bluuebunny/crossref_metadata_2025_split huggingface dataset:
Editorial: accelerated infliximab induction—it's time to settle the debate! Authors' reply
Authors: Sebastian Shaji , Kennedy Nicholas A. , Subramanian Sreedhar , Raine Tim 
Published: October 2019

LINKED CONTENTThis article is linked to Sebastian et al and Chedid and Kane papers. To view these articles, visit https://doi.org/10.1111/apt.15456 and https://doi.org/10.1111/apt.15483.
Gene‐based association analysis for bivariate time‐to‐event data through functional regression with copula models
Authors: Wei Yue , Liu Yi , Sun Tao , Chen Wei , Ding Ying 
Published: October 2019

AbstractSeveral gene‐based association tests for time‐to‐event traits have been proposed recently to detect whether a gene region (containing multiple variants), as a set, is associated with the survival outcome. However, for bivariate survival outcomes, to the best of our knowledge, there is no statistical method that can be directly applied for gene‐based association analysis. Motivated by a genetic study to discover the gene regions associated with the progression of a bilateral eye disease, age‐related macular degeneration (AMD), we implement a novel functional regression (FR) method under the copula framework. Specifically, the effects of variants within a gene region are modeled through a functional linear model, which then contributes to the marginal survival functions within the copula. Generalized score test statistics are derived to test for the association between bivariate survival traits and the genetic region. Extensive simulation studies are conducted to evaluate the type I error control and power performance of the proposed approach, with comparisons to several existing methods for a single survival trait, as well as the marginal Cox FR model using the robust sandwich estimator for bivariate survival traits. Finally, we apply our method to a large AMD study, the Age‐related Eye Disease Study, and to identify the gene regions that are associated with AMD progression.
Vaccines for emerging pathogens: from research to the clinic. Part two
Authors: Williamson E D 
Published: October 2019

Summary
For this two-part Clinical & Experimental Immunology Review Series, Guest Editor E. Diane Williamson invited experts in their fields to contribute articles on the status of vaccine research and development for emerging pathogens. Part One addressed our progress in developing vaccines for emerging and re-emerging viruses and considered current work on effective vaccines for bacterial pathogens. In this edition of the journal, we are pleased to present Part Two, in which our authors emphasise the importance of vaccine formulation and of the use of effective delivery vehicles, as well as the prospects for licensure for current candidate vaccines.
Identification of pigments related to allergic tattoo reactions in 104 human skin biopsies
Authors: Serup Jørgen , Hutton Carlsen Katrina , Dommershausen Nils , Sepehri Mitra , Hesse Bernhard , Seim Christian , Luch Andreas , Schreiver Ines 
Published: October 2019

AbstractBackgroundRed tattoos are prone to allergic reactions. The identity of the allergen(s) is mostly unknown.ObjectivesChemical analysis of human skin biopsies from chronic allergic reactions in red tattoos to identify culprit pigment(s) and metals.Material and methodsOne hundred four dermatome biopsies were analyzed by matrix‐assisted laser desorption/ionization tandem mass spectrometry (MALDI‐MS/MS) for identification of commonly used organic pigments. Metal concentrations were assessed by inductively coupled plasma (ICP)‐MS and x‐ray fluorescence (XRF). Fourteen patients had cross‐reactions in other red tattoos.ResultsIn total, the identified pigments were mainly azo Pigment Red (P.R.) 22 (35%), P.R. 210 (24%), P.R. 170 (12%), P.R. 5 (0.9%), P.R. 112 (0.9%), and Pigment Orange (P.O.) 13 (11%). P.R. 122 (0.9%) and Pigment Violet (P.V.) 23 (8%) were also common. P.R. 22, P.R. 170, and P.R. 210 also dominated in patients with cross‐reactions. In 22% of the biopsies, no red pigment was detected. Element analysis indicated the presence of the sensitizers nickel and chromium.ConclusionsP.R. 22, P.R. 170, and P.R. 210 were identified as the prevailing pigments behind chronic allergic reactions in red tattoos. The epitope causing the reaction might be a pigment‐degradation product. Metal contamination may derive from different sources, and its role in red tattoo allergy cannot be ascertained.
Making Territory and Negotiating Citizenship in a Climate Mitigation Initiative in Indonesia
Authors: Setyowati Abidah B. 
Published: October 2019

