bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased prevalence of light chain monoclonal gammopathy of undetermined significance (LC‐MGUS) in first‐degree relatives of individuals with multiple myeloma
Authors: Greenberg Alexandra J. , Vincent Rajkumar S. , Larson Dirk R. , Dispenzieri Angela , Therneau Terry M. , Colby Colin L. , Phelps Tara K. , Kumar Shaji K. , Katzmann Jerry A. , Kyle Robert A. , Slager Susan L. , Vachon Celine M. 
Published: February 2012

SummaryPreviously, we reported increased risk of heavy‐chain (HC) monoclonal gammopathy of undetermined significance (MGUS) among first‐degree (1°) relatives of multiple myeloma (MM) or HC‐MGUS probands. This study investigated whether there was comparable risk for light‐chain (LC) MGUS among 911 relatives of the same HC‐MGUS/MM probands versus a reference population of 21 463. Seventeen 1° relatives had LC‐MGUS (adjusted prevalence = 1·7%, 95% CI = 0·9–2·6%). There was increased risk of LC‐MGUS in relatives of MM probands (RR = 3·4, 95% CI = 2·0–5·5). We saw no increased risk in relatives of HC‐MGUS probands. We conclude that the prevalence of LC‐MGUS is significantly higher among 1° relatives of MM probands compared to the reference population.
BCR‐ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia
Authors: Roy Swagata , Jørgensen Heather G. , Roy Poornima , Abed El Baky Mohamed , Melo Junia V. , Strathdee Gordon , Holyoake Tessa L. , Bartholomew Chris 
Published: February 2012

SummaryMECOM oncogene expression correlates with chronic myeloid leukaemia (CML) progression. Here we show that the knockdown of MECOM (E) and MECOM (ME) isoforms reduces cell division at low cell density, inhibits colony‐forming cells by 34% and moderately reduces BCR‐ABL1 mRNA and protein expression but not tyrosine kinase catalytic activity in K562 cells. We also show that both E and ME are expressed in CD34+ selected cells of both CML chronic phase (CML‐CP), and non‐CML (normal) origin. Furthermore, MECOM mRNA and protein expression were repressed by imatinib mesylate treatment of CML‐CP CD34+ cells, K562 and KY01 cell lines whereas imatinib had no effect in non‐CML BCR‐ABL1 −ve CD34+ cells. Together these results suggest that BCR‐ABL1 tyrosine kinase catalytic activity regulates MECOM gene expression in CML‐CP progenitor cells and that the BCR‐ABL1 oncoprotein partially mediates its biological activity through MECOM. MECOM gene expression in CML‐CP progenitor cells would provide an in vivo selective advantage, contributing to CML pathogenesis.
Buffering and plasticity in vital rates of oldfield rodents
Authors: Reed Aaron W. , Slade Norman A. 
Published: February 2012

Summary1. Under the hypothesis of environmental buffering, populations are expected to minimize the variance of the most influential vital rates; however, this may not be a universal principle. Species with a life span <1 year may be less likely to exhibit buffering because of temporal or seasonal variability in vital rate sensitivities. Further, plasticity in vital rates may be adaptive for species in a variable environment with reliable cues.2. We tested for environmental buffering and plasticity in vital rates using stage‐structured matrix models from long‐term data sets in four species of grassland rodents. We used periodic matrices to estimate stochastic elasticity for each vital rate and then tested for correlations with a standardized coefficient of variation for each rate.3. We calculated stochastic elasticities for individual months to test for an association between increased reproduction and the influence of reproduction, relative to survival, on the population growth rate.4. All species showed some evidence of buffering. The elasticity of vital rates of Peromyscus leucopus (Rafinesque, 1818), Sigmodon hispidus Say & Ord, 1825 and Microtus ochrogaster (Wagner, 1842) was negatively related to vital rate CV. Elasticity and vital rate CV were negatively related in Peromyscus maniculatus (Wagner, 1845), but the relationship was not statistically significant. Peromyscus leucopus and M. ochrogaster showed plasticity in vital rates; reproduction was higher following months where elasticity for reproduction exceeded that of survival.5. Our results suggest that buffering is common in species with fast life histories; however, some populations that exhibit buffering are capable of responding to short‐term variability in environmental conditions through reproductive plasticity.
Hepatic tyrosine aminotransferase and glucocorticoid abuse in meat cattle
Authors: BERTARELLI D. , BALBO A. , CARLETTI M. , CANNIZZO T. , GIROLAMI F. , NEBBIA C. 
Published: February 2012

