bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Serum Serotonin Predicts Increased Risk for Hip Fracture and Nonvertebral Osteoporotic Fractures: The MrOS Sweden Study
Authors: Kristjansdottir Hallgerdur Lind , Lewerin Catharina , Lerner Ulf H , Waern Ewa , Johansson Helena , Sundh Daniel , Karlsson Magnus , Cummings Steve R , Zetterberg Henrik , Lorentzon Mattias , Ohlsson Claes , Mellström Dan 
Published: May 2018

ABSTRACT

Because several studies have implicated serotonin as a regulator of bone mass, we here explore its potential association on fracture risk and falls, as on bone mineral density (BMD) and muscle strength, in humans. Serum levels of serotonin were analyzed in 950 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based study MrOS Sweden. Men taking selective serotonin reuptake inhibitors (SSRIs) had a mean value of 31.2 μg/L compared with 159.4 μg/L in those not taking SSRIs. SSRI users were excluded from further analysis. During 10-year follow-up, 224 men exhibited fractures, including 97 nonvertebral osteoporotic fractures (57 hip fractures), and 86 vertebral fractures. Serotonin was associated with hip fracture in linear analysis (hazard ratio [HR] = 1.27, 95% confidence interval [CI] 1.03–1.58) and to all fractures in a nonlinear manner, when quintiles of serotonin was included in quadratic terms (HR = 1.12, 95% CI 1.04–1.21). Men in serotonin quintile 5 had, in multivariable analysis, a HR of 2.30 (95% CI 1.31–4.02) for hip fracture and 1.82 (95% CI 1.17–2.85) for nonvertebral fractures compared with men in quintiles 1 to 4. Men in quintile 1 had, in multivariable analysis, a HR of 1.76 (95% CI 1.03–2.99) for nonvertebral fractures compared with men in quintiles 2 to 4. No association was found with vertebral fractures. Individuals in serotonin quintile 1 had higher prevalence of falls compared with quintiles 2 to 5 (odds ratio = 1.90, 95% CI 1.26–2.87). Serotonin was positively associated with hand-grip strength (r = 0.08, p = 0.02) and inversely with hip BMD (r = −0.10, p = 0.003). To assess the association between SSRIs and falls and fractures, the total MrOS Sweden cohort was examined (n = 3014). SSRI users (n = 90) had increased prevalence of falls (16% versus 33%, p = 0.0001) and increased rate of incident fractures (28.0 versus 44.7 per 1000 person-years, p = 0.018). We present novel data showing that high levels of serotonin predict an increased risk for hip fracture and nonvertebral osteoporotic fractures. © 2018 American Society for Bone and Mineral Research.
Robust Trabecular Microstructure in Type 2 Diabetes Revealed by Individual Trabecula Segmentation Analysis of HR-pQCT Images
Authors: Starr Jessica F , Bandeira Leonardo C , Agarwal Sanchita , Shah Ankit M , Nishiyama Kyle K , Hu Yizhong , McMahon Donald J , Guo X Edward , Silverberg Shonni J , Rubin Mishaela R 
Published: May 2018

