bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of CCAAT/Enhancer Binding Protein (C/EBP) Alpha (CEBPA) and Runt‐Related Transcription Factor 1 (RUNX1) Expression in Patients with De Novo Acute Myeloid Leukemia
Authors: Salarpour Fatemeh , Goudarzipour Kourosh , Mohammadi Mohammad Hossein , Ahmadzadeh Ahmad , Faraahi Sara , Farsani Mehdi Allahbakhshian 
Published: September 2017

SummaryThe CCAAT/enhancer binding protein (C/EBP) alpha (CEBPA) and Runt‐related transcription factor 1 (RUNX1) genes have been traditionally regarded as two essential genes involved in normal myeloid maturation. Although the link between mutations in these genes and the development of acute myeloid leukemia (AML) has been extensively documented, the ramifications of gene expression dysregulations of CEBPA and RUNX1 has drawn less attention. The present study investigated CEBPA and RUNX1 gene expression levels in 96 primary AML specimens against a normal control group by way of real‐time RT‐PCR. Our results reveal that CEBPA and RUNX1 gene expression levels were unexpectedly and significantly higher in patients with AML when compared to the levels detected in the normal control group (P < 0.0001). Furthermore, the correlation between CEBPA and RUNX1 was significant and positive (P‐value: 0.011, r: 0.257).Our data contradicts the widely established role of CEBPA and RUNX1 in myeloid differentiation, as we saw lower levels of CEBPA and RUNX1 expression to be exhibited in patients with AML. Likely, our data demonstrates that higher levels of CEBPA and RUNX1 expression were closely correlated with reduced myeloid maturation, but this idea needs to approved. It suggests that despite the current established functions of genes involved in cell differentiation, the leukemogenesis process has the capability to transform normal hematopoietic precursors in a manner that may employ the differentiation related gene at the service of malignancy.
Construction of an Exome‐Wide Risk Score for Schizophrenia Based on a Weighted Burden Test
Authors: Curtis David 
Published: September 2017

SummaryPolygenic risk scores obtained as a weighted sum of associated variants can be used to explore association in additional data sets and to assign risk scores to individuals. The methods used to derive polygenic risk scores from common SNPs are not suitable for variants detected in whole exome sequencing studies. Rare variants, which may have major effects, are seen too infrequently to judge whether they are associated and may not be shared between training and test subjects. A method is proposed whereby variants are weighted according to their frequency, their annotations and the genes they affect. A weighted sum across all variants provides an individual risk score. Scores constructed in this way are used in a weighted burden test and are shown to be significantly different between schizophrenia cases and controls using a five‐way cross‐validation procedure. This approach represents a first attempt to summarise exome sequence variation into a summary risk score, which could be combined with risk scores from common variants and from environmental factors. It is hoped that the method could be developed further.
IMPACT OF COOPERATIVES MEMBERSHIP ON ECONOMY IN EASTERN OROMIA: THE CASE OF HARAMAYA AGRICULTURAL FARMERS’ COOPERATIVE UNION (HAFCU)
Authors: DEBELA Megersa , DIRIBA Sisay , BEKELE Hailemichael 
Published: September 2017

ABSTRACTThis study attempts to analyse the impact of cooperatives on the smallholders’ income, productivity, marketed surplus and saving in East Hararghe Zone of Haramaya District. The study is based on primary cross‐sectional data collected from cooperative member and non‐cooperative member household heads. The propensity score matching (PSM) estimates complemented by a bias correction matching (BCM) and Lewbel instrumental variable (IV) regression estimation shows that cooperatives have a positive impact on smallholders’ income and productivity. The findings have strong policy implications. The rural development of the country should work toward strengthening and expanding the existing rural organizations through training and capacity building programmes. It is important particularly establishing new rural‐based organizations that enable rural households to engage in business activities. Doing that may help reduce poverty and increase smallholders’ income, productivity, and capital accumulation.
Differential diagnosis and comorbidity of ADHD and anxiety in adults
Authors: Grogan Katie , Gormley Claire I. , Rooney Brendan , Whelan Robert , Kiiski Hanni , Naughton Marie , Bramham Jessica 
Published: September 2017

