Trudy , Newman Peter J. , Volkman Brian F. , Newman Debra K. 
Published: April 2011

AbstractImmunoreceptor tyrosine-based inhibitory motif (ITIM)–containing receptors inhibit cellular responsiveness to immunoreceptor tyrosine-based activation motif (ITAM)–linked receptors. Although tyrosine phosphorylation is central to the initiation of both inhibitory ITIM and stimulatory ITAM signaling, the events that regulate receptor phosphorylation are incompletely understood. Previous studies have shown that ITAM tyrosines engage in structure-inducing interactions with the plasma membrane that must be relieved for phosphorylation to occur. Whether ITIM phosphorylation is similarly regulated and the mechanisms responsible for release from plasma membrane interactions to enable phosphorylation, however, have not been defined. PECAM-1 is a dual ITIM-containing receptor that inhibits ITAM-dependent responses in hematopoietic cells. We found that the PECAM-1 cytoplasmic domain is unstructured in an aqueous environment but adopts an α-helical conformation within a localized region on interaction with lipid vesicles that mimic the plasma membrane. The lipid-interacting segment contains the C-terminal ITIM tyrosine and a serine residue that undergo activation-dependent phosphorylation. The N-terminal ITIM is excluded from the lipid-interacting segment, and its phosphorylation is secondary to phosphorylation of the membrane-interacting C-terminal ITIM. On the basis of these findings, we propose a novel model for regulation of inhibitory signaling by ITIM-containing receptors that relies on reversible plasma membrane interactions and sequential ITIM phosphorylation.
Joint analysis of transcriptional and post- transcriptional brain tumor data: searching for emergent properties of cellular systems
Authors: Fronza Raffaele , Tramonti Michele , Atchley William R , Nardini Christine 
Published: April 2011

Abstract

Background
Advances in biotechnology offer a fast growing variety of high-throughput data for screening molecular activities of genomic, transcriptional, post-transcriptional and translational observations. However, to date, most computational and algorithmic efforts have been directed at mining data from each of these molecular levels (genomic, transcriptional, etc.) separately. In view of the rapid advances in technology (new generation sequencing, high-throughput proteomics) it is important to address the problem of analyzing these data as a whole, i.e. preserving the emergent properties that appear in the cellular system when all molecular levels are interacting. We analyzed one of the (currently) few datasets that provide both transcriptional and post-transcriptional data of the same samples to investigate the possibility to extract more information, using a joint analysis approach.

Results
We use Factor Analysis coupled with pre-established knowledge as a theoretical base to achieve this goal. Our intention is to identify structures that contain information from both mRNAs and miRNAs, and that can explain the complexity of the data. Despite the small sample available, we can show that this approach permits identification of meaningful structures, in particular two polycistronic miRNA genes related to transcriptional activity and likely to be relevant in the discrimination between gliosarcomas and other brain tumors.

Conclusions
This suggests the need to develop methodologies to simultaneously mine information from different levels of biological organization, rather than linking separate analyses performed in parallel.
Long term culture of mesenchymal stem cells in hypoxia promotes a genetic program maintaining their undifferentiated and multipotent status
Authors: Basciano Leticia , Nemos Christophe , Foliguet Bernard , de Isla Natalia , de Carvalho Marcelo , Tran Nguyen , Dalloul Ali 
Published: April 2011

