bluuebunny/crossref_metadata_2025_split huggingface dataset:
Waves of Maturation and Senescence in Micro-Structural MRI Markers of Human Cortical Myelination over the Lifespan
Authors: Grydeland Håkon , Vértes Petra E. , Váša František , Romero-Garcia Rafael , Whitaker Kirstie , Alexander-Bloch Aaron F. , Bjørnerud Atle , Patel Ameera X. , Sedervicius Donatas , Tamnes Christian K. , Westlye Lars T. , White Simon R. , Walhovd Kristine B. , Fjell Anders M. , Bullmore Edward T. 
Published: May 2018

AbstractSeminal human brain histology work has demonstrated developmental waves of myelination. Here, using a micro-structural magnetic resonance imaging (MRI) marker linked to myelin, we studied fine-grained age differences to deduce waves of growth, stability, and decline of cortical myelination over the life-cycle. In 484 participants, aged 8-85 years, we fitted smooth growth curves to T1- to T2-weighted ratio in each of 360 regions from one of 7 cytoarchitectonic classes. From the first derivatives of these generally inverted-U trajectories, we defined three milestones: the age at peak growth; the age at onset of a stable plateau; and the age at the onset of decline. Age at peak growth had a bimodal distribution comprising an early (pre-pubertal) wave of primary sensory and motor cortices and a later (post-pubertal) wave of association, insular and limