bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal stem cells in psoriatic lesions affect the skin microenvironment through circular RNA
Authors: Liu Ruifeng , Chang Wenjuan , Li Juan , Cheng Yueai , Dang Erle , Yang Xiaohong , Wang Qiang , Wang Gang , Li Xinhua , Zhang Kaiming
Published: January 2019

Psoriasis is an autoimmune skin disease. Our previous studies revealed abnormal immune regulation of skin mesenchymal stem cells (S‐MSCs) in psoriatic lesions. Circular RNA (circRNA) molecules were recently discovered as a new class of non‐coding regulatory RNAs. Their role in the pathogenesis of psoriasis has not yet been studied. To explore potential circRNA‐mediated mechanisms of S‐MSCs in the pathogenesis of psoriasis, we sequenced mRNAs and circRNAs of MSCs from normal skin and psoriatic lesions, followed by functional prediction and interaction analyses. In total, 129 circRNAs were differentially expressed, including 123 up‐regulated and 6 down‐regulated circRNAs, in MSCs from psoriatic lesions. Pathway analysis showed that the genes significantly down‐regulated in psoriatic as compared to normal S‐MSCs were mainly involved in JAK‐STAT signalling. According to a circRNA‐miRNA‐mRNA interaction network, the expression of circRNAs associated with these mRNAs was also down‐regulated in MSCs of psoriatic skin lesions. Knockdown of the circRNA gene chr2:206992521|206994966 reduced the capacity of S‐MSCs to inhibit T‐cell proliferation upon co‐culture in normal as well as lesion‐derived S‐MSCs. Secreted‐cytokine profiles (IL‐6, IL‐11 and hepatocyte growth factor) were also similar in normal and lesion‐derived S‐MSCs after circRNA knockdown. Thus, the circRNA chr2:206992521|206994966 in S‐MSCs from psoriatic lesions affects the activity of T lymphocytes in local lesions by influencing their cytokine secretion. Taken together, our findings indicate that circRNA mediates the role of S‐MSCs in the pathogenesis of psoriasis.
An Exploratory Study of Custody Challenges Experienced by Affirming Mothers of Transgender and Gender‐Nonconforming Children
Authors: Kuvalanka Katherine A. , Bellis Camellia , Goldberg Abbie E. , McGuire Jenifer K.
Published: January 2019

Family courts have lacked familiarity with evidence‐based recommendations regarding the best interests of transgender and gender‐nonconforming (TGNC) children, resulting in some affirming parents losing physical and/or legal custody. This exploratory, qualitative study with 10 affirming mothers of TGNC children who had experienced custody‐related challenges reported on salient themes, including “blame” for causing children's gender nonconformity, coercion by ex‐partners, bias in the courts, negative impact on children, emotional and financial toll on participants, and the critical importance of adequate resources. Findings indicate the need for better‐educated family court professionals, as well as socioemotional support and financial and legal assistance for affirming parents of TGNC children.
Family Court Enhancement Project: Improving Access to Justice
Authors: McKeig Anne K. , Madden Mary
Published: January 2019

In 2013, Minnesota's Fourth Judicial District was one of four courts in the country selected by the U.S. Department of Justice, Office on Violence Against Women to receive a Family Court Enhancement Project (FCEP) grant, a multiyear demonstration initiative designed to build the capacity of court systems and partner stakeholders to improve child custody decision making in cases involving domestic violence. The FCEP enabled the project sites to explore, implement, and assess new and innovative court and noncourt procedures and practices. This article is an exploration of the outcomes of this project.
Microbial and macroinvertebrate communities, but not leaf decomposition, change along a mining‐induced salinity gradient
Authors: Vander Vorste Ross , Timpano Anthony J. , Cappellin Catie , Badgley Brian D. , Zipper Carl E. , Schoenholtz Stephen H.
Published: January 2019

Natural levels of salinity in aquatic ecosystems drive biodiversity patterns across broad spatial scales; however, less is known about changes in biotic communities and the ecosystem functions they support along anthropogenic salinisation gradients. Resource extraction often causes salinisation of freshwater ecosystems which may extirpate salinity‐sensitive macroinvertebrates and microbes and thus reduce rates of organic matter decomposition.

We quantified bacterial (16S), fungal (ITS) and macroinvertebrate taxonomic richness, composition, and β‐diversity across the resulting gradient of specific conductance (annual mean: 25–1,383 μS/cm) in 24 headwater streams in the eastern U.S.A. variously influenced by surface coal mining but selected to minimise habitat and water‐quality differences other than salinity. Furthermore, we measured rates of organic matter decomposition in submersed leaf packs (Quercus alba) across these same sites.

Bacterial and reach‐wide macroinvertebrate richness was reduced along the mining‐induced salinity gradient whereas fungal or leaf‐pack macroinvertebrate richness remained similar. Community composition of microbes and macroinvertebrates changed along the salinity gradient, with mining‐influenced sites becoming increasingly dissimilar to reference sites as salinity increased. Beta‐diversity was driven by taxonomic replacement rather than nestedness for microbial and macroinvertebrate communities.

Organic matter decomposition rates in mining‐influenced streams were not reduced even at mean specific conductance levels 10× higher than reference sites. We attribute maintenance of decomposition rates to salinity tolerance of both fungi and macroinvertebrate shredders found in leaf packs.

