bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Incident Hip Fracture with the Estimated Femoral Strength by Finite Element Analysis of DXA Scans in the Study of Osteoporotic Fractures
Authors: Yang Lang , Palermo Lisa , Black Dennis M , Eastell Richard 
Published: June 2014

ABSTRACT

A bone fractures only when loaded beyond its strength. The purpose of this study was to determine the association of femoral strength, as estimated by finite element (FE) analysis of dual-energy X-ray absorptiometry (DXA) scans, with incident hip fracture in comparison to hip bone mineral density (BMD), Fracture Risk Assessment Tool (FRAX), and hip structure analysis (HSA) variables. This prospective case-cohort study included a random sample of 1941 women and 668 incident hip fracture cases (295 in the random sample) during a mean ± SD follow-up of 12.8 ± 5.7 years from the Study of Osteoporotic Fractures (n = 7860 community-dwelling women ≥67 years of age). We analyzed the baseline DXA scans (Hologic 1000) of the hip using a validated plane-stress, linear-elastic finite element (FE) model of the proximal femur and estimated the femoral strength during a simulated sideways fall. Cox regression accounting for the case-cohort design assessed the association of estimated femoral strength with hip fracture. The age–body mass index (BMI)-adjusted hazard ratio (HR) per SD decrease for estimated strength (2.21; 95% CI, 1.95–2.50) was greater than that for total hip (TH) BMD (1.86; 95% CI, 1.67–2.08; p &lt; 0.05), FN BMD (2.04; 95% CI, 1.79–2.32; p &gt; 0.05), FRAX scores (range, 1.32–1.68; p &lt; 0.0005), and many HSA variables (range, 1.13–2.43; p &lt; 0.005), and the association was still significant (p &lt; 0.05) after further adjustment for hip BMD or FRAX scores. The association of estimated strength with incident hip fracture was strong (Harrell's C index 0.770), significantly better than TH BMD (0.759; p &lt; 0.05) and FRAX scores (0.711–0.743; p &lt; 0.0001), but not FN BMD (0.762; p &gt; 0.05). Similar findings were obtained for intracapsular and extracapsular fractures. In conclusion, the estimated femoral strength from FE analysis of DXA scans is an independent predictor and performs at least as well as FN BMD in predicting incident hip fracture in postmenopausal women. © 2014 American Society for Bone and Mineral Research.
Dose response of umeclidinium administered once or twice daily in patients with COPD: A pooled analysis of two randomized, double‐blind, placebo‐controlled studies
Authors: Donohue James F. , Kalberg Christopher , Shah Palvi , Beerahee Misba , Mehta Rashmi , Gunawan Rudy , Church Alison 
Published: June 2014

AbstractUmeclidinium (UMEC) is an inhaled long‐acting muscarinic antagonist approved in the US and EU for the once‐daily (QD) treatment of chronic obstructive pulmonary disease (COPD); it is not indicated for the treatment of asthma. To fully characterize the dose–response relationship of UMEC in patients with COPD, a pooled analysis of data from two randomized, placebo‐controlled, cross‐over, dose‐ranging studies was performed, evaluating UMEC at doses of 15.6–1000 mcg QD and 15.6–250 mcg twice daily (BID). The primary endpoint was trough forced expiratory volume in one second (FEV1) at the end of each study's treatment period (Day 8/Day 15). A population model‐based analysis using total daily UMEC dose was used for the primary analysis comparing QD and BID dosing. A physiological effect (Emax) model was optimal in defining the relationship between UMEC dose and the primary endpoint, demonstrating a clear monotonic dose response over QD and BID dosing regimens. UMEC doses ≥62.5 mcg QD were differentiated from lower doses and BID dosing did not provide benefit over QD dosing. The potency (ED50) estimate was 33 mcg with QD dosing. These data indicate that UMEC 62.5 mcg and 125 mcg QD provide lung function benefits that warrant further investigation for the treatment of COPD.
Doppler evaluation of ocular vessels in patients with primary open angle glaucoma
Authors: Suprasanna K. , Shetty Chandrakant M. , Charudutt S. , Kadavigere Rajagopal 
Published: June 2014