AbstractBackgroundIn the bone marrow, hematopietic and mesenchymal stem cells form a unique niche in which the oxygen tension is low. Hypoxia may have a role in maintaining stem cell fate, self renewal and multipotency. However, whereas most studies addressed the effect of transientin vitroexposure of MSC to hypoxia, permanent culture under hypoxia should reflect the better physiological conditions.ResultsMorphologic studies, differentiation and transcriptional profiling experiments were performed on MSC cultured in normoxia (21% O2) versus hypoxia (5% O2) for up to passage 2. Cells at passage 0 and at passage 2 were compared, and those at passage 0 in hypoxia generated fewer and smaller colonies than in normoxia. In parallel, MSC displayed (>4 fold) inhibition of genes involved in DNA metabolism, cell cycle progression and chromosome cohesion whereas transcripts involved in adhesion and metabolism (CD93, ESAM, VWF, PLVAP, ANGPT2, LEP, TCF1) were stimulated. Compared to normoxic cells, hypoxic cells were morphologically undifferentiated and contained less mitochondrias. After this lag phase, cells at passage 2 in hypoxia outgrew the cells cultured in normoxia and displayed an enhanced expression of genes (4-60 fold) involved in extracellular matrix assembly (SMOC2), neural and muscle development (NOG, GPR56, SNTG2, LAMA) and epithelial development (DMKN). This group described herein for the first time was assigned by the Gene Ontology program to "plasticity".ConclusionThe duration of hypoxemia is a critical parameter in the differentiation capacity of MSC. Even in growth promoting conditions, hypoxia enhanced a genetic program that maintained the cells undifferentiated and multipotent. This condition may better reflect thein vivogene signature of MSC, with potential implications in regenerative medicine.
Expression ratio of CCND1 to CDKN2A mRNA predicts RB1 status of cultured cancer cell lines and clinical tumor samples
Authors: Mizuarai Shinji , Machida Takumitsu , Kobayashi Tsutomu , Komatani Hideya , Itadani Hiraku , Kotani Hidehito 
Published: April 2011

Abstract

Background
The retinoblastoma product (RB1) is frequently deregulated in various types of tumors by mutation, deletion, or inactivation through association with viral oncoproteins. The functional loss of RB1 is recognized to be one of the hallmarks that differentiate cancer cells from normal cells. Many researchers are attempting to develop anti-tumor agents that are preferentially effective against RB1-negative tumors. However, to identify patients with RB1-negative cancers, it is imperative to develop predictive biomarkers to classify RB1-positive and -negative tumors.

Results
Expression profiling of 30 cancer cell lines composed of 16 RB1-positive and 14 RB1-negative cancers was performed to find genes that are differentially expressed between the two groups, resulting in the identification of an RB1 signature with 194 genes. Among them, critical RB1 pathway components CDKN2A and CCND1 were included. We found that microarray data of the expression ratio of CCND1 and CDKN2A clearly distinguished the RB1 status of 30 cells lines. Measurement of the CCND1/CDKN2A mRNA expression ratio in additional cell lines by RT-PCR accurately predicted RB1 status (12/12 cells lines). The expression of CCND1/CDKN2A also correlated with RB1 status in xenograft tumors in vivo. Lastly, a CCND1/CDKN2A assay with clinical samples showed that uterine cervical and small cell lung cancers known to have a high prevalence of RB1-decifiency were predicted to be 100% RB1-negative, while uterine endometrial or gastric cancers were predicted to be 5-22% negative. All clinically normal tissues were 100% RB1-positive.

Conclusions
We report here that the CCND1/CDKN2A mRNA expression ratio predicts the RB1 status of cell lines in vitro and xenograft tumors and clinical tumor samples in vivo. Given the high predictive accuracy and quantitative nature of the CCND1/CDKN2A expression assay, the assay could be utilized to stratify patients for anti-tumor agents with preferential effects on either RB1-positive or -negative tumors.
Health-Related Quality of Life in Non–Small-Cell Lung Cancer: An Update of a Systematic Review on Methodologic Issues in Randomized Controlled Trials
Authors: Claassens Lily , van Meerbeeck Jan , Coens Corneel , Quinten Chantal , Ghislain Irina , Sloan Elizabeth K. , Wang Xin Shelly , Velikova Galina , Bottomley Andrew 
Published: April 2011