Our study informs theory linking anthropogenic alteration of biotic communities to rates of ecosystem functions by providing evidence that taxonomic replacement and stressor‐tolerance of specific functional groups along a mining‐induced salinity gradient can maintain certain ecosystem functions, at least within the studied salinity range. We therefore advise against generalising biodiversity–ecosystem function relationships in other salinised systems, but caution that organic matter decomposition may be altered at salinity levels above those observed in our study and that other ecosystem functions may be affected by loss of salinity‐sensitive taxa.
Global patterns of body size evolution in squamate reptiles are not driven by climate
Authors: Slavenko Alex , Feldman Anat , Allison Allen , Bauer Aaron M. , Böhm Monika , Chirio Laurent , Colli Guarino R. , Das Indraneil , Doan Tiffany M. , LeBreton Matthew , Martins Marcio , Meirte Danny , Nagy Zoltán T. , Nogueira Cristiano de C. , Pauwels Olivier S. G. , Pincheira‐Donoso Daniel , Roll Uri , Wagner Philipp , Wang Yuezhao , Meiri Shai
Published: January 2019

Aim

Variation in body size across animal species underlies most ecological and evolutionary processes shaping local‐ and large‐scale patterns of biodiversity. For well over a century, climatic factors have been regarded as primary sources of natural selection on animal body size, and hypotheses such as Bergmann's rule (the increase of body size with decreasing temperature) have dominated discussions. However, evidence for consistent climatic effects, especially among ectotherms, remains equivocal. Here, we test a range of key hypotheses on climate‐driven size evolution in squamate reptiles across several spatial and phylogenetic scales.

Location

Global.

Time period

Extant.

Major taxa studied

Squamates (lizards and snakes).

Methods

We quantified the role of temperature, precipitation, seasonality and net primary productivity as drivers of body mass across ca. 95% of extant squamate species (9,733 spp.). We ran spatial autoregressive models of phylogenetically corrected median mass per equal‐area grid cell. We ran models globally, across separate continents and for major squamate clades independently. We also performed species‐level analyses using phylogenetic generalized least square models and linear regressions of independent contrasts of sister species.

Results

Our analyses failed to identify consistent spatial patterns in body size as a function of our climatic predictors. Nearly all continent‐ and family‐level models differed from one another, and species‐level models had low explanatory power.

Main conclusions

The global distribution of body mass among living squamates varies independently from the variation in multiple components of climate. Our study, the largest in spatial and taxonomic scale conducted to date, reveals that there is little support for a universal, consistent mechanism of climate‐driven size evolution within squamates.
Global trade‐offs of functional redundancy and functional dispersion for birds and mammals
Authors: Cooke Robert S. C. , Bates Amanda E. , Eigenbrod Felix
Published: January 2019

Aim

The diversity of birds and mammals is typically described in separate analyses, but species may play similar roles. Here, we develop a comparative trait framework for birds and mammals to provide a global quantification of the similarity of species roles (functional redundancy) and the breadth of roles across taxa (functional dispersion). We predict different contributions of birds and mammals to redundancy and dispersion, and unique geographical patterns of redundancy and dispersion by including both taxa.

Location

Global.

Time period

Contemporary.

Major taxa studied

Birds and mammals.

Methods

We systematically select, compile and impute the same six traits (i.e., a common currency of traits) across 15,485 bird and mammal species from multiple databases. We use these six traits to compute functional redundancy and functional dispersion for birds and mammals across all 825 terrestrial ecoregions. We then calculate the standardized effect size (SES) of these observed values compared with null expectations, based on a randomization of species composition (i.e., independent of differences in species richness).

Results

We find that species‐rich regions, such as the Neotropics, have high functional redundancy coupled with low functional dispersion, characterizing a global trade‐off. Thus, in general, as species richness increases, the similarity in species functional roles also increases. We therefore suggest that different processes generate species richness/functional redundancy and functional dispersion, leading to a novel, and generally non‐tropical, distribution of hotspots of high functional dispersion across Madagascar, Eastern Asia and Western USA.

Main conclusions

We recommend consideration of both the similarity and the breadth of functional roles across species pools, including taxa that may play similar roles. We therefore suggest that functional redundancy, as a means of insurance, and functional dispersion, as an indicator of response diversity, should be evaluated further as conservation objectives.
Climate‐driven convergent evolution of plumage colour in a cosmopolitan bird
Authors: Romano Andrea , Séchaud Robin , Hirzel Alexandre H. , Roulin Alexandre
Published: January 2019

Aim

The investigation of phenotypic diversity across geographical gradients is pivotal to understanding the evolution and adaptive functions of alternative phenotypes. The aim of the present study was to investigate whether the polymorphism in ventral plumage colouration observed in the cosmopolitan common barn owl group is determined by climatic factors, such as temperature and rainfall, consistent with Gloger’s and Bogert’s biogeographical rules.

Location

World.

Time period

1809–2017.

Major taxa studied

Tyto alba species complex.

Methods

We analysed the variation in heritable melanin‐based plumage colour according to annual temperature and rainfall in 9,110 individuals of the cosmopolitan barn owl, with three distinct evolutionary lineages representing its entire distribution range: the Afro‐European Tyto alba, occurring between Scandinavia and South Africa, the American Tyto furcata, found from southern Canada to Patagonia, and the Australasian Tyto javanica, living between the Himalayan Plateau and Tasmania.