ABSTRACT

Type 2 diabetes (T2D) patients have an increased fracture risk, which may be partly explained by compromised bone microarchitecture within the cortical bone compartment. Data on trabecular bone parameters in T2D are contradictory. By high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular microarchitecture is preserved, yet larger trabecular holes are detected in T2D by MRI and DXA-based trabecular bone scores are abnormal. To determine if there are differences in trabecular microstructure, connectivity, and alignment in postmenopausal women with T2D as compared with controls, we performed an individual trabecula segmentation (ITS) analysis on HR-pQCT scans of the distal radius and tibia in 92 women with (n = 42) and without (n = 50) T2D. Unadjusted analyses showed that T2D subjects had greater total trabecular bone volume, trabecular plate volume fraction, plate number density, plate junction density, and axial alignment at the radius and tibia, and increased plate tissue fraction, but decreased rod tissue fraction and rod length at the radius (p &lt; 0.05 for all). After adjustments for clinical covariates, plate number density and plate junction density remained higher at the radius and tibia, whereas total trabecular bone volume was increased and trabecular rod length was decreased at the radius. These differences remained significant after adjustment for hip BMD and trabecular volumetric bone density. Notably, the increased plate-like ITS qualities were seen in those with T2D duration of &lt;10 years, whereas ITS parameters in subjects with T2D duration ≥10 years did not differ from those of control subjects. In conclusion, postmenopausal women with early T2D had a greater plate-like and less rod-like trabecular network. This early advantage in trabecular plate quality does not explain the well-established increased fracture risk in these patients and does not persist in the later stage of T2D. © 2018 American Society for Bone and Mineral Research.
Conditional Deletion of Sost in MSC-Derived Lineages Identifies Specific Cell-Type Contributions to Bone Mass and B-Cell Development
Authors: Yee Cristal S , Manilay Jennifer O , Chang Jiun C , Hum Nicholas R , Murugesh Deepa K , Bajwa Jamila , Mendez Melanie E , Economides Aris E , Horan Daniel J , Robling Alexander G , Loots Gabriela G 
Published: May 2018

ABSTRACT

Sclerostin (Sost) is a negative regulator of bone formation and blocking its function via antibodies has shown great therapeutic promise by increasing both bone mass in humans and animal models. Sclerostin deletion in Sost KO mice (Sost−/−) causes high bone mass (HBM) similar to sclerosteosis patients. Sost−/− mice have been shown to display an up to 300% increase in bone volume/total volume (BV/TV), relative to age-matched controls. It has been postulated that the main source of skeletal sclerostin is the osteocyte. To understand the cell-type specific contributions to the HBM phenotype described in Sost−/− mice, as well as to address the endocrine and paracrine mode of action of sclerostin, we examined the skeletal phenotypes of conditional Sost loss-of-function (SostiCOIN/iCOIN) mice with specific deletions in (1) the limb mesenchyme (Prx1-Cre; targets osteoprogenitors and their progeny); (2) midstage osteoblasts and their progenitors (Col1-Cre); (3) mature osteocytes (Dmp1-Cre); and (4) hypertrophic chondrocytes and their progenitors (ColX-Cre). All conditional alleles resulted in significant increases in bone mass in trabecular bone in both the femur and lumbar vertebrae, but only Prx1-Cre deletion fully recapitulated the amplitude of the HBM phenotype in the appendicular skeleton and the B-cell defect described in the global KO. Despite WT expression of Sost in the axial skeleton of Prx1-Cre deleted mice, these mice also had a significant increase in bone mass in the vertebrae, but the sclerostin released in circulation by the axial skeleton did not affect bone parameters in the appendicular skeleton. Also, both Col1 and Dmp1 deletion resulted in a similar 80% significant increase in trabecular bone mass, but only Col1 and Prx1 deletion resulted in a significant increase in cortical thickness. We conclude that several cell types within the Prx1-osteoprogenitor-derived lineages contribute significant amounts of sclerostin protein to the paracrine pool of Sost in bone. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
Persistence of a Posaconazole‐Mediated Drug‐Drug Interaction With Ranolazine After Cessation of Posaconazole Administration: Impact of Obesity and Implications for Patient Safety
Authors: Chow Christina R. , Harmatz Jerold S. , Ryan Michael J. , Greenblatt David J. 
Published: May 2018

