bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemometric Approaches for Developing Infrared Nanosensors to Image Anthracyclines
Authors: Bonis-O’Donnell Jackson Travis Del , Pinals Rebecca , Jeong Sanghwa , Thakrar Ami , Wolfinger Russ , Landry Markita
Published: September 2018

Generation, identification, and validation of optical probes to image molecular targets in a biological milieu remains a challenge. Synthetic molecular recognition approaches leveraging the intrinsic near-infrared fluorescence of single-walled carbon nanotubes is a promising approach for chronic biochemical imaging in tissues. However, generation of nanosensors for selective imaging of molecular targets requires a heuristic approach. Here, we present a chemometric platform for rapidly screening libraries of candidate single-walled carbon nanotube nanosensors against biochemical analytes to quantify fluorescence response to small molecules including vitamins, neurotransmitters, and chemotherapeutics. We further show this approach can be leveraged to identify biochemical analytes that selectively modulate the intrinsic near-infrared fluorescence of candidate nanosensors. Chemometric analysis thus enables identification of nanosensor-analyte ‘hits’ and also nanosensor fluorescence signaling modalities such as wavelength-shifts that are optimal for translation to biological imaging. Through this approach, we identify and characterize a nanosensor for the chemotherapeutic anthracycline doxorubicin, which provides an up to 17 nm fluorescence red-shift and exhibits an 8 µM limit of detection, compatible with peak circulatory concentrations of doxorubicin common in therapeutic administration. We demonstrate selectivity of this nanosensor over dacarbazine, a chemotherapeutic commonly co-injected with DOX. Lastly, we demonstrate nanosensor tissue compatibility for imaging of doxorubicin in muscle tissue by incorporating nanosensors into the mouse hindlimb and measuring nanosensor response to exogenous DOX administration. Our results motivate chemometric approaches to nanosensor discovery for chronic imaging of drug partitioning into tissues and towards real-time monitoring of drug accumulation.
Modular preprocessing pipelines can reintroduce artifacts into fMRI data
Authors: Lindquist Martin A. , Geuter Stephan , Wager Tor D. , Caffo Brian S.
Published: September 2018

The preprocessing pipelines typically used in both task and restingstate fMRI (rs-fMRI) analysis are modular in nature: They are composed of a number of separate filtering/regression steps, including removal of head motion covariates and band-pass filtering, performed sequentially and in a flexible order. In this paper we illustrate the shortcomings of this approach, as we show how later preprocessing steps can reintroduce artifacts previously removed from the data in prior preprocessing steps. We show that each regression step is a geometric projection of data onto a subspace, and that performing a sequence of projections can move the data into subspaces no longer orthogonal to those previously removed, reintroducing signal related to nuisance covariates. Thus, linear filtering operations are not commutative, and the order in which the preprocessing steps are performed is critical. These issues can arise in practice when any combination of standard preprocessing steps—including motion regression, scrubbing, component-based correction, global signal regression, and temporal filtering—are performed sequentially. In this work we focus primarily on rs-fMRI. We illustrate the problem both theoretically and empirically through application to a test-retest rs-fMRI data set, and suggest remedies. These include (a) combining all steps into a single linear filter, or (b) sequential orthogonalization of covariates/linear filters performed in series.
A low-cost DIY device for high resolution, continuous measurement of microbial growth dynamics
Authors: Sasidharan Kalesh , Martinez-Vernon Andrea S. , Chen Jing , Fu Tiantian , Soyer Orkun S
Published: September 2018

High-resolution data on microbial growth dynamics allow characterisation of microbial physiology, as well as optimisation of genetic alterations thereof. Such data are routinely collected using bench-top spectrophotometers or so-called plate readers. These equipments present several drawbacks: (i) measurements from different devices cannot be compared directly, (ii) proprietary nature of devices makes it difficult for standardisation methods to be developed across devices, and (iii) high costs limit access to devices, which can become a bottleneck for researchers, especially for those working with anaerobic organisms or at higher containment level laboratories. These limitations could be lifted, and data reproducibility improved, if the scientific community could adopt standardised, low-cost and open-source devices that can be built in-house. Here, we present such a device, MicrobeMeter, which is a do-it-yourself (DIY), simple, yet robust photometer with continuous data-logging capability. It is built using 3D-printing and open-source Arduino platform, combined with purpose-built electronic circuits. We show that MicrobeMeter displays linear relation between culture density and turbidity measurement for microbes from different phylogenetic domains. In addition, culture density estimated from MicrobeMeter measurements produced less variance compared against three commercial bench-top spectrophotometers, indicating that its measurements are less affected by the differences in cell types. We show the utility of MicrobeMeter, as a programmable wireless continuous measurement device, by collecting long-term growth dynamics up to 458 hours from aerobic and anaerobic cultures. We provide a full open-source description of MicrobeMeter and its implementation for faster adaptation and future development by the scientific community. The blueprints of the device, as well as ready-to-assemble kit versions are also made available throughwww.humanetechnologies.co.uk.
CONFESS: Fluorescence-based single-cell ordering in R
Authors: Motakis Efthymios , Low Diana H.P.
Published: September 2018

