bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Genetic Loci Control Calcium Absorption and Femur Bone Mass as Well as Their Response to Low Calcium Intake in Male BXD Recombinant Inbred Mice
Authors: Reyes Fernandez Perla C , Replogle Rebecca A , Wang Libo , Zhang Min , Fleet James C 
Published: December 2015

ABSTRACT

Low dietary calcium (Ca) intake during growth limits peak bone mass but physiological adaptation can prevent this adverse effect. To assess the genetic control on the physiologic response to dietary Ca restriction (RCR), we conducted a study in 51 BXD lines fed either 0.5% (basal) or 0.25% (low) Ca diets from ages 4 to 12 weeks (n = 8/line/diet). Ca absorption (CaAbs), femur bone mineral density (BMD), and bone mineral content (BMC) were examined. ANCOVA with body size as covariate was used to detect significant line and diet main effects, and line-by-diet interactions. Body size–corrected residuals were used for linkage mapping and to estimate heritability (h2). Loci controlling the phenotypes were identified using composite interval mapping on each diet and for the RCR. h2 of basal phenotypes (0.37–0.43) and their RCR (0.32–0.38) was moderate. For each phenotype, we identified multiple quantitative trait loci (QTL) on each diet and for the RCR. Several loci affected multiple traits: Chr 1 (88.3–90.6 cM, CaAbs, BMC), Chr 4 (45.8–49.2 cM, CaAbs, BMD, BMC), Chr 8 (28.6–31.6 cM, CaAbs, BMD, RCR), and Chr 15 (13.6–24 cM, BMD, BMC; 32.3–36 cM, CaAbs RCR, BMD). This suggests that gene clusters may regulate interdependent bone-related phenotypes. Using in silico expression QTL (eQTL) mapping and bioinformatic tools, we identified novel candidates for the regulation of bone under Ca stress (Ext1, Deptor), and for the first time, we report genes modulating Ca absorption (Inadl, Sc4mol, Sh3rf1, and Dennd3), and both Ca and bone metabolism (Tceanc2, Tll1, and Aadat). Our data reveal gene-by-diet interactions and the existence of novel relationships between bone and Ca metabolism during growth. © 2015 American Society for Bone and Mineral Research.
UGT1A1 genotype‐dependent dose adjustment of belinostat in patients with advanced cancers using population pharmacokinetic modeling and simulation
Authors: Peer Cody J. , Goey Andrew K. L. , Sissung Tristan M. , Erlich Sheryl , Lee Min‐Jung , Tomita Yusuke , Trepel Jane B. , Piekarz Richard , Balasubramaniam Sanjeeve , Bates Susan E. , Figg William D. 
Published: December 2015

AbstractBelinostat is a second‐generation zinc‐binding histone deacetylase inhibitor that is approved for peripheral T‐cell lymphoma and is currently being studied in small cell lung cancer and other advanced carcinomas as a 48‐hour continuous intravenous infusion. Belinostat is predominantly metabolized by UGT1A1, which is polymorphic. Preliminary analyses revealed a difference in belinostat clearance based on UGT1A1 genotype. A 2‐compartment population pharmacokinetic (PK) model was developed and validated that incorporated the UGT1A1 genotype, albumin, and creatinine clearance on the clearance parameter; body weight was a significant covariate on volume. Simulated doses of 600 and 400 mg/m2/24 h given to patients considered extensive or impaired metabolizers, respectively, provided equivalent AUCs. This model and subsequent simulations supported additional PK/toxicity and pharmacogenomics/toxicity analyses to suggest a UGT1A1 genotype‐based dose adjustment to normalize belinostat exposure and allow for more tolerable therapy. In addition, global protein lysine acetylation was modeled with PK and demonstrated a reversible belinostat exposure/response relationship, consistent with previous reports.
Markers of mesterolone abuse in sulfate fraction for doping control in human urine
Authors: Kiousi P. , Angelis Y. S. , Fragkaki A. G. , Abushareeda W. , Alsayrafi M. , Georgakopoulos C. , Lyris E. 
Published: December 2015