ObjectivesThe aim of this study was to examine symptom profiles of people diagnosed with attention‐deficit/hyperactivity disorder (ADHD) and/or anxiety (ANX) in order to determine the validity of widely used ADHD and ANX rating scales for differential diagnostic use and to develop modified measures that take symptom overlap into account.DesignA cross‐sectional design was used to assess differences in rating scale scores between clinical (n = 52) and control (n = 74) samples as well as differences among subgroups of the clinical sample (22 ADHD; 16 ADHD + ANX; 14 ANX).MethodParticipants completed an online questionnaire where they responded to the Conners Adult ADHD Rating Scale (CAARS; Conners, Erhardt, & Sparrow, ) and State Trait Anxiety Inventory scales (STAI; Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, ).ResultsResults showed that the CAARS and STAI had limited sensitivity and specificity and may lack in ability to differentially diagnose ADHD and/or ANX. Cluster analysis was used to guide the proposal of modifications for the two scales, which were to use inattentive items only for the CAARS and to exclude state ANX‐present items on the STAI for use in differential diagnosis. Further parametric analysis supported these proposed modifications.ConclusionsClinicians should be made aware of the limitations of the CAARS and STAI scales in terms of specificity, when used to inform differential diagnosis of ADHD and ANX. Further analysis on the psychometric properties of these modified scales is needed in order to confirm that they are valid and reliable scales.Practitioner points

Clinical implications

It is possible that widely used self‐report rating scales are not valid for use in the context of assessing adult ADHD when ANX is present.

Clinicians should take alternative approaches to measuring ADHD symptoms in the context of ANX.

Findings of the present study suggest the use of inattentive items only for the CAARS and to exclude state ANX‐present items on the STAI for differential diagnostic use.

Limitations of the study

The sample sizes of the clinical subgroups were relatively small.

Diagnoses were not confirmed using a semi‐structured clinical interview.

Alternative cluster approaches (e.g., two‐step clustering using larger samples) would provide further insight.
The role of sustained attention, maternal sensitivity, and infant temperament in the development of early self‐regulation
Authors: Frick Matilda A. , Forslund Tommie , Fransson Mari , Johansson Maria , Bohlin Gunilla , Brocki Karin C. 
Published: September 2017

This study investigated infant predictors of early cognitive and emotional self‐regulation from an intrinsic and caregiving environmental perspective. Sustained attention, reactive aspects of infant temperament, and maternal sensitivity were assessed at 10 months (n = 124) and early self‐regulation (including executive functions, EF, and emotion regulation) was assessed at 18 months. The results indicated that sustained attention predicted early EF, which provide empirical support for the hierarchical framework of EF development, advocating early attention as a foundation for the development of cognitive self‐regulation. Maternal sensitivity and surgency predicted emotion regulation, in that infants of sensitive mothers showed more regulatory behaviours and a longer latency to distress, whereas high levels of surgency predicted low emotion regulation, suggesting both the caregiving environment and temperament as important in the development of self‐regulation. Interaction effects suggested high sustained attention to be a protective factor for children of insensitive mothers, in relation to emotion regulation. In addition, high levels of maternal sensitivity seemed to foster development of emotion regulation among children with low to medium levels of sustained attention and/or surgency. In all, our findings point to the importance of both intrinsic and extrinsic factors in infant development of self‐regulation.
Bias‐corrected estimation of the Rudas–Clogg–Lindsay mixture index of fit
Authors: Reiczigel Jenő , Ispány Márton , Tusnády Gábor , Michaletzky György , Marozzi Marco 
Published: September 2017

Rudas, Clogg, and Lindsay (1994,J. R Stat Soc. Ser. B, 56, 623) introduced the so‐called mixture index of fit, also known as pi‐star (π*), for quantifying the goodness of fit of a model. It is the lowest proportion of ‘contamination’ which, if removed from the population or from the sample, makes the fit of the model perfect. The mixture index of fit has been widely used in psychometric studies. We show that the asymptotic confidence limits proposed by Rudaset al. (1994,J. R Stat Soc. Ser. B, 56, 623) as well as the jackknife confidence interval by Dayton (,Br. J. Math. Stat. Psychol., 56, 1) perform poorly, and propose a new bias‐corrected point estimate, a bootstrap test and confidence limits for pi‐star. The proposed confidence limits have coverage probability much closer to the nominal level than the other methods do. We illustrate the usefulness of the proposed method in practice by presenting some practical applications to log‐linear models for contingency tables.
Repurposing a novel parathyroid hormone analogue to treat hypoparathyroidism
Authors: Krishnan Venkatesh , Ma Yanfei L , Chen Catherine Z , Thorne Natasha , Bullock Heather , Tawa Gregory , Javella‐Cauley Christy , Chu Shaoyou , Li Weiming , Kohn Wayne , Adrian Mary D , Benson Charles , Liu Lifei , Sato Masahiko , Zheng Wei , Pilon Andre M , Yang N. Nora , Bryant Henry U 
Published: September 2017