Purpose This study is an update of a systematic review of health-related quality-of-life (HRQOL) methodology reporting in non–small-cell lung cancer (NSCLC) randomized controlled trials (RCTs). The objective was to evaluate HRQOL methodology reporting over the last decade and its benefit for clinical decision making. Methods A MEDLINE systematic literature review was performed. Eligible RCTs implemented patient-reported HRQOL assessments and regular oncology treatments for newly diagnosed adult patients with NSCLC. Included studies were published in English from August 2002 to July 2010. Two independent reviewers evaluated all included RCTs. Results Fifty-three RCTs were assessed. Of the 53 RCTs, 81% reported that there was no significant difference in overall survival (OS). However, 50% of RCTs that were unable to find OS differences reported a significant difference in HRQOL scores. The quality of HRQOL reporting has improved; both reporting of clinically significant differences and statistical testing of HRQOL have improved. A European Organisation for Research and Treatment of Cancer HRQOL questionnaire was used in 57% of the studies. However, reporting of HRQOL hypotheses and rationales for choosing HRQOL instruments were significantly less than before 2002 (P < .05). Conclusion The number of NSCLC RCTs incorporating HRQOL assessments has considerably increased. HRQOL continues to demonstrate its importance in RCTs, especially in those studies in which no OS difference is found. Despite the improved quality of HRQOL methodology reporting, certain aspects remain underrepresented. Our findings suggest need for an international standardization of HRQOL reporting similar to the CONSORT guidelines for clinical findings.
Prediction of Venous Thromboembolism in Patients With Cancer by Measuring Thrombin Generation: Results From the Vienna Cancer and Thrombosis Study
Authors: Ay Cihan , Dunkler Daniela , Simanek Ralph , Thaler Johannes , Koder Silvia , Marosi Christine , Zielinski Christoph , Pabinger Ingrid 
Published: April 2011

Purpose Patients with cancer are at increased risk of venous thromboembolism (VTE). Laboratory tests measuring the overall thrombophilic tendency might be useful to assess VTE risk. The aim of this study was to investigate thrombin generation, a key process in hemostasis, as predictor of cancer-associated VTE. Patients and Methods The Vienna Cancer and Thrombosis Study (CATS) is a prospective observational cohort study of patients with newly diagnosed cancer or progression of disease after remission. The study end point is occurrence of objectively confirmed symptomatic or fatal VTE within a follow-up period of 2 years. Thrombin generation was measured with a commercially available assay. Results One thousand thirty-three patients with malignancies of the breast (n = 151), lung (n = 148), upper (n = 44) and lower gastrointestinal tract (n = 125), pancreas (n = 67), kidney (n = 34), prostate (n = 122), and brain (n = 134) or lymphoma (n = 126), multiple myeloma (n = 26), and other tumor types (n = 56) were observed for a median observation period of 517 days. VTE occurred in 77 patients (7.5%). Patients with elevated peak thrombin (defined as values ≥ 611 nM thrombin, representing the 75th percentile of the total study population) had an increased risk of VTE with a hazard ratio of 2.1 (95% CI, 1.3 to 3.3, P = .002) in multivariable analysis including age, sex, surgery, chemotherapy, and radiotherapy. The cumulative probability of developing VTE after 6 months was significantly higher in patients with elevated peak thrombin than in those with lower peak thrombin (11% v 4%; log-rank test: P = .002). Conclusion Measurement of thrombin generation may help identify patients with cancer at high risk of VTE.
Hydrogen Atom Adsorption on Aluminum Clusters: An Electronic Structures Density Functional Study
Authors: Viet Bac Phung Thi , Ogawa Hiroshi 
Published: April 2011

ABSTRACTProperties of hydrogenated icosahedral aluminum clusters were investigated using density functional theory in comparison with those of aluminum bulk systems. Two surface models simulating f.c.c. and icosahedral (111) surfaces were introduced. Results show that the H atom interacts weakly with surface of clusters when the cluster size is increased. The migration energy of H atom between neighboring T and O sites becomes smaller for icosahedral subsurface than for either bulk material or the f.c.c. subsurface. The results indicate that the icosahedral surface is more favored for H atom to adsorp than f.c.c. surface, the icosahedral surface increases the migration barriers of H atom from the surface to the subsurface.