Modern high-throughput single-cell technologies facilitate the efficient processing of hundreds of individual cells to comprehensively study their morphological and genomic heterogeneity. Fluidigm’s C1 Auto Prep system isolates fluorescence-stained cells into specially designed capture sites, generates high-resolution image data and prepares the associated cDNA libraries for mRNA sequencing. Current statistical methods focus on the analysis of the gene expression profiles and ignore the important information carried by the images. Here we propose a new direction for single-cell data analysis and develop CONFESS, a customized cell detection and fluorescence signal estimation model for images coming from the Fluidigm C1 system. Applied to a set of HeLa cells expressing fluorescence cell cycle reporters, the method predicted the progression state of hundreds of samples and enabled us to study the spatio-temporal dynamics of the HeLa cell cycle. The output can be easily integrated with the associated single-cell RNA-seq expression profiles for deeper understanding of a given biological system. CONFESS R package is available at Bioconductor (http://bioconductor.org/packages/release/bioc/html/CONFESS.html).
Image analysis for taxonomic identification of Javanese butterflies
Authors: de Vetter Saskia , Vos Rutger
Published: September 2018

Taxonomic experts classify millions of specimens, but this is very time-consuming and therefore expensive. Image analysis is a way to automate identification and was previously done at Naturalis Biodiversity Center for slipper orchids (Cypripedioideae) by the program ‘OrchID’. This program operated by extracting a pre-defined number of features from images, and these features were used to train artificial neural networks (ANN) to classify out-of-sample images. This program was extended to work for a collection of Javanese butterflies, donated to Naturalis by the Van Groenendael-Krijger Foundation. Originally, for the orchids, an image was divided into a pre-defined number of horizontal and vertical bins and the mean blue-green-red values of each bin were calculated (BGR method) to obtain image features. In the extended implementation, characteristic image features were extracted using the SURF algorithm implemented in OpenCV and clustered with the BagOfWords method (SURF-BOW method). In addition, a combination of BGR- and SURF-BOW was implemented to extract both types of features in a single dataset (BGR-SURF method). A selection of the butterfly and orchid images was made to create datasets with at least 5 and at most 50 specimens per species. The SURF-BOW and BGR-SURF methods were applied to both selected datasets, and the original BGR method was applied to the selected butterfly dataset. PCA plots were made to inspect visually how well the applied methods discriminated among the species. For the butterflies, both genus and species appeared to cluster together in the plots of the SURF-BOW method. However, no obvious clustering was noticeable for the orchid plots. The performance of the ANNs was validated by a stratified k-fold cross validation. For the butterflies, the BGR-SURF method scored best with an accuracy of 77%, against 71% for the SURF-BOW method and 66% for the BGR method, all for chained genus and species prediction with k = 10. The new methods could not improve the accuracy of the orchid classification with k = 10, which was 75% on genus, 52% on genus and section and 48% on genus, section and species in the original framework and now less than 25% for all. The validation results also showed that at least about 15 specimens per species were necessary for a good prediction with the SURF-BOW method. The BGR-SURF method was found to be the best of these methods for butterflies, but the original BGR method was best for the slipper orchids. In the future these methods may be tested with other datasets, for example with mosquitoes. In addition, other classifiers may be tested for better performance, like support vector machines.
Remotely sensed indicators and open-access biodiversity data to assess bird diversity patterns in Mediterranean rural landscapes
Authors: Ribeiro Inês , Proença Vânia , Ruiz Pere Serra , Palma Jorge , Domingo Cristina , Pons Xavier , Domingos Tiago
Published: September 2018

Changes in ecosystem area are often used to assess human impacts on habitats and estimate biodiversity change. However, because species respond to structural changes at fine spatial scales the use of area alone may not capture all relevant changes. Operational costs limit the assessment of biodiversity change at a simultaneously fine spatial resolution and large scales. The development of cost-effective and expedite methods to monitor biodiversity change is therefore required. We use open access satellite imagery and biodiversity data to investigate the importance of variables of habitat extent and structure in explaining species richness and community dissimilarity of forest and open-land birds at the regional scale. Moreover, because Mediterranean landscapes are subject to seasonal dynamics, we explore the indicator value of remotely sensed variables measured in spring and summer. A large-scale dataset of bird occurrence data, including 8042 observations and 78 species, distributed by 40 landscape-sized cells, was assembled from GBIF after controlling for data quality. We found that summer satellite imagery, when the green perennial vegetation is more apparent, is particularly suited to model the diversity patterns of forest species, because distribution of tree cover in the landscape is well captured. Summer data is also useful to monitor the perennial elements that shape landscape structure and the habitat of open-land species. Specifically, mean NDVI and a second-order NDVI texture variable, were found to be good indicators of forest and open-land habitats, respectively. The use of spring imagery appears to be useful to monitor habitat structure within open-land habitat patches. Overall, NDVI texture measures were found to be good predictors of bird diversity patterns at large scales. Also, we were able to successfully conduct a regional scale analysis using open-access data, which illustrates their potential to inform large scale biodiversity monitoring.
Stress-induced changes in the S-palmitoylation and S-nitrosylation of synaptic proteins
Authors: Zareba-Koziol Monika , Bartkowiak-Kaczmarek Anna , Figiel Izabela , Krzystyniak Adam , Wojtowicz Tomasz , Bijata Monika , Wlodarczyk Jakub
Published: September 2018