ABSTRACTPurposeTo assess ocular blood flow in patients with primary open angle glaucoma (POAG) with or without progressive visual field loss in comparison with controls.MethodsColor Doppler imaging was performed on 78 eyes with established POAG (25 with progressive visual field loss and 53 with stable visual field) and 78 control eyes. Peak systolic velocity, end diastolic velocity (EDV), and resistance index (RI) were measured in the ophthalmic (OA), central‐retinal, and medial and lateral posterior ciliary arteries.ResultsPeak systolic velocity and EDV were lower and RI was higher in the ocular vessels of eyes with POAG (p < .01). The OA and medial posterior ciliary arteries RI was higher, and the OA EDV was lower in glaucomatous eyes with progressive than with stable visual field loss. The receiver operating characteristic curve showed the optimal cutoff RI to be 0.847.ConclusionsOcular blood flow appears compromised in eyes with POAG, particularly in those with progressive visual field loss. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:486–491, 2014
Usefulness of intracardiac echocardiography with a mechanical probe for catheter‐based interventions: A 10‐year prospective registry
Authors: Rigatelli Gianluca , Dell'Avvocata Fabio , Giordan Massimo , Viceconte Nicola , Osanna Rocco Aldo , Braggion Gabriele , Aggio Silvio , Cardaioli Paolo , Chen Jack P. 
Published: June 2014

ABSTRACTBackgroundThe clinical outcome benefit of intracardiac echocardiography (ICE) with a mechanical probe during congenital heart disease interventions has not been fully investigated. We reported the long‐term results of a prospective registry of interatrial shunt closure guided by mechanical ICE.MethodsWe enrolled 537 patients (mean age 48 ± 19.0 years, 378 females) submitted to ICE‐aided procedures in a prospective registry over a 10‐year period (September 2003‐September 2013). All patients underwent transesophageal echocardiography (TEE) before the planned procedure. We evaluated (1) structure identification capability, (2) fossa ovale and interatrial septum component measurement, (3) procedure monitoring capability, (4) procedural and fluoroscopy times, and radiograph dose, (5) probe‐related complications.ResultsICE was successfully performed and was able to correctly identify the structures previously assessed by TEE in all patients. In 24 patients (4.5%), ICE allowed better anatomy definition than TEE. In 35 other patients (6.5%), ICE identified structures not observed by TEE, which led to change indications to interventions or the operative technique to be used. In 131 patients (24.4%), ICE evaluation led to change the planned device to be implanted. There was only one probe‐related complication (0.2%).ConclusionsMechanical ICE may offer a valid alternative to conventional TEE in guiding congenital heart disease interventional procedures. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:534–543, 2014
Challenges Faced by Patients With Progressive Supranuclear Palsy and their Families
Authors: Moore Theresa , Guttman Mark 
Published: June 2014

AbstractThe literature is inadequate for understanding the challenges experienced by people with PSP and their families. Therefore, the aim of this study was to understand the challenges of people with PSP and their caregivers and identify their priority need. In this qualitative study, five focus groups were conducted with people with PSP and/or their family caregivers, one group with long‐term care staff, and one with community caregivers. Data were analyzed using fundamental qualitative description. Four themes were identified: knowledge, services, research, and symptoms. Knowledge challenges were identified as the priority need, with the most common challenges in this category being lack of knowledge of PSP among community workers, physicians, patients, and family members. Service challenges involved service access and interactions with physicians, community workers, private caregivers, and long‐term care staff. Research challenges related to the lack of research and the failure of health care providers or PSP organizations to communicate research findings. Symptoms most often identified as challenging were falls, mobility, vision, mood or thinking, speech, and swallowing. Participants identified their priority need as dissemination of information about PSP. This has not been captured in previous research. This information needs to reach doctors, long‐term care staff, community workers, patients, families, and the general public. Subsequent activities to meet this need are summarized. These activities resulted in three new resources: a brochure for patients and families; an information packet for physicians; and a webinar for staff in long‐term care and community.
Existence results for a nonlinear version of Rotenberg model with infinite maturation velocities
Authors: Boumhamdi Mounir , Latrach Khalid , Zeghal Ahmed 
Published: June 2014

