bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Geriatric Assessment and 2-Year Mortality in Elderly Patients Hospitalized for Heart Failure
Authors: Rodriguez-Pascual Carlos , Paredes-Galan Emilio , Vilches-Moraga Arturo , Ferrero-Martinez Ana Isabel , Torrente-Carballido Marta , Rodriguez-Artalejo Fernando 
Published: March 2014

Background—
In older adults hospitalized for heart failure, a poor score on a comprehensive geriatric assessment (CGA) is associated with worse prognosis during hospitalization and at 1 month after discharge. However, the association between the CGA score and long-term mortality is uncertain.

Methods and Results—
This is a prospective study of 487 patients aged ≥75 years admitted for decompensated heart failure. At discharge, a CGA score (range, 0–10) was calculated based on limitation in activities of daily living, mobility limitation, comorbidity, cognitive decline, and previous medication use. The analysis of the association between the CGA score and 2-year subsequent mortality was performed with Cox regression and adjusted for the main confounders. A 1-point increase in the CGA score was associated with a 19% higher mortality (hazard ratio, 1.19; 95% confidence interval, 1.11–1.27). Results were similar regardless of age, sex, left ventricular ejection fraction, and the coexistence of atrial fibrillation, ischemic heart disease, or hypertensive cardiopathy. All components of the CGA score showed a consistent association with higher death risk: the hazard ratio (95% confidence interval) of mortality was 1.78 (1.25–2.54) with ≥3 versus 0 limitations in activities of daily living, 1.36 (1.0–1.86) with moderate or severe versus no or mild limitation in mobility, 1.98 (1.29–3.03) with a ≥5 versus ≤1 score on the Charlson index, 2.48 (1.84–3.34) with previous cognitive decline, and 1.77 (0.99–3.18) in those using ≥8 versus ≤3 medications.

Conclusions—
The score on a simple CGA is associated with long-term mortality in older patients hospitalized for heart failure.
Campanula teutana, a new isophyllous Campanula (Campanulaceae) from the Adriatic region
Authors: Bogdanović Sandro , Brullo Salvatore , Rešetnik Ivana , Satovic Zlatko , Liber Zlatko 
Published: March 2014

The Balkan Peninsula and the amphi-Adriatic region are biodiversity centres with a high number of Campanula species, some of them with restricted and isolated distributions. Among those is the morphologically, karyologically and genetically well-defined linage of isophyllous Campanula species of the garganica clade, taxonomically treated as Campanula ser. Garganicae. In the central Adriatic, on the Island of Vis (Croatia), an isophyllous Campanula was found growing in rocky crevices of calcareous sea cliffs among chasmophytic vegetation with extremely challenging ecological conditions. Based on morphological characters (monopodial growth form, cordate to ovate basal leaves, campanulate corolla, presence of obtuse hairs at the base of filaments, capsule opening by basal pores and brown shiny seeds) the unidentified plant from the Island of Vis falls into ser. Garganicae. To establish the phylogenetic position and relationships of the unknown Campanula among other species of the garganica clade, nuclear ITS and chloroplast trnL-F sequences as well as comparative morphology, karyology and scanning electron microscopy of seeds were used. Due to its campanulate corolla the plants from Vis are morphologically close to C. portenschlagiana from the eastern Adriatic, from which they differ in several quantitative floral characters. The karyological analysis revealed a diploid chromosome number (2n = 34), while SEM analysis showed that seed coat of new taxon has weakly striate testa, thin wavy striped radial walls and slightly marked lumen. Additionally, molecular data show that the Vis taxon is clearly separated as a distinct species from other species of ser. Garganicae. Therefore, it is described and illustrated as a new species, Campanula teutana Bogdanović & Brullo. Because of the small number of individuals within the single population, C. teutana should be included on the Red List of the vascular flora of Croatia as an endangered species (EN).
A new species of Lindernia (Linderniaceae) from India
Authors: PRASAD MANGAVAYAL GOVINDAN 
Published: March 2014