This manuscript describes the direct detection of mesteroloe sulfo‐conjugated metabolites by liquid chromatography/quadrupole/time of flight mass spectrometry (LC/Q/TOFMS) with special focus on evaluation of their retrospective detectability and their structure elucidation. A comparison of their long‐term detectability, with the mesterolone main metabolite (1α‐methyl‐5α‐androstan‐3α‐ol‐17‐one) excreted in glucuronide fraction and detected by gas chromatography/high resolution mass spectrometry (GC/HRMS), is also presented.Studies on mesterolone were performed with samples obtained from two excretion studies after single oral administration of Proviron© by healthy volunteers. Potential sulfate metabolites were detected in post administration samples after liquid–liquid extraction (LLE) with ethyl acetate and LC/TOFMS analysis, in negative mode. Twelve mesterolone sulfate metabolites from the first excretion study and nine from the second were subsequently confirmed by LC/Q/TOFMS. Finally, six mesterolone sulfate metabolites were considered important taking into account their abundance and long‐term detectability, encoded as M1, M2, M4, M5, M6 and M7. The proposed mesterolone sulfate metabolites M1, M2, M4 and M5 (excreted as sulfates) have the same retrospectivity with the main mesterolone metabolite, excreted in glucuronide fraction.For metabolite characterization, LC fractionation was performed. The metabolites were identified and characterized by GC/MS, after solvolysis and derivatization. Combined mass spectra data from trimethyl‐silyl (TMS), TMS‐enolTMS and methoxime‐TMS derivatives were taken into account for the characterization of these metabolites. It was concluded that M1 is 1α‐methyl‐5α‐androstan‐3β‐ol‐17 one, M2 is 1α‐methyl‐5α‐androstan‐3α‐ol‐17 one, M4 is 1α‐methyl‐5a‐androstan‐3β, 16z‐diol‐17‐one, M5 is 1α‐methyl‐5α‐androstan‐17z,4ξ‐diol‐3one, M6 is 1α‐methyl‐5α‐androstan‐3z,6z‐diol‐17‐one and M7 is 4z‐hydroxy‐1α‐methyl‐5α‐androstan‐3,17‐dione. Copyright © 2015 John Wiley & Sons, Ltd.
Synthesis of Diisocyanate‐Containing Thiophenes and Their Use in PDMS‐Based Segmented Polymers
Authors: Grübel Matthias , Meister Simon , Schulze Ulrich , Raftopoulos Konstantinos N. , Baumer Franziska , Papadakis Christine M. , Nilges Tom , Rieger Bernhard 
Published: December 2015

A synthesis route to siloxane‐based thermoplastic elastomers (TPE) with functional hard blocks is described. The photophysical functionality is provided by oligothiophenes, namely terthiophene and bithiophene. Polyaddition of isocyanate‐bearing thiophenes and amine‐terminated siloxanes yields polymers incorporating a bisurea structure motive. Phase separation and strong hydrogen bonds provide ordering of the thiophenes, which is shown by wide‐angle X‐ray scattering (WAXS) and X‐ray powder diffraction (XRD). Fluorescence measurements reveal a strong red shift of emission of polymer films compared with polymer solutions, thus confirming the existence of hard block segments with an enhanced π system and higher charge–carrier mobility. Tuning of the optical band gap by different polymer compositions and various post polymerization treatments is demonstrated.
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Self‐Organization of Gold Nanoparticle Assemblies with 3D Spatial Order and Their External Stimuli Responsiveness
Authors: Köhn Serrano Melissa S. , König Tobias A. F. , Haataja Johannes S. , Löbling Tina I. , Schmalz Holger , Agarwal Seema , Fery Andreas , Greiner Andreas 
Published: December 2015

Gold nanoparticles (AuNP) with pyridyl end‐capped polystyrenes (PS‐4VP) as “quasi‐monodentate” ligands self‐assemble into ordered PS‐4VP/AuNP nanostructures with 3D hexagonal spatial order in the dried solid state. The key for the formation of these ordered structures is the modulation of the ratio AuNP versus ligands, which proves the importance of ligand design and quantity for the preparation of novel ordered polymer/metal nanoparticle conjugates. Although the assemblies of PS‐4VP/AuNP in dispersion lack in high dimensional order, strong plasmonic interactions are observed due to close contact of AuNP. Applying temperature as an external stimulus allows the reversible distortion of plasmonic interactions within the AuNP nanocomposite structures, which can be observed directly by naked eye. The modulation of the macroscopic optical properties accompanied by this structural distortion of plasmonic interaction opens up very interesting sensoric applications.
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Comprehensive characterization of the effects of ellagic acid and urolithins on colorectal cancer and key‐associated molecular hallmarks: MicroRNA cell specific induction of CDKN1A (p21) as a common mechanism involved
Authors: González‐Sarrías Antonio , Núñez‐Sánchez María Ángeles , Tomé‐Carneiro Joao , Tomás‐Barberán Francisco A. , García‐Conesa María Teresa , Espín Juan Carlos 
Published: December 2015