Bertarelli, D., Balbo, A., Carletti, M., Cannizzo, T., Girolami, F., Nebbia, C. Hepatic tyrosine aminotransferase and glucocorticoid abuse in meat cattle. J. vet. Pharmacol. Therap. 35, 596–603.Besides being extensively applied as therapeutical remedies, glucocorticoids (GCs) – most notably dexamethasone or prednisolone – are also illegally used in livestock for growth‐promoting purposes. This study was designed to assess the suitability of liver tyrosine aminotransferase (TAT), a gluconeogenic enzyme known to be induced by GCs, to act as a reliable candidate biomarker to screen for GC abuse in cattle. Enzyme activity was measured spectrophotometrically in liver cytosols or in cell extracts, and TAT gene expression was determined by real‐time PCR. Compared with untreated veal calves, a notable scatter (20‐fold) and much higher median values (3‐fold) characterized TAT specific activity in liver samples from commercially farmed veal calves. A time‐related increase in both enzyme activity and gene expression was detected in rat hepatoma cell lines treated with dexamethasone concentrations (10−8 or 10−9 m) in the range of those recorded in noncompliant samples from EU official controls. In experimental studies in which finishing bulls were administered GCs at growth‐promoting dosages, however, no such changes were recorded in dexamethasone‐treated animals; a statistically significant rise in liver TAT activity (+95%) only occurred in prednisolone‐treated bulls. Although further research is needed to characterize the GC‐mediated response in cattle liver, TAT does not appear to be a specific and sensitive biomarker of GC abuse in the bovine species.
A homologue of the human STRIPAK complex controls sexual development in fungi
Authors: Bloemendal Sandra , Bernhards Yasmine , Bartho Kathrin , Dettmann Anne , Voigt Oliver , Teichert Ines , Seiler Stephan , Wolters Dirk A. , Pöggeler Stefanie , Kück Ulrich 
Published: February 2012

SummarySexual development in fungi is a complex process involving the generation of new cell types and tissues – an essential step for all eukaryotic life. The characterization of sterile mutants in the ascomycete Sordaria macrospora has led to a number of proteins involved in sexual development, but a link between these proteins is still missing. Using a combined tandem‐affinity purification/mass spectrometry approach, we showed in vivo association of developmental protein PRO22 with PRO11, homologue of mammalian striatin, and SmPP2AA, scaffolding subunit of protein phosphatase 2A. Further experiments extended the protein network to the putative kinase activator SmMOB3, known to be involved in sexual development. Extensive yeast two‐hybrid studies allowed us to pinpoint functional domains involved in protein–protein interaction. We show for the first time that a number of already known factors together with new components associate in vivo to form a highly conserved multi‐subunit complex. Strikingly, a similar complex has been described in humans, but the function of this so‐called striatin interacting phosphatase and kinase (STRIPAK) complex is largely unknown. In S. macrospora, truncation of PRO11 and PRO22 leads to distinct defects in sexual development and cell fusion, indicating a role for the fungal STRIPAK complex in both processes.
The impact of sirolimus on sex hormones in male adolescent kidney recipients
Authors: Cavanaugh Teresa M. , Schoenemen Heather , Goebel Jens 
Published: February 2012