Results

Although the geographical distribution of colour morphs is heterogeneous among the lineages, in all of them plumage colour becomes darker with increasing annual rainfall, indicating a convergent selection of darker morphs in humid habitats possibly to improve camouflage against the dark environment and/or to repel water more efficiently. Moreover, in T. alba and T. furcata, melanization increases at decreasing temperature, suggesting its possible role in thermoregulation.

Discussion

These findings provide convincing evidence of repeated evolution of similar body colouration patterns at a worldwide scale compatible with the main biogeographical rules, while emphasizing the possible role of melanin‐based traits in animal adaptation to climate change.
Redefining temperate forest responses to climate and disturbance in the eastern United States: New insights at the mesoscale
Authors: Druckenbrod Daniel L. , Martin‐Benito Dario , Orwig David A. , Pederson Neil , Poulter Benjamin , Renwick Katherine M. , Shugart Herman H.
Published: January 2019

Aim

Climate and disturbance alter forest dynamics, from individual trees to biomes and from years to millennia, leaving legacies that vary with local, meso‐ and macroscales. Motivated by recent insights in temperate forests, we argue that temporal and spatial extents equivalent to that of the underlying drivers are necessary to characterize forest dynamics across scales. We focus specifically on characterizing mesoscale forest dynamics because they bridge fine‐scale (local) processes and the continental scale (macrosystems) in ways that are highly relevant for climate change science and ecosystem management. We revisit ecological concepts related to spatial and temporal scales and discuss approaches to gain a better understanding of climate–forest dynamics across scales.

Location

Eastern USA.

Time period

Last century to present.

Major taxa studied

Temperate broadleaf forests.

Methods

We review regional literature of past tree mortality studies associated with climate to identify mesoscale climate‐driven disturbance events. Using a dynamic vegetation model, we then simulate how these forests respond to a typical climate‐driven disturbance.

Results

By identifying compound disturbance events from both a literature review and simulation modelling, we find that synchronous patterns of drought‐driven mortality at mesoscales have been overlooked within these forests.

Main conclusions

As ecologists, land managers and policy‐makers consider the intertwined drivers of climate and disturbance, a focus on spatio‐temporal scales equivalent to those of the drivers will provide insight into long‐term forest change, such as drought impacts. Spatially extensive studies should also have a long temporal scale to provide insight into pathways for forest change, evaluate predictions from dynamic forest models and inform development of global vegetation models. We recommend integrating data collected from spatially well‐replicated networks (e.g., archaeological, historical or palaeoecological data), consisting of centuries‐long, high‐resolution records, with models to characterize better the mesoscale response of forests to climate change in the past and in the future.
Fascin in lamellipodia contributes to cell elasticity by controlling the orientation of filamentous actin
Authors: Tanaka Minami , Fujii Yuki , Hirano Kazumi , Higaki Takumi , Nagasaki Akira , Ishikawa Ryoki , Okajima Takaharu , Katoh Kaoru
Published: January 2019

Fascin, an actin‐bundling protein, is present in the filopodia and lamellipodia of growth cones. However, few studies have examined lamellipodial fascin because it is difficult to observe. In this study, we evaluated lamellipodial fascin. We visualized the actin meshwork of lamellipodia in live growth cones by super‐resolution microscopy. Fascin was colocalized with the actin meshwork in lamellipodia. Ser39 of fascin is a well‐known phosphorylation site that controls the binding of fascin to actin filaments. Fluorescence recovery after photobleaching experiments with confocal microscopy showed that binding of fascin was controlled by phosphorylation of Ser39 in lamellipodia. Moreover, TPA, an agonist of protein kinase C, induced phosphorylation of fascin and dissociation from actin filaments in lamellipodia. Time series images showed that dissociation of fascin from the actin meshwork was induced by TPA. As fascin dissociated from actin filaments, the orientation of the actin filaments became parallel to the leading edge. The angle of actin filaments against the leading edge was changed from 73° to 15°. This decreased the elasticity of the lamellipodia by 40%, as measured by atomic force microscopy. These data suggest that actin bundles made by fascin contribute to elasticity of the growth cone.
Intramucosal colorectal carcinoma with lymphovascular invasion: clinicopathological characteristics of nine cases
Authors: Hashimoto Hirotsugu , Horiuchi Hajime , Kurata Atsushi , Kikuchi Hiroyuki , Okuyama Rikiya , Usui Genki , Masuda Yoshio , Kuroda Masahiko , Inoue Shigeru , Furushima Kaoru , Matsuhashi Nobuyuki , Harihara Yasushi , Morikawa Teppei
Published: January 2019

Aims

Recent studies have provided the concept of invasive intramucosal colorectal carcinoma (CRC), and a case of intramucosal CRC with lymphatic invasion has been reported; however, the characteristics of such cases and the risk of lymph node metastasis have never been investigated. Therefore, we aimed to assess the pathological characteristics of intramucosal CRCs with lymphovascular invasion as well as the possibility of lymph node metastasis as an indication for additional surgery.

Methods and results

To delineate the histological features of intramucosal CRCs with lymphovascular invasion, we analysed several histological features and compared their incidence among nine such cases, as well as 20 other cases of intramucosal CRCs without lymphovascular invasion. High‐grade tumour budding and a pattern of ‘eosinophilic cytoplasm and round nuclei with inflammatory reaction (ERI)’ were morphological characteristics of intramucosal CRCs with lymphovascular invasion, compared with those without lymphovascular invasion (both P < 0.05). Among the seven lymph node‐dissected cases of intramucosal CRCs with lymphovascular invasion, none showed lymph node metastasis.