ScopeEllagitannins, ellagic acid, and the colonic metabolites urolithins (Uros) exhibit anticancer effects against colon cells, but a comprehensive molecular analysis has not been done. Herein, we used a panel of cell lines to first time evaluate the antiproliferative properties and accompanying molecular responses of two ellagitannin metabolites mixtures mimicking the situation in vivo and of each individual metabolite.Methods and resultsWe examined cell growth, cell cycle, apoptosis, and the expression of related genes and microRNAs (miRs) in a panel of nonmalignant and malignant colon cell lines. Regardless of the composition, the mixed metabolites similarly inhibited proliferation, induced cycle arrest, and apoptosis. All the metabolites contributed to these effects, but Uro‐A, isourolithin A, Uro‐C, and Uro‐D were more potent than Uro‐B and ellagic acid. Despite molecular differences between the cell lines, we discerned relevant changes in key cancer markers and corroborated the induction of CDKN1A (cyclin‐dependent kinase inhibitor 1A gene (p21, Cip1); encoding p21) as a common step underlying the anticancer properties of Uros. Interestingly, cell‐unique downregulation of miR‐224 or upregulation of miR‐215 was found associated with CDKN1A induction.ConclusionPhysiologically relevant mixtures of Uros exert anticancer effects against colon cancer cells via a common CDKN1A upregulatory mechanism. Other associated molecular responses are however heterogeneous and mostly cell‐specific.
Joint state and parameter robust estimation of stochastic nonlinear systems
Authors: Stojanovic Vladimir , Nedic Novak 
Published: December 2015

SummarySuccessful implementation of many control strategies is mainly based on accurate knowledge of the system and its parameters. Besides the stochastic nature of the systems, nonlinearity is one more feature that may be found in almost all physical systems. The application of extended Kalman filter for the joint state and parameter estimation of stochastic nonlinear systems is well known and widely spread. It is a known fact that in measurements, there are inconsistent observations with the largest part of population of observations (outliers). The presence of outliers can significantly reduce the efficiency of linear estimation algorithms derived on the assumptions that observations have Gaussian distributions. Hence, synthesis of robust algorithms is very important. Because of increased practical value in robust filtering as well as the rate of convergence, the modified extended Masreliez–Martin filter presents the natural frame for realization of the joint state and parameter estimator of nonlinear stochastic systems. The strong consistency is proved using the methodology of an associated ODE system. The behaviour of the new approach to joint estimation of states and unknown parameters of nonlinear systems in the case when measurements have non‐Gaussian distributions is illustrated by intensive simulations. Copyright © 2015 John Wiley & Sons, Ltd.
N‐acetyl cysteine‐mediated effective attenuation of methoxychlor‐induced granulosa cell apoptosis by counteracting reactive oxygen species generation in caprine ovary
Authors: Bhardwaj Jitender Kumar , Saraf Priyanka 
Published: December 2015

ABSTRACTMethoxychlor (MXC), an organochloride insecticide, is a potent toxicant‐targeting female reproductive system and known to cause follicular atresia by inducing apoptosis within granulosa cells. Oxidative stress plays a pivotal role in apoptosis; thus, this study focuses on the ameliorative action of N‐acetyl cysteine (NAC) on MXC‐induced oxidative stress and apoptosis within granulosa cell of caprine ovary. Classic histology, fluorescence assay, and biochemical parameters were employed to evaluate the effect of varied concentration of NAC (1, 5, and 10 mM) on granulosa cell apoptosis after 24, 48, and 72 h exposure duration. Histomorphological studies revealed that NAC diminished the incidence of apoptotic attributes like condensed or marginated chromatin, pyknosis, crescent‐shaped nucleus, empty cell spaces, and degenerated cellular structure along with the presence of cytoplasmic processes within granulosa cells in dose‐ and time‐dependent manner. NAC significantly downregulated the percentage of MXC‐induced granulosa cell apoptosis within healthy ovarian follicle with its increasing dose, maximum at 10 mM concentration. It also significantly (p < 0.05) upregulated the activity of antioxidant enzymes, namely catalase, superoxide dismutase, and glutathione‐s‐transferase, along with ferric reducing antioxidant power further declining lipid peroxidation in the MXC‐treated caprine ovary. The results revealed a negative correlation between apoptosis frequency and antioxidant enzymes’ activity (rCAT = −0.67, rSOD = −0.56, rGST = −0.31; p < 0.05) while a positive correlation was observed with lipid peroxidation (r = 0.63; p < 0.05) after NAC supplementation. Thus, NAC supplementation reduces the MXC‐generated oxidative stress that perhaps declines the ROS generating signal transduction pathway of apoptosis, thereby preventing MXC‐induced granulosa cell apoptosis and follicular atresia. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 156–166, 2017.
Characterizing adult attention-deficit/hyperactivity-disorder and comorbid borderline personality disorder: ADHD symptoms, psychopathology, cognitive functioning and psychosocial factors
Authors: O’Malley G.K. , McHugh L. , Mac Giollabhui N. , Bramham J. 
Published: December 2015

