bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombopoiesis‐stimulating agents and myelodysplastic syndromes
Authors: Brierley Charlotte K. , Steensma David P. 
Published: February 2015

SummaryThrombocytopenia in patients with myelodysplastic syndromes (MDS) is a frequent cause of haemorrhage‐related morbidity and mortality, and is associated with increased risk of leukaemic transformation and reduced overall survival. In addition, thrombocytopenia in MDS limits the tolerability and therapeutic efficacy of disease‐modifying therapies, such as azacitidine or lenalidomide. The recombinant human erythropoietin (rHuEPO) erythropoiesis‐stimulating agents, epoetin and darbepoetin, are an established component of anaemia management in lower‐risk MDS. Their success has, in turn, driven the development of haematopoietic growth factors targeting thrombocytopenia. While recombinant thrombopoietin (THPO) proved too immunogenic for clinical use, novel thrombopoiesis‐stimulating agents (TSAs) have the potential to reduce bleeding events, decrease dependency on platelet transfusions and extend exposure to disease‐modifying therapies. Two TSAs, eltrombopag and romiplostim, have demonstrated benefit in chronic immune thrombocytopenia purpura (ITP) and safety and efficacy data for use of these agents in MDS is growing. However, important safety concerns remain, such as the potential for stimulation of neoplastic myeloid clones by THPO agonists. In this narrative review, we discuss the rationale and biological mechanism for TSAs in MDS, describe the agents currently available and their mechanism of action, and present current clinical data relating to TSA safety and efficacy in the context of MDS.
CD22ΔE12 as a molecular target for RNAi therapy
Authors: Uckun Fatih M. , Ma Hong , Cheng Jianjun , Myers Dorothea E. , Qazi Sanjive 
Published: February 2015

SummaryB‐precursor acute lymphoblastic leukaemia (BPL) is the most common form of cancer in children and adolescents. Our recent studies have demonstrated that CD22ΔE12 is a characteristic genetic defect of therapy‐refractory clones in paediatric BPL and implicated the CD22ΔE12 genetic defect in the aggressive biology of relapsed or therapy‐refractory paediatric BPL. The purpose of the present study is to evaluate the biological significance of the CD22ΔE12 molecular lesion in BPL and determine if it could serve as a molecular target for RNA interference (RNAi) therapy. Here we report a previously unrecognized causal link between CD22ΔE12 and aggressive biology of human BPL cells by demonstrating that siRNA‐mediated knockdown of CD22ΔE12 in primary leukaemic B‐cell precursors is associated with a marked inhibition of their clonogenicity. Additionally, we report a nanoscale liposomal formulation of CD22ΔE12‐specific siRNA with potent in vitro and in vivo anti‐leukaemic activity against primary human BPL cells as a first‐in‐class RNAi therapeutic candidate targeting CD22ΔE12.
Recognizing preschool children with primary teeth needing dental treatment because of caries‐related toothache
Authors: Daher Anelise , Abreu Mauro H.N.G. , Costa Luciane R. 
Published: February 2015

AbstractObjectivesThe Dental Discomfort Questionnaire (DDQ), which is an observational instrument that assesses dental pain in preschool children, has not been extensively tested for its ability to identify dental treatment needs in this population. This study aimed to explore the accuracy of the Brazilian version of the DDQ (DDQ‐B) to identify preschool children needing dental treatment.MethodsThe participants were 326 children (57.7% boys), aged 15–72 months [mean 49.8, standard deviation (SD) 14.8], who were examined to assess their dental treatment needs at the same time that their parents filled out the DDQ‐B. The DDQ‐B median score (outcome variable) was compared to the median index of dental treatment needs or categories (nonparametric tests). The area under the receiver operating characteristic (ROC) curve (AUC) and diagnostic tests were performed to test the DDQ‐B accuracy for identifying preschoolers with untreated teeth needing dental treatment. The data were analysed using SPSS 19.0, and the significance level was set at 5%.ResultsOverall, 326 questionnaires were completed and considered for analyses. Additionally, 63.5% of children had untreated teeth needing dental care. The median DDQ‐B score, 2.0 (first‐third quartile 1.0–5.0), was positively associated with the median index for needing dental care, 3.0 (0.0–5.0) (ρ = 0.49, P < 0.001). Children with more invasive intervention needs, such as pulp therapy, 5.0 (2.0–7.0), and extraction, 6.0 (4.0–8.5), had the highest DDQ‐B scores (P < 0.001). The DDQ‐B could identify children with more invasive dental care needs [AUC 0.86, 95% confidence interval (CI) 0.80–0.91, P < 0.001]. A score of 5 or higher was a reliable cut‐off point to confirm that children who were screened with caries‐related toothache by the DDQ‐B do, in fact, have untreated teeth needing dental treatment, especially for pulpal care and extraction.ConclusionsThe DDQ‐B is an accurate observational tool for identifying preschool children with dental treatment needs; children who scored 5 or higher require dental care for more invasive procedures.
Bone healing at implants with different surface configurations: an experimental study in dogs
Authors: Beolchini Marco , Lang Niklaus P. , Gómez Moreno Gerardo , Iezzi Giovanna , Botticelli Daniele , Calvo Guirado José Luis 
Published: February 2015