The precise regulation of synaptic integrity is critical for neuronal network connectivity and proper brain function. Essential aspects of the activity and localization of synaptic proteins are regulated by posttranslational modifications. S-palmitoylation is a reversible covalent modification of the cysteine with palmitate. It modulates affinity of the protein for cell membranes and membranous compartments. Intracellular palmitoylation dynamics are regulated by other posttranslational modifications, such as S-nitrosylation. Still unclear, however, are the ways in which this crosstalk is affected in brain pathology, such as stress-related disorders. Using a newly developed mass spectrometry-based approach (Palmitoylation And Nitrosylation Interplay Monitoring), we analyzed the endogenous S-palmitoylation and S-nitrosylation of postsynaptic density proteins at the level of specific single cysteines in a mouse model of chronic stress. Our results suggest that atypical mechanism of crosstalk between the S-palmitoylation and S-nitrosylation of synaptic proteins might be one of the major events associated with chronic stress disorders.
Pulse-Chase Labeling of Protein Antigens with [35S]Methionine
Authors: DeCaprio James , Kohl Thomas O.
Published: September 2018

Pulse-chase labeling of antigens with [35S]methionine is used to determine the relative half-life of a protein. In this protocol, intracellular unlabeled methionine levels are reduced by starvation of cells for 0.5–1 h, and then the cells are briefly labeled with [35S]methionine to create the pulse of newly synthesized proteins. Upon completion of cell labeling, the addition of Chasing medium containing an excess of unlabeled methionine is used to create the chase, reducing the likelihood that any remaining [35S]methionine will be incorporated into newly synthesized proteins. Labeling and chasing reactions of adherent cells can be directly performed in cell culture dishes in an incubator, whereas suspension cells are labeled and chased in a polypropylene tube kept in a water bath set at 37°C. At intervals after the pulse, aliquots of chased labeled cells are collected and pelleted with the option of immediately preparing cell lysates or freezing and storing the cell pellets at −80°C. Upon cell lysis and antigen purification by immunoprecipitation, SDS-PAGE-resolved proteins can be fixed on the gel and enhanced with fluorography or can be transferred to a nitrocellulose or polyvinylidene fluoride (PVDF) membrane followed by autoradiography or exposure in a phosphorimager. Membrane blotting has the advantage of allowing for detection of the target of interest by probing with an antigen-specific antibody to confirm that equal amounts of steady-state levels of the target protein were immunoprecipitated at each interval.
Administering Anesthesia to Rabbits
Authors: Greenfield Edward A.
Published: September 2018

Anesthesia is used to sedate animals during injections or during operations where unexpected or rapid movements would endanger the animal. This protocol outlines how to administer anesthesia to rabbits—from preanesthesia preparations to postoperative care.
Centromere and Kinetochore Assembly in Xenopus laevis Egg Extract
Authors: Flores Servin Julio C. , Straight Aaron F.
Published: September 2018

During cell division, chromosomes must be equally segregated to daughter cells. Centromeres, the primary interaction site between chromosomes and microtubules, mediate faithful chromosome segregation during mitosis. Functional studies of centromere proteins in cells have proven difficult, as mutation or deletion of most centromeric proteins often results in cell lethality. In this protocol, sperm chromatin or reconstituted chromatin arrays, together with Xenopus laevis egg extracts, are used to overcome these limitations and study centromere and kinetochore assembly in vitro. X. laevis egg extract is a powerful tool, as it can be readily cycled in vitro by addition of calcium and easily modified biochemically. Coupled with the addition of customizable reconstituted chromatin arrays or sperm chromatin, X. laevis egg extract provides distinct advantages over cell-based approaches in which similar experiments would not be feasible. Following incubation in egg extract, reconstituted centromeric chromatin arrays and sperm chromatin specifically assemble core centromere and kinetochore components that can be analyzed via immunofluorescence.
Analysis of intermittent instabilities in switching power converters using Filippov’s method
Authors: Muppala Kumar Kavitha , A. Kavitha , Duraisamy John Christilda Nancy
Published: September 2018

Purpose

In the design and development stage of the power converter systems, an abnormal intermittency is naturally experienced in nonautonomous system because of coupling of the interference signals. The study of identifying the possible conditions at which such an undesirable operation emerges is vital. Hence, the purpose of this paper is to explore the intermittent instabilities that evolve in the voltage-mode controlled quadratic buck converter when the sinusoidal interference signal coupled in reference voltage.

Design/methodology/approach

Voltage-mode controlled quadratic buck converter with the sinusoidal interference signal coupled in reference voltage manifests a symmetrical period-doubling bifurcation in intermittent periods for significant interference signal strength with the frequency near to the switching frequency or its rational multiples. The complete dynamics of the system is investigated for the various inference signal frequencies by numerical simulations.