ABSTRACTFor almost two decades, the concept of Payments for Ecosystem Services (PES) has been widely adopted in Indonesia, in policy initiatives ranging from pilot projects to more established PES schemes and Reducing Emissions from Deforestation and Forest Degradation (REDD+) programmes. Drawing on a case study of a REDD+ initiative in Aceh, Indonesia, this article analyses how the initiative became an avenue to renegotiate political authority, territory and citizenship. Analysis of relevant documents, combined with focus group discussions and interviews at local and national levels, reveals the complex processes by which the authority to govern forest is claimed and legitimized through the revision of provincial land‐use plans, and shows how citizenship is rearticulated through participatory mapping processes. The article demonstrates that the initiative has been negotiated and reshaped to conform to local aspirations for greater control over forests and to achieve broader development goals. The discourses of green economy and REDD+ have provided the Aceh government and communities with a new ‘surface of engagement’ to express Acehnese struggles over territory and citizenship by aligning with global climate change issues.
Online engineering education for manufacturing technology: Is a remote experiment a suitable tool to teach competences for “Working 4.0”?
Authors: Terkowsky Claudius , Frye Silke , May Dominik 
Published: October 2019

AbstractThe demands of modern industry contexts (so‐called Industry 4.0) are going to reshape the working world of future engineers. It seems obvious that these technological developments will affect higher education institutions with increasing intensity. For years, there has been a vivid discussion on the IT competences, which need to be developed by students in order to face emerging technology changes. To tackle the question regarding industry expectations towards future engineers, in this article a remote laboratory at a German university is analysed to identify potentials for future‐oriented teaching and learning in the light of the required competences for “Working 4.0”. Current scientific studies and industry agendas about Working 4.0 competences are identified, connected learning objectives are derived and the focused remote laboratory is linked to these objectives. As a result, it can be shown that this educational setting has the potential to reflect the complexity of Working 4.0. However, the results also show that the examined laboratory addresses only some of the competences in the context of Industry 4.0. Furthermore, it is argued in how far industry demands serve as the only basis for educational development efforts. The scientific studies and the industry agenda offer a limited and more political perspective on educational development. Nevertheless, based on the research in this article, it can be argued that remote labs (and online labs in general) have the potential to lift traditional laboratory‐based engineering education to a modern engineering education 4.0.
Dorsal hippocampus cholinergic and nitrergic neurotransmission modulates the cardiac baroreflex function in rats
Authors: Ferreira‐Junior Nilson Carlos , Lagatta Davi Campos , Kuntze Luciana Bärg , Fujiwara Eduardo Akira , Firmino Egidi Mayara Silva , Borges‐Assis Anna Bárbara , Resstel Leonardo Barbosa Moraes , Sampaio Karla Nívea 
Published: October 2019

AbstractHippocampus is a limbic structure involved in the baroreflex and chemoreflex control that receives extensive cholinergic input from basal forebrain. Hippocampal muscarinic receptors activation by acetylcholine might evoke nitric oxide synthesis, which is an important neuromodulator of cardiovascular responses. Thus, we hypothesize that cholinergic and nitrergic neurotransmission within the DH modulates the baroreflex and chemoreflex function. We have used vasoactive drugs (phenylephrine and sodium nitroprusside), and potassium cyanide infused peripherally to induce, respectively, baroreflex or chemoreflex responses in awake animals. Bilateral injection into the DH of the acetylcholinesterase inhibitor (neostigmine) reduced baroreflex responses. Meanwhile, the non‐selective muscarinic receptor antagonist (atropine) or the M1‐selective muscarinic receptor antagonist increased baroreflex responses (pirenzepine). Furthermore, the neuronal nitric oxide synthase inhibitor (N‐propyl) or the intracellular NO scavenger (carboxy‐PTIO) increased baroreflex responses, as well as the selective inhibitor of NO‐sensitive guanylyl cyclase (ODQ), increased the baroreflex responses. Besides, bilateral administration of an ineffective dose of a neuronal nitric oxide synthase inhibitor abolished the reduction in the baroreflex responses evoked by an acetylcholinesterase inhibitor. On the other hand, we have demonstrated that hippocampal cholinergic neurotransmission did not influence the chemoreflex function. Taken together, our findings suggest that nNOS‐derived nitric oxide in the DH participates in acetylcholine‐evoked baroreflex responses.
Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions
Authors: Anderson Lyndsey L. , Absalom Nathan L. , Abelev Sarah V. , Low Ivan K. , Doohan Peter T. , Martin Lewis J. , Chebib Mary , McGregor Iain S. , Arnold Jonathon C. 
Published: October 2019