Background and PurposeHuman parathyroid hormone (PTH) is critical for maintaining physiological calcium homeostasis and plays an important role in the formation and maintenance of the bone. Full‐length PTH and a truncated peptide form are approved for treatment of hypoparathyroidism and osteoporosis respectively. Our initial goal was to develop an improved PTH therapy for osteoporosis, but clinical development was halted. The novel compound was then repurposed as an improved therapy for hypoparathyroidism.Experimental ApproachA longer‐acting form of PTH was synthesised by altering the peptide to increase cell surface residence time of the bound ligand to its receptor. In vitro screening identified a compound, which was tested in an animal model of osteoporosis before entering human trials. This compound was subsequently tested in two independent animal models of hypoparathyroidism.Key ResultsThe peptide identified, LY627‐2K, exhibited delayed internalization kinetics. In an ovariectomy‐induced bone loss rat model, LY627‐2K demonstrated improved vertebral bone mineral density and biomechanical properties at skeletal sites and a modest increase in serum calcium. In a Phase I clinical study, dose‐dependent increases in serum calcium were reproduced. These observations prompted us to explore a second indication, hypoparathyroidism. In animal models of this disease, LY627‐2K restored serum calcium, comparing favourably to treatment with wild‐type PTH.Conclusions and ImplicationsWe summarize the repositioning of a therapeutic candidate with substantial preclinical and clinical data. Our results support its repurposing and continued development, from a common indication (osteoporosis) to a rare disease (hypoparathyroidism) by exploiting a shared molecular target.Linked ArticlesThis article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc
ELEMENTS OF THE CULTURAL LANDSCAPE AS FIGURES OF SPEECH
Authors: SITWELL O.F.G. 
Published: September 2017

It is argued that some elements of the cultural landscape take the form they do because they are the equivalents of the figures of speech of normal language. The paper examines: 1) the role played by figures of speech in normal language, 2) a model of the individual human person derived from physiological psychology capable of replicating the relevant patterns of observed speech and behaviour, 3) three figures of speech that (a) denote values, and (b) can be expressed in the landscape. It should be possible to test the thesis by means of systematic research.La thèse de ce compte‐rendu est que certains elements du paysage culturel sont des transformations de certaines figures du discours de tous les jours. II s'agit d'une enquête sur : I) le rôle joué dans la langue par certaines figures du discours ; 2) un modèle de l'être humain qui est fonde sur des recherches des psychologues physiologiques, et qui peut reproduire les locutions figuratives et leurs transformations dans le paysage ; 3) trois figures du discours qui (a) signifient certaines valeurs, et (b) peuvent s'exprimer dans le paysage. Cette these serait capable de verification par la recherche systématique.
Age‐related changes in and determinants of macular ganglion cell‐inner plexiform layer thickness in normal Chinese adults
Authors: Huo Yan J , Guo Yan , Li Lei , Wang Huai Z , Wang Ya X , Thomas Ravi , Wang Ning L 
Published: September 2017