Findings

Here, the intermittent instabilities are verified using a simple Filippov’s method with supporting evidence of Floquet multipliers (eigenvalues) movement. The analytical result obtained is found to agree well with the simulation results.

Practical implications

Power supplies are liable to an ambiguous complex behavior when it is seldom protected against the interference signal. The experimental study has made an attempt to explicit a detailed behavior observed in voltage-mode controlled quadratic buck converter when a sinusoidal intruding signal of different amplitude and frequency are coupled with the reference voltage. Such an analysis gives considerable focus for the power electronics engineers to meet the design requirements.

Originality/value

To the authors’ knowledge, all the research works on intermittent instabilities in power converters are analyzed only using conventional method of Poincare map technique which emerges to be complicated when the order of the system is higher. Alternatively, in this paper, Filippov’s technique is used for stability analysis of periodic orbit. The evolution of bifurcation point is predicted by the calculating the Floquet multipliers of monodromy matrix, and it is known to achieve the same objective as the Poincare map technique in much more straightforward way.
Constrained optimization of the magnetostrictive actuator with the use of penalty function method
Authors: Knypinski Lukasz , Kowalski Krzysztof , Nowak Lech
Published: September 2018

Purpose

The purpose of this paper is to elaborate algorithm and software for the optimization of the actuator–capacitor system taking the dynamics parameters into account. The system is applied for driving the valve of plasma gun. Two optimization strategies are proposed and pondered. The penalty function approach has been expanded in detail.

Design/methodology/approach

The field-circuit mathematical model of the dynamics operation consists of the strongly coupled equations of the transient electromagnetic fields and the equations of the electric circuit. The numerical implementation is based on finite element method and step-by-step Cranck–Nicholson procedure. The genetic algorithm has been used in the optimization procedure. The sigmoidal transformation has been applied to adjust the classical external penalty function method to the genetic algorithm.

Findings

The modification consists in adaptation of the penalty function to the genetic algorithm. In the proposed approach, operations involving successive iterations of increasing penalty function and operations containing genetic iterations are intertwined with each other. The differences between these two procedures are getting blurred. The proposed approach is very effective. It is possible to achieve optimal solution even more than ten times faster than using the classical method.

Originality/value

The proposed approach can be successfully applied to designing and optimization of different electromagnetic devices, including functional constraints.
A parallel finite element algorithm for nonstationary incompressible magnetohydrodynamics equations
Authors: Tang Qili
Published: September 2018

Purpose

The purpose of this paper is to design a parallel finite element (FE) algorithm based on fully overlapping domain decomposition for solving the nonstationary incompressible magnetohydrodynamics (MHD).

Design/methodology/approach

The fully discrete Euler implicit/explicit FE subproblems, which are defined in the whole domain with vast majority of the degrees of freedom associated with the particular subdomain, are solved in parallel. In each subproblem, the linear term is treated by implicit scheme and the nonlinear term is solved by explicit one.

Findings

For the algorithm, the almost unconditional convergence with optimal orders is validated by numerical tests. Some interesting phenomena are presented.

Originality/value

The proposed algorithm is effective, easy to realize with low communication costs and preferred for solving the strong nonlinear MHD system.
A landscape approach for cost‐effective large‐scale forest restoration
Authors: Molin Paulo Guilherme , Chazdon Robin , Frosini de Barros Ferraz Silvio , Brancalion Pedro H. S.
Published: September 2018

Achieving global targets for forest restoration will require cost‐effective strategies to return agricultural land to forest, while minimizing implementation costs and negative outcomes for agricultural production.

We present a landscape approach for optimizing the cost‐effectiveness of large‐scale forest restoration. Across three different landscapes within Brazil's Atlantic Forest biodiversity hotspot, we modelled landscape scenarios based on spatially explicit data on the probability of natural regeneration, restoration costs, land opportunity costs, and forest restoration outcomes for increasing carbon stocking and landscape connectivity. We compare benefits of our cost‐reduction approach to the legally mandated riparian restoration and randomly distributed approaches.

Compared with riparian prioritization and considering both implementation and opportunity costs, our cost‐reduction scenario produced the greatest savings (20.9%) in mechanized agricultural landscapes.

When only considering implementation costs, our cost‐reduction scenario led to the highest savings (38.4%) in the landscape with highest forest cover where natural regeneration potential is highest and enables cost‐effective carbon stocking and connectivity.