AbstractObjectiveCannabidiol (CBD) has been approved by the US Food and Drug Administration (FDA) to treat intractable childhood epilepsies, such as Dravet syndrome and Lennox‐Gastaut syndrome. However, the intrinsic anticonvulsant activity of CBD has been questioned due to a pharmacokinetic interaction between CBD and a first‐line medication, clobazam. This recognized interaction has led to speculation that the anticonvulsant efficacy of CBD may simply reflect CBD augmenting clobazam exposure. The present study aimed to address the nature of the interaction between CBD and clobazam.MethodsWe examined whether CBD inhibits human CYP3A4 and CYP2C19 mediated metabolism of clobazam and N‐desmethylclobazam (N‐CLB), respectively, and performed studies assessing the effects of CBD on brain and plasma pharmacokinetics of clobazam in mice. We then used the Scn1a+/− mouse model of Dravet syndrome to examine how CBD and clobazam interact. We compared anticonvulsant effects of CBD‐clobazam combination therapy to monotherapy against thermally‐induced seizures, spontaneous seizures and mortality in Scn1a+/− mice. In addition, we used Xenopus oocytes expressing γ‐aminobutyric acid (GABA)A receptors to investigate the activity of GABAA receptors when treated with CBD and clobazam together.ResultsCBD potently inhibited CYP3A4 mediated metabolism of clobazam and CYP2C19 mediated metabolism of N‐CLB. Combination CBD‐clobazam treatment resulted in greater anticonvulsant efficacy in Scn1a+/− mice, but only when an anticonvulsant dose of CBD was used. It is important to note that a sub‐anticonvulsant dose of CBD did not promote greater anticonvulsant effects despite increasing plasma clobazam concentrations. In addition, we delineated a novel pharmacodynamic mechanism where CBD and clobazam together enhanced inhibitory GABAA receptor activation.SignificanceOur study highlights the involvement of both pharmacodynamic and pharmacokinetic interactions between CBD and clobazam that may contribute to its efficacy in Dravet syndrome.
GATORopathies: The role of amino acid regulatory gene mutations in epilepsy and cortical malformations
Authors: Iffland Philip H. , Carson Vincent , Bordey Angelique , Crino Peter B. 
Published: October 2019

AbstractThe mechanistic target of rapamycin (mTOR) pathway has been implicated in a growing number of malformations of cortical development (MCD) associated with intractable epilepsy. Mutations in single genes encoding mTOR pathway regulatory proteins have been linked to MCD such as focal cortical dysplasia (FCD) types IIa and IIb, hemimegalencephaly (HME), and megalencephaly. Recent studies have demonstrated that the GATOR1 protein complex, comprised of DEPDC5, NPRL3, and NPRL2, plays a pivotal role in regulating mTOR signaling in response to cellular amino acid levels and that mutations in DEPDC5, NPRL3, or NPRL2 are linked to FCD, HME, and seizures. Histopathological analysis of FCD and HME tissue specimens resected from individuals harboring DEPDC5, NPRL3, or NPRL2 gene mutations reveals hyperactivation of mTOR pathway signaling. Family pedigrees carrying mutations in either DEPDC5 or NPRL3 share clinical phenotypes of epilepsy and MCD, as well as intellectual and neuropsychiatric disabilities. Interestingly, some individuals with seizures associated with DEPDC5, NPRL3, or NPRL2 variants exhibit normal brain imaging suggesting either occult MCD or a role for these genes in non‐lesional neocortical epilepsy. Mouse models resulting from knockdown or knockout of either Depdc5 or Nprl3 exhibit altered cortical lamination, neuronal dysmorphogenesis, and enhanced neuronal excitability as reported in models resulting from direct mTOR activation through expression of its canonical activator RHEB. The role of the GATOR1 proteins in regulating mTOR signaling suggest plausible options for mTOR inhibition in the treatment of epilepsy associated with mutations in DEPDC5, NPRL3, or NPRL2.
Stifle radiography in Thoroughbreds from 6 to 18 months of age
Authors: Santschi E. M. , Prichard M. A. , Whitman J. L. , Batten C. A. , Strathman T. A. , Canada N. C. , Morehead J. P. 
Published: October 2019