Conclusions

In intramucosal CRCs with lymphovascular invasion, high‐grade tumour budding and the ‘ERI’ pattern are morphological characteristics that are distinct from those of non‐invasive CRC, which is synonymous with high‐grade dysplasia. Further studies using a larger number of cases by focusing on the above‐mentioned histological pattern are expected to clarify the potential of lymph node metastasis of such cases.
Complementarity among dragonflies across a pondscape in a rural landscape mosaic
Authors: Briggs Andrew J. , Pryke James S. , Samways Michael J. , Conlong Des E.
Published: January 2019

Networks of ponds (pondscapes) are becoming increasingly significant for resilient landscape planning in rural areas. Farmland and forestry ponds are habitat islands that support heterogeneous communities of aquatic organisms.

Species richness, Dragonfly Biotic Index (DBI), Shannon's index, and species composition are used here to assess the complementary conservation value of adult dragonfly assemblages associated with forty ponds across a protected area‐sugarcane‐forestry mosaic.

Despite differences in environmental variables among the various ponds, dragonfly species richness, DBI, Shannon index scores, as well as responses to particular environmental variables, did not differ between ponds in sugarcane, plantation forestry, and protected areas. Dragonfly composition differed in response to vegetation cover.

Our results highlight the importance of catchment and regional management for all ponds within the pondscape, and show that ponds in the transformed areas (i.e. sugarcane and forestry areas) are important contributors to regional conservation. As the various ponds were complementary in their dragonfly assemblages, we recommend conservation focus at the level of the pondscape rather than on individual ponds.
Exploring the possibility of predicting long‐term oxidative stability in prototype skincare formulations using various lipid oxidation initiators
Authors: Thomsen Birgitte Raagaard , Taylor Richard , Hermund Ditte Baun , Soerensen Ann‐Dorit Molke , Heung Shuk Yee , Hyldig Grethe , Blenkiron Peter , Jacobsen Charlotte
Published: January 2019

Objective

The purpose of this study was to identify an effective lipid oxidation initiator which could predict, within 1 month, the long‐term oxidative stability of a prototype skincare formulation. The main purpose was to find a potential initiator not to assess oxidation stability of the formulations.

Methods

Four initiators (below) were examined in three steps:

Reaction kinetics using a Clark electrode (Oxygraph);

Effect of adding an initiator on the product's physical and oxidative stability in prototype skincare formulations by visual observation, peroxide value and headspace GC‐MS determination of volatile oxidation products; and

Ability to differentiate unstable vs. stable prototype creams by initiator addition.

The four initiators explored were:

FeCl2/H2O2,

FeCl3/ascorbic acid,

2,2′‐Azobis(2,4‐dimethylvaleronitrile) (AMVN) and

2,2′‐Azobis(2‐methylpropionamidine) dihydrochloride (AAPH)

Results

In Oxygraph, the initiator systems FeCl2/H2O2 and FeCl3/ascorbic acid were good accelerators of oxygen consumption. The addition of FeCl2/H2O2 to prototype formulations did not affect the physical stability. However, the addition of FeCl3/ascorbic acid to prototype formulations resulted in phase separation and FeCl3/ascorbic acid was therefore deemed unusable. Moreover, the addition of AAPH or AMVN resulted in an increased and decreased viscosity respectively.

In the oxidation stability study, peroxide value increased significantly when AMVN was added. However, the peroxide value remained low for the other initiators and the control (no initiator). The secondary volatile oxidation product, butanal, increased most with the FeCl2/H2O2 addition.

Three out of the four initiators did not have the ability to rank the stable and unstable formulations in accordance with the result obtained for volatile oxidation products after 42 days of storage at 20°C of formulations without initiator. Only, FeCl2/H2O2 was able to rank the formulations in accordance with the oxidative stability observed for volatile oxidation products after 42 days of storage.

Conclusion

FeCl2/H2O2 showed potential as an initiator to predict the oxidative stability of skincare formulations, but more studies are needed to confirm the result in a broader range of products over a longer time.
Effect of heating and acidic pH on characteristics of wheat gluten suspension
Authors: Garg Swati , Cran Marlene J. , Mishra Vijay Kumar
Published: January 2019

The effects of different pH treatments with and without heating on the characteristics of wheat gluten suspension was investigated. At pH 1, maximum changes in colour were observed with a concurrent 65% decrease in protein free‐thiol content compared to the control gluten. The SDS‐Extractability of protein (SDS‐EP) chromatogram eluted at lower retention time and the presence of bands at the top lane even during reducing conditions in SDS‐PAGE gel suggested complex formation involving bonds other than disulphides. An increase in the free‐amino group content and the presence of an additional peak at a higher retention time in the SDS‐EP chromatogram was suggestive of hydrolysis. At pH 2 and 3, similar decreases in SDS‐EPs and free‐thiol content indicated formation of complexes. When heated, the free‐thiol content of the dispersions increased compared to the non‐heated dispersions indicating disruption of disulphide bonds with changes in gluten structure and size distribution.
How much does household food insecurity explain income inequalities in untreated dental caries?
Authors: Ferreira Fernanda Morais , Gomes Monalisa Cesarino , Granville‐Garcia Ana Flávia , Santin Gabriela Cristina , Pintarelli Tatiana Pegoretti , Feltrin Juliana , Fraiz Fabian Calixto
Published: January 2019

Background

The pathway by which socioeconomic disadvantages are manifested in the occurrence of dental caries remains unclear.