Synthesis and applications. We present a guide for forest restoration planning that maximizes specific outcomes with minimal costs and reduction of agricultural production. Furthermore, we show how policies could encourage prioritization of low‐cost restoration via natural regeneration, increasing cost‐effectiveness. While our study focuses on Brazil's Atlantic Forest, the approach can be parameterized for other regions.
Dietary Fumonisin and Growth Impairment in Children and Animals: A Review
Authors: Chen Chen , Riley Ronald T. , Wu Felicia
Published: September 2018

Fumonisins are mycotoxins produced primarily by the fungiFusarium verticillioidesandF. proliferatum, which colonize maize in tropical, subtropical, and temperate climates worldwide. Fumonisin exposure is the highest in rural populations that consume large amounts of maize and maize products. Among them, infants and young children are the most vulnerable when they are weaned onto maize‐based foods. Therefore, it is critical to understand the impact of fumonisin on children's health and growth. This review describes the evidence linking fumonisin exposure to child growth impairment. First, toxicological studies that attempt to elucidate the mechanism by which fumonisin may impair growth are discussed. Next, a description is given of candidate biomarkers for accurately capturing fumonisin exposure in humans. Potential human health effects of fumonisin exposure beyond growth impairment, including esophageal cancer and neural tube defects (NTDs), are briefly described. We review epidemiological studies that collectively show an increasing weight of evidence linking fumonisin exposure to growth impairment, particularly in world regions where young children consume maize‐based weaning foods. Additionally, the evidence linking fumonisin exposure to growth impairment in plants and a variety of animal species are reviewed. Finally, we describe interventions to reduce fumonisin in parts of the world where dietary fumonisin exposure is high and is likely to predispose populations to increased health risk.
Stability of Bioactive Compounds and Antioxidant Activities of Kenaf Seed Oil‐in‐Water Nanoemulsions under Different Storage Temperatures
Authors: Cheong Ai Mun , Tan Chin Ping , Nyam Kar Lin
Published: September 2018

Kenaf seed oil‐in‐water nanoemulsions (NANO) stabilized by sodium caseinate (SC), beta‐cyclodextrin (β‐CD), and Tween 20 (T20) have been optimized and shown to improve in vitro bioaccessibility and physicochemical stability in the previous study. The main objective of this study was to evaluate the stability of bioactive compounds and antioxidants in the NANO during storage at different temperatures (4 °C, 25 °C, and 40 °C). An evaluation of the antioxidant activities of each emulsifier showed that SC had good scavenging capability with 97.6% ABTS radical scavenging activity. Therefore, SC which was used as one of the main emulsifiers could further enhanced the antioxidant activity of NANO. At week 8 of storage, NANO that stored at 4 °C had maintained the best bioactive compounds stability and antioxidant activities with 90% retention of vitamin E and 65% retention of phytosterols. These results suggested that 4 °C would be the most suitable storage temperature for NANO containing naturally present vitamin E and phytosterols. From the accelerated storage results at 40 °C, NANO containing vitamin E and phytosterols had maintained half of its initial concentration until week 4 and week 2 of storage, which is equivalent to 16 weeks and 8 weeks of storage at room temperature, respectively.

Practical Application

The results of this study provide a better understanding on the stability of bioactive compounds and antioxidant activities in oil‐in‐water nanoemulsions that stabilized by similar ternary emulsifiers during storage at different temperatures. In addition, this study could be used as a predictive model to estimate the shelf life of bioactive compounds encapsulated in the form of nanoemulsions.
A genome‐wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes
Authors: Meng Weihua , Shah Kaanan P. , Pollack Samuela , Toppila Iiro , Hebert Harry L. , McCarthy Mark I. , Groop Leif , Ahlqvist Emma , Lyssenko Valeriya , Agardh Elisabet , Daniell Mark , Kaidonis Georgia , Craig Jamie E. , Mitchell Paul , Liew Gerald , Kifley Annette , Wang Jie Jin , Christiansen Mark W. , Jensen Richard A. , Penman Alan , Hancock Heather A. , Chen Ching J. , Correa Adolfo , Kuo Jane Z. , Li Xiaohui , Chen Yii‐der I. , Rotter Jerome I. , Klein Ronald , Klein Barbara , Wong Tien Y. , Morris Andrew D. , Doney Alexander S.F. , Colhoun Helen M. , Price Alkes L. , Burdon Kathryn P. , Groop Per‐Henrik , Sandholm Niina , Grassi Michael A. , Sobrin Lucia , Palmer Colin N.A. ,   Wellcome Trust Case Control Consortium 2 (WTCCC2), Surrogate markers for Micro‐ and Macro‐vascular hard endpoints for Innovative diabetes Tools (SUMMIT) study group
Published: September 2018

Purpose

Diabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy.

Methods

A genome‐wide association approach was applied. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. Significant Single Nucleotide Polymorphisms (SNPs) were taken forward for meta‐analysis using multiple Caucasian cohorts.

Results

Five hundred and sixty cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a p value of 4.05 × 10−9. Two nearby SNPs, rs10765219 and rs11018670 also showed promising p values (p values = 7.41 × 10−8 and 1.23 × 10−8, respectively). In the meta‐analysis using multiple Caucasian cohorts (excluding GoDARTS), rs10765219 and rs11018670 showed associations for diabetic retinopathy (p = 0.003 and 0.007, respectively), while the p value of rs3913535 was not significant (p = 0.429).