SummaryThe radiographic appearance of the stifle of young horse changes during the first 18 months of life but is not well described in Thoroughbreds. Our objective was to describe the radiographic appearance of the Thoroughbred stifle from 5 to 18 months of age and determine whether limiting exercise impacts the prevalence of radiographic abnormalities (RA). Bilateral stifle radiographs were obtained at a mean of 161 days of age in 141 subjects (set 1) and 347 days (set 2), and in 114 available subjects at 534 days (set 3), and graded for RA of the trochlear ridges (TR) and medial femoral condyle (MFC). The impact of exercise limits on RA was determined from a subgroup of subjects with set 1 RA that had 30–90 days limited exercise. Stifle RA were present in 50 subjects (35%) at set 1: 39 TR and 11 MFC. At set 2, 24 subjects (15.6%) had RA: 13 TR and 11 MFC. Set 1 RA had resolved in 36 (72%) subjects, persisted in 11 (22%) and changed location in 3. Ten of 91 (11%) subjects developed new RA at set 2. Twenty‐seven subjects were unavailable for set 3 imaging, 6 with LTR RA at set 2. At set 3, 12/114 (11%) subjects had RA: 5 TR and 7 MFC. Set 2 RA resolved in 9 (50%) subjects, persisted in 8 (44%), and changed location in one. Three of 96 subjects developed new RA at set 3. Radiographic abnormality prevalence at set 3 was not different after limiting exercise. It was concluded that RA in the TR and MFC are common in 6‐month‐old Thoroughbreds and often resolve by 18 months. Radiographic abnormalities that develop later (~12 months of age) are less likely to resolve.
Unfolding Relations among Mindful Parenting, Recurrent Conflict, and Adolescents’ Externalizing and Internalizing Problems
Authors: Park Ye Rang , Nix Robert L. , Duncan Larissa G. , Coatsworth J. Douglas , Greenberg Mark T. 
Published: October 2019

The current study examined unfolding relations among mothers’ mindful parenting, parent–adolescent recurrent conflict, and adolescents’ externalizing and internalizing problems. In a community sample of 117 families (31% black, Asian, American Indian, or Latino), parents and adolescents (52% female; average age = 12.13 years) were followed over 15 months. Parents answered questions about mindful parenting and recurrent conflict, and adolescents reported on their own externalizing and internalizing problems. Path analyses indicated that higher levels of mindful parenting were significantly related to lower levels of recurrent conflict 2–3 months later, controlling for previous levels of recurrent conflict. Moreover, lower levels of recurrent conflict were significantly related to lower levels of externalizing problems and internalizing problems 1 year later, controlling for previous levels of those problems. Subgroup analyses indicated that relations were comparable across subgroups defined by adolescent gender, race, parent marital status, and family financial strain. The effects of mindful parenting were robust even after accounting for other indicators of positive and supportive parenting, namely inductive reasoning and warmth in the parent–adolescent relationship. These findings highlight the potential of mindful parenting to improve family interactions and adolescent adjustment.
Phylogenetic placement of environmental sequences using taxonomically reliable databases helps to rigorously assess dinophyte biodiversity in Bavarian lakes (Germany)
Authors: Gottschling Marc , Chacón Juliana , Žerdoner Čalasan Anže , Neuhaus Stefan , Kretschmann Juliane , Stibor Herwig , John Uwe 
Published: October 2019

Abstract

Reliable determination of organisms is a prerequisite to explore their spatial and temporal occurrence and to study their evolution, ecology, and dispersal. In Europe, Bavaria (Germany) provides an excellent study system for research on the origin and diversification of freshwater organisms including dinophytes, due to the presence of extensive lake districts and ice age river valleys. Bavarian freshwater environments are ecologically diverse and range from deep nutrient‐poor mountain lakes to shallow nutrient‐rich lakes and ponds.

We obtained amplicon sequence data (V4 region of small subunit‐rRNA, c. 410 bp long) from environmental samples collected at 11 sites in Upper Bavaria. We found 186 operational taxonomic units (OTUs) associated with Dinophyceae that were further classified by means of a phylogenetic placement approach.

