bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Double-Blind Trial of Enalapril in Older Patients With Heart Failure and Preserved Ejection Fraction
Authors: Kitzman Dalane W. , Hundley W. Gregory , Brubaker Peter H. , Morgan Timothy M. , Moore J. Brian , Stewart Kathryn P. , Little William C. 
Published: June 2010

Background—
Exercise intolerance is the primary symptom in older patients with heart failure and preserved ejection fraction (HFPEF); however, little is known regarding its mechanisms and therapy.

Methods and Results—

Seventy-one stable elderly (70±1 years) patients (80% women) with compensated HFPEF and controlled blood pressure were randomized into a 12-month follow-up double-blind trial of enalapril 20 mg/d versus placebo. Assessments were peak exercise oxygen consumption; 6-minute walk test; Minnesota Living with HF Questionnaire; MRI; Doppler echocardiography; and vascular ultrasound. Compliance by pill count was excellent (94%). Twenty-five patients in the enalapril group versus 34 in the placebo group completed the 12-month follow-up. During follow-up, there was no difference in the primary outcome of peak exercise oxygen consumption (enalapril, 14.5±3.2 mL/kg/min; placebo, 14.3±3.4 mL/kg/min;
P
=0.99), or in 6-minute walk distance, aortic distensibility (the primary mechanistic outcome), left ventricle mass, or neurohormonal profile. The effect size of enalapril on peak exercise oxygen consumption was small (0.7%; 95% CI, 4.2% to 5.6%). There was a trend toward improved Minnesota Living with HF Questionnaire total score (
P
=0.07), a modest reduction in systolic blood pressure at peak exercise (
P
=0.02), and a marginal improvement in carotid arterial distensibility (
P
=0.04).

Conclusions—
In stable, older patients with compensated HFPEF and controlled blood pressure, 12 months of enalapril did not improve exercise capacity or aortic distensibility. These data, combined with those from large clinical event trials, suggest that angiotensin inhibition does not substantially improve key long-term clinical outcomes in this group of patients. This finding contrasts sharply with observations in HF with reduced EF and highlights our incomplete understanding of this important and common disorder.
Potential amplification of territorial advertisement markings by black-backed jackals (Canis mesomelas)
Authors: Hayward Matt , Hayward Gina 
Published: June 2010

AbstractOptimality theory suggests that territorial scent marks are under selective pressure through the information they provide about competitive quality/reproductive status and so should be situated to maximize their detection to alert conspecifics that they are intruding upon the territory of a resident. Factors that increase mark detectability are consequently beneficial to both resident and intruder by allowing tactical withdrawal by intruders and, thus, reducing the costs of conflict. We tested whether black-backed jackals (Canis mesomelas) preferentially deposited territory marks on substrates (rocks or faeces) in two separate sites in South Africa's Addo Elephant National Park. Elephant (Loxodonta africana) dung piles were preferentially defecated upon by jackals in both sites. Where black rhinoceros (Diceros bicornis) was present at relatively high density, rhino middens were also preferentially marked by jackals; however, jackals resorted to defecating on elevated surfaces, such as rocks, where rhinos were scarce. We hypothesize that the odour of elephant and rhino dung may increase the detectability of jackal markings while providing an additional olfactory signal component, while rocks and elephant dung provide visual amplification. Manipulative experimentation will be necessary to confirm our multimodal amplification hypothesis.
The effect of crowding and density on male mating behaviour in the rose bitterling (Rhodeus ocellatus)
Authors: Reichard Martin , Smith Carl , Casalini Mara 
Published: June 2010