Conclusion

This genome‐wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene.
The Sjögren's syndrome-associated autoantigen Ro52/TRIM21 modulates follicular B cell homeostasis and immunoglobulin production
Authors: Brauner S , Ivanchenko M , Thorlacius G E , Ambrosi A , Wahren-Herlenius M
Published: September 2018

Systemic rheumatic diseases are characterized by abnormal B cell activation with autoantibody production and hypergammaglobulinaemia. Ro52/SSA, also denoted tripartite motif (TRIM)21, is a major autoantigen in Sjögren's syndrome and systemic lupus erythematosus. Interestingly, TRIM21-deficient mice develop systemic autoimmunity with B cell-driven manifestations such as autoantibodies, hypergammaglobulinaemia and glomerulonephritis following tissue injury. The mechanisms by which TRIM21-deficiency leads to enhanced B cell activation and antibody production are, however, not well understood, and to further elucidate the role of TRIM21 in systemic autoimmunity, we investigated the B cell phenotype and antibody responses of Trim21−/− mice following immunization with thymus-dependent (TD) and thymus-independent (TI) antigens. We found that TRIM21-deficient mice developed significantly higher specific antibody titres than their wild-type counterparts upon B cell receptor (BCR) engagement by TD and TI type II antigens, and this was accompanied by an altered B cell phenotype. Furthermore, BCR cross-linking, but not anti-CD40 stimulation, in vitro resulted in a significantly higher proliferation of Trim21−/− cells. We also observed that splenic follicular B cells were expanded not only in immunized mice but also already in young, unmanipulated Trim21−/− mice, and transcriptomic analysis of these cells revealed an up-regulation of genes associated with B cell differentiation, indicating a role for TRIM21 in their regulation. In conclusion, in this study we describe a link between the rheumatic autoantigen Ro52/TRIM21 and increased antibody production associated with follicular B cell expansion, implicating a potential role for Ro52/TRIM21 in the pathogenesis of systemic autoimmune diseases.
Autoimmunity to heterogeneous nuclear ribonucleoprotein A1 in psoriatic patients and correlation with disease severity
Authors: Guarneri Claudio , Aguennouz Mohammed , Guarneri Fabrizio , Polito Francesca , Benvenga Salvatore , Cannavò Serafinella Patrizia
Published: September 2018

Background and objectives

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP‐A1) has been postulated as an autoantigen of psoriasis, but correlation between serum levels of anti‐hnRNP‐A1 autoantibodies and the severity of disease has not been investigated. We aimed to assess the frequency of anti‐hnRNP‐A1 autoimmunity in patients with moderate to severe psoriasis and in healthy controls, and to determine the correlation between serum levels of anti‐hnRNP‐A1 autoantibodies and disease severity.

Patients and methods

We performed a case‐control study on 40 adult psoriatic patients with a PASI (Psoriasis Area and Severity Index) of > 10 and 40 healthy controls matched for age and gender. Immunoblotting was used to assess serum levels of anti‐hnRNP‐A1 autoantibodies.

Results

Anti‐hnRNP‐A1 autoantibodies were found in 9/40 psoriatic patients (22.5 %) but in no healthy controls. The PASI was significantly higher in anti‐hnRNP‐A1‐positive patients than in anti‐hnRNP‐A1‐negative patients (40.33 ± 3.24 vs 26.06 ± 9.28, p = 0.0001). In patients positive for anti‐hnRNP‐A1, serum levels of such autoanti­bodies were correlated with the PASI (R = 0.89, p = 0.001).

Conclusions

Consistent with reports in the literature, our results suggest a role of anti‐hnRNP‐A1 autoimmunity in psoriasis, although probably not as the primary cause or initial/fundamental event. Unlike previously published reports, our results also suggest that anti‐hnRNP‐A1 autoimmunity is particularly frequent among psoriatic patients with more severe disease. Further studies are necessary with a larger number of patients.
Adjuvante Behandlung des schweren/refraktären bullösen Pemphigoids mit Protein‐A‐Immunadsorption
Authors: Hübner Franziska , Kasperkiewicz Michael , Knuth‐Rehr Diana , Shimanovich Iakov , Hübner Joachim , Süfke Sven , Muck Philip , Zillikens Detlef , Schmidt Enno
Published: September 2018

Hintergrund

Mittels Immunadsorption (IA) können Immunglobuline und Immunkomplexe aus dem Plasma entfernt werden. Während dieses therapeutische Verfahren beim Pemphigus vulgaris bereits etabliert ist, wird es bei anderen blasenbildenden Autoimmundermatosen bislang nur sporadisch eingesetzt. Das bullöse Pemphigoid (BP) spricht zwar meist gut auf eine Therapie mit topischen und systemischen Kortikosteroiden an, jedoch könnte bei Patienten mit ausgedehnten Läsionen oder bei einem Rezidiv die rasche Reduktion der pathogenen Autoantikörper eine effektive adjuvante Therapie darstellen.

Patienten und Methodik

Fallserie mit 20 Patienten (13 Frauen, 7 Männer; mittleres Alter 78,6 Jahre; 56–94 Jahre) mit schwerem oder refraktärem BP, die zusätzlich zur Basistherapie bestehend aus Prednisolon (0,25–0,5 mg/kg/d), Dapson (1,0–1,5 mg/kg/d) und Clobetasolpropionat 0,05 % Salbe (läsional 2 x/d) mit Protein‐A‐IA (3 IAs an aufeinander folgenden Tagen) behandelt wurden. Die durchschnittliche Nachbeobachtungszeit betrug 33,6 Monate (1–84 Monate).