Aim

To explore how much the association between untreated dental caries and income inequalities is related to household food insecurity (HFI).

Design

A population‐based study was conducted with a sample of 466 12‐year‐old students. Dental caries was evaluated by an examiner who had undergone calibration exercises. HFI was assessed using the Food Insecurity Scale validated for Brazilian Portuguese. Poisson regression models were created to determine associations between dental caries and both household income and HFI. The proportion of the income effect on dental caries explained by HFI was determined by the variation in percentages between the crude prevalence ratio (PRc) for dental caries and this measure adjusted by HFI (PRa).

Results

The prevalence of dental caries was higher among children from families with a per capita household income lower than US$ 71 (PR: 1.69; 95%CI: 1.15‐2.49) or from US$ 71 to US$ 142 (PR: 1.50; 95%CI: 1.04‐2.17). Moreover, 14% of the association between a low income and dental caries was explained by HFI.

Conclusions

Differences in the prevalence of dental caries in schoolchildren related to socioeconomic inequalities could partially be attributed to HFI in low‐income families.
On distance graph coloring problems
Authors: de Freitas Rosiane , Dias Bruno , Maculan Nelson , Szwarcfiter Jayme
Published: January 2019

One of the most important classes of combinatorial optimization problems is graph coloring, and there are several variations of this general problem involving additional constraints either on vertices or edges. They constitute models for real applications, such as channel assignment in mobile wireless networks. In this work, we consider some coloring problems involving distance constraints as weighted edges, modeling them as distance geometry problems (DGPs). Thus, the vertices of the graph are considered as embedded on the real line and the coloring is treated as an assignment of positive integers to the vertices, while the distances correspond to line segments, where the goal is to find their feasible intersection. We formulate these coloring problem variants and show feasibility conditions for some problems. We also propose implicit enumeration methods for some of the optimization problems based on branch‐and‐prune algorithms proposed for DGPs in the literature. An empirical analysis was undertaken, considering equality and inequality constraints, and uniform and arbitrary set of distances. As the main contributions, we propose new variations of vertex coloring problems in graphs, involving a new theoretical model in distance geometry (DG) for vertex coloring problems with generalized adjacency constraints, promoting the correlation between graph theory and DG fields. We also give a characterization and formal proof of polynomial cases for special graph classes, since the general main problem is NP‐complete.
Integrated optimization model for distribution network design: a case study of the clothing industry
Authors: Liu Ming , Xu Xifen , Zhang Ding
Published: January 2019

Distribution network design affects a firm's operating costs and its customer service level. In this paper, we consider distribution network design for improving the closed‐loop logistics in a clothing company. We formulate the problem as a mixed‐integer nonlinear programming model with an objective of minimizing the annual operating costs. Our model simultaneously determines the optimal number of regional distribution centers (RDCs), identifies location and relative size for each RDC, allocates each city distribution center to a specific RDC, decides on supply ratio for each contracted plant, and specifies the annual operating costs and service level for the best scenario, as well as other scenarios. Test results show that this marketing initiative at the studied company can effectively reduce its annual operating costs. Although this paper is a specific case study, it provides several managerial insights and modeling references for similar facility location and allocation problems.
Deviation measure in second‐order stochastic dominance with an application to enhanced indexing
Authors: Goel Anubha , Sharma Amita
Published: January 2019

Deviation measures form a separate class of functionals applied to the difference of a random variable to its mean value. In this paper, we aim to introduce a deviation measure in the second‐order stochastic dominance (SSD) criterion to select an optimal portfolio having a higher utility of deviation from its mean value than that of the benchmark portfolio. A new strategy, called deviation SSD (DSSD), is proposed in portfolio optimization. Performance of the proposed model in an application to enhanced indexing is evaluated and compared to other two standard portfolio optimization models that employ SSD criterion on lower partial moments of order one (LSSD) and tail risk measure (TSSD). We use historical data of 16 global indices to assess the performance of the proposed model. In addition to this, we solved the models on simulated data, capturing the joint dependence between indices using historical data of two data sets, each data set comprising six indices. The simulated data are generated by first fitting the autoregressive moving average–Glosten–Jagannathan–Runkle–generalized autoregressive conditional heteroscedastic model on historical data to determine marginal distributions, and thereafter capture the dependence structure using the best fitted regular vine copula. The portfolios from DSSD model achieve higher excess mean return than TSSD model and lower variance, downside deviation, and conditional value‐at‐risk than LSSD model. Also, portfolios from DSSD model demonstrate higher values of information ratio, stable tail‐adjusted return ratio and Sortino ratio than the other two models. Lastly, DSSD model is observed to produce well‐diversified portfolios compared to LSSD model.
Conformation‐specific antibodies against multiple amyloid protofibril species from a single amyloid immunogen
Authors: Bonito‐Oliva Alessandra , Schedin‐Weiss Sophia , Younesi Shahab S. , Tiiman Ann , Adura Carolina , Paknejad Navid , Brendel Matt , Romin Yevgeniy , Parchem Ronald J. , Graff Caroline , Vukojević Vladana , Tjernberg Lars O. , Terenius Lars , Winblad Bengt , Sakmar Thomas P. , Graham W Vallen
Published: January 2019