Cavanaugh TM, Schoenemen H, Goebel J. The impact of sirolimus on sex hormones in male adolescent kidney recipients.Abstract: While it is known that sirolimus affects sex hormones in adult kidney transplant patients, there is a scarcity of data on its effects on sex hormone levels in adolescent kidney recipients. The objective of this study is to describe the impact of sirolimus on the sex hormones in this patient population. This is a retrospective review of male adolescent renal transplant patients transitioned to sirolimus. Baseline and subsequent annual testosterone levels were collected. Linear regression was undertaken to determine the predictors of testosterone levels. Four African Americans and 11 Caucasians, median age of 15 yr (11–18) in 2008, were included. Mean time post‐transplant was 81 ± 37 months. Mean testosterone values were the following: 336 ± 135 ng/dL (n = 8) at baseline, 349 ± 130 ng/dL (n = 15) one yr later, and 360 ± 132 ng/dL (n = 13) two yr later (normal range for adult males: 350–970 ng/dL). Seven (47%) patients experienced a decrease in testosterone levels. Time on sirolimus was associated with decreased testosterone (r = 0.643, p = 0.010). Testosterone levels in pubertal male kidney transplant recipients on sirolimus may be suppressed, especially if they have been treated with sirolimus for several years. These data need to be confirmed in a larger study.
Tacrolimus as a risk factor for tuberculosis and outcome of treatment with rifampicin in solid organ transplant recipients
Authors: Ha Y.E. , Joo E.J. , Park S.Y. , Wi Y.M. , Kang C.I. , Chung D.R. , Joh J.W. , Lee S.K. , Song J.H. , Peck K.R. 
Published: February 2012

AbstractBackgroundThe purpose of this study was to investigate the incidence, risk factors, and treatment outcome of tuberculosis (TB) in solid organ transplant (SOT) recipients treated with rifampicin.MethodsThe incidence density of TB was calculated by a retrospective cohort study. Risk factors for TB were analyzed by a nested case–control study. Treatment outcome and effects of anti‐TB drugs on immunosuppressants and allograft were compared between patients whose initial 2‐month intensive regimen included rifampicin and those whose intensive regimen did not.ResultsAmong the 2144 SOT recipients over 16 years, 40 cases of TB were found (1.7%). The incidence density was 372 cases per 105 patient years (95% confidence interval [CI], 270–503), which was 4 times higher than for the general Korean population (90 cases per 105 person years). The median time to the development of TB was 234 days (range, 33–3940 days). The use of tacrolimus (odds ratio [OR] 4.90; 95% CI, 1.74–13.80; P = 0.003) and cytomegalovirus (CMV) infection within the prior 3 months (OR 4.62; 95% CI, 1.44–14.87; P = 0.01) were found to be risk factors for TB. Patients whose intensive regimen included rifampicin were more likely to have an increased dose of calcineurin inhibitors than patients whose intensive regimen did not include rifampicin (13/15 [86.7%] vs. 3/14 [21.4%], P = 0.001). Graft rejection and mortality did not differ between the 2 groups.ConclusionsUse of tacrolimus and CMV infection were major risk factors for TB in SOT recipients. The graft outcome and mortality did not differ whether rifampicin was used or not during the first 2‐month intensive phase.
Epibiotic traits of the invasive red seaweed Acanthophora spicifera in La Paz Bay, South Baja California (Eastern Pacific)
Authors: Ávila Enrique , Méndez‐Trejo María del Carmen , Riosmena‐Rodríguez Rafael , López‐Vivas Juan M. , Sentíes Abel 
Published: February 2012

AbstractThe aim of this study was to analyze the interaction of a non‐native macroalga (Acanthophora spicifera) with native macroalgae (Sargassum spp.) and sponge assemblages in a subtropical embayment of the Mexican Pacific. The intensity of A. spicifera epiphytism on the native seaweed Sargassum varied significantly over time and was inversely related to the Sargassum density and size. The higher intensity (up to 28 individuals per host plant) occurred when Sargassum was smaller and was lower in density (senescence period). The lower intensity was recorded during the growth period of Sargassum and the subsequent increase in intensity was attributed to a high fragmentation period of A. spicifera, which was evidenced by a decrease in its average size and biomass and by the presence of larger free‐floating accumulations on the subtidal zone. The facultative interaction between A. spicifera and Sargassum appears to be neutral, as no negative or positive effects were found for epiphytic or basibiont seaweeds. However, this invasive seaweed characteristically monopolizes almost all types of hard substrate, and its effects on other algae and benthic organisms should be investigated. Moreover, A. spicifera was often epizoic on epilithic sponges. This invasive seaweed was found anchored on the sponge tissue by rhizome‐like structures. In addition, free‐floating fronds of A. spicifera were frequently found carrying small pieces of the basibiont sponge in its basis (60% of them with eggs and embryos), which suggests a novel facilitation mechanism for some sponge species, as the A. spicifera epizoism could favor fragmentation, dispersal and recruitment of these invertebrates. This study shows that A. spicifera is not only a species that adapts rapidly to the new conditions of the receiving environment but, due to its epibiotic traits, it can directly interact with and influence the life histories of some native species.
Blinded Continuous Monitoring of Nuisance Parameters in Clinical Trials
Authors: Friede Tim , Miller Frank 
Published: February 2012