Ergebnisse

Bei der Mehrzahl der Patienten zeigte sich ein rascher und langandauernder Therapieeffekt. Nach einem Monat befanden sich acht Patienten (von 19 nachbeobachteten, 42 %) und zum Zeitpunkt des letzten Kontakts (nach 1–84 Monaten) 13 Patienten (68 %) in kompletter Remission. Die Anti‐BP180‐Autoantikörper wurden nicht nur initial (um 92 %) gesenkt, sondern lagen auch nach ein und drei Monaten im Mittel bei 26 % und 13 % des Wertes vor Therapiebeginn (p < 0,001). Bei Differenzierung in vortherapierte bzw. therapienaive Patienten zeigten sich in beiden Subgruppen signifikante Absenkungen der Anti‐BP180NC16A‐Antikörper‐Spiegel zu allen Zeitpunkten. Unerwünschte Ereignisse traten bei dreizehn (65 %) der 20 Patienten auf, Drei der Ereignisse waren schwer und zwei davon wahrscheinlich oder möglicherweise in Zusammenhang mit der IA.

Schlussfolgerungen

Die IA ist eine effektive adjuvante Therapieoption bei den in aller Regel älteren Patienten mit einem schweren und/oder therapierefraktären BP.
Influence of larval density and dietary nutrient concentration on performance, body protein, and fat contents of black soldier fly larvae (Hermetia illucens)
Authors: Barragan‐Fonseca Karol B. , Dicke Marcel , van Loon Joop J.A.
Published: September 2018

Performance and body composition of insect larvae depend on quality and quantity of their diet, and on biotic factors such as larval density. We investigated the effect of dietary nutrient concentration and larval rearing density on survival, development, growth, and protein and fat contents of larvae of the black soldier fly (BSF), Hermetia illucens L. (Diptera: Stratiomyidae). Neonate larvae were fed with a low (NC1), intermediate (NC2), or high nutrient concentration (NC3), and with four rearing densities (50, 100, 200, or 400 larvae per container). Two feeding regimes (FR) were tested: in FR1, the amount of diet added during the experiment was based on the visually estimated larval mass present, whereas in FR2, a fixed feeding ration of 0.6 g of food per larva was applied at the start. FR1 resulted in food limitation, resulting in significantly lower body crude protein content on diet NC1 than on NC2 at larval densities 100 and 200. Larval crude fat content was higher on diets with higher nutrient concentration and at lower larval densities. For FR2, development time was shorter on diets with higher nutrient concentration and at lower larval densities. Individual larval weight and total larval yield increased with higher nutrient concentration at all four larval densities. At lower nutrient concentration, higher larval density resulted in higher individual larval weight and total larval yield, revealing an interaction between larval density and dietary quality. Larval crude protein content was higher at lower densities and lower nutrient concentration. Larval crude fat was higher at higher larval densities and nutrient concentrations. This study indicates that larval protein content is regulated within narrow limits, whereas larval crude fat content is strongly affected by nutrient concentration and by larval density.
Successful pregnancies in patients with BCR‐ABL‐positive leukemias treated with interferon‐alpha therapy during the tyrosine kinase inhibitors era
Authors: Balsat Marie , Etienne Madeleine , Elhamri Mohamed , Hayette Sandrine , Salles Gilles , Thomas Xavier
Published: September 2018

Background

Management of pregnant patients with BCR‐ABL‐positive leukemia is challenging. Managing a patient who has been diagnosed while pregnant requires a different approach as compared to a patient who plans to become pregnant while on the treatment with tyrosine kinase inhibitor (TKI). Interferon (IFN)‐alpha is a useful option in both situations due to teratogenic potential of TKIs.

Methods

We presented a series of 12 successful pregnancies in 11 women with BCR‐ABL‐positive leukemia, whose leukemia was managed with IFN‐alpha throughout their pregnancy.

Results

All children have normal growth and development. All patients remained at least in hematological response and could start or resume TKI after delivery or breastfeeding.

Conclusion

Because of the increased risk of teratogenicity and spontaneous abortion in female patient with pregnancy, when receiving TKI, IFN‐alpha can be considered a safe drug to be administered throughout pregnancy and could represent the drug of choice in this situation during the era of TKI therapy.
Reliability and validity of patient‐reported outcome instruments in US adults with hemophilia B and caregivers in the B‐HERO‐S study
Authors: Buckner Tyler W. , Sidonio Robert , Guelcher Christine , Kessler Craig M. , Witkop Michelle , Clark David , Owens Wendy , Fridman Moshe , Iyer Neeraj N. , Cooper David L.
Published: September 2018

Objective

To assess the reliability and validity of six patient‐reported outcomes (PRO) instruments for evaluating health‐related quality of life in adults with mild‐severe hemophilia B and caregivers of children with hemophilia B, including affected women/girls.