AbstractImportanceConsideration of age‐related changes in macular ganglion cell‐inner plexiform layer (mGCIPL) thickness are important for glaucoma progression analysis.BackgroundTo report age‐related changes in and the determinants of high‐definition optical coherence tomography (HD‐OCT) measurements of mGCIPL thickness.DesignCross‐sectional study.Participants326 healthy adults.MethodsAll subjects underwent Cirrus HD‐OCT measurements of mGCIPL. One‐way analysis of variance (ANOVA) was used to compare mGCIPL thickness between 7 decades based age groups and macular sectors. Multiple regression analysis determined the association between mGCIPL thickness and age, gender, intraocular pressure (IOP), peripapillary retinal nerve fibre layer thickness (pRNFL) and spherical equivalent.Main Outcome MeasuresChange in mGCIPL thickness and determinants of thickness.ResultsMean mGCIPL thickness in 295 subjects was 80.80 ± 6.42 μm. Mean mGCIPL decreased by 0.12 μm (95% CI [confidence interval], 0.09–0.16) with every year of age; 1.61 μm (95% CI, 0.08–2.41) per decade. It showed two steep declines with age, first in the fifth and next in the seventh decade with relative stability between them. mGCIPL thickness was associated with pRNFL thickness (β = 0.30, P < 0.001) and IOP (β = −0.19, P = 0.03) but not with gender (β = −1.09, P = 0.116) or spherical equivalent (β = −0. 24, P = 0.145).Conclusions and RelevanceMean mGCIPL thickness showed a small age‐related linear decrease with two steep drops in the fifth and seventh decades. Thinner mGCIPL was independently associated with age, thinner pRNFL and higher IOP. These factors should be considered if using mGCIPL to detect progression of glaucoma and other optic neuropathies characterized by the loss of retinal ganglion cells.
9‐cis‐Retinoic acid induces a distinct regulatory dendritic cell phenotype that modulates murine delayed‐type allergy
Authors: Kraus Lea‐Franziska , Scheurmann Natalie , Frenzel Denis F. , Tasdogan Alpaslan , Weiss Johannes M. 
Published: September 2017

SummaryBackgroundHand eczema, which is frequently caused by delayed‐type allergy, is treated with 9‐cis‐retinoic acid (9cisRA). However, knowledge on how 9cisRA modulates skin immunity is sparse.ObjectiveAs dendritic cells (DCs) are central in the pathogenesis of contact allergy, we investigated 9cisRA modulation of DC function in murine contact hypersensitivity (CHS).Methods9cisRA‐differentiated DCs (9cisRA‐DCs) were analysed for phenotype and function. In vivo 9cisRA‐DCs were tested in the CHS model.Results9cisRA induces the differentiation of a distinct CD103− CD207− regulatory DC phenotype. CD11c+ DCs differentiated with 9cisRA have lower expression of major histocompatibility complex‐II and costimulatory molecules, but conversely have higher expression of the inhibitory coreceptor PD1‐L. 9cisRA‐DC culture does not induce the expression of proinflammatory cytokines, but strongly enhances osteopontin (OPN) secretion. 9cisRA‐DCs are compromised in the induction of T cell proliferation in vitro, but efficiently convert naive T cells into regulatory T cells (Tregs). Notably, OPN‐deficient 9cisRA‐DCs show a loss of Treg‐inducing function, which is re‐established by substituting OPN. In vivo, in allergic mice, allergen‐primed 9cisRA‐DCs suppress allergic inflammation and induce Treg accumulation in skin draining lymph nodes.ConclusionsThis study describes 9cisRA‐mediated differentiation of a distinct DC phenotype that relies on OPN for Treg transformation and suppresses established CHS through Treg induction.
Liver transplantation in critically ill patients: Preoperative predictive factors of post‐transplant mortality to avoid futility
Authors: Michard Baptiste , Artzner Thierry , Lebas Benjamin , Besch Camille , Guillot Max , Faitot François , Lefebvre François , Bachellier Philippe , Castelain Vincent , Maestraggi Quentin , Schneider Francis 
Published: September 2017

AbstractBackgroundThe allocation of liver transplants to patients with acute liver failure (ALF) and acute‐on‐chronic liver failure (ACLF) with multi‐organ failure who are admitted in ICU remains controversial due to their high post‐transplant mortality rate and the absence of identified mortality risk factors.MethodsWe performed a single‐center retrospective cohort study to determine the post‐transplant mortality rate of patients with ALF and ACLF requiring ICU care prior to liver transplant (LT) and identified pretransplant factors of post‐transplant mortality.ResultsEighty‐four patients (29 with ALF and 55 with ACLF) received a liver transplant while they were hospitalized at the ICU. Their mean model for end‐stage liver disease (MELD) score was 41, and their mean sequential organ failure assessment (SOFA) was 15 the day before transplant. The overall 1‐year survival rate was 66%. In multivariate analysis, pretransplant lactate level and acute respiratory distress syndrome (ARDS) were the only two independent factors associated with post‐transplant mortality. The absence of ARDS and a pretransplant lactate level< 5 mmol/L led to the identification of a subgroup of ICU patients with a good 1‐year post‐transplant survival (>80%).ConclusionsLow lactatemia lactate level and the absence of ARDS could be useful criteria in selecting those patients in ICU who could be eligible for liver transplant.
Trends in mean growth and stability in temperate vertebrate populations
Authors: Leung Brian , Greenberg Daniel A. , Green David M. 
Published: September 2017