We engineered and employed a chaperone‐like amyloid‐binding protein Nucleobindin 1 (NUCB1) to stabilize human islet amyloid polypeptide (hIAPP) protofibrils for use as immunogen in mice. We obtained multiple monoclonal antibody (mAb) clones that were reactive against hIAPP protofibrils. A secondary screen was carried out to identify clones that cross‐reacted with amyloid beta‐peptide (Aβ42) protofibrils, but not with Aβ40 monomers. These mAbs were further characterized in several in vitro assays, in immunohistological studies of a mouse model of Alzheimer's disease (AD) and in AD patient brain tissue. We show that mAbs obtained by immunizing mice with the NUCB1‐hIAPP complex cross‐react with Aβ42, specifically targeting protofibrils and inhibiting their further aggregation. In line with conformation‐specific binding, the mAbs appear to react with an intracellular antigen in diseased tissue, but not with amyloid plaques. We hypothesize that the mAbs we describe here recognize a secondary or quaternary structural epitope that is common to multiple amyloid protofibrils. In summary, we report a method to create mAbs that are conformation‐sensitive and sequence‐independent and can target more than one type of protofibril species.
Enamel matrix derivative stabilizes blood clot and improves clinical healing in deep pockets after flapless periodontal therapy: A Randomized Clinical Trial
Authors: Graziani Filippo , Gennai Stefano , Petrini Morena , Bettini Laura , Tonetti Maurizio
Published: January 2019

Aim

An acute phase response is induced after non‐surgical periodontal treatment (SRP). The main aim of this study was to compare acute phase (24‐hr) and medium‐term (3‐months) inflammation and clinical outcomes after SRP with or without application of enamel matrix derivative (EMD) in sites with probing pocket depth (PPD) ≥ 6 mm.

Methods

Thirty‐eight periodontitis‐affected subjects were randomized to SRP or SRP + EMD. Periodontal parameters were recorded at baseline and 3 months. Serum samples were collected at baseline, 1 and 90 days after treatment.

Results

Both treatments triggered an intense acute inflammation on day 1, which regressed to baseline values at 3 months. D‐dimer and cystatin C levels did not show sharp increases in SRP + EMD group 24 hr after treatment, compared to SRP. Significant difference between groups was observed for D‐dimer (p < 0.001). EMD application was also associated with better periodontal healing as shown by greater PPD reduction and clinical attachment level gain in sites with PPD ≥ 6 mm, and higher number of cases with no residual PPD ≥ 6 mm (p < 0.05) at 3 months.

Conclusions

EMD application after non‐SRP resulted in lower fibrinolysis, and better periodontal healing of deep pockets. These initial observations warrant further investigations on the potential to modulate both local and systemic outcomes of non‐SRP. NCT03544931
Influence of different diagnostic criteria on gestational diabetes mellitus incidence and medical expenditures in China
Authors: He Zonglin , Xie Huatao , Liang Shangqiang , Tang Yuan , Ding Wenjing , Wu Yanxin , Ming Wai‐kit
Published: January 2019

Aims/Introduction

To summarize the development of the criteria for diagnosing gestational diabetes mellitus (GDM) in China, and investigate how different GDM diagnostic criteria influence the national prevalence of GDM, the national health system and the economic burden of GDM in China.

Materials and Methods

Retrospectively using data from women undergoing a 2‐h, 75‐g oral glucose tolerance test at 24–28 gestational weeks in the First Affiliated Hospital of Jinan University (Guangzhou, Guangdong, China) from January 2011 to December 2017, the prevalence rate of GDM and its impacts on the national health system were evaluated using different criteria (the 7th edition textbook criteria, National Diabetes Data Group 1979, World Health Organization 1985, European Association for the Study of Diabetes 1996, Japan 2002, American Diabetes Association [ADA] 2011 [International Association of the Diabetes and Pregnancy Study Groups], and National Institute for Heath and Care Excellence 2015).

Results

The incidence rates of GDM based on the ADA 2011 and National Institute for Heath and Care Excellence 2015 were, respectively, 22.94% (P < 0.01) and 21.72% (P < 0.01), over threefold higher than implementing the 7th edition textbook criteria (P < 0.001). On the contrary, the incidence rates of GDM diagnosed with the National Diabetes Data Group 1979 and World Health Organization 1985 guidelines were significantly less than the 7th edition textbook criteria (P < 0.001). From 2001 to 2016, the estimated national cost of treating GDM rose from ¥3.9 billion to ¥27.4 billion after implementing the ADA 2011 guidelines.

Conclusions

With the implementation of ADA 2011 (International Association of the Diabetes and Pregnancy Study Groups) guidelines, there are fewer adverse perinatal outcomes and cases of type 2 diabetes mellitus in the long term, but the medical costs increased significantly, and the cost‐effectiveness of diagnostic criteria in China is still yet to be confirmed.
Utilization of the validated Psoriasis Epidemiology Screening Tool to identify signs and symptoms of psoriatic arthritis among those with psoriasis: a cross‐sectional analysis from the US‐based Corrona Psoriasis Registry
Authors: Mease P.J. , Palmer J.B. , Hur P. , Strober B.E. , Lebwohl M. , Karki C. , Reed G.W. , Etzel C.J. , Greenberg J.D. , Helliwell P. S.
Published: January 2019

Background

Despite increasing awareness of the disease, rates of undiagnosed psoriatic arthritis (PsA) are high in patients with psoriasis (PsO). The validated Psoriasis Epidemiology Screening Tool (PEST) is a five‐item questionnaire developed to help identify PsA at an early stage.