AbstractObjectiveTo study osseointegration of implants with surface modifications by the use of fluoroboric acid and/or H2O2 installed in conventional sites or sites with circumferential marginal defects.Material and methodsFour implants with different surfaces were used. One basic surface (ZirTi®) was sandblasted with zirconium microspheres and acid etched additionally with hydrofluoric acid. A second surface was treated with fluoroboric acid instead of hydrofluoric acid. The remainder of the other two surfaces was additionally treated with H2O2. The edentulous mandibles of 6 foxhound dogs were used to randomly install 8.5‐mm‐long implants with the different surfaces and to study the histological healing after 1 and 3 months. To study osteoconductivity, additional four recipient sites were prepared with the coronal region being widened so that a 4 mm deep and 0.85 mm wide marginal defect resulted after the placement of the four implants with different surfaces. No filler material or membranes were used, and a fully submerged healing was allowed for 3 months.ResultsAt the conventional sites, new bone formation ranged between 68.5% and 74.9% after 1 month. After 3 months, bone‐to‐implant contact ranged from 72.6% at the ZirTi® surface to 84.1% at the fluoroboric acid‐treated implants, the difference being statistically significant. At the sites with marginal defects, bone formation ranged from 0.77 mm at the surface treated with fluoroboric acid and H2O2, to 1.93 mm at the surface treated with fluoroboric acid alone.ConclusionsFluoroboric acid treatment alone of titanium implant surfaces resulted in improved osseointegration and osteoconductivity after 3 months.
Can Development Aid Help Promote Foreign Direct Investment? Evidence from Central Asia
Authors: Arazmuradov Annageldy 
Published: February 2015

AbstractThere is a continuing debate on the effectiveness of development aid. One less obvious angle on this issue is the question of the likely impact of aid on foreign direct investment (FDI). This paper tests whether aid had any impact on incomingFDIin CentralAsian economies during the period 1993–2008. A simple panel model suggests that (a) aid had a moderate complementary effect on inwardFDI, (b) there was a crowding‐out effect such that domestic investment reducedFDIstocks, (c) natural resources were a key attraction for private capital, and (d) increases in development aid offset the crowding‐out effect of domestic capital onFDI. It is argued that donors should target aid to enhance the climate for inward investment.
In Praise of Expansionary Fiscal Contraction
Authors: Congdon Tim 
Published: February 2015

AbstractTextbook orthodoxy maintains that increases in the cyclically adjusted budget balance (i.e. reductions in the deficit) withdraw demand from an economy. Those Keynesian economists who believe that fiscal policy is the most powerful single influence on changes in demand expect ‘fiscal contraction’ to be accompanied by below‐trend growth or even declines in output. This article, a response to Martin Wolf's 2013 Wincott Memorial Lecture, considers this Keynesian view. Using a database prepared by the International Monetary Fund, it shows that since the 1980s ‘expansionary fiscal contractions’ have been the norm and not the exception in the USA and the UK. Keynesian support for fiscal activism is unsupported by a large body of recent evidence.
Internal Markets, Management by Targets, and Quasi‐Markets: An Analysis of Health Care Reforms in the English NHS
Authors: Niemietz Kristian 
Published: February 2015