AbstractIn this paper, we present some existence results on L1 spaces of a nonlinear boundary value problem derived from a model introduced by Rotenberg (1983) describing the growth of a cell population. Each cell of this population is distinguished by its degree of maturity μ ∈ [0,1] and its maturation velocity v. The biological boundary at μ = 0 and μ = 1 are fixed and tightly coupled through the mitosis. At mitosis, daughter cells and mother cells are related by a general reproduction rule, which covers all known biological ones. In this work, the maturation velocity is allowed to be infinite, that is, v ∈ [0, + ∞ ). This hypothesis introduce some mathematical difficulties, which are overcomed by using a measure of weak noncompactness adapted to the problem and a recent fixed point theorem (Theorem 3.2) involving weakly compact operators on nonreflexive Banach spaces. Copyright © 2014 John Wiley & Sons, Ltd.
Crystal structures of ligand‐bound octaprenyl pyrophosphate synthase from Escherichia coli reveal the catalytic and chain‐length determining mechanisms
Authors: Han Xu , Chen Chun‐Chi , Kuo Chih‐Jung , Huang Chun‐Hsiang , Zheng Yingying , Ko Tzu‐Ping , Zhu Zhen , Feng Xinxin , Wang Ke , Oldfield Eric , Wang Andrew H.‐J. , Liang Po‐Huang , Guo Rey‐Ting , Ma Yanhe 
Published: June 2014

ABSTRACTOctaprenyl pyrophosphate synthase (OPPs) catalyzes consecutive condensation reactions of one allylic substrate farnesyl pyrophosphate (FPP) and five homoallylic substrate isopentenyl pyrophosphate (IPP) molecules to form a C40 long‐chain product OPP, which serves as a side chain of ubiquinone and menaquinone. OPPs belongs to the trans‐prenyltransferase class of proteins. The structures of OPPs from Escherichia coli were solved in the apo‐form as well as in complexes with IPP and a FPP thio‐analog, FsPP, at resolutions of 2.2–2.6 Å, and revealed the detailed interactions between the ligands and enzyme. At the bottom of the active‐site tunnel, M123 and M135 act in concert to form a wall which determines the final chain length. These results represent the first ligand‐bound crystal structures of a long‐chain trans‐prenyltransferase and provide new information on the mechanisms of catalysis and product chain elongation. Proteins 2015; 83:37–45. © 2014 Wiley Periodicals, Inc.
Light‐yield improvement trends in mixed scintillation crystals
Authors: Sidletskiy Oleg , Gektin Alexander , Belsky Andrei 
Published: June 2014

The behavior of light yield in a wide range of inorganic scintillation crystals formed by isovalent substitution of anions or cations was investigated. The correlation between improvement of light yield in mixed crystals, and the ratios of volumes occupied by the competing atoms (ions) has been analyzed. A phenomenological approach to the prediction of light yield in mixed scintillation crystals allows us to predict the optimal combination of mixing components to reach the best scintillation performance.Relation between the rate of light‐yield improvement and ratio of the volumes occupied by the substituted atoms.
Black Tea Extract and its Thearubigins Relieve the Sildenafil‐Induced Delayed Gut Motility in Mice: A Possible Role of Nitric Oxide
Authors: Murad Hussam A. S. , Abdallah Hossam M. 
Published: June 2014

In this study we hypothesize that a standardized black tea aqueous extract (BTE) and thearubigins, its main polyphenolic pigments, will improve sildenafil‐induced delay in gastric emptying (GE) and small intestinal transit (SIT) in mice. Twenty groups of mice (n = 8) were given a phenol red meal, and three sets of experiments were performed. In the first and second sets, effects of different concentrations of BTE, thearubigins (TRs), and sildenafil (SLD), alone and in combinations, on GE and SIT were measured. In the third set, influence of nω‐Nitro‐l‐arginine methyl ester hydrochloride (l‐NAME) pretreatment on effects of these treatments was tested.Black tea extract (3% and 4.5%) and thearubigins (50 and 60 mg/kg) dose‐dependently increased GE and SIT, whereas BTE 6% and thearubigins 70 mg/kg did not affect them. Sildenafil dose‐dependently reduced both GE and SIT. Combination of metoclopramide, BTE 4.5%, thearubigins 60, or l‐NAME with sildenafil (5 mg/kg) reversed its motility‐delaying effects. Pretreatment with l‐NAME followed by BTE 4.5%, thearubigins 60, BTE 4.5% + sildenafil 5, or thearubigins 60 + sildenafil 5 only partially affected the accelerating effects of BTE 4.5% and thearubigins 60. In conclusion, a standardized BTE and its thearubigins improve the sildenafil‐induced delayed gut motility in mice. This improvement was partially blocked by l‐NAME suggesting a possible role of nitric oxide. Thus, BTE 4.5% or TRs 60 mg/kg solution could be considered a reliever therapy for the sildenafil‐induced dyspepsia. Copyright © 2014 John Wiley & Sons, Ltd.
Electron attachment to some naphthoquinone derivatives: long‐lived molecular anion formation
Authors: Asfandiarov N. L. , Pshenichnyuk S. A. , Vorob'ev A. S. , Nafikova E. P. , Elkin Y. N. , Pelageev D. N. , Koltsova E. A. , Modelli A. 
Published: June 2014