Objectives

To assess the risk of possible undiagnosed PsA among patients with PsO and characterize patients based on PEST scores.

Methods

This study included all patients enrolled in the Corrona PsO Registry with data on all five PEST questions. Demographics, clinical characteristics and patient‐reported outcomes were compared in Corrona PsO Registry patients with PEST scores ≥3 and <3 using t‐tests for continuous variables and chi‐squared tests for categorical variables; scores ≥3 may indicate PsA.

Results

Of 1516 patients with PsO, 904 did not have dermatologist‐reported PsA; 112 of these 904 patients (12.4%) scored ≥3 and were significantly older, female, less likely to be working, and had higher BMI than patients with scores <3. They also had significantly longer PsO duration, were more likely to have nail PsO and had worse health status, pain, fatigue, Dermatology Life Quality Index and activity impairment.

Conclusions

Improved PsA screening is needed in patients with PsO because the validated PEST identified over one‐tenth of registry patients who were not noted to have PsA as having scores ≥3, who could have had undiagnosed PsA. Appropriate, earlier care is important because these patients were more likely to have nail PsO, worse health‐related quality of life and worse activity impairment.
Neurological disorders are associated with bullous pemphigoid
Authors: Papakonstantinou E. , Limberg M.M. , Gehring M. , Kotnik N. , Kapp A. , Gibbs B.F. , Raap U.
Published: January 2019

Background

Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease with an increased incidence particularly among the elderly. Several studies have recently reported an association between BP and neurological disorders.

Objective

To evaluate the association between BP and neurological disorders in a single centre in Germany.

Methods

We retrospectively assessed 183 patients with BP (diagnosed between 2011 and 2015) and 348 age‐ and sex‐matched controls for neurological disorders. The latter were confirmed either by a neurologist or psychiatrist.

Results

Overall, there was a highly statistically significant association between BP and neurological disorders (P < 0.0001). These included dementia (P < 0.0001), Parkinson`s disease (P = 0.0434), stroke (P = 0.0015) and other neurological disorders but not Alzheimer's diseases, which was more common among patients in the control group.

Conclusion

Our cohort of bullous pemphigoid and neurological disorders demonstrates a significant association between bullous pemphigoid and neurological disorders, including dementia, Parkinson's disease and stroke. These observations support the need for future studies in order to elucidate the immunological mechanisms responsible for these comorbidities.
A Policy Paradox: Response to Theodora Ooms
Authors: Strach Patricia
Published: January 2019

It's hard to look at the 2018 family separation policies of the U.S. federal government (and ensuing uproar) at the border with Mexico and not think that family policy should play a key role in American politics. But it doesn't. As Ooms argues in her masterful recounting of the history of family policy, the field has made major advances, but family policy remains largely unknown and undervalued by academics, policymakers, media, and the general public. Ooms herself says that it would be helpful “if more political scientists were interested in family issues as well as more family scholars and practitioners learned about political science and policymaking.” As a political scientist, I can say definitively that writing about families and public policy is an uphill battle in my field. The challenges that I face in doing so are not that different from what family policy scholars face more generally.
Poor transcript‐protein correlation in the brain: negatively correlating gene products reveal neuronal polarity as a potential cause
Authors: Moritz Christian P. , Mühlhaus Timo , Tenzer Stefan , Schulenborg Thomas , Friauf Eckhard
Published: January 2019

Transcription, translation, and turnover of transcripts and proteins are essential for cellular function. The contribution of those factors to protein levels is under debate, as transcript levels and cognate protein levels do not necessarily correlate due to regulation of translation and protein turnover. Here we propose neuronal polarity as a third factor that is particularly evident in the CNS, leading to considerable distances between somata and axon terminals. Consequently, transcript levels may negatively correlate with cognate protein levels in CNS regions, i.e., transcript and protein levels behave reciprocally. To test this hypothesis, we performed an integrative inter‐omics study and analyzed three interconnected rat auditory brainstem regions (cochlear nuclear complex, CN; superior olivary complex, SOC; inferior colliculus, IC) and the rest of the brain as a reference. We obtained transcript and protein sets in these regions of interest (ROIs) by DNA microarrays and label‐free mass spectrometry, and performed principal component and correlation analyses. We found 508 transcript|protein pairs and detected poor to moderate transcript|protein correlation in all ROIs, as evidenced by coefficients of determination from 0.34 to 0.54. We identified 57‐80 negatively correlating gene products in the ROIs and intensively analyzed four of them for which the correlation was poorest. Three cognate proteins (Slc6a11, Syngr1, Tppp) were synaptic and hence candidates for a negative correlation because of protein transport into axon terminals. Thus, we systematically analyzed the negatively correlating gene products. Gene ontology analyses revealed overrepresented transport/synapse‐related proteins, supporting our hypothesis. We present 30 synapse/transport‐related proteins with poor transcript|protein correlation. In conclusion, our analyses support that protein transport in polar cells is a third factor that influences the protein level and, thereby, the transcript|protein correlation.