AbstractThere have been two major attempts to introduce market mechanisms into England's National Health Service: the ‘internal market’ reform project of the 1990s, and the ‘quasi‐market’ of the 2000s. Despite their similarities, the former attempt was on balance unsuccessful while the latter succeeded. This article examines and compares the outcomes of the two periods, analysing the reasons for their relative successes and failures. It goes on to highlight options for future reforms that would build on those achievements.
Microtubule‐associated protein tau promotes neuronal class II β‐tubulin microtubule formation and axon elongation in embryonic Xenopus laevis
Authors: Liu Yuanyuan , Wang Chen , Destin Giovanny , Szaro Ben G. 
Published: February 2015

AbstractCompared with its roles in neurodegeneration, much less is known about microtubule‐associated protein tau's normal functions in vivo, especially during development. The external development and ease of manipulating gene expression of Xenopus laevis embryos make them especially useful for studying gene function during early development. To study tau's functions in axon outgrowth, we characterized the most prominent tau isoforms of Xenopus embryos and manipulated their expression. None of these four isoforms were strictly analogous to those commonly studied in mammals, as all constitutively contained exon 10, which is preferentially removed from mammalian fetal tau isoforms, as well as exon 8, which in mammals is rare. Nonetheless, like mammalian tau, Xenopus tau exhibited alternative splicing of exon 4a, which in mammals distinguishes ‘big’ tau of peripheral neurons, and exon 6. Strongly suppressing tau expression with antisense morpholino oligonucleotides only modestly compromised peripheral nerve outgrowth of intact tadpoles, but severely disrupted neuronal microtubules containing class II β‐tubulins while leaving other microtubules largely unperturbed. Thus, the relatively mild dependence of axon development on tau likely resulted from having only a single class of microtubules disrupted by its loss. Also, consistent with its greater expression in long peripheral axons, boosting expression of ‘big’ tau increased neurite outgrowth significantly and enhanced tubulin acetylation more so than did the smaller isoform. These data demonstrate the utility of Xenopus as a tool to gain new insights into tau's functions in vivo.
Providing decision support for replenishment operations using a genetic algorithms based fuzzy system
Authors: Ho G. T. S. , Lau H. C. W. , Choy K. L. , Lee C. K. M. , Lam H. Y. 
Published: February 2015

AbstractOwing to the shockwaves brought by the recent financial tsunami, most enterprises are facing tremendous challenges in maintaining the good liquidity of their own companies. In order to sustain a desirable level of cash flow for expanding business, inventory needs to be well organized because unnecessary inventory that ties up the capital in the business would prevent the enterprises from making investments. Because the existing approaches to replenishment are inflexible and unsophisticated, a new customer‐based responsive replenishment system embracing online analytical processing, fuzzy logic and genetic algorithm is proposed in this paper. This system could determine accurate and realistic order quantities based on all possible and relevant variables that affect the order quantity for each item that needs to be replenished. Once the quantity has been accurately identified, the company can increase the level of customer satisfaction while minimizing stocks. Furthermore, rather than static rule repositioning, the proposed dynamic rule refining ability makes the replenishment system self‐ameliorating by using genetic algorithm to investigate the possible fuzzy rule candidates for a more accurate inventory management model. A study has been conducted in a case company for the validation of the feasibility of the proposed system. After performing a spatial analysis, the results obtained indicate that the proposed responsive replenishment system is capable of ensuring improved inventory control performance in the case company.
The ribB FMN riboswitch from Escherichia coli operates at the transcriptional and translational level and regulates riboflavin biosynthesis
Authors: Pedrolli Danielle , Langer Simone , Hobl Birgit , Schwarz Julia , Hashimoto Masayuki , Mack Matthias 
Published: February 2015

FMN riboswitches are genetic elements that, in many bacteria, control genes responsible for biosynthesis and/or transport of riboflavin (vitamin B2). We report that the Escherichia coli ribB FMN riboswitch controls expression of the essential gene ribB coding for the riboflavin biosynthetic enzyme 3,4‐dihydroxy‐2‐butanone‐4‐phosphate synthase (RibB; EC 4.1.99.12). Our data show that the E. coli ribB FMN riboswitch is unusual because it operates at the transcriptional and also at the translational level. Expression of ribB is negatively affected by FMN and by the FMN analog roseoflavin mononucleotide, which is synthesized enzymatically from roseoflavin and ATP. Consequently, in addition to flavoenzymes, the E. coli ribB FMN riboswitch constitutes a target for the antibiotic roseoflavin produced by Streptomyces davawensis.
Spawning habitats of Cape horse mackerel (Trachurus capensis) in the northern Benguela upwelling region
Authors: Kreiner Anja , Yemane Dawit , Stenevik Erling Kåre 
Published: February 2015

