bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of early life stress interacting and sex‐specific quantitative trait loci impacting cocaine responsiveness
Authors: Bagley Jared R. , Szumlinski Karen K. , Kippin Tod E. 
Published: March 2019

Background and PurposeAddiction vulnerability involves complex gene X environment interactions leading to a pathological response to drugs. Identification of the genes involved in these interactions is an important step in understanding the underlying neurobiology and rarely have such analyses examined sex‐specific influences. To dissect this interaction, we examined the impact of prenatal stress (PNS) on cocaine responsiveness in male and female mice of the BXD recombinant inbred panel.Experimental ApproachBXD strains were subjected to timed mating and assigned to PNS or control groups. PNS dams were subjected to restraint stress (1‐hr restraint, three times daily) starting between embryonic day (E) 11 and 14 and continued until parturition. Adult male and female, control and PNS offspring were tested for locomotor response to initial and repeated cocaine injections (sensitization) as well as cocaine‐induced conditioned place preference (CPP).Key ResultsStrain, PNS, and sex interacted to modulate initial and sensitized cocaine‐induced locomotion, as well as CPP. Moreover, a quantitative trait locus (QTL) interacting with PNS regulating initial locomotor response to cocaine (chromosome X, 37.91 to 50.95 Mb) was identified. Also PNS‐independent, female‐specific QTLs regulating CPP (chromosome 11, 65.50 to 81.31 Mb) and sensitized cocaine‐induced locomotion (chromosome 16, 95.79 to 98.32 Mb) were identified. Publicly available mRNA expression data were utilized to identify cis‐eQTL and transcript covariation with the behavioural phenotype to prioritize candidate genes; including Aifm1.Conclusions and ImplicationsThese QTL encompass genes that may moderate genetic susceptibility to PNS and interact with sex to determine adult responsiveness to cocaine and addiction vulnerability.LINKED ARTICLESThis article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc
Debate on the treatment of multiple sclerosis: Experience from an intractable multiple sclerosis case with rebound syndrome after fingolimod cessation
Authors: Kuroda Hiroshi , Nishiyama Shuhei , Matsumoto Yuki , Misu Tatsuro , Fujihara Kazuo , Aoki Masashi 
Published: March 2019

AbstractBackgroundFingolimod is an effective disease‐modifying drug for relapsing–remitting multiple sclerosis (RRMS), but drug discontinuation might cause rebound syndrome, defined as massive and prolonged exacerbation of MS. We report a case of intractable MS with rebound syndrome after fingolimod cessation.Case presentationA 54‐year‐old patient with RRMS had been disease activity‐free for 9 years during fingolimod treatment. However, she discontinued fingolimod by her own decision out of concern for progressive multifocal leukoencephalopathy. Five weeks after drug cessation, she developed progressive weakness in the left leg. Expanded Disability Status Scale scores worsened from 2.0 to 6.0. Blood tests showed recovery of lymphocyte count (1000/mm3) from the previous counts. Cerebrospinal fluid examination showed almost normal results, except for marked elevation of myelin basic protein (1420 pg/mL). Brain magnetic resonance imaging showed a massive lesion in the right frontal lobe with open‐ring enhancement and a small enhancing lesion in the left parietal lobe. Based on diagnosis as exacerbation of RRMS, the patient was treated with intravenous methylprednisolone, followed by oral dimethyl fumarate. However, 5‐month use of DMF could not remit the disease activity, leading to fingolimod reinitiation.ConclusionsRebound syndrome is an intractable complication of exit strategy for fingolimod‐treated RRMS patients. To lower the risk for rebound syndrome, specific mechanisms of rebound syndrome are to be clarified. Furthermore, concise risk stratification for progressive multifocal leukoencephalopathy in fingolimod treatment is imperative. Taken together, the risk–benefit analysis for fingolimod treatment, including rebound syndrome as well as progressive multifocal leukoencephalopathy, is required to initiate the drug.
Conservation through the lens of (mal)adaptation: Concepts and meta‐analysis
Authors: Derry Alison Margaret , Fraser Dylan J. , Brady Steven P. , Astorg Louis , Lawrence Elizabeth R. , Martin Gillian K. , Matte Jean‐Michel , Negrín Dastis Jorge Octavio , Paccard Antoine , Barrett Rowan D. H. , Chapman Lauren J. , Lane Jeffrey E. , Ballas Chase G. , Close Marissa , Crispo Erika 
Published: March 2019