AbstractObjectiveTo characterize adults with comorbid attention-deficit/hyperactivity-disorder (ADHD) and borderline personality disorder (BPD) with regard to ADHD symptoms, psychopathology, cognitive functioning and psychosocial factors.MethodA between-group design compared a group of individuals diagnosed with ADHD (n = 40) with a group diagnosed with BPD and who also met the criteria for ADHD (ADHD + BPD) (n = 20).ResultsSignificant differences were observed for both childhood and current impulsivity symptoms, whereby ADHD + BPD exhibited increased impulsivity; no differences on self-report and cognitive measures of impulsivity were reported. The ADHD + BPD group scored significantly higher on measures of depression, anxiety and numerous other axis I and II conditions. The ADHD + BPD group scored significantly lower on most measures of intellectual functioning and attention, however largely not on those relating to response inhibition. Furthermore, group differences were observed for psychosocial factors, including education, substance use and criminal record.ConclusionComorbid ADHD and BPD is characterized by more symptoms of impulsivity, additional psychopathology, comparatively lower intellectual and attentional functioning and increased psychosocial difficulties.
A single-blind, randomised controlled trial on the effects of lithium and quetiapine monotherapy on the trajectory of cognitive functioning in first episode mania: A 12-month follow-up study
Authors: Daglas R. , Cotton S.M. , Allott K. , Yücel M. , Macneil C.A. , Hasty M.K. , Murphy B. , Pantelis C. , Hallam K.T. , Henry L.P. , Conus P. , Ratheesh A. , Kader L. , Wong M.T.H. , McGorry P.D. , Berk M. 
Published: December 2015

AbstractBackgroundCognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania.MethodsThe design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points.ResultsThere was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition.ConclusionAlthough the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.
Montreal Cognitive Assessment Performance in HIV/AIDS: Impact of Systemic Factors
Authors: Koenig Noshin , Fujiwara Esther , Gill M. John , Power Christopher 
Published: December 2015

AbstractBackground: A large proportion of people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) suffer from neurocognitive impairment (NCI). The causes of the NCI are multifold in HIV infection although a subset of HIV/AIDS patients are affected by the spectrum syndrome, HIV-associated neurocognitive disorder (HAND). We investigated the Montreal Cognitive Assessment (MoCA) in relation to clinical, demographic and laboratory findings as well as its ability to predict symptomatic HAND (sHAND) among patients with HIV/AIDS. Methods: All subjects were receiving regular HIV care including CD4+ T cell counts, plasma viral load measurements, clinical evaluations and antiretroviral therapy. The diagnosis of sHAND was based upon clinical, neuroimaging, and neuropsychological assessments.Results: Among HIV-1 seropositive subjects (n=125), ethnicity, education and employment were positively correlated with their MoCA scores (p<0.05). In contrast, polypharmacy, central nervous system penetration-effectiveness (CPE) score, antiretroviral drug exposure, substance use and nucleoside/nucleotide reverse transcriptase inhibitor side effects were negatively correlated with MoCA scores (p<0.05). Of note, MoCA scores were not associated with CD4 T cell nadir levels, age, peak viral load, or veterans aging cohort study index. In subjects with or without sHAND, mean MoCA scores differed (sHAND, 22.8±3.51; non-HAND 25.2±2.64) (p<0.05) with a receiver operating characteristic curve showing an area under curve of 0.71 and an optimal MoCA cut-off value of 23.5 when compared to the established diagnostic paradigm. Conclusions: MoCA scores were generally lower in this HIV/AIDS population compared to reported scores in the general population. MoCA performance was associated with multiple clinical variables but displayed limited predictive utility in detecting sHAND.
Community Stroke Rehabilitation: How Do Rural Residents Fare Compared With Their Urban Counterparts?
Authors: Allen Laura , McIntyre Amanda , Janzen Shannon , Richardson Marina , Meyer Matthew , Ure David , Teasell Robert 
Published: December 2015