AbstractSpawning habitat preference of horse mackerel, an important commercial fish species in Namibia, was studied off the Namibian coast using data collected during surveys conducted during 2000–2005. To assess spawning habitat preference two approaches were adopted: modelling the distribution of eggs and larvae using a generalized additive model, and assessing the link between the distribution of eggs (larvae) and the distribution of the environmental variables using the empirical cumulative distribution function. Horse mackerel were found to spawn over a wide range of environmental variables, indicating that they are robust to environmental changes. Taking into account the large‐scale warming experienced in the Benguela Current Large Marine Ecosystem and the expected future changes in the environment with climate change, the result of this study is important towards assessing the possible consequences of climate change.
Synthesis: climate effects on biodiversity, abundance and distribution of marine organisms in the Benguela
Authors: Jarre Astrid , Hutchings Laurence , Kirkman Stephen P. , Kreiner Anja , Tchipalanga Pedro C.M. , Kainge Paulus , Uanivi Uatjavi , van der Plas Anja K. , Blamey Laura K. , Coetzee Janet C. , Lamont Tarron , Samaai Toufiek , Verheye Hans M. , Yemane Dawit G. , Axelsen Bjoern E. , Ostrowski Marek , Stenevik Erling K. , Loeng Harald 
Published: February 2015

AbstractThe NansClim project (2010–2013) represented a regional collaboration to assess the effects of climate on Benguela dynamics. Based on in situ (since the 1960s in Namibia and South Africa and 1985 in Angola) and satellite (since the 1980s) observations, the project focussed on four subsystems, namely the Angola subtropical, northern Benguela upwelling, southern Benguela upwelling and Agulhas Bank. This contribution summarizes the findings for selected key questions, ranging from changes in the physico‐chemical habitats, plankton, pelagic and demersal fish communities, to cross‐cutting evaluation at subsystem and regional scales. The results underline the overriding importance to of considering the combined effects of climate and fishing as drivers of the dynamics of the ecosystem components. Each subsystem currently continues to function largely as a separate entity as described in earlier reviews. However, some changes have been observed across several subsystems, e.g., a coherent shift from one relatively stable period to another occurred in the northern and southern Benguela in the mid‐1990s. Future climate change could weaken the boundaries between the four subystems. The findings underline the need for continued regional research collaboration and regional surveys focussed at ecosystem, rather than resource, assessment. Our conclusions include implications for ecosystem‐based fisheries management, and recommendations for future regional research.
Combined association of leisure‐time physical activity and fruit and vegetable consumption with depressive symptoms in older Taiwanese: Results of a national cohort study
Authors: Chi Shu‐Huang , Wang Jiun‐Yi , Tsai Alan C 
Published: February 2015

AimsTo determine the independent and combined associations of leisure‐time physical activity (LTPA) and fruit and vegetable consumption with subsequent new depressive symptoms in Taiwanese aged ≥53 years.MethodsWe analyzed the 1999 and 2003 datasets of the Taiwan Longitudinal Survey on Aging and used the Center for Epidemiologic Studies Depression scale (score 0–30) to rate depressive symptoms. We excluded those who had depressive symptoms (Center for Epidemiologic Studies Depression scale ≥10) at baseline, and carried out logistic regression analysis to determine the associations of LTPA and fruit and vegetable consumption, independently or in combination, with new depressive symptoms 4 years later (n = 2630).ResultsIndependently, high LTPA was associated with reduced new depressive symptoms (OR 0.75, 95% CI 0.57–0.99); higher fruit and vegetable consumption showed the same trend, but was not significant. Combining high fruit (OR 0.61, 95% CI 0.41–0.89), vegetable (OR 0.49, 95% CI 0.26–0.93) or fruit and vegetable (OR 0.39, 95% CI 0.20–0.77) consumption with high LTPA all further reduced the likelihood of developing subsequent new depressive symptoms beyond LPTA alone.ConclusionThe simultaneous presence of several good lifestyle habits increases the beneficial effect of reducing the risk of developing depressive symptoms in older adults. Thus, older adults are encouraged to have as many good lifestyle habits as possible to reduce the risk of depressive symptoms. Geriatr Gerontol Int 2016; 16: 244–251.
Three screening methods for cognitive dysfunction using the Mini‐Mental State Examination and Korean Dementia Screening Questionnaire
Authors: Choi Seong Hye , Park Moon Ho 
Published: February 2015

