bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria
Authors: Mordmüller Benjamin , Sulyok Mihály , Egger-Adam Diane , Resende Mafalda , de Jongh Willem A , Jensen Mette H , Smedegaard Helle Holm , Ditlev Sisse B , Soegaard Max , Poulsen Lars , Dyring Charlotte , Calle Carlos Lamsfus , Knoblich Annette , Ibáñez Javier , Esen Meral , Deloron Philippe , Ndam Nicaise , Issifou Saadou , Houard Sophie , Howard Randall F , Reed Steven G , Leroy Odile , Luty Adrian J F , Theander Thor G , Kremsner Peter G , Salanti Ali , Nielsen Morten A 
Published: January 2019

Abstract

Background
Malaria in pregnancy has major impacts on mother and child health. To complement existing interventions, such as intermittent preventive treatment and use of impregnated bed nets, we developed a malaria vaccine candidate with the aim of reducing sequestration of asexual “blood-stage” parasites in the placenta, the major virulence mechanism.

Methods
The vaccine candidate PAMVAC is based on a recombinant fragment of VAR2CSA, the Plasmodium falciparum protein responsible for binding to the placenta via chondroitin sulfate A (CSA). Healthy, adult malaria-naive volunteers were immunized with 3 intramuscular injections of 20 μg (n = 9) or 50 μg (n = 27) PAMVAC, adjuvanted with Alhydrogel or glucopyranosyl lipid adjuvant in stable emulsion (GLA-SE) or in a liposomal formulation with QS21 (GLA-LSQ). Allocation was random and double blind. The vaccine was given every 4 weeks. Volunteers were observed for 6 months following last immunization.

Results
All PAMVAC formulations were safe and well tolerated. A total of 262 adverse events (AEs) occurred, 94 (10 grade 2 and 2 grade 3) at least possibly related to the vaccine. No serious AEs occurred. Distribution and severity of AEs were similar in all arms. PAMVAC was immunogenic in all participants. PAMVAC-specific antibody levels were highest with PAMVAC-GLA-SE. The antibodies inhibited binding of VAR2CSA expressing P. falciparum-infected erythrocytes to CSA in a standardized functional assay.

Conclusions
PAMVAC formulated with Alhydrogel or GLA-based adjuvants was safe, well tolerated, and induced functionally active antibodies. Next, PAMVAC will be assessed in women before first pregnancies in an endemic area.

Clinical Trials Registration
EudraCT 2015-001827-21; ClinicalTrials.gov NCT02647489.
A mixed DG method and an HDG method for incompressible magnetohydrodynamics
Authors: Qiu Weifeng , Shi Ke 
Published: January 2019

Abstract
In this paper we propose and analyze a mixed discontinuous Galerkin (DG) method and an hybridizable DG (HDG) method for the stationary magnetohydrodynamics (MHD) equations with two types of boundary (or constraint) conditions. The mixed DG method is based on a recent work proposed by Houston et al. (2009, A mixed DG method for linearized incompressible magnetohydrodynamics. J. Sci. Comput., 40, 281–314) for the linearized MHD. With two novel discrete Sobolev embedding type estimates for the discontinuous polynomials, we provide a priori error estimates for the method on the nonlinear MHD equations. In the smooth case we have optimal convergence rate for the velocity, magnetic field and pressure in the energy norm; the Lagrange multiplier only has suboptimal convergence order. With the minimal regularity assumption on the exact solution, the approximation is optimal for all unknowns. To the best of our knowledge, these are the first a priori error estimates for DG methods for the nonlinear MHD equations. In addition, we also propose and analyze the first divergence-free HDG method for the problem with several unique features comparing with the mixed DG method.
Evaluating the effect of data standardization and validation on patient matching accuracy
Authors: Grannis Shaun J , Xu Huiping , Vest Joshua R , Kasthurirathne Suranga , Bo Na , Moscovitch Ben , Torkzadeh Rita , Rising Josh 
Published: January 2019

Abstract

Objective
This study evaluated the degree to which recommendations for demographic data standardization improve patient matching accuracy using real-world datasets.