AbstractEvolutionary approaches are gaining popularity in conservation science, with diverse strategies applied in efforts to support adaptive population outcomes. Yet conservation strategies differ in the type of adaptive outcomes they promote as conservation goals. For instance, strategies based on genetic or demographic rescue implicitly target adaptive population states whereas strategies utilizing transgenerational plasticity or evolutionary rescue implicitly target adaptive processes. These two goals are somewhat polar: adaptive state strategies optimize current population fitness, which should reduce phenotypic and/or genetic variance, reducing adaptability in changing or uncertain environments; adaptive process strategies increase genetic variance, causing maladaptation in the short term, but increase adaptability over the long term. Maladaptation refers to suboptimal population fitness, adaptation refers to optimal population fitness, and (mal)adaptation refers to the continuum of fitness variation from maladaptation to adaptation. Here, we present a conceptual classification for conservation that implicitly considers (mal)adaptation in the short‐term and long‐term outcomes of conservation strategies. We describe cases of how (mal)adaptation is implicated in traditional conservation strategies, as well as strategies that have potential as a conservation tool but are relatively underutilized. We use a meta‐analysis of a small number of available studies to evaluate whether the different conservation strategies employed are better suited toward increasing population fitness across multiple generations. We found weakly increasing adaptation over time for transgenerational plasticity, genetic rescue, and evolutionary rescue. Demographic rescue was generally maladaptive, both immediately after conservation intervention and after several generations. Interspecific hybridization was adaptive only in the F1 generation, but then rapidly leads to maladaptation. Management decisions that are made to support the process of adaptation must adequately account for (mal)adaptation as a potential outcome and even as a tool to bolster adaptive capacity to changing conditions.
Effect of postcuring immersed in water under hydraulic pressure on fatigue performance of large‐diameter pultruded carbon/glass hybrid rod
Authors: Li Chenggao , Xian Guijun , Li Hui 
Published: March 2019

AbstractA pultruded carbon fibre core (CFC) and glass fibre shell (GFS) hybrid fiber reinforced polymer (HFRP) rod with the diameter of 19 mm was developed. It was kept immersed in water in a self‐designed pressure chamber device with adjustable hydraulic pressure (20 MPa); after immersion, the tension‐tension fatigue performance was measured at stress levels of 41.7%, 33.4%, and 25.0%. Significant postcuring of resin was observed, resulting in the increase in Tgs for the core and shell layers. There was no significant decrease in the tensile strength of the hybrid rod. The fatigue failure of the hybrid rod was accompanied by debonding of CFC/GFS interface, redistribution of cyclic load, and catastrophic splitting or bursting of GFS. The immersion in water under hydraulic pressure led to a significant increase in fatigue life. The increase in the fatigue life was because of the improvement in interface bonding strength and toughness of the resin owing to the postcuring of the resin. After fatigue, significant degradation in the residual interface bonding strength was observed for the hybrid rods.
Epigenetic regulation of B cell fate and function during an immune response
Authors: Zhang Yan , Good‐Jacobson Kim L. 
Published: March 2019

SummaryThe humoral immune response requires coordination of molecular programs to mediate differentiation into unique B cell subsets that help clear the infection and form immune memory. Epigenetic modifications are crucial for ensuring that the appropriate genes are transcribed or repressed during B cell differentiation. Recent studies have illuminated the changes in DNA methylation and histone post‐translational modifications that accompany the formation of germinal center and antibody‐secreting cells during an immune response. In particular, the B cell subset‐specific expression and function of DNA methyltransferases and histone‐modifying complexes that mediate epigenome changes have begun to be unravelled. This review will discuss the recent advances in this field, as well as highlight critical questions about the relationship between epigenetic regulation and B cell fate and function that are yet to be answered.
Molecular pathogenesis of germinal center‐derived B cell lymphomas
Authors: Pasqualucci Laura 
Published: March 2019

SummaryB cell lymphomas comprise a heterogeneous group of genetically, biologically, and clinically distinct neoplasms that, in most cases, originate from the clonal expansion of B cells in the germinal center (GC). In recent years, the advent of novel genomics technologies has revolutionized our understanding of the molecular pathogenesis of lymphoid malignancies as a multistep process that requires the progressive accumulation of multiple genetic and epigenetic alterations. A common theme that emerged from these studies is the ability of lymphoma cells to co‐opt the same biological programs and signal transduction networks that operate during the normal GC reaction, and misuse them for their own survival advantage. This review summarizes recent progress in the understanding of the genetic and epigenetic mechanisms that drive the malignant transformation of GC B cells. These insights provide a conceptual framework for the identification of cellular pathways that may be explored for precision medicine approaches.
Germinal center‐derived lymphomas: The darkest side of humoral immunity
Authors: Mlynarczyk Coraline , Fontán Lorena , Melnick Ari 
Published: March 2019