A new species, Lindernia tamilnadensis is described and illustrated from Vijayanarayanam, Tirunelveli district of Tamil Nadu, India. The species shows similarity with a worldwide distributed species, Lindernia rotundifolia in its leaf and seed characters but differs mainly in comparatively smaller floral parts, lanceolate calyx lobes, in the absence of trichomes at the base of the anterior corolla lobes, the presence of staminodal appendages, undeflexed fruiting pedicels and globose capsules. Detailed description, illustration and other relevant notes are provided.
Chronic cerebrospinal venous insufficiency in Ménière disease
Authors: Di Berardino Federica , Alpini Dario Carlo , Bavera Pietro Maria , Cecconi Piero , Farabola Mario , Mattei Valentina , Ambrosetti Umberto , Cesarani Antonio 
Published: March 2014

Objectives The aim of this study was to focus on patients suffering from cochleo-vestibular disorder with and without Ménière disease (MD) in order to verify whether chronic cerebrospinal drainage abnormalities could play a role in the etiopathogenesis of endolymphatic hydrops. Methods Fifty-two volunteers were enrolled and subdivided into two groups: 24 definite MD and 28 not-MD. Both magnetic resonance venography imaging with contrast-enhanced imaging of the venous cerebrospinal system (MRV) and venous echo-color Doppler (ECD) were performed. Results MRV showed abnormalities in 83% of MD and 57% of not-MD subjects ( p < 0.001). Asymmetrical cervical venous flow, assessed by MRV, was confirmed by ECD in 62.5% of MD but in only 21.5% of not-MD subjects ( p<0.001). Conclusion Chronic cerebrospinal venous insufficiency might be the anatomical background, which provides a predisposing factor for the development of endolymphatic hydrops in MD patients.
Involvement of redox balance in in vitro osteoclast formation of RAW 264.7 macrophage cells in response to LPS
Authors: Odkhuu Erdenezaya , Koide Naoki , Tsolmongyn Bilegtsaikhan , Jambalganiin Ulziisaikhan , Naiki Yoshikazu , Komatsu Takayuki , Yoshida Tomoaki , Yokochi Takashi 
Published: March 2014

Here we report that LPS induces osteoclast (OC) formation in murine RAW 264.7 macrophage cells in RPMI-1640 medium but not in α-minimum essential medium (α-MEM) as the original culture medium. LPS-induced OC formation in both media was examined to clarify the differential response. Receptor activator of NF-κB ligand induced OC formation in either α-MEM or RPMI-1640 medium. However, LPS-induced OC formation in RAW 264.7 cells maintained in RPMI-1640 medium, but not α-MEM, which was also supported by mouse bone marrow-derived macrophages, although they were less sensitive to LPS than RAW 264.7 cells. LPS augmented the expression of nuclear factor of activated T-cells (NFATc1) as a key transcription factor of osteoclastogenesis in cells maintained in RPMI-1640 medium, but reduced it in cells maintained in α-MEM. A high concentration of LPS was cytotoxic against cells maintained in α-MEM. Glutathione exclusively present in RPMI-1640 medium prevented LPS-induced cell death in α-MEM and augmented LPS-induced NFATc1 expression, followed by enhanced LPS-induced OC formation. LPS induced higher generation of reactive oxygen species in α-MEM than RPMI-1640 medium. An antioxidant enhanced LPS-induced OC formation, whereas a pro-oxidant reduced it. Taken together, redox balance in the culture condition was suggested to regulate in vitro LPS-induced OC formation.
Combinatorial effects of malaria season, iron deficiency, and inflammation determine plasma hepcidin concentration in African children
Authors: Atkinson Sarah H. , Armitage Andrew E. , Khandwala Shivani , Mwangi Tabitha W. , Uyoga Sophie , Bejon Philip A. , Williams Thomas N. , Prentice Andrew M. , Drakesmith Hal 
Published: March 2014

Key Points
Iron status, erythropoietic drive, inflammation, and malaria season combine to control dynamic fluctuations of hepcidin in African children. At the end of the malaria season, hepcidin is low and ID is more prevalent, so iron therapy may be beneficial at this time.
BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6
Authors: Tobiume Makoto , Shinohara Tsutomu , Kuno Takahira , Mukai Shinji , Naruse Keishi , Hatakeyama Nobuo , Ogushi Fumitaka 
Published: March 2014