AbstractAimConsiderable controversy exists over the nature of the “Biodiversity Crisis.” While some studies suggest declining diversity, others suggest no loss on average. Population declines necessarily precede species loss and may therefore be a more sensitive metric. We examine trends in abundances to test the hypotheses: (1) losses are experienced disproportionately by some taxa, in particular amphibians; (2) positive trends in alien or unexploited species mask declines in native or exploited species, respectively; (3) populations are becoming more unstable, and variances of within‐population growth rates are increasing.LocationFreshwater and terrestrial habitats in North America and Europe.MethodsWe analysed abundances of 4,343 population time series of 983 species of temperate amphibians, birds, bony fishes, reptiles and mammals from 1970 to 2014. Population mean trends were estimated using a state‐space model to account for observation error, and then, linear mixed‐effects models were used to test mean differences among groups. As a measure of instability, trends over time in variance of population growth rates were analysed using a Breusch–Pagan test for heteroscedacity, and integrated across populations using meta‐analysis.ResultsMean trends for amphibians suggested a systematic decline, whereas birds, reptiles and mammals were increasing, on average, and freshwater fishes showed no net change in general. Origin and exploitation status did not explain the mean patterns. Large‐bodied birds and range‐restricted mammals exhibited stronger increases compared to their counterparts. For all taxonomic groups, population fluctuations have been increasing overall.Main conclusionsAddressing amphibian declines should be a priority in temperate regions. Comparatively, the lack of broad declines in the other vertebrate classes is promising and not attributable to increases in alien or non‐exploited species. Yet, caution remains warranted given that patterns of increasing variance suggested that populations are generally becoming more unstable, even in temperate, developed nations, with arguably the strongest environmental regulations.
Insulin resistance and cardiovascular outcomes in the ORIGIN trial
Authors: Gerstein Hertzel C. , Ferrannini Ele , Riddle Matthew C. , Yusuf Salim ,   ORIGIN Trial Investigators
Published: September 2017

AimsIn the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial (Clinicaltrials.gov: NCT000069784), titrated doses of basal insulin glargine targeting fasting normoglycaemia had a neutral effect on cardiovascular outcomes. The dose of insulin required to achieve normoglycaemia provides a unique measurement of each individual's resistance to insulin's action, and was therefore used to examine the link between insulin resistance and cardiovascular outcomes.Materials and MethodsSelf‐titration of insulin doses targeting a fasting plasma glucose ≤5.3 mmoL/L (95 mg/dL) was promoted at every visit and cardiovascular and other serious health outcomes were ascertained. All analyses were restricted to participants allocated to insulin glargine, who added it to lifestyle or 1 glucose‐lowering oral agent at randomization. Normoglycaemia was defined as a fasting plasma glucose <5.6 mmol/L and HbA1c <6% at the 2‐year visit. The median of the natural logarithm of insulin doses (expressed per kg of fat‐free mass), recorded at every visit from randomization until either the penultimate visit or the first occurrence of a cardiovascular outcome, was analysed.ResultsHigher median insulin doses did not reflect incident cardiovascular events overall or in the subset that achieved normoglycaemia. When the dose taken before a cardiovascular event or the penultimate visit was analysed, the adjusted hazard of the composite of cardiovascular death, myocardial infarction or stroke was 0.94 (95% CI 0.88, 1.00) per unit higher dose overall, and 0.91 (95% CI 0.81, 1.01) in the normoglycaemic subset.ConclusionsInsulin resistance may not promote cardiovascular outcomes in individuals with dysglycaemia.