SummaryOne of the unusual features of germinal center (GC) B cells is that they manifest many hallmarks of cancer cells. Accordingly, most B‐cell neoplasms originate from the GC reaction, and characteristically display abundant point mutations, structural genomic lesions, and clonal diversity from the genetic and epigenetic standpoints. The dominant biological theme of GC‐derived lymphomas is mutation of genes involved in epigenetic regulation and immune receptor signaling, which come into play at critical transitional stages of the GC reaction. Hence, mechanistic studies of these mutations reveal fundamental insight into the biology of the normal and malignant GC B cell. The BCL6 transcription factor plays a central role in establishing the GC phenotype in B cells, and most lymphomas are dependent on BCL6 to maintain survival, proliferation, and perhaps immune evasion. Many lymphoma mutations have the commonality of enhancing the oncogenic functions of BCL6, or overcoming some of its tumor suppressive effects. Herein, we discuss how unique features of the GC reaction create vulnerabilities that select for particular lymphoma mutations. We examine the interplay between epigenetic programming, metabolism, signaling, and immune regulatory mechanisms in lymphoma, and discuss how these are leading to novel precision therapy strategies to treat lymphoma patients.
Conjunctival bacterial and fungal flora and cutaneous fungal flora in healthy domestic rabbits (Oryctolagus cuniculus)
Authors: Bourguet A. , Desprez I. , Volait L. , Guyonnet A. , Pignon C. , Boulouis H. J. , Guillot J. , Chahory S. 
Published: March 2019

ObjectivesTo determine the normal conjunctival bacterial and fungal flora in healthy rabbits, to compare the fungal flora from the conjunctival sac with periocular cutaneous fungal flora and to evaluate potential changes in type of micro‐organisms over time.Materials and MethodsSamples from 50 pet rabbits with a normal ophthalmic examination were obtained from conjunctival sacs using sterile cotton swabs and from the interpupillary skin space using a piece of sterile carpet. Samples were collected twice, 4 weeks apart, and cultured to evaluate bacterial and fungal populations.ResultsBacteria were recovered from 35.9% of conjunctival swabs. Corynebacterium species (32.4%), Staphylococcus species (18.3%), Pasteurella species (9.9%) and Moraxella species (8.5%) were the most frequently isolated organisms. Fungi were recovered from 14.6% of conjunctival swabs. The most common fungal genera were Aspergillus (37%), Scopulariopsis (14.8%) and Penicillium (11.1%). Fungal cultures from periocular integument yielded positive results in 96.3% of samples; the same fungal organism was isolated in both conjunctival and cutaneous culture in nine of 20 rabbits (45%). When comparing results 4 weeks apart in 32 of 50 animals, only three rabbits with a positive bacterial culture and one rabbit with a positive fungal culture had the same result at the subsequent test.Clinical SignificanceFungi and bacteria isolated from the conjunctival sac of rabbits may represent transient seeding from the environment. To our knowledge, this is the first report of fungal composition of the conjunctival sac of rabbits and evaluation of the potential transient nature of both bacterial and fungal composition of this conjunctival flora.
The Impact of Government Borrowing Costs on Fiscal Discipline
Authors: Tkačevs Oļegs , Vilerts Kārlis 
Published: March 2019

SummaryThis paper studies the impact of government borrowing costs on fiscal discipline against the background of unprecedentedly low interest rates in advanced economies brought about by ultra‐expansionary monetary policies of recent years. Applying the panel data econometric approach for a sample of OECD and 11 early euro area countries over the period 1985–2015, the study suggests a positive and statistically significant impact of government borrowing costs on cyclically adjusted primary balances, indicating that a decrease in borrowing costs leads to a deterioration of fiscal policy stance. The findings herein also suggest that this effect in the euro area seems to be driven by a group of its peripheral rather than core countries and appears to work through the expenditure (more specifically, current expenditure) channel. From the economic policy perspective, these findings imply that monetary policy measures resulting in ultra‐low interest rates may cause negative side effects for fiscal discipline.
A comparison of oral flecainide and amiodarone for the treatment of recurrent supraventricular tachycardia in children
Authors: Hill Allison C. , Silka Michael J. , Bar‐Cohen Yaniv 
Published: March 2019