AbstractBackgroundPneumonitis is a rare complication of bacillus Calmette-Guerin (BCG) immunotherapy seen in patients with urothelial cancer following the repeated administration of BCG. However, no case of BCG-induced pleurisy has been reported.Case presentationWe here report the first case of pneumonitis with lymphocytic pleurisy following bacillus Calmette-Guerin (BCG) immunotherapy. Although marked T helper cell alveolitis was found by bronchoalveolar lavage and transbronchial biopsies, no acid-fast bacillus could be identified in recovered BALF or pleural effusion. The lymphocyte stimulation test of BCG was strongly positive. However, levels of serum and bronchoalveolar lavage fluid KL-6, a useful marker for hypersensitivity pneumonitis (HP), were within normal ranges.ConclusionWe speculate that the pathogenesis of our case may be a hypersensitive reaction to the proteic component of BCG entering the lung and pleural space, which is different from the etiology of the common type of HP.
Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models
Authors: Wang Xue , Kim Jun-Ran , Lee Seong-Baek , Kim Young-Joon , Jung Moon Young , Kwon Hyung-Wook , Ahn Young-Joon 
Published: March 2014

Abstract

Background
Alzheimer’s disease (AD) is the most common type of presenile and senile dementia. The human β-amyloid precursor cleavage enzyme (BACE-1) is a key enzyme responsible for amyloid plaque production, which implicates the progress and symptoms of AD. Here we assessed the anti-BACE-1 and behavioral activities of curcuminoids from rhizomes of Curcuma longa (Zingiberaceae), diarylalkyls curcumin (CCN), demethoxycurcumin (DMCCN), and bisdemethoxycurcumin (BDMCCN) against AD Drosophila melanogaster models.

Methods
Neuro-protective ability of the curcuminoids was assessed using Drosophila melanogaster model system overexpressing BACE-1 and its substrate APP in compound eyes and entire neurons. Feeding and climbing activity, lifespan, and morphostructural changes in fly eyes also were evaluated.

Results
BDMCCN has the strongest inhibitory activity toward BACE-1 with 17 μM IC50, which was 20 and 13 times lower than those of CCN and DMCCN respectively. Overexpression of APP/BACE-1 resulted in the progressive and measurable defects in morphology of eyes and locomotion. Remarkably, supplementing diet with either 1 mM BDMCCN or 1 mM CCN rescued APP/BACE1-expressing flies and kept them from developing both morphological and behavioral defects. Our results suggest that structural characteristics, such as degrees of saturation, types of carbon skeleton and functional group, and hydrophobicity appear to play a role in determining inhibitory potency of curcuminoids on BACE-1.

Conclusion
Further studies will warrant possible applications of curcuminoids as therapeutic BACE-1 blockers.
Mesenchymal cell interaction with ovarian cancer cells induces a background dependent pro-metastatic transcriptomic profile
Authors: Lis Raphael , Touboul Cyril , Halabi Najeeb M , Madduri Abishek Sainath , Querleu Denis , Mezey Jason , Malek Joel A , Suhre Karsten , Rafii Arash 
Published: March 2014

AbstractBackgroundThe cross talk between the stroma and cancer cells plays a major role in phenotypic modulation. During peritoneal carcinomatosis ovarian cancer cells interact with mesenchymal stem cells (MSC) resulting in increased metastatic ability. Understanding the transcriptomic changes underlying the phenotypic modulation will allow identification of key genes to target. However in the context of personalized medicine we must consider inter and intra tumoral heterogeneity. In this study we used a pathway-based approach to illustrate the role of cell line background in transcriptomic modification during a cross talk with MSC.MethodsWe used two ovarian cancer cell lines as a surrogate for different ovarian cancer subtypes: OVCAR3 for an epithelial and SKOV3 for a mesenchymal subtype. We co-cultured them with MSCs. Genome wide gene expression was determined after cell sorting. Ingenuity pathway analysis was used to decipher the cell specific transcriptomic changes related to different pro-metastatic traits (Adherence, migration, invasion, proliferation and chemoresistance).ResultsWe demonstrate that co-culture of ovarian cancer cells in direct cellular contact with MSCs induces broad transcriptomic changes related to enhance metastatic ability. Genes related to cellular adhesion, invasion, migration, proliferation and chemoresistance were enriched under these experimental conditions. Network analysis of differentially expressed genes clearly shows a cell type specific pattern.ConclusionThe contact with the mesenchymal niche increase metastatic initiation and expansion through cancer cells’ transcriptome modification dependent of the cellular subtype. Personalized medicine strategy might benefit from network analysis revealing the subtype specific nodes to target to disrupt acquired pro-metastatic profile.
Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout
Authors: Lipsky Peter E , Calabrese Leonard H , Kavanaugh Arthur , Sundy John S , Wright David , Wolfson Marsha , Becker Michael A 
Published: March 2014