SummaryDetermination of a clinical trial's size is an important task in the planning of any trial because of the direct implications of the sample size on feasibility, costs and timelines. However, sample size calculations are often subject to substantial uncertainty due to limited prior information on the size of nuisance parameters such as variances or event rates. Continuous monitoring of the nuisance parameter in clinical trials has been proposed as a tool to size trials appropriately. With this approach, the nuisance parameter is continuously monitored during the trial. The trial is stopped when the actual estimate for the nuisance parameter and sample size fulfil a stopping criterion. Continuous monitoring can therefore be viewed as a stochastic process with stopping time. We describe the bias that occurs with unblinded continuous monitoring of the variance in clinical trials by means of a simulation study. Then we propose a procedure for blinded continuous monitoring that does not require breaking the treatment code during the on-going study and show that the procedure does not suffer from the same biases as observed in unblinded monitoring. Results on the performance properties of such designs are given and the designs are compared with blinded re-estimation procedures with a single data look. By means of asymptotic theoretical arguments and finite sample size simulations we find that the variability in sample size is smaller with blinded continuous monitoring than with blinded sample size re-estimation whenever the power for both designs is close to the target value. Repeated sample size re-estimation is in between continuous monitoring and sample size re-estimation in this respect. Furthermore, we present a hypertension trial where blinded sample size re-estimation with a single data look was applied and we investigate the properties of blinded continuous monitoring in this setting. Finally we close with a brief discussion.
GROWTH, UNEMPLOYMENT AND ENDOGENOUS TECHNICAL PROGRESS: A HICKSIAN RESOLUTION OF HARROD'S KNIFE‐EDGE
Authors: Palley Thomas I. 
Published: February 2012

ABSTRACTThis paper presents a neo‐Kaleckian growth model with unemployment, endogenous technical progress, and a steady‐state requirement of balanced labor demand and supply growth. There are two key innovations: first, a Marx–Hicks unemployment rate–profit rate channel affecting labor‐saving technical progress; second, a Keynesian unemployment rate channel affecting saving and investment. Changes in the unemployment rate change the profit rate, rebalancing effective labor supply and employment growth. This provides a Hicksian resolution of Harrod's knife‐edge. The Keynesian unemployment rate channel strengthens the growth benefits of a lower unemployment rate, potentially obviating any growth–unemployment trade‐off.
Home range and shelter site selection in the greater hedgehog tenrec in the dry deciduous forest of Western Madagascar
Authors: Levesque D. L. , Rakotondravony D. , Lovegrove B. G. 
Published: February 2012

AbstractInformation on the spatial distribution and habitat use of the Tenrecidae (Supraorder: Afrotheria) of Madagascar are severely lacking. Here, we present the first data available on home range size, as well as further data on population distribution and rest site selection of a large tenrec, the greater hedgehog tenrec (Setifer setosus). Data were collected over two rainy seasons in the dry deciduous woodland of Western Madagascar, in Ankarafantsika National Park. Home ranges were surprisingly large for a 200–300‐g animal: males had an average home range (95% minimum convex polygon) of 13.7 ± 4.9 ha (n = 5), and females of 6.7 ± 2.0 ha (n = 5). A high overlap between multiple individuals of the opposite sex supports a promiscuous mating system for this species. Daytime shelter sites proved to be highly variable and differed between sex and reproductive status.
Metformin reduces vascular production of vasoconstrictor prostanoids in fructose overloaded rats
Authors: Puyó A. M. , Borroni J. S. , Boudou S. , Santander Y. , Carranza A. , Donoso A. S. , Peredo H. A. 
Published: February 2012