AbstractBackgroundSupraventricular tachycardia (SVT) in children can be difficult to treat when first‐line therapies (beta‐blockade or digoxin) are not effective. Both flecainide and amiodarone are used as second‐line therapies. We sought to compare the efficacy and safety of flecainide and amiodarone in pediatric patients with recurrent SVT.MethodsPediatric patients treated with oral flecainide or oral amiodarone for SVT between 2006 and 2015 were studied. Tachycardia mechanisms included orthodromic reciprocating tachycardia (ORT), intra‐atrial reentrant tachycardia (IART), and ectopic atrial tachycardia (EAT). Outcomes were classified as full success, partial success (requiring additional intervention), or failure.ResultsSeventy‐four patients were included (median age 46 days, range 1 day to 19 years). Flecainide was used in 47 patients and amiodarone in 27 patients. Full success was achieved in 68% and 59%, respectively (P = 0.28). Partial success was achieved in 13% and 19%, respectively (P = 0.12). Treatment failed in 19% and 22%, respectively (P = 0.97). Ten crossover patients received the second medication after the first failed. Of five amiodarone‐to‐flecainide crossovers, four achieved success on flecainide alone. Of five flecainide‐to‐amiodarone crossovers, two achieved success. Minor adverse events occurred in 9% of flecainide and 22% of amiodarone patients (P = 0.16). No significant differences were seen by arrhythmia subtype (36 EAT, 28 ORT, 10 IART), congenital heart disease (n = 38), or age group (56 infants).ConclusionsOral flecainide and amiodarone achieved meaningful arrhythmia control in 81% and 78% of pediatric patients with recurrent SVT, respectively. Those who failed amiodarone had encouraging outcomes when changed to flecainide.
Economic Effects of Workfare Reforms for Single Mothers: Benefit Substitution and Labour Supply Responses*
Authors: Johnsen Julian Vedeler , Reiso Katrine Holm 
Published: March 2019

AbstractWe analyse the economic effects of nationwide Norwegian reforms on the state benefit programme targeting single mothers. Our results show that for each reduction of 100 Norwegian kroner (NOK) in benefit payments from the programme, single mothers replaced 65 NOK through benefit substitution. Their labour supply and disposable income also increased in the short term. However, the reforms doubled the poverty rate among single mothers in the long term. The reforms led to a total net gain to public expenditure of 3.6 billion NOK (449 million euros) during the 1998–2008 period, corresponding to a 14 percent decrease in total benefit payments to single mothers.
Metalloproteinases in chronic and acute wounds: A systematic review and meta‐analysis
Authors: Tardáguila‐García Aroa , García‐Morales Esther , García‐Alamino Josep M. , Álvaro‐Afonso Francisco Javier , Molines‐Barroso Raúl Juan , Lázaro‐Martínez José Luis 
Published: March 2019

AbstractA systematic review and meta‐analysis were undertaken in order to explore the influence of matrix metalloproteinases and their diagnostic methods in chronic and acute wounds. Searches were conducted in the PubMed (Medline) and Embase (Elsevier) databases from inception to late November 2017. We included clinical trials enrolling patients with cutaneous chronic and acute wounds where a validated diagnostic method was employed for metalloproteinases. We excluded in vitro, animal or preclinical studies, nonoriginal articles, and studies without available data for analysis. In addition, references of narrative and systematic reviews were scrutinized for additional articles. Eight studies met the inclusion criteria. Results revealed that the most frequently determined matrix metalloproteinases were MMP‐2 and MMP‐9, and were found in 54.5% of wounds. MMP‐9 was present in more than 50% of the chronic wounds with a range from 37 to 78%. However, metalloproteinases were found in only 20% of acute wounds, and other types of metalloproteinases were also observed (MMP‐2 and MMP‐3). On the basis of the available evidence, high levels of metalloproteinases have been correlated with significantly delayed wound healing in wounds of a variety of etiologies.
Awareness of alcohol marketing, ownership of alcohol branded merchandise, and the association with alcohol consumption, higher-risk drinking, and drinking susceptibility in adolescents and young adults: a cross-sectional survey in the UK
Authors: Critchlow Nathan , MacKintosh Anne Marie , Thomas Christopher , Hooper Lucie , Vohra Jyotsna 
Published: March 2019