Open science badges

This article has received a badge for *Open Materials* and *Open Data* because it provided all relevant information to reproduce the study in the manuscript and because it made the data publicly available. The data can be accessed at https://osf.io/ha28n/. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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Inhibition of bioenergetics provides novel insights into recruitment of PINK1‐dependent neuronal mitophagy
Authors: Shin Yea Seul , Ryall James G. , Britto Joanne M. , Lau Chew L. , Devenish Rodney J. , Nagley Phillip , Beart Philip M.
Published: January 2019

Contributions of damaged mitochondria to neuropathologies have stimulated interest in mitophagy. We investigated triggers of neuronal mitophagy by disruption of mitochondrial energy metabolism in primary neurons. Mitophagy was examined in cultured murine cerebellar granule cells after inhibition of mitochondrial respiratory chain by drugs rotenone, 3‐nitropropionic acid, antimycin A, and potassium cyanide, targeting complexes I, II, III, and IV, respectively. Inhibitor concentrations producing slow cellular demise were determined from analyses of cellular viability, morphology of neuritic damage, plasma membrane permeability, and oxidative phosphorylation. Live cell imaging of dissipation of mitochondrial membrane potential (ΔΨm) by drugs targeting mitochondrial complexes was referenced to complete depolarization by carbonyl cyanide m‐chlorophenyl hydrazone. While inhibition of complexes I, III and IV effected rapid dissipation of ΔΨm, inhibition of complex II using 3‐nitropropionic acid led to minimal depolarization of mitochondria. Nonetheless, all respiratory chain inhibitors triggered mitophagy as indicated by increased aggregation of mitochondrially localized PINK1. Mitophagy was further analyzed using a dual fluorescent protein biosensor reporting mitochondrial relocation to acidic lysosomal environment. Significant acidification of mitochondria was observed in neurons treated with rotenone or 3‐nitropropionic acid, revealing mitophagy at distal processes. Neurons treated with antimycin A or cyanide failed to show mitochondrial acidification. Minor dissipation of ΔΨm by 3‐nitropropionic acid coupled with vigorous triggering of mitophagy suggested depolarization of mitochondria is not a necessary condition to trigger mitophagy. Moreover, weak elicitation of mitophagy by antimycin A, subsequent to loss of ΔΨm, suggested that mitochondrial depolarization is not a sufficient condition for triggering robust neuronal mitophagy. Our findings provide new insight into complexities of mitophagic clearance of neuronal mitochondria.

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Positioning Strategies for Animal‐Friendly Products: A Social Dilemma Approach
Authors: van Riemsdijk Lenka , Ingenbleek Paul T. M. , van der Veen Gerrita , van Trijp Hans C. M.
Published: January 2019

Many consumers express concerns about the welfare of animals in agriculture, but often refrain from purchasing animal‐friendly alternatives that address their concerns. To support consumers in making choices in line with their values and attitudes, this study approaches consumer animal‐friendly product choice as a dilemma between maximizing the buyer's self‐interest and maximizing societal interest. To address this social dilemma, we developed and tested positioning strategies that reinforce the animal welfare label with complementary consumption values (functional, emotional, social, and epistemic). The results from a choice experiment with Dutch chicken meat shoppers showed that two strategies—emotional and epistemic—effectively increase consumer value perceptions. These insights imply that animal‐friendly products positioned to invoke emotion or curiosity drive consumers towards animal‐friendly product choices, and that these strategies are most effective for consumers who base their choice solely on maximizing either self‐interest or societal interest.
Medical emergency department attendance of under 16‐year‐olds with dental problems
Authors: Parten Nicola J. , Taylor Greig D. , Currie Charlotte C. , Durham Justin , Vernazza Christopher R.
Published: January 2019

Background

Medical emergency departments (MED) are under increasing pressure in the UK with suggestions that unnecessary attendances to MED, which may include dental problems, are to blame.

Objectives

The aim of this cross‐sectional study was to examine the period prevalence of under 16‐year‐olds attendance to medical emergency departments (MED) with oral and dental problems over a 5‐year period and investigate reason for attendance. This cross‐sectional study was carried out as part of a service evaluation at the Newcastle upon Tyne Hospitals NHS Foundation Trust.

Methods

Retrospective data were collected between 1 January 2012 and 31 December 2016 from the MED database using coding and a free text search of all paediatric attendances. The data were then analysed using descriptive statistics.

Results

Over the 5‐year period, 135 760 under 16‐year‐olds attended the MED. Of these, 868 (0.6%) attended for dental problems. The most common dental reasons for attendance were as follows: Candida accounted for 22.6% of the 0‐ to 5‐year‐olds; dental trauma accounted for 29.5% of 6‐ to 11‐year‐olds; and mandibular fractures accounted for 18.9% of the 12‐ to 16‐year‐olds. Of those who attended the MED for dental problems, 28.5% resided in areas with an Index of Multiple Deprivation decile of 1, the areas of highest deprivation in the UK.

Conclusion

Many of the diagnoses may have been appropriately managed elsewhere in the community, which may result in improved treatment provision and tailored care pathways, as well as reducing strain on the MED. Further research is needed to investigate why patients attend MED with dental problems.