RATIONALEElectron Affinity (EA) is one of the fundamental properties of a molecule. EA values can be measured with various experimental methods, although their availability is still relatively limited. We make an attempt to use Dissociative Electron Attachment Spectroscopy (DEAS) data for evaluation of the EAs of twelve naphthoquinone (NQ) derivatives.METHODSNaphthoquinone (NQ) and eleven of its hydroxyl derivatives were investigated by means of DEAS. A combined investigation of NQ and juglone by means of the Electron Transmission Spectroscopy (ETS) and DEAS techniques, with the support of density functional theory (DFT) calculations, allowed us to elucidate the empty‐level structures of NQ and its hydroxyl derivatives.RESULTSAll molecules under investigation form extremely long‐lived molecular anions associated with three resonant states (except for NQ, where only two long‐lived resonances were observed). The hydroxyl substituents of NQ cause an increase in EA and number of internal degrees of freedom (N), and, as a result, an increase in the mean electron autodetachment lifetimes of the molecular negative ions (NIs). Evaluation of the EAs from the measured lifetimes of the molecular NIs through a simple Arrhenius approximation gives results in reasonable agreement with those obtained with DFT calculations.CONCLUSIONSNI lifetime measurements by means of a modified DEAS instrumentation can provide quantitative data of EA. A simple Arrhenius approximation seems to be adequate to describe the process of electron detachment from molecular anions. Copyright © 2014 John Wiley & Sons, Ltd.
Reversible platypnea‐orthodeoxia syndrome induced by rapidly progressive interstitial pneumonia in a patient with polymyositis
Authors: Yamakawa Hideaki , Yoshida Masahiro , Baba Yuri , Ishikawa Takeo , Takagi Masamichi , Kuwano Kazuyoshi 
Published: June 2014

AbstractWe report a case of platypnea‐orthodeoxia that developed in a 64‐year‐old Japanese woman during an episode of rapidly progressive interstitial pneumonia with polymyositis. Pulmonary infiltrates were predominant in the bilateral lower lobes. The patient was treated successfully with early administration of immunosuppressive therapies and polymyxin B‐immobilized fiber column‐direct hemoperfusion, and her platypnea‐orthodeoxia improved with resolution of the underlying parenchymal lung disease. Reports of platypnea‐orthodeoxia syndrome with interstitial pneumonia are extremely rare. The recognition that platypnea‐orthodeoxia syndrome may occur in multiple disease states, including interstitial pneumonia, is crucial to the understanding of this perplexing disorder.
Molecular Aspects of Adipoepithelial Transdifferentiation in Mouse Mammary Gland
Authors: Prokesch A. , Smorlesi A. , Perugini J. , Manieri M. , Ciarmela P. , Mondini E. , Trajanoski Z. , Kristiansen K. , Giordano A. , Bogner-Strauss J.G. , Cinti Saverio 
Published: June 2014