AimTo screen for and determine cognitive dysfunction, cognitive tests and/or informant reports are commonly used. However, these cognitive tests and informant reports are not always available. The present study investigated three screening methods using the Mini‐Mental State Examination (MMSE) as the cognitive test, and the Korean dementia screening questionnaire (KDSQ) as the informant report.MethodsParticipants were recruited from the Korea Clinical Research Center for Dementia of South Korea, and included 2861 patients with Alzheimer's disease (dementia), 3519 patients with mild cognitive impairment and 1375 controls with no cognitive dysfunction. Three screening methods were tested: (i) MMSE alone (MMSEcut‐off); (ii) a conventional combination of MMSE and KDSQ (MMSE+KDSQcut‐off); and (iii) a decision tree with MMSE and KDSQ (MMSE+KDSQdecision tree).ResultsFor discriminating any cognitive dysfunction from controls, MMSE+KDSQcut‐off had the highest area under the receiver operating characteristic curve (0.784). For discriminating dementia from controls, MMSE+KDSQcut‐off had the highest area under the receiver operating characteristic curve (0.899). For discriminating mild cognitive impairment from controls, MMSEcut‐off had the highest area under the receiver operating characteristic curve (0.683). MMSE+KDSQdecision tree showed the highest sensitivity for all discriminations. For overall classification accuracy, MMSE+KDSQdecision tree had the highest value (70.0%).ConclusionsThese three methods had different advantageous properties for screening and staging cognitive dysfunction. As there might be different availability across clinical settings, these three methods can be selected and used according to situational needs. Geriatr Gerontol Int 2016; 16: 252–258.
The Pharmacological Treatment of Migraine in Brazil
Authors: Krymchantowski Abouch Valenty , Jevoux Carla da Cunha 
Published: February 2015

Background/ObjectivesMigraine is a chronic, disabling, and recurrent illness. Despite its burden, preventive medications are often underused, while acute strategies are frequently used injudiciously. Patients may benefit from comprehensive approaches with general informative orientation and formal medication strategies. In developing countries like Brazil, the access to comprehensive tertiary headache centers or updated specialists is somewhat limited, as are the resources available out of some private specialty care clinics. In addition, centers from the public system may not deliver effective care. The aim of this review is to perform a general description of the pharmacological treatments of migraine in tertiary headache centers of Brazil.MethodsThe data of 4 public and 6 private tertiary centers under the care of 16 neurologists involved with headache assistance in different cities of Brazil were gathered. Answers to questions directed to headache specialists, and analyzing data from previous care of patients was used to estimate a description of the general pharmacological approach used in Brazilian centers. The therapeutic options adopted by general practitioners were not considered as those from other medical specialties and holistic medicine, which also treat migraine on a common basis.ResultsEstimated data of nearly 4800 patients from 16 neurologists acting in headache clinics from 2005 to 2013 were collected. Headache approach by specialists in Brazil is basically divided into 2 groups. The public services, which assist nonpaying patients, deliver traditional and noncomprehensive approaches as well as prescribe mostly monotherapy. Roughly 30% of their patients do not receive preventive treatments that are generally tricyclic antidepressants or β‐blockers. Private centers, which are usually where paying people attend, as well as a few public centers of excellence, use multidisciplinary approaches and combination of drugs, despite the usual allegation of scarce evidence. Nearly 90% of the patients from these centers receive the prescription of preventive treatments, which are generally tricyclic antidepressants and/or neuromodulators and/or β‐blockers.CommentsThere is no consensus on whether patients turning to private tertiary centers are different from those seen in public nonpaying services. However, since it is directly related to economic status and public services may render free specific medications as well as official dispensation of work, it may be argued that patients have less headache impact, and suboptimal care is delivered in these instances. As for the studied private centers as well as for the few public excellence centers, care provided is usually varied, includes a combination of drugs, and prevention is commonly used.