AbstractFemale density and resource availability are two key variables that shape mating systems. Theory predicts that reproductive skew will amplify with increased male density and decreasing availability of resources, though limited empirical evidence suggests that this may not always be the case. Here we tested mean crowding, defined as the number of males per unit of resource, and density per se, defined as the number of individuals present per unit area, to investigate their effect on the mating system of Rhodeus ocellatus, a fish with a promiscuous, resource-based mating system. Males were exposed to combinations of high and low levels of crowding and density, while the operational sex ratio was held constant. High levels of crowding significantly affected the proportion of mussel spawning sites defended by males and the proportion of mussels into which sperm was released. In contrast to theoretical predictions, neither density nor crowding influenced overall male aggressive behaviours. Density, but not crowding, had a significant effect on male courtship rate, which arose as a possible trade-off between intra-sexual competition and inter-sexual behaviour. We discuss the results in the context of mating system evolution.
Why Did Ümmü Gülsüm Go to Court? Ottoman Legal Practice between History and Anthropology
Authors: Ergene Boğaç 
Published: June 2010

AbstractThis article offers a critical assessment of the existing literature on Ottoman courts of law, which characterizes the court's operations as single-mindedly legalistic and socially disinterested. There is a conceptual discrepancy between this literature and recent legal and anthropological studies of modern Islamic courts, which highlight the influence on the court's actions of communal considerations, such as the desire to make peace among disputants. With reference to a specific rape incident in eighteenth-century Anatolia, I propose in this article a characterization of Ottoman legal practice that acknowledges the contextual and socially-bounded nature of the court's actions.
Why Aren't Women Sharī'a Court Judges? The Case of Syria
Authors: Cardinal Monique 
Published: June 2010

AbstractWomen make up 14% of the judiciary in Syria and work at all levels of the ordinary courts, both civil and criminal. However, they do not hold office in the personal status courts, special courts that apply codified religious law. This essay presents all opinions, both majority and minority, that explain the legal and social reasons for the non-appointment of women to the Muslim personal status courts known as sharī'a courts. I discuss how religious texts and classical Islamic legal doctrine are used today to undermine women's judicial power and oppose their appointment to the ordinary courts. If a woman cannot act as a sharī'a court judge, then who can? I attempt to answer this all-important question within the Syrian context. The main source of data is interviews conducted with eighty judges and public prosecutors of Damascus and Aleppo between May 2004 and July 2007.
Whose Past Is Our Prologue?
Authors:   Fraser
Published: June 2010

AbstractAlthough globalization promotes homogenization, what we are observing is an intricate and bewildering, worldwide chaos of plans and values. Could some part of history be identified as a prologue to our epoch and, for that reason, used as a guide in our search for ways and means of dealing with that storm of values and plans? I suggest that there can be no prologue to the tensions and problems of globalizing humanity because no prior epoch possessed the promises and threats of our epoch, in the dimensions and intensities we observe them. This essay suggests that the history of humankind as a single social entity—with its unique problems is just beginning. A global community of instant everywhere is only now being constructed. This essay visits that construction process. It recommends that the cries of globalization be explored with the help of the integrated, interdisciplinary study of time for the purpose of helping us appreciate the nature and details of the global changes.
The Undiscovered Country: Sonnets of a Wayfarer
Authors: Turner Frederick 
Published: June 2010

AbstractIn a group of poems several time-related themes are explored in imagistic and narrative terms. The sequence imagines answers to such questions as: What would it feel like to live a second life? If medical science can extend life for many, what would be the sociopolitical implications? How much would such experience replicate mystical conceptions such as reincarnation, afterlife, etc? How would memory survive such a massive reorganization of brain and body? What would be the moral and psychological consequences of not having the pressure of death in one's future? How would personal relationships be affected? What are the implications for authentic living?
Endothelial-derived tissue factor pathway inhibitor regulates arterial thrombosis but is not required for development or hemostasis
Authors: White Thomas A. , Johnson Tucker , Zarzhevsky Natalia , Tom Cindy , Delacroix Sinny , Holroyd Eric W. , Maroney Susan A. , Singh Ripudamanjit , Pan Shuchong , Fay William P. , van Deursen Jan , Mast Alan E. , Sandhu Gurpreet S. , Simari Robert D. 
Published: June 2010