Abstract
The circular, reversible conversion of the mammary gland during pregnancy and involution is a paradigm of physiological tissue plasticity. The two most prominent cell types in mammary gland, adipocytes and epithelial cells, interact in an orchestrated way to coordinate this process. Previously, we showed that this conversion is at least partly achieved by reciprocal transdifferentiation between mammary adipocytes and lobulo-alveolar epithelial cells. Here, we aim to shed more light on the regulators of mammary transdifferentiation. Using immunohistochemistry with cell type-specific lipid droplet-coating markers (Perilipin1 and 2), we show that cells with an intermediate adipoepithelial phenotype exist during and after pregnancy. Nuclei of cells with similar transitional structural characteristics are highly positive for Elf5, a master regulator of alveologenesis. In cultured adipocytes, we could show that transient and stable ectopic expression of Elf5 induces expression of the milk component whey acidic protein, although the general adipocyte phenotype is not affected suggesting that additional pioneering factors are necessary. Furthermore, the lack of transdifferentiation of adipocytes during pregnancy after clearing of the epithelial compartment indicates that transdifferentiation signals must emanate from the epithelial part. To explore candidate genes potentially involved in the transdifferentiation process, we devised a high-throughput gene expression study to compare cleared mammary fat pads with developing, contralateral controls at several time points during pregnancy. Incorporation of bioinformatic predictions of secretory proteins provides new insights into possible paracrine signaling pathways and downstream transdifferentiation factors. We discuss a potential role for osteopontin (secreted phosphoprotein 1 [Spp1]) signaling through integrins to induce adipoepithelial transdifferentiation. Stem Cells 2014;32:2756–2766
Elevated O-GlcNAc Levels Activate Epigenetically Repressed Genes and Delay Mouse ESC Differentiation Without Affecting Naïve to Primed Cell Transition
Authors: Speakman Christopher M. , Domke Tanja C.E. , Wongpaiboonwattana Wikrom , Sanders Kelly , Mudaliar Manikhandan , van Aalten Daan M.F. , Barton Geoffrey J. , Stavridis Marios P. 
Published: June 2014

Abstract
The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). In EBs, expression of mesodermal and endodermal markers is also delayed. However, the transition of naïve cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation remains unchanged. Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. Stem Cells 2014;32:2605–2615
Notch1 Stimulation Induces a Vascularization Switch With Pericyte-Like Cell Differentiation of Glioblastoma Stem Cells
Authors: Guichet Pierre-Olivier , Guelfi Sophie , Teigell Marisa , Hoppe Liesa , Bakalara Norbert , Bauchet Luc , Duffau Hugues , Lamszus Katrin , Rothhut Bernard , Hugnot Jean-Philippe 
Published: June 2014

Abstract
Glioblastoma multiforms (GBMs) are highly vascularized brain tumors containing a subpopulation of multipotent cancer stem cells. These cells closely interact with endothelial cells in neurovascular niches. In this study, we have uncovered a close link between the Notch1 pathway and the tumoral vascularization process of GBM stem cells. We observed that although the Notch1 receptor was activated, the typical target proteins (HES5, HEY1, and HEY2) were not or barely expressed in two explored GBM stem cell cultures. Notch1 signaling activation by expression of the intracellular form (NICD) in these cells was found to reduce their growth rate and migration, which was accompanied by the sharp reduction in neural stem cell transcription factor expression (ASCL1, OLIG2, and SOX2), while HEY1/2, KLF9, and SNAI2 transcription factors were upregulated. Expression of OLIG2 and growth were restored after termination of Notch1 stimulation. Remarkably, NICD expression induced the expression of pericyte cell markers (NG2, PDGFRβ, and α-smooth muscle actin [αSMA]) in GBM stem cells. This was paralleled with the induction of several angiogenesis-related factors most notably cytokines (heparin binding epidermal growth factor [HB-EGF], IL8, and PLGF), matrix metalloproteinases (MMP9), and adhesion proteins (vascular cell adhesion molecule 1 [VCAM1], intercellular adhesion molecule 1 [ICAM1], and integrin alpha 9 [ITGA9]). In xenotransplantation experiments, contrasting with the infiltrative and poorly vascularized tumors obtained with control GBM stem cells, Notch1 stimulation resulted in poorly disseminating but highly vascularized grafts containing large vessels with lumen. Notch1-stimulated GBM cells expressed pericyte cell markers and closely associated with endothelial cells. These results reveal an important role for the Notch1 pathway in regulating GBM stem cell plasticity and angiogenic properties. Stem Cells 2015;33:21–34