ObjectivesTo explore awareness of alcohol marketing and ownership of alcohol branded merchandise in adolescents and young adults in the UK, what factors are associated with awareness and ownership, and what association awareness and ownership have with alcohol consumption, higher-risk drinking and susceptibility.DesignOnline cross-sectional survey conducted during April–May 2017.SettingThe UK.ParticipantsAdolescents and young adults aged 11–19 years in the UK (n=3399).Main outcome measuresAlcohol Use Disorders Identification Test–Consumption (AUDIT-C) (0–12) and indication of higher-risk consumption (>5 AUDIT-C) in current drinkers. Susceptibility to drink (yes/no) in never drinkers.ResultsEighty-two per cent of respondents were aware of at least one form of alcohol marketing in the past month and 17% owned branded merchandise. χ2tests found that awareness of marketing and ownership of branded merchandise varied within drinking variables. For example, higher awareness of alcohol marketing was associated with being a current drinker (χ2=114.04, p<0.001), higher-risk drinking (χ2=85.84, p<0.001), and perceived parental (χ2=63.06, p<0.001) and peer approval of consumption (χ2=73.08, p<0.001). Among current drinkers, multivariate regressions (controlling for demographics and covariates) found that marketing awareness and owning branded merchandise was positively associated with AUDIT-C score and higher-risk consumption. For example, current drinkers reporting medium marketing awareness were twice as likely to be higher-risk drinkers as those reporting low awareness (adjusted OR (AOR)=2.18, 95% CI 1.39 to 3.42, p<0.001). Among never drinkers, respondents who owned branded merchandise were twice as likely to be susceptible to drinking as those who did not (AOR=1.98, 95% CI 1.20 to 3.24, p<0.01).ConclusionsYoung people, above and below the legal purchasing age, are aware of a range of alcohol marketing and almost one in five own alcohol branded merchandise. In current drinkers, alcohol marketing awareness was associated with increased consumption and greater likelihood of higher-risk consumption. In never drinkers, ownership of branded merchandise was associated with susceptibility.
Implications of the local haemodynamic forces on the phenotype of coronary plaques
Authors: Bourantas Christos V , Zanchin Thomas , Sakellarios Antonis , Karagiannis Alexios , Ramasamy Anantharaman , Yamaji Kyohei , Taniwaki Masanori , Heg Dik , Moschovitis Aris , Fotiadis Dimitrios , Mihalis Lampros , Baumbach Andreas , Torii Ryo , Serruys Patrick , Garcia-Garcia Hector M , Windecker Stephan , Räber Lorenz 
Published: March 2019

AimTo examine the effect of endothelial shear stress (ESS) on the dynamic changes in plaque phenotype.MethodsPatients with myocardial infarction that had intravascular ultrasound-virtual histology (IVUS-VH) and optical coherence tomography (OCT) at baseline and 13-month follow-up were studied. The IVUS-VH data were used to reconstruct the nonculprit vessels, and in the obtained models the ESS was estimated in 3 mm segments. Plaque morphology was derived in each segment from IVUS-VH and OCT. Disease progression was defined as the presence of ≥2 out of the following criteria: reduction in lumen area, increase in plaque burden and change of plaque morphology to a more vulnerable phenotype. Linear mixed effects models were used to assess the effect of ESS in different phenotypes.ResultsSixty-eight vessels were included in the analysis. Low ESS was associated with plaque progression in all phenotypes. The effect of ESS on plaque burden (p for interaction=0.467) and phenotype (p for interaction=0.188) was similar in all plaque types, whereas the effect of ESS on the changes in lumen dimensions was more prominent in disease-free (β=0.70, p<0.001) than fibrotic/fibrocalcific (β=0.28, p<0.001) or lipid-rich plaques (β=0.15, p=0.015). Standalone IVUS-VH misclassified plaque morphology in one-third of the cases leading to erroneous estimations about the effect of ESS on plaque evolution in different phenotypes.ConclusionsThe effect of ESS on plaque progression is similar in all phenotypes and cannot be accurately assessed by standalone IVUS-VH which often misclassifies plaque morphology. Therefore, multimodality imaging should be considered to examine the implications of ESS on plaque evolution.Clinical trial registrationNCT00962416; Post-results.