AbstractThe antianginal agent ranolazine (Ranexa®) is metabolized primarily by cytochrome P450‐3A (CYP3A) enzymes. Coadministration with strong CYP3A inhibitors, such as ketoconazole and posaconazole, is contraindicated due to risk of QT prolongation from high levels of ranolazine. This study evaluated the time course of recovery from the posaconazole drug interaction in normal‐weight and otherwise healthy obese subjects. Subjects received single doses of ranolazine in the baseline control condition, again during coadministration of posaconazole, and at 4 additional time points during the 2 weeks after posaconazole discontinuation. With posaconazole coadministration, the geometric mean ratio of ranolazine area under the concentration curve (AUC) increased by a factor of 3.9 in normals and by 2.8 in obese subjects. Posttreatment washout of posaconazole was slow in normals (mean half‐life 36 hours) and further prolonged in obese subjects (64 hours). Recovery of ranolazine AUC toward baseline was delayed. AUC remained significantly elevated above baseline in normal‐weight and obese subjects for 7‐14 days after stopping posaconazole. Current product labeling does not address the need for delay or a reduced dose of ranolazine after discontinuation of a strong CYP3A inhibitor before ranolazine can be safely administered. We recommend that administration of ranolazine should be limited to 500 mg twice daily for 7 days after posaconazole discontinuation in patients with body mass index 18.5‐24.9 kg/m2 and for 12 days in patients with body mass index ≥35 kg/m2 after ranolazine is resumed.
LOSP: A putative marker of parasperm lineage in male reproductive system of the prosobranch mollusk Littorina obtusata
Authors: Lobov Arseniy A. , Maltseva Arina L. , Starunov Viktor V. , Babkina Irina Y. , Ivanov Vadim A. , Mikhailova Natalia A. , Granovitch Andrey I. 
Published: May 2018

AbstractReproductive isolation is the key attribute of biological species and establishment of the reproductive barriers is an essential event for speciation. Among the mechanisms of reproductive isolation, gamete incompatibility due to the variability of gamete interaction proteins may drive fast divergence even in sympatry. However, the number of available models to study this phenomenon is limited. In case of internally fertilized invertebrates, models to study gamete incompatibility and sperm competition mechanisms are restricted to a single taxon: insects. Here, we propose a group of closely related Littorina species as a new model for such studies. Particularly since periwinkles are already thoroughly studied in terms of morphology, physiology, ecology, phylogeny, and ecological speciation. Earlier, we have identified the first species‐specific Littorina sperm protein (LOSP) with no known conservative domains or homologies. LOSP is relatively abundant component of sperm extracts and might be involved in gamete incompatibility. Here, we characterize its definitive localization and mRNA expression pattern in the male reproductive system by immunocytochemistry and RNA in situ hybridization. We demonstrate that LOSP distribution is limited to the parasperm cells. Losp gene expression occurs only at the early stages of parasperm development. The protein is stored within granules of mature parasperm and, most likely, is released after ejaculation inside female reproductive system. Thus, LOSP is the only described molluscan paraspermal protein to date, and there is a possibility for LOSP to be involved in gamete incompatibility since heterospermy is a common phenomenon among Littorina.
Synthesis and Biological Activities of 1‐Azaaurone Derivatives
Authors: Zhang Min , Li Ting , Qian Min , Li Kailu , Qin Yukun , Zhao Ting , Yang Liu‐Qing 
Published: May 2018

A series of 1‐azaaurone derivatives were designed and synthesized from 3,5‐dimethoxyaniline and 2‐chloroacetonitrile. Their structures were characterized by melting point, 1H NMR, IR, and elemental analysis, as well as 13C NMR. The target compounds were evaluated for antitumor activities against human hepatocellular liver carcinoma cell line (HepG‐2) and human cervix carcinoma cell line (Hela) using methyl thiazolyl tetrazolium method. The results revealed that several 1‐azaaurones exhibited strong proliferation inhibition efficacy against HepG‐2 and Hela with an IC50 range of 5.6–8.8 μg/mL without damaging normal cell.
Transgelin-2 in immunity: Its implication in cell therapy
Authors: Jo Suin , Kim Hye-Ran , Mun YeVin , Jun Chang-Duk 
Published: May 2018