AbstractThe antithrombotic surface of endothelium is regulated in a coordinated manner. Tissue factor pathway inhibitor (TFPI) localized at the endothelial cell surface regulates the production of FXa by inhibiting the TF/VIIa complex. Systemic homozygotic deletion of the first Kunitz (K1) domain of TFPI results in intrauterine lethality in mice. Here we define the cellular sources of TFPI and their role in development, hemostasis, and thrombosis using TFPI conditional knockout mice. We used a Cre-lox strategy and generated mice with a floxed exon 4 (TFPIFlox) which encodes for the TFPI-K1 domain. Mice bred into Tie2-Cre and LysM-Cre lines to delete TFPI-K1 in endothelial (TFPITie2) and myelomonocytic (TFPILysM) cells resulted in viable and fertile offspring. Plasma TFPI activity was reduced in the TFPITie2 (71% ± 0.9%, P < .001) and TFPILysM (19% ± 0.6%, P < .001) compared with TFPIFlox littermate controls. Tail and cuticle bleeding were unaffected. However, TFPITie2 mice but not TFPILysM mice had increased ferric chloride–induced arterial thrombosis. Taken together, the data reveal distinct roles for endothelial- and myelomonocytic-derived TFPI.
Recurrent BRAF mutations in Langerhans cell histiocytosis
Authors: Badalian-Very Gayane , Vergilio Jo-Anne , Degar Barbara A. , MacConaill Laura E. , Brandner Barbara , Calicchio Monica L. , Kuo Frank C. , Ligon Azra H. , Stevenson Kristen E. , Kehoe Sarah M. , Garraway Levi A. , Hahn William C. , Meyerson Matthew , Fleming Mark D. , Rollins Barrett J. 
Published: June 2010

Abstract
Langerhans cell histiocytosis (LCH) has a broad spectrum of clinical behaviors; some cases are self-limited, whereas others involve multiple organs and cause significant mortality. Although Langerhans cells in LCH are clonal, their benign morphology and their lack (to date) of reported recurrent genomic abnormalities have suggested that LCH may not be a neoplasm. Here, using 2 orthogonal technologies for detecting cancer-associated mutations in formalin-fixed, paraffin-embedded material, we identified the oncogenic BRAF V600E mutation in 35 of 61 archived specimens (57%). TP53 and MET mutations were also observed in one sample each. BRAF V600E tended to appear in younger patients but was not associated with disease site or stage. Langerhans cells stained for phospho-mitogen–activated protein kinase kinase (phospho-MEK) and phospho-extracellular signal-regulated kinase (phospho-ERK) regardless of mutation status. High prevalence, recurrent BRAF mutations in LCH indicate that it is a neoplastic disease that may respond to RAF pathway inhibitors.
Right and left heart failure in severe H1N1 influenza A infection
Authors: Brown S.M. , Pittman J. , Miller R.R. , Horton K.D. , Markewitz B. , Hirshberg E. , Jones J. , Grissom C.K. 
Published: June 2010

Influenza infection can affect cardiac function. The recent pandemic of H1N1 influenza A provided an opportunity to study echocardiographic findings in critically ill infected patients.We hypothesised that critically ill patients with H1N1 infection would have a higher incidence of right and left heart failure than is seen in unselected populations of patients with septic shock and/or acute respiratory distress syndrome (ARDS).We retrospectively studied all patients admitted to four intensive care units at three hospitals in Salt Lake County, UT, USA, with laboratory-confirmed H1N1 infection in whom a clinical echocardiogram was available.23 out of 48 patients had qualifying echocardiograms. Right ventricular (RV) dilatation (50–80%) and at least moderate systolic impairment (23%) were common, higher than the range described in general populations with ARDS. Left ventricular systolic dysfunction was present in 17% of patients. No single echocardiographic parameter was associated with 28-day mortality or ventilator-free days to 28 days.Critically ill patients with H1N1 infection frequently exhibit right heart dilatation and failure. RV basal dilatation was extremely common. These patients have less left heart failure than expected on the basis of prior descriptions of influenza myopericarditis or of general populations of septic patients.
Super-sparse principal component analyses for high-throughput genomic data
Authors: Lee Donghwan , Lee Woojoo , Lee Youngjo , Pawitan Yudi 
Published: June 2010