The maximum likelihood tree inferred from a well‐curated reference alignment comprised a systematically representative set of 251 dinophytes, covering the currently known molecular diversity and OTUs linked to type material if possible. Environmental OTUs were scattered across the reference tree, but accumulated mostly in freshwater lineages, with 79% of OTUs placed in either Apocalathium, Ceratium, or Peridinium, the most frequently encountered taxa in Bavaria based on morphology.

Twenty‐one Bavarian OTUs showed identical sequences to already known and vouchered accessions, two of which are linked to type material, namely Palatinus apiculatus and Theleodinium calcisporum. Particularly within Peridiniaceae, delimitation of Peridinium species was based on the intraspecific sequence variation.

Our approach indicates that high‐throughput sequencing of environmental samples is effective for reliable determination of dinophyte species in Bavarian lakes. We further discuss the importance of well‐curated reference databases that remain to be developed in the future.
Beyond translation: Engaging with culturally and linguistically diverse consumers
Authors: Harrison Reema , Walton Merrilyn , Chitkara Upma , Manias Elizabeth , Chauhan Ashfaq , Latanik Monika , Leone Desiree 
Published: October 2019

AbstractBackgroundIn the context of an effective consumer engagement framework, there is potential for health‐care delivery to be safer. Consumers from culturally and linguistically diverse (CALD) backgrounds may experience several barriers when trying to engage about their health care, and they are not acknowledged sufficiently in contemporary strategies to facilitate patient engagement.MethodsFour focus group discussions were facilitated by bilingual fieldworkers in Arabic, Mandarin, Turkish and Dari in a district of Sydney, Australia that has a high proportion of CALD consumers. Each group included 5‐7 health‐care consumers who, using a topic guide, discussed their experiences of barriers and facilitators when engaging with health‐care services in Australia. Thematic analysis was undertaken to identify, analyse and report patterns in the data.ResultsIn all, 24 consumers participated. Six inter‐related themes emerged: navigating the health system; seeking meaningful interpretation; understanding and managing expectations; respectful professional care; accessing services; and feeling unsafe.ConclusionsThe incorporation of strategies such as professional interpreters and migrant health workers may go some way to addressing the needs of culturally or linguistically diverse consumers and facilitate communication, but do not sufficiently address the range of barriers to consumer engagement identified in this work. Understanding consumer experience in the context of the complex factors that may be associated with poor engagement and poor outcomes such as health literacy, cultural, educational and linguistic background, and health‐care setting or condition, may contribute to better understanding about how to deliver quality health care to these patients.
The effects of ozone, ultrasound and coating with shellac and lysozyme–chitosan on fresh egg during storage at ambient temperature. Part II: microbial quality, eggshell breaking strength and FT‐NIR spectral analysis
Authors: Yüceer Muhammed , Caner Cengiz 
Published: October 2019

SummaryThis research aims to investigate and compare the effect of different treatments, including gaseous ozone (6‐ppm/4‐min), ultrasound (450 W/4‐min), and coatings of shellac and lysozyme–chitosan (L–C), on fresh eggs during the storage for six weeks at ambient temperature. The internal quality analysis was performed in Part I. In Part II, the bacterial qualities, Fourier transform near‐infrared (FT‐NIR) spectral image and eggshell breaking strength were monitored. Ozone and ultrasound helped to maintain bacterial quality, but had an adverse effect on shell strength. Coated eggs had the highest value of strength (shellac: 3.63 ± 0.54 kgf; L–C: 3.56 ± 0.54 kgf) and ultrasound‐treated eggs had the lowest strength (3.13 ± 0.78 kgf) in egg top. FT‐NIR measurement showed that all treatments resulted in a decrease in absorption bands throughout storage. Overall, among the treatments investigated, the coatings were the best for enhancing shelf life with higher strength in eggshell breakage, while the ozone and ultrasound only helped to keep the microbial quality and enhance the shelf life.
T cell addiction: can pathogenic T cells be controlled using dopamine receptors?
Authors: Bain Kym A. , Milling Simon 
Published: October 2019

SummaryCrosstalk between the immune system and the nervous system, via neurotransmitters such as dopamine, is increasingly of interest as we begin to learn how lymphocytes in peripheral tissues can both produce and respond to these molecules. This crosstalk can modulate immune responses by influencing the local tissue environment and can, for instance, influence the activation status and migration of T cells. Immune cells also use neurotransmitters to communicate with each other. Understanding how neurotransmitters influence the immune system may provide novel approaches for targeting diseases associated with tissue‐specific inflammation, such as psoriasis.