Abstract
Transgelin-2 is a small 22-kDa actin-binding protein implicated in actin dynamics, which stabilizes actin structures and participates in actin-associated signaling pathways. Much curiosity regarding transgelin-2 has centered around its dysregulation in tumor development and associated diseases. However, recent studies have shed new light on the functions of transgelin-2, the only transgelin family member present in leukocytes, in the context of various immune responses. In this review, we outlined the biochemical properties of transgelin-2 and its physiological functions in T cells, B cells, and macrophages. Transgelin-2 regulates T cell activation by stabilizing the actin cytoskeleton at the immunological synapse. Transgelin-2 in B cells also participates in the stabilization of T cell–B cell conjugates. While transgelin-2 is expressed at trace levels in macrophages, its expression is highly upregulated upon lipopolysaccharide stimulation and plays an essential role in macrophage phagocytosis. Since transgelin-2 increases T cell adhesion to target cells via boosting the "inside-out" costimulatory activation of leukocyte function-associated antigen 1, transgelin-2 could be a suitable candidate to potentiate the antitumor response of cytotoxic T cells by compensating for the lack of costimulation in tumor microenvironment. We discussed the feasibility of using native or engineered transgelin-2 as a synergistic molecule in cell-based immunotherapies, without inducing off-target disturbance in actin dynamics in other cells.
Transgelin-2, the only transgelin family member present in leukocytes, stabilizes actin structures and actively involves in the context of various immune responses.
AFM nano‐mechanical study of the beating profile of hiPSC‐derived cardiomyocytes beating bodies WT and DM1
Authors: Dinarelli S. , Girasole M. , Spitalieri P. , Talarico R.V. , Murdocca M. , Botta A. , Novelli G. , Mango R. , Sangiuolo F. , Longo G. 
Published: May 2018

AbstractMyotonic Dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults, characterized by a variety of multisystemic features and associated with cardiac anomalies. Among cardiac phenomena, conduction defects, ventricular arrhythmias, and dilated cardiomyopathy represent the main cause of sudden death in DM1 patients. Patient‐specific induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) represent a powerful in vitro model for molecular, biochemical, and physiological studies of disease in the target cells. Here, we used an Atomic Force Microscope (AFM) to measure the beating profiles of a large number of cells, organized in CM clusters (Beating Bodies, BBs), obtained from wild type (WT) and DM1 patients. We monitored the evolution over time of the frequency and intensity of the beating. We determined the variations between different BBs and over various areas of a single BB, caused by morphological and biomechanical variations. We exploited the AFM tip to apply a controlled force over the BBs, to carefully assess the biomechanical reaction of the different cell clusters over time, both in terms of beating frequency and intensity. Our measurements demonstrated differences between the WT and DM1 clusters highlighting, for the DM1 samples, an instability which was not observed in WT cells. We measured differences in the cellular response to the applied mechanical stimulus in terms of beating synchronicity over time and cell tenacity, which are in good agreement with the cellular behavior in vivo. Overall, the combination of hiPSC‐CMs with AFM characterization can become a new tool to study the collective movements of cell clusters in different conditions and can be extended to the characterization of the BB response to chemical and pharmacological stimuli.
Performance comparison of deep sequencing platforms for detecting HIV‐1 variants in the pol gene
Authors: Nicot Florence , Jeanne Nicolas , Raymond Stéphanie , Delfour Olivier , Carcenac Romain , Lefebvre Caroline , Sauné Karine , Delobel Pierre , Izopet Jacques 
Published: May 2018

The present study compares the performances of an in‐house sequencing protocol developed on MiSeq, the Sanger method, and the 454 GS‐FLX for detecting and quantifying drug‐resistant mutations (DRMs) in the human immunodeficiency virus polymerase gene (reverse transcriptase [RT] and protease [PR]). MiSeq sequencing identified all the resistance mutations detected by bulk sequencing (n = 84). Both the MiSeq and 454 GS‐FLX platforms identified 67 DRMs in the RT and PR regions, but a further 25 DRMs were identified by only one or other of them. Pearson’s analysis showed good concordance between the percentage of drug‐resistant variants determined by MiSeq and 454 GS‐FLX sequencing (ρ = .77, P < .0001). The MiSeq platform is as accurate as the 454 GS‐FLX Roche system for determining RT and PR DRMs and could be used for monitoring human immunodeficiency virus type 1 drug resistance.
Timing of glacial retreat in the Wicklow Mountains, Ireland, conditioned by glacier size and topography
Authors: Tomkins Matt D. , Dortch Jason M. , Hughes Philip D. , Huck Jonny J. , Tonkin Toby N. , Barr Iestyn D. 
Published: May 2018