Abstract
Introduction
The efficacy of pegloticase, a polyethylene glycol (PEG)-conjugated mammalian recombinant uricase, approved for chronic refractory gout, can be limited by the development of antibodies (Ab). Analyses from 2 replicate, 6-month, randomized controlled trials were performed to characterize Ab responses to pegloticase.

Methods
Anti-pegloticase, anti-PEG, and anti-uricase Ab were determined by validated enzyme-linked immunosorbent assays. Ab titers were analyzed for possible relationships with serum pegloticase concentrations, serum uric acid (sUA) lowering, and risk of infusion reactions (IRs).

Results
Sixty-nine (41%) of 169 patients receiving pegloticase developed high titer anti-pegloticase Ab (> 1:2430) and 40% (67/169) developed anti-PEG Ab; 1 patient receiving placebo developed high titer anti-pegloticase Ab. Only 14% (24/169) of patients developed anti-uricase Ab, usually at low titer. In responders, patients showing sustained UA lowering, mean anti-pegloticase titers at week 25 (1:837 ± 1687 with biweekly and 1:2025 ± 4506 with monthly dosing) were markedly lower than in nonresponders (1:34,528 ± 42,228 and 1:89,658 ± 297,797, respectively). Nonresponder status was associated with reduced serum pegloticase concentrations. Baseline anti-pegloticase Ab, evident in 15% (31/212) of patients, did not predict subsequent loss of urate-lowering response. Loss of sUA response preceded IRs in 44 of 56 (79%) pegloticase-treated patients.

Conclusions
Loss of responsiveness to pegloticase is associated with the development of high titer anti-pegloticase Ab that increase clearance of pegloticase and are associated with a loss of the sUA lowering effect and increased IR risk. Pre-infusion sUA can be used as a surrogate for the presence of deleterious anti-pegloticase Ab.

Trial registration
NCT00325195. Registered 10 May 2006, NCT01356498. Registered 27 October 2008.
Quantitative reconstruction of leukocyte subsets using DNA methylation
Authors: Accomando William P , Wiencke John K , Houseman E Andres , Nelson Heather H , Kelsey Karl T 
Published: March 2014

Abstract
Background
Cell lineage-specific DNA methylation patterns distinguish normal human leukocyte subsets and can be used to detect and quantify these subsets in peripheral blood. We have developed an approach that uses DNA methylation to simultaneously quantify multiple leukocyte subsets, enabling investigation of immune modulations in virtually any blood sample including archived samples previously precluded from such analysis. Here we assess the performance characteristics and validity of this approach.

Results
Using Illumina Infinium HumanMethylation27 and VeraCode GoldenGate Methylation Assay microarrays, we measure DNA methylation in leukocyte subsets purified from human whole blood and identify cell lineage-specific DNA methylation signatures that distinguish human T cells, B cells, NK cells, monocytes, eosinophils, basophils and neutrophils. We employ a bioinformatics-based approach to quantify these cell types in complex mixtures, including whole blood, using DNA methylation at as few as 20 CpG loci. A reconstruction experiment confirms that the approach could accurately measure the composition of mixtures of human blood leukocyte subsets. Applying the DNA methylation-based approach to quantify the cellular components of human whole blood, we verify its accuracy by direct comparison to gold standard immune quantification methods that utilize physical, optical and proteomic characteristics of the cells. We also demonstrate that the approach is not affected by storage of blood samples, even under conditions prohibiting the use of gold standard methods.