AbstractBackgroundPrincipal component analysis (PCA) has gained popularity as a method for the analysis of high-dimensional genomic data. However, it is often difficult to interpret the results because the principal components are linear combinations of all variables, and the coefficients (loadings) are typically nonzero. These nonzero values also reflect poor estimation of the true vector loadings; for example, for gene expression data, biologically we expect only a portion of the genes to be expressed in any tissue, and an even smaller fraction to be involved in a particular process. Sparse PCA methods have recently been introduced for reducing the number of nonzero coefficients, but these existing methods are not satisfactory for high-dimensional data applications because they still give too many nonzero coefficients.ResultsHere we propose a new PCA method that uses two innovations to produce an extremely sparse loading vector: (i) a random-effect model on the loadings that leads to an unbounded penalty at the origin and (ii) shrinkage of the singular values obtained from the singular value decomposition of the data matrix. We develop a stable computing algorithm by modifying nonlinear iterative partial least square (NIPALS) algorithm, and illustrate the method with an analysis of the NCI cancer dataset that contains 21,225 genes.ConclusionsThe new method has better performance than several existing methods, particularly in the estimation of the loading vectors.
Copine A plays a role in the differentiation of stalk cells and the initiation of culmination in Dictyostelium development
Authors: Smith Tasha S , Pineda Jaimie M , Donaghy Alex C , Damer Cynthia K 
Published: June 2010

Abstract

Background
Copines are calcium-dependent phospholipid-binding proteins found in diverse eukaryotic organisms. We are studying the function of copines in Dictyostelium discoideum, a single-celled amoeba that undergoes cell differentiation and morphogenesis to form multicellular fruiting bodies when placed in starvation conditions. Previously, we showed that Dictyostelium cells lacking the copine A (cpnA) gene are not able to complete the developmental cycle, arresting at the slug stage. The aim of this study is to further characterize the developmental defect of the cpnA- cells.

Results
Time-lapse imaging revealed that cpnA- cells exhibited delayed aggregation and made large mounds that formed one large slug as compared to the smaller slugs of the wild-type cells. While the prespore cell patterning appeared to be normal within the cpnA- slugs, the prestalk cell patterning was different from wild-type. When cpnA- cells were mixed with a small percentage of wild-type cells, chimeric fruiting bodies with short stalks formed. When a small percentage of cpnA- cells was mixed with wild-type cells, the cpnA- cells labeled with GFP were found located throughout the chimeric slug and in both the stalk and sporehead of the fruiting bodies. However, there appeared to be a small bias towards cpnA- cells becoming spore cells. When cpnA- cells were developed in buffer containing EGTA, they were also able to differentiate into either stalk or spore cells to form fruiting bodies with short stalks.

Conclusions
Our results indicate that CpnA is involved in the regulation of aggregation, slug size, and culmination during Dictyostelium development. More specifically, CpnA appears to be involved in the function and differentiation of prestalk cells and plays a role in a calcium-regulated signaling pathway critical to triggering the initiation of culmination.
Asymmetrical hippocampal connectivity in mesial temporal lobe epilepsy: evidence from resting state fMRI
Authors: Pereira Fabrício RS , Alessio Andréa , Sercheli Maurício S , Pedro Tatiane , Bilevicius Elizabeth , Rondina Jane M , Ozelo Helka FB , Castellano Gabriela , Covolan Roberto JM , Damasceno Benito P , Cendes Fernando 
Published: June 2010