Summary1 Metformin is a hypoglycaemic drug currently used to increase insulin sensitivity in the treatment of type 2 diabetes and metabolic syndrome. Its main mechanism of action is through activation of AMP‐activated protein kinase, an enzyme that regulates cellular and whole organ metabolism.2 The fructose‐overloaded rat is an experimental model with features that resemble human metabolic syndrome. We have previously reported alterations in vascular prostanoids (PR) in this model.3 The aim of this study was to analyse the effects of metformin treatment on blood pressure, metabolic parameters and PR production in aorta and mesenteric vascular bed (MVB) from fructose‐overloaded animals. Four groups of male Sprague–Dawley rats were used: control, fructose overloaded (10% w/v fructose), metformin treated (50 mg kg−1 day−1) and fructose‐overloaded treated with metformin.4 Rats with fructose overload had significantly elevated systolic blood pressure, glycaemia, triglyceridaemia, cholesterolaemia and insulinaemia compared with controls. Except for insulinaemia, metformin limited all these increases in fructose‐overloaded animals.5 Fructose overload reduced prostacyclin levels in aorta and MVB, but prostaglandin E2 levels were only reduced in MVB. Metformin treatment reduced the levels of the vasoconstrictor prostaglandins, PGF2α and thromboxane, in both vascular preparations from fructose‐overloaded rats. PGF2α levels were significantly reduced by metformin in controls.6 In conclusion, one of the mechanisms by which metformin reduced blood pressure in this model is by decreasing vasoconstrictor prostaglandin production.
Tramadol inhibits the contractility of isolated caprine detrusor muscle
Authors: Kumar A. , Prabha R. , Paul T. , Margaret Shanthi F. X. , George J. , Peedicayil J. , Ernest K. 
Published: February 2012

Summary1 The atypical opioid analgesic tramadol has been shown to provide beneficial clinical and urodynamic effects in patients with detrusor overactivity. The effect of tramadol on isolated detrusor muscle has not been studied. This study investigated the ability of tramadol to inhibit acetylcholine (ACh)‐induced contractility of the isolated caprine (goat) detrusor muscle. The effect of three concentrations (30, 100 and 300 μm) of tramadol on 10 caprine detrusor strips contracted by the addition of 100, 200 or 400 μm ACh was studied. The sensitivity of tramadol‐induced inhibition of ACh responses to treatment with the β‐adrenoceptor antagonist propranolol (1 μm) and the opioid receptor antagonist naloxone (100 μμ) was also studied.2 Tramadol caused a concentration‐dependent inhibition of ACh‐induced detrusor contraction that was reversed by raising the concentration of ACh. Propranolol, but not naloxone, reversed the tramadol‐induced inhibition of contractions to ACh in the detrusor.3 These results suggest that tramadol inhibits ACh‐induced contractility of the isolated detrusor. They also suggest that tramadol does so by an indirect anticholinergic mechanism involving the stimulation of β‐adrenoceptors. Tramadol may be useful in managing clinical conditions requiring relaxation of the detrusor muscle. Although the concentrations of tramadol needed to relax the detrusor were relatively high, these could be clinically attained via intravesical administration.
Impact of Deductibles on Initiation and Continuation of Psychotherapy for Treatment of Depression
Authors: Fishman Paul A. , Ding Victoria , Hubbard Rebecca , Ludman Evette J. , Pabiniak Chester , Stewart Christine , Morales Leo , Simon Gregory E. 
Published: February 2012

ObjectiveTo estimate the impact of deductibles on the initiation and continuation of psychotherapy for depression.Data Sources/Study SettingData from health care encounters and claims from Group Health Cooperative, a large integrated health care system in Washington State, was merged with information from a centralized behavioral health triage call center to conduct study analyses.Study DesignA retrospective observational design using a hierarchical logistic regression model was used to estimate initiation and continuation probabilities for use of psychotherapy, adjusting for key sociodemographic/economic factors and prior use of behavioral health services relevant to individual decisions to seek mental health care.Data Collection/Extraction MethodsAnalyses were based on merged datasets on patient enrollment, insurance benefits, use of mental health and general medical services and information collected by a triage specialist at a centralized behavioral health call center.Principal FindingsAmong individuals with unmet deductibles between $100 and $500, we found a statistically significant lower likelihood of making an initial visit, but there was no statistically significant effect on making an initial or subsequent visit among individuals that had met their deductible.ConclusionsUnmet deductibles appear to influence the likelihood of initiating psychotherapy for treating depression.