ABSTRACTReconstructing the deglacial history of palaeo‐glaciers provides vital information on retreat processes, information which can inform predictions of the future behaviour of many of the world's glaciers. On this basis, this paper presents 170 Schmidt Hammer exposure ages from moraine boulders and glacially sculpted bedrock to reveal the post‐Last Glacial Maximum (LGM) history of the Wicklow Mountains, Ireland. These data suggest that large ice masses survived for 4–7 ka after retreat of the Irish Sea Ice Stream and were sustained by summit ice fields until ∼16.6 ka. Post‐LGM retreat was driven by climate and involved numerous short‐term ice front oscillations (≤1 ka), with widespread moraine deposition during Heinrich Stadial 1. In contrast, marked asynchroneity in the timing of Younger Dryas deglaciation is closely linked to snow redistribution which demonstrates the sensitivity of small cirque glaciers (≤1 km2) to local topography. This result has important implications for palaeoclimate reconstructions as cirque glacier dynamics may be (at least partly) decoupled from climate. This is further complicated by post‐depositional processes which can result in moraine ages (e.g. 10Be) which post‐date retreat. Future palaeoclimate studies should prioritize cirques where snow‐contributing areas are small and where post‐depositional disturbance of moraines is limited.
Analysis of the nexus between population, water resources and Global Food Security highlights significance of governance and research investments and policy priorities
Authors: Yunusa Isa AM , Zerihun Ayalsew , Gibberd Mark R 
Published: May 2018

AbstractBACKGROUNDAnalyses of sensitivity of Global Food Security (FS) score to a key set of supply or demand factors often suggest population and water supply as being the most critical and on which policies tend to focus. To explore other policy options, we characterized the nexus between GFS and a set of supply or demand factors including population, agricultural and industrial water uses, agricultural publications (as a surrogate for investment in agricultural research and development (R&D)) and corruption perception index (CPI), to reveal opportunities for attaining enduring GFS.RESULTSWe found that despite being the primary driver of demand for food, population showed no significant correlation with FS scores. Similarly, agricultural water use was poorly correlated with GFS scores, except in countries where evaporation exceeds precipitation and irrigation is significant. However, FS had a strong positive association with industrial water use as a surrogate for overall industrialization. Recent expansions in cultivated land area failed to yield concomitant improvements in FS score since such expansions have been mostly into marginal lands with low productivity and thus barely compensated for lands retired from cropping in several developed economies. However, FS was positively associated with agricultural R&D investments, as it was with the CPI scores. The apparent and relative strengths of these drivers on FS outcome amongst countries were in the order: industrial water‐use ≈ publication rate ≈ corruption perception ≫ agricultural water use > population.CONCLUSIONSWe suggest that to enshrine enduring food security, policies should prioritize (1) increased R&D investments that address farmer needs and (2) governance mechanisms that promote accountability in both research and production value chains. © 2018 Society of Chemical Industry
An effective FoV restriction approach to mitigate VR sickness on mobile devices
Authors: Kim Sehoon , Lee Seungheon , Kala Nupur , Lee Jaesung , Choe Wonhee 
Published: May 2018

AbstractIt has been noted that restricting field of view (FoV) is effective to mitigate virtual reality (VR) sickness, but it is prone to reduce the immersiveness. We propose an effective FoV restriction approach to mitigate VR sickness on mobile devices. The proposed approach includes a practical and reliable method for measuring VR sickness and a method of effectively limiting the FoV on mobile VR devices. Experimental result shows that the proposed method reduces VR sickness by 31.4%. The method was successfully applied to a VR application.
Online travel behaviour across cohorts: The impact of social influences and attitude on hotel booking intention
Authors: Confente Ilenia , Vigolo Vania 
Published: May 2018

AbstractCohort theory suggests that each generation or cohort differs from others in terms of values and consumption behaviour, including travel behaviour. The literature on online travel behaviour has primarily focused on specific generations; less attention has been paid to cross‐generational research. Adopting the theory of reasoned action framework, this study explores the role of social influences and attitude on online hotel booking intentions across 4 cohorts: Generation Y, Generation X, baby boomers, and the silent generation. Based on a sample of 557 tourists, findings reveal significant differences among cohorts regarding intention to book online.