Materials and Methods
We used 4 manually reviewed datasets, containing a random selection of matches and nonmatches. Matching datasets included health information exchange (HIE) records, public health registry records, Social Security Death Master File records, and newborn screening records. Standardized fields including last name, telephone number, social security number, date of birth, and address. Matching performance was evaluated using 4 metrics: sensitivity, specificity, positive predictive value, and accuracy.

Results
Standardizing address was independently associated with improved matching sensitivities for both the public health and HIE datasets of approximately 0.6% and 4.5%. Overall accuracy was unchanged for both datasets due to reduced match specificity. We observed no similar impact for address standardization in the death master file dataset. Standardizing last name yielded improved matching sensitivity of 0.6% for the HIE dataset, while overall accuracy remained the same due to a decrease in match specificity. We noted no similar impact for other datasets. Standardizing other individual fields (telephone, date of birth, or social security number) showed no matching improvements. As standardizing address and last name improved matching sensitivity, we examined the combined effect of address and last name standardization, which showed that standardization improved sensitivity from 81.3% to 91.6% for the HIE dataset.

Conclusions
Data standardization can improve match rates, thus ensuring that patients and clinicians have better data on which to make decisions to enhance care quality and safety.
Risk Factors for Community-Acquired Extended-Spectrum Beta-Lactamase–Producing Enterobacteriaceae Infections—A Retrospective Study of Symptomatic Urinary Tract Infections
Authors: Goyal Dheeraj , Dean Nathan , Neill Sarah , Jones Peter , Dascomb Kristin 
Published: January 2019

Abstract

Background
Community-acquired extended-spectrum beta-lactamase–producing Enterobacteriaceae (ESBL) infections are an evolving public health problem. Identifying predictive risk factors may improve patient management.

Methods
We identified 251 adult inpatients admitted to a 22-hospital system with an ESBL urinary tract infection (UTI) between 2001 and 2016. Cases were matched 1:1 with controls who had a UTI at admission with non-ESBL Enterobacteriaceae. Cases with a history of ESBL infections or hospitalization within 3 months of index admission were excluded. Univariate and multiple logistic regression were used to identify risk factors associated with ESBL UTIs.

Results
In univariate analysis, history of repeated UTIs, neurogenic bladder, urinary catheter presence at admission, and exposure to outpatient third-generation cephalosporins or fluoroquinolones within 3 months were associated with higher risk of ESBL UTIs. When controlling for severity of illness and comorbid conditions, history of repeated UTIs (adjusted odds ratio [aOR], 6.40; 95% confidence interval [CI], 3.42–12.66; P &lt; .001), presence of urinary catheter at admission (aOR, 2.36; 95% CI, 1.15–4.98; P &lt; .05), and prior antibiotic exposure (aOR, 7.98; 95% CI, 2.92–28.19; P &lt; .001) remained associated with risk of ESBL infection.

Conclusions
Patients in the community with indwelling urinary catheters, history of recurrent UTIs, or recent antimicrobial use are at higher risk for de novo ESBL Enterobacteriaceae UTIs.
The Mind in the Old English Prose Psalms
Authors: Faulkner Amy 
Published: January 2019

Abstract
The Prose Psalms, an Old English translation of the first 50 psalms into prose, have often been overshadowed by the other translations attributed to Alfred the Great: the Old English Pastoral Care, with its famous preface, and the intellectually daring Old English translations of Boethius’s Consolation of Philosophy and Augustine’s Soliloquies. However, this article proposes that, regardless of who wrote them, the Prose Psalms should be read alongside the Old English Consolation and the Soliloquies: like the two more well-studied translations, the Prose Psalms are concerned with the mind and its search for true understanding. This psychological interest is indicated by the prevalence of the word mod (‘mind’) in the Old English text, which far exceeds references to the faculty of the intellect in the Romanum source. Through comparison with the Consolation and the Soliloquies, this article demonstrates that all three texts participate in a shared tradition of psychological imagery. The three translations may well, therefore, be the result of a single scholarly environment, perhaps enduring for several decades, in which multiple scholars read the same Latin, patristic writings on psychology, discussed these ideas among themselves, and thereby developed the vernacular discourse observable in these three translations. Whether this environment was identical with the scholarly circle which Alfred gathered at the West Saxon court remains a matter for debate.
Behavioural Characterizations of Naivete for Time-Inconsistent Preferences
Authors: Ahn David S , Iijima Ryota , Le Yaouanq Yves , Sarver Todd 
Published: January 2019