AbstractBackground: Rural living has been demonstrated to have an effect on a person’s overall health status, and rural residing individuals often have decreased access to health and specialized rehabilitation services. Aim: The aim of this study was to determine if there are differences in recovery from stroke between urban and rural-dwelling stroke survivors accessing an in-home, community-based, interdisciplinary, stroke rehabilitation program. Methods: Data from a cohort of 1222 stroke survivors receiving care from the Community Stroke Rehabilitation Teams between January 2009 and June 2013 was analyzed. This program delivers stroke rehabilitation care directly in a person’s home and community. Functional and psychosocial outcomes were evaluated at baseline, discharge, and six -month follow-up. A series of multiple linear regression analyses was performed to determine if rural versus urban status was a significant predictor of discharge and 6-month health outcomes. Results: The mean age of the rural cohort was 68.8 (±13.1) years (53.6% male), and the urban cohort was 68.4 (±13.0) years (44.8% male). A total of 278 (35.4%) individuals were classified as living in a rural area using the Rurality Index for Ontario. In multivariate linear regression analysis, no significant differences on the Functional Independence Measure, the Stroke Impact Scale, the Hospital Anxiety and Depression Scale, or the Reintegration to Normal Living Index were found between urban and rural cohorts. Conclusions: When provided with access to a home-based, specialized stroke rehabilitation program, rural dwelling stroke survivors make and maintain functional gains comparable to their urban-living counterparts.
Georgia and the Anatolian Turks in the 12th and 13th centuries
Authors: Peacock A.C.S. 
Published: December 2015

AbstractThis article presents a study of the political and military relations of the Kingdom of Georgia and the Muslims of Anatolia from the 12th century AD up to the Mongol conquest of the region in the mid 13th century. Georgia's expansion during the 12th century and the web of marriage alliance that the Muslim rulers of Anatolia wove to protect themselves drew her into conflict even with distant principalities with which she shared no border, such as the Artukids of Mardin. Meanwhile, Erzurum appears to have been obliged to acknowledge Georgian suzerainty for much of the 12th and early 13th centuries. In the 13th century, however, the Mongol threat forced the Seljuks of Rüm and Georgia to form an alliance, and Georgians came to form a significant part of the Seljuk army. This alliance was sealed with a marriage between the Seljuk sultan and a member of the Georgian ruling house, the Bagratids, and the Seljuks appear to have derived prestige from their association with the Bagratid dynasty.
Stressreduktion durch Binaurale Stimulation? Eine experimentelle Untersuchung zum Effekt einer Alpha-Stimulation auf die psychophysiologische Entspannungsreaktion
Authors: Schamber Georg , Meinicke Eva , Schäfer Thomas 
Published: December 2015

Zusammenfassung. Binaurale Stimulationen sind akustisch erzeugte Schwebungen, die im Hirnwellenspektrum liegen und daher als Möglichkeit diskutiert werden, neurophysiologische Entspannungszustände zu induzieren. Die Qualität und Aussagekraft bisheriger Studien ist wissenschaftlich jedoch stark umstritten. In der vorliegenden Arbeit ist daher der Effekt einer binauralen Alpha-Stimulation auf subjektive und physiologische Entspannungs-Parameter untersucht worden. Hierzu wurden 102 Probanden zufällig drei Gruppen zugewiesen: (1) Audio-Beschallung mit binauraler Stimulation, (2) Audio-Beschallung ohne binaurale Stimulation, (3) keine akustische Beschallung. Die subjektive Entspannung wurde vor und nach einer 20-minütigen Stimulation erfasst, die physiologische Entspannungsreaktion über Herzrate, Atemfrequenz und ausgewählte Parameter der Herzratenvariabilität während der Intervention erhoben. Die Ergebnisse zeigen keine spezifische Zunahme an subjektiver oder physiologischer Entspannung. Der aktuelle Forschungsstand zur binauralen Stimulation wird im Lichte dieses Ergebnisses diskutiert.