AbstractBackgroundMesial temporal lobe epilepsy (MTLE), the most common type of focal epilepsy in adults, is often caused by hippocampal sclerosis (HS). Patients with HS usually present memory dysfunction, which is material-specific according to the hemisphere involved and has been correlated to the degree of HS as measured by postoperative histopathology as well as by the degree of hippocampal atrophy on magnetic resonance imaging (MRI). Verbal memory is mostly affected by left-sided HS, whereas visuo-spatial memory is more affected by right HS. Some of these impairments may be related to abnormalities of the network in which individual hippocampus takes part. Functional connectivity can play an important role to understand how the hippocampi interact with other brain areas. It can be estimated via functional Magnetic Resonance Imaging (fMRI) resting state experiments by evaluating patterns of functional networks. In this study, we investigated the functional connectivity patterns of 9 control subjects, 9 patients with right MTLE and 9 patients with left MTLE.ResultsWe detected differences in functional connectivity within and between hippocampi in patients with unilateral MTLE associated with ipsilateral HS by resting state fMRI. Functional connectivity resulted to be more impaired ipsilateral to the seizure focus in both patient groups when compared to control subjects. This effect was even more pronounced for the left MTLE group.ConclusionsThe findings presented here suggest that left HS causes more reduction of functional connectivity than right HS in subjects with left hemisphere dominance for language.
Tobramycin at subinhibitory concentration inhibits the RhlI/R quorum sensing system in a Pseudomonas aeruginosaenvironmental isolate
Authors: Babić Fedora , Venturi Vittorio , Maravić-Vlahoviček Gordana 
Published: June 2010

Abstract

Background
Antibiotics are not only small molecules with therapeutic activity in killing or inhibiting microbial growth, but can also act as signaling molecules affecting gene expression in bacterial communities. A few studies have demonstrated the effect of tobramycin as a signal molecule on gene expression at the transcriptional level and its effect on bacterial physiology and virulence. These have shown that subinhibitory concentrations (SICs) of tobramycin induce biofilm formation and enhance the capabilities of P. aeruginosa to colonize specific environments.

Methods
Environmental P. aeruginosa strain PUPa3 was grown in the presence of different concentrations of tobramycin and it was determined at which highest concentration SIC, growth, total protein levels and translation efficiency were not affected. At SIC it was then established if phenotypes related to cell-cell signaling known as quorum sensing were altered.

Results
In this study it was determined whether tobramycin sensing/response at SICs was affecting the two independent AHL QS systems in an environmental P. aeruginosa strain. It is reasonable to assume that P. aeruginosa encounters tobramycin in nature since it is produced by niche mate Streptomyces tenebrarius. It was established that SICs of tobramycin inhibited the RhlI/R system by reducing levels of C4-HSL production. This effect was not due to a decrease of rhlI transcription and required tobramycin-ribosome interaction.

Conclusions
Tobramycin signaling in P. aeruginosa occurs and different strains can have a different response. Understanding the tobramycin response by an environmental P. aeruginosa will highlight possible inter-species signalling taking place in nature and can possible also have important implications in the mode of utilization for human use of this very important antibiotic.
Effects of bevacizumab plus irinotecan on response and survival in patients with recurrent malignant glioma: a systematic review and survival-gain analysis
Authors: Xu Tao , Chen Juxiang , Lu Yicheng , Wolff Johannes EA 
Published: June 2010

Abstract

Background
The combination of bevacizumab and irinotecan is a new chemotherapy protocol increasingly used for recurrent malignant glioma. Results from phase II trials suggest this drug combination is beneficial to patients, but no conclusive comparisons between this and other treatment protocols have been published.

Methods
We performed a systematic review and survival gain analysis of phase II studies to evaluate the efficacy and safety of bevacizumab plus irinotecan treatment. To do this, we utilized a preexisting database from which the mean overall survival and response rate of patients could be predicted. Survival gain, which characterized the influence of treatment, was defined as the difference between observed and predicted mean overall survival. Response gain was calculated similarly.

Results
741 cohorts were enrolled in the database. Among them, 282 cohorts were based on recurrent adult HGG, mean reported median overall survival was 10.96 ± 8.4 months, and mean response rate was 18.9% ± 20.5. We found that compared with other treatment protocols, bevacizumab plus irinotecan largely improved response rates (P = 0.00002) and had a possible moderate effect on overall survival time (P = 0.024). Hemorrhage, thromboembolic complications, and gastrointestinal toxicities were the most frequently reported side effects.

Conclusion
The combination of bevacizumab and irinotecan might improve outcome in patients with recurrent malignant glioma. Randomized controlled trials are recommended to evaluate this treatment protocol and the additional value of irinotecan.