Methods

Adults with hemophilia B and caregivers completed separate online surveys containing several PRO instruments, which were administered to adult participants only (EQ‐5D‐5L, Brief Pain Inventory v2 Short Form, Hemophilia Activities List, and International Physical Activities Questionnaire), both adults and caregivers (Patient Health Questionnaire [PHQ‐9]), or caregivers only (Generalized Anxiety Disorder 7‐Item [GAD‐7] scale). Construct validity and item‐total correlation were assessed using Pearson product‐moment correlation, internal consistency was assessed using Cronbach’s alpha coefficient, and known‐group validity was assessed by comparisons to self‐reported characteristics based on the Kruskal‐Wallis test.

Results

Patient‐reported outcomes instruments generally showed satisfactory reliability for adults (n = 299) and caregivers (n = 150). In adults, PRO instruments generally showed high construct validity. Most PRO instruments showed expected significant differences among known groups for adults and caregivers. PHQ‐9 and GAD‐7 did not show significant differences among caregiver age groups.

Conclusions

Patient‐reported outcomes instruments administered in B‐HERO‐S demonstrated reliability and validity in the broader population of adults with hemophilia B and caregivers when including all severities and genders.
Tooth formation and eruption – lessons learnt from cleidocranial dysplasia
Authors: Kreiborg Sven , Jensen B. L.
Published: September 2018

The principles of formation, renewal, and eruption of teeth are discussed. Numerous genetic aberrations may affect the formation and eruption of teeth. Cleidocranial dysplasia (CCD), caused by mutations in the runt‐related transcription factor 2 (RUNX2) gene, is such a condition. The dental phenotype includes problems in both tooth formation (multiple supernumerary permanent teeth) and tooth eruption (lack of shedding of primary teeth and delayed or arrested eruption of permanent teeth). Clinical studies, animal models, and molecular biology studies have documented that RUNX2 is of paramount importance for osteoblast differentiation, for regression of the dental lamina, and for osteoclastogenesis in the dental follicle and the periodontal ligament. Jensen & Kreiborg, 25 yr ago, proposed a treatment strategy to be applied to patients with CCD, focussing on the importance of early treatment to promote spontaneous eruption of permanent teeth through extraction of primary teeth, surgical removal of supernumerary teeth, and removal of bone covering the first formed permanent teeth at the time when root formation of the permanent teeth has reached half or two‐thirds of their final length. This strategy still seems valid and seems to lead to reduction in the burden of care for patients compared with the treatment protocols otherwise recommended.
Optimizing quality and safety of dental materials
Authors: Dahl Jon E. , Stenhagen Ida S.R.
Published: September 2018

This paper discusses aspects of quality and safety improvement of the most commonly used dental restorative materials, the resin‐based composites. From a patient's perspective, long‐lasting resin‐based restorations without complications are important. Recurrent caries and fracture are the most common causes for restoration failures. Proper handling and curing of the composites improve the mechanical properties of the restorations and increase safety by reducing exposure to residual methacrylate monomers. A number of compounds have been introduced in restorative materials to reduce the risk of recurrent caries, even though a real breakthrough has not yet been achieved. It is concluded that simple measures may improve the quality and safety of resin‐based composite restorations.
Peri‐implant diseases
Authors: Klinge Björn , Klinge Anna , Bertl Kristina , Stavropoulos Andreas
Published: September 2018

When celebrating 100 yr of dental research in the Nordic dental research community (i.e. Nordisk Odontologisk Förening (NOF)), it is relevant to include dental implant treatment. In essence, the successful progress of implant treatment has added both to the quality of life for patients and also to many aspects of professional development and job satisfaction for dentists. When appreciating the success story it also seems relevant to highlight some of the problems related to this treatment. Both technical and biological complications have often been ignored when reporting long‐term results following implant treatment. Different opinions have been expressed in relation to the etiology of peri‐implant diseases. Some even choose to ignore this condition as a clinical problem. This article presents a short overview of peri‐implant diseases (i.e. peri‐implant mucositis and peri‐implantitis). The lack of internationally agreed disease definitions for peri‐implant diseases, as with periodontitis, results in wide variation of estimates for the occurrence of peri‐implant diseases when epidemiological data are reported. The profession still strives to find and define the best way to deal with peri‐implant diseases once they are accurately diagnosed. Awareness of the tissue conditions in the peri‐implant area, and relevant action when indicated, seems to be critical for the continued long‐term successful outcome of dental implant treatment.
Financial Knowledge and Household Saving: Evidence from the Survey of Consumer Finances
Authors: Kim Kyoung Tae , Yuh Yoonkyung
Published: September 2018

This study analyzed the relationship between financial knowledge and household saving behavior using the 2016 Survey of Consumer Finances (SCF) dataset. The results from a hierarchical model showed that both objective knowledge and perceived financial knowledge were positively related to the likelihood of being a saver. The explanatory power of the regression models increased significantly when financial knowledge variables were added. Furthermore, the results were robust across different measurements of household savings and additional analyses using the 2015 National Financial Capability Study (NFCS) dataset. Educators, policymakers, and financial institutions can benefit from these results as they develop programs, policies, and products to motivate and promote saving behavior.