Abstract
We propose non-parametric definitions of absolute and comparative naivete. These definitions leverage ex ante choice of menu to identify predictions of future behaviour and ex post (random) choices from menus to identify actual behaviour. The main advantage of our definitions is their independence from any assumed functional form for the utility function representing behaviour. An individual is sophisticated if she is indifferent ex ante between retaining the option to choose from a menu ex post or committing to her actual distribution of choices from that menu. She is naive if she prefers the flexibility in the menu, reflecting a mistaken belief that she will act more virtuously than she actually will. We propose two definitions of comparative naivete and explore the restrictions implied by our definitions for several prominent models of time inconsistency.
Studying the dawn of de novo gene emergence in mice reveals fast integration of new genes into functional networks
Authors: Xie Chen , Bekpen Cemalettin , Künzel Sven , Keshavarz Maryam , Krebs-Wheaton Rebecca , Skrabar Neva , Ullrich Kristian , Tautz Diethard 
Published: January 2019

AbstractThe de novo emergence of new transcripts has been well documented through genomic analyses. However, a functional analysis, especially of very young protein-coding genes, is still largely lacking. Here we focus on three loci that have evolved from previously intergenic sequences in the house mouse (Mus musculus) and are not present in its closest relatives. We have obtained knockouts and analyzed their phenotypes, including a deep transcriptomic analysis, based on a dedicated power analysis. We show that the transcriptional networks are significantly disturbed in the knockouts and that all three genes have effects on phenotypes that are related to their expression patterns. This includes behavioral effects, skeletal differences and the regulation of the reproduction cycle in females. Substitution analysis suggests that all three genes have directly obtained an activity, without new adaptive substitutions. Our findings support the hypothesis that de novo genes can quickly adopt functions without extensive adaptation.Impact statementNew protein-coding genes emerging out of non-coding sequences can become directly functional without signatures of adaptive protein changes
A novel small molecule screening platform for disrupting toxic tau oligomers in cells
Authors: Lo Chih Hung , Lim Colin Kin-Wye , Ding Zhipeng , Wickramasinghe Sanjula , Braun Anthony R. , Rhoades Elizabeth , Thomas David D. , Sachs Jonathan N. 
Published: January 2019

AbstractTauopathies, including Alzheimer’s disease, are a group of neurodegenerative disorders characterized by pathological aggregation of the microtubule binding protein tau. Recent studies suggest that toxic tau oligomers, which are soluble and distinct from insoluble beta-sheet fibrils, are central players in neuronal cell death. To exploit this new therapeutic window, we engineered two first-in-class FRET based biosensors that monitor tau conformations in cells. Because this new technology platform operates in cells, it enables high-throughput screening of small molecules that target tau oligomers while avoiding the uncertainties of idiosyncraticin vitropreparations of tau assemblies from purified protein. We found a small molecule, MK-886, that disrupts tau oligomers and reduces tau-induced cell cytotoxicity with nanomolar potency. Using SPR and an advanced single-molecule FRET technique, we show that MK-886 directly binds to tau and specifically perturbs the folding of tau monomer in the proline-rich and microtubule-binding regions. Furthermore, we show that MK-886 accelerates the tau aggregation lag phase using a thioflavin-T assay, implying that the compound stabilizes a non-toxic, on-pathway oligomer. The technology described here should generalize to the study and targeting of conformational ensembles within the aggregation pathways of most intrinsically disordered proteins.
The UTX Tumor Suppressor Directly Senses Oxygen to Control Chromatin and Cell Fate
Authors: Chakraborty Abhishek A. , Laukka Tuomas , Myllykoski Matti , Ringel Alison E. , Booker Matthew A. , Tolstorukov Michael Y. , Meng Yuzhong Jeff , Meier Sam , Jennings Rebecca B. , Creech Amanda L. , Herbert Zachary T. , Spinelli Jessica , McBrayer Samuel K. , Olenchock Benjamin A. , Jaffe Jacob D. , Haigis Marcia C. , Beroukhim Rameen , Signoretti Sabina , Koivunen Peppi , Kaelin William G. 
Published: January 2019

AbstractMammalian cells express multiple 2-oxoglutarate (OG)-dependent dioxygenases, including many chromatin regulators. The oxygen affinities, and hence oxygen sensing capabilities, of the 2-oxoglutarate (OG)-dependent dioxygenases reported to date vary widely. Hypoxia can affect chromatin, but whether this reflects a direct effect on chromatin-modifying dioxygenases, or indirect effects caused by the hypoxic-induction of the HIF transcription factor or the endogenous 2-OG competitor 2-hydroxyglutarate (2-HG), is unclear. Here we report that hypoxia induces a HIF- and 2-HG-independent histone modification signature consistent with KDM inactivation. We also show that the H3K27 histone demethylase KDM6A (also called UTX), but not its paralog KDM6B, is oxygen-sensitive. KDM6A loss, like hypoxia, prevented H3K27me3 erasure and blocked differentiation. Conversely, restoring H3K27me3 homeostasis in hypoxic cells reversed these effects. Therefore, oxygen directly affects chromatin regulators to control cell fate.One Sentence SummaryKDM6A demethylase activity is diminished under hypoxic conditions and causes changes in gene expression programs that govern cell fate.
An improved control efficacy against tobacco bacterial wilt by an engineered Pseudomonas mosselii expressing the ripAA gene from phytopathogenic Ralstonia solanacearum
Authors: Zhuo Tao , Chen Shiting , Fan Xiaojing , Hu Xun , Zou Huasong 
Published: January 2019

AbstractThe environmental bacterium Pseudomonas mosselii produces antagonistic secondary metabolites with inhibitory effects on multiple plant pathogens, including Ralstonia solanacearum, the causal agent of bacterial wilt. In this study, an engineered P. mosselii strain was generated to express R. solanacearum ripAA, which determines incompatible interactions with tobacco plants. The ripAA gene together with its native promoter was integrated into the P. mosselii chromosome. The resulting strain showed no difference in antimicrobial activity against R. solanacearum. Promoter-LacZ fusion and RT-PCR experiments demonstrated that the ripAA gene was transcribed in culture media. Compared with that of the wild type, the engineered strain reduced the disease index by 9.1% for bacterial wilt on tobacco plants. A transcriptome analysis was performed to identify differentially expressed genes in tobacco plants, and the results revealed that ethylene-and jasmonate-dependent defense signaling pathways were induced. These data demonstrated that the engineered P. mosselii expressing ripAA enables improved biological control against tobacco bacterial wilt by the activation of host defense responses.ImportanceNowadays, the use of biocontrol agents is more and more popular in agriculture, but they cannot replaced of chemical agents mostly, due to the poorer control effect. So the study about how to improve the efficacy of biocontrol agents become necessary and urgent. We increase the efficacy against plant pathogen through introducing an avirulence gene from plant pathogen into the biocontrol agent based on “gene to gene” hypothesis. The new engineered strain can improve the systemic resistance and elicit primary immune response of plants. Our research not only provides a new strategy for genetic modification of biocontrol agent, a number of avirulence gene from pathogen or plant can be tested to be expressed in different biocontrol agents to antagonize plant disease, but also help the study of interaction between phythopathogenic avirulence gene and host.
Stepping up to market participation of smallholder agriculture in rural areas of Indonesia
Authors: Mariyono Joko 
Published: January 2019

PurposeThe purpose of this paper is to analyse factors that determine farmers’ intention to commercialise vegetable-based agribusiness ventures in rural areas and assess the effect of commercialisation on farmers’ income.Design/methodology/approachThe study used a regression approach. Market participation and farmers’ income were hypothesised to be dependent on other external factors. This study employed data compiled from a quantitative survey of 357 farm households located in four major vegetable producing regions of rural East Java and Bali, Indonesia.FindingsResults indicate that household attributes, business environment, supporting facilities and farm characteristics determined farmers to commercialise vegetable farming. Access to credit, seed technology and farm site played high contribution to the market participation. Ultimately, commercial vegetable farming provides an economic advantage regarding increased income. Land fragmentation and status of landholding were identified to influence the net revenue of vegetable farming.Research limitations/implicationsThis study has a limitation concerning the number of samples and the availability of data and information. The number of samples is 357 which is about 4 per cent of the total population.Practical implicationsEstablishment of vegetable agribusiness terminals with all market infrastructures, adequate access to market information, credit and human capital investment through training and extension services are also required, will boost market participation. Re-structuring land ownership might be the best step to augment farmers’ income, through consolidation of fragmented fertile lands devoted to intensive vegetable farming.Originality/valueThis study was purposely conducted in rural areas where there were subsistence farmers, as this is to improve farmers’ income by commercialising vegetable crops. A novel feature of this finding is the role of access to credit in the commercialisation of vegetable farming and the impact of landholding status on the profitability of intensive farming of high-valued vegetables.
Social norms in the salesforce: justice and relationalism
Authors: Benoit Ilgım Dara , Brashear Alejandro Thomas , Foreman Jeffrey , Chelariu Christian , Bergman Shawn 
Published: January 2019

PurposeThis paper aims to examine the role of social norms of justice and relationalism in salesperson–sales manager relationships, and their role in developing salesforce commitment and turnover.Design/methodology/approachThis study uses structural equation modeling to analyze survey data from 402 business-to-business salespeople.FindingsAs discrete foundational norms, distributive, procedural and interactional (interpersonal, informational) justice develop higher-order norms of relationalism, which then reflect on increased commitment and reduced turnover intention of the salesforce. Among the justice norms, interpersonal justice has the strongest impact on relationalism.Research limitations/implicationsThe paper shows how each justice norm has a distinct impact in shaping relational norms, and that interpersonal justice has the highest impact. In addition, with enhanced relationalism salespeople become more committed and have lower turnover intentions. Future research could use a longitudinal study, present manager’s side in the model and measure and compare the impact of supervisor- versus organization-focused justice.Practical implicationsTo enhance relationalism, and thus in turn increase commitment and decrease turnover intention of salesforce, sales managers should pay attention to the salespeople’s perceptions of justice norms (distributive, procedural, informational and interpersonal justice), especially interpersonal justice, as it has the highest impact on relationalism. The specific ways to enhance justice perceptions are discussed.Originality/valueThis paper is the first to show how each justice norm is unique in its importance to shape the relationship between sales manager and salespeople in a way that increases the quality of relational norms, governing the relational process into a highly committed one. It also shows that among the four justice norms, interactional justice has the highest impact on relationalism. In addition, this is the first study to show that relationalism decreases turnover intention of salespeople.
The assessment of an integrated bio-filter systems for the wastewaters treatment in arid regions (Touggourt, Algeria)
Authors: Amiri Khaled , Hartani Tarik , Zeddouri Aziez 
Published: January 2019

Purpose
The purpose of this paper is to assess the water quality parameters resulting on: First, the flow direction in biofilters (ascending or descending), second, constructed wetland (CW) with local plant species and third, the combined system for the removal of organic matter and nutrients pollutants from water in arid regions.

Design/methodology/approach
An integrated system is presented and tested in situ with a vertical up-flow and down-flow biofilters. Two configurations schemes are followed by a three separated horizontal subsurface CWs: two planted with Phragmites australis, Typha latifolia and the third unplanted. The methodology is based on a statistical analysis of the collected data.

Findings
The present experiment demonstrated that the wetlands planted with P. australis and T. latifolia showed the highest removal. Moreover, T. latifolia performed better than P. australis for most of the parameters, notably in the first system, whereas the wetland efficiency indicated that P. australis contributed greatly to the removal of TP in the first system and NO3-N in the second system. In general, for the highest removal efficiencies of the combined biofilters and wetlands system, the present study demonstrated that the first system performed better than the second for all the parameters.

Originality/value
The originality of the research is that it compares in situ two biofilter systems: vertical up-flow and down-flow biofilters. To avoid the effects of domestic wastewater that is discharged directly without treatment in the Oued Righ channel or in the lake, this integrated system can be one of the alternatives for wastewater treatment, as it reveals the need to protect aquatic ecosystems in arid regions, and can decrease the risks to human health and the environment.