Conclusions
Cell mixture distributions within peripheral blood can be assessed accurately and reliably using DNA methylation. Thus, precise immune cell differential estimates can be reconstructed using only DNA rather than whole cells.
Monitoring ferumoxide-labelled neural progenitor cells and lesion evolution by magnetic resonance imaging in a model of cell transplantation in cerebral ischaemia
Authors: Panizzo Rachael A , Gadian David G , Sowden Jane C , Wells Jack A , Lythgoe Mark F , Ferretti Patrizia 
Published: March 2014

Efficacy of neural stem/progenitor cell (NPC) therapies after cerebral ischaemia could be better evaluated by monitoring in vivo migration and distribution of cells post-engraftment in parallel with analysis of lesion volume and functional recovery. Magnetic resonance imaging (MRI) is ideally placed to achieve this, but still poses several challenges. We show that combining the ferumoxide MRI contrast agent Endorem with protamine sulphate (FePro) improves iron oxide uptake in cells compared to Endorem alone and is non-toxic. Hence FePro complex is a better contrast agent than Endorem for monitoring NPCs. FePro complex-labelled NPCs proliferated and differentiated normally in vitro, and upon grafting into the brain 48 hours post-ischaemia they were detected in vivo by MRI. Imaging over four weeks showed the development of a confounding endogenous hypointense contrast evolution at later timepoints within the lesioned tissue. This was at least partly due to accumulation within the lesion of macrophages and endogenous iron. Neither significant NPC migration, assessed by MRI and histologically, nor a reduction in the ischaemic lesion volume was observed in NPC-grafted brains. Crucially, while MRI provides reliable information on engrafted cell location early after an ischaemic insult, pathophysiological changes to ischaemic lesions can interfere with cellular imaging at later timepoints.
Improving Money’s Worth Ratio Calculations: The Case of Singapore’s Pension Annuities
Authors: Fong Joelle H. , Lemaire Jean , Tse Yiu K. 
Published: March 2014

Abstract
This paper contributes to a better understanding of the risks involved in a life annuity investment. We study the full distribution of weighted annuity benefits and quantify risk measures such as dispersion and skewness, thereby extending the usefulness of the popular money’s worth valuation framework for life annuities. Using data from pension annuities in Singapore, we also introduce several risk measures that might appeal to less financially sophisticated retirees. A more detailed and accurate picture of the risk of investing in life annuities emerges, enabling prospective annuitants to differentiate among products that may appear seemingly uniform in terms of money’s worth, but vary widely in terms of their risk attributes.
Control of cellular motility by neuropilin-mediated physical interactions
Authors: Li Xiaobo , Parker Matthew W. , Kooi Craig W. Vander 
Published: March 2014

AbstractThe neuropilin (Nrp) family consists of multifunctional cell surface receptors with critical roles in a number of different cell and tissue types. A core aspect of Nrp function is in ligand-dependent cellular migration, where it controls the multistep process of cellular motility through integration of ligand binding and receptor signaling. At a molecular level, the role of Nrp in migration is intimately connected to the control of adhesive interactions and cytoskeletal reorganization. Here, we review the physiological role of Nrp in cellular adhesion and motility in the cardiovascular and nervous systems. We also discuss the emerging pathological role of Nrp in tumor cell migration and metastasis, providing motivation for continued efforts toward developing Nrp inhibitors.
Epigenetic regulations through DNA methylation and hydroxymethylation: clues for early pregnancy in decidualization
Authors: Gao Fei , Das Sanjoy K. 
Published: March 2014

AbstractDNA methylation at cytosines is an important epigenetic modification that participates in gene expression regulation without changing the original DNA sequence. With the rapid progress of high-throughput sequencing techniques, whole-genome distribution of methylated cytosines and their regulatory mechanism have been revealed gradually. This has allowed the uncovering of the critical roles played by DNA methylation in the maintenance of cell pluripotency, determination of cell fate during development, and in diverse diseases. Recently, rediscovery of 5-hydroxymethylcytosine, and other types of modification on DNA, have uncovered more dynamic aspects of cell methylome regulation. The interaction of DNA methylation and other epigenetic changes remodel the chromatin structure and determine the state of gene transcription, not only permanently, but also transiently under certain stimuli. The uterus is a reproductive organ that experiences dramatic hormone stimulated changes during the estrous cycle and pregnancy, and thus provides us with a unique model for studying the dynamic regulation of epigenetic modifications. In this article, we review the current findings on the roles of genomic DNA methylation and hydroxymethylation in the regulation of gene expression, and discuss the progress of studies for these epigenetic changes in the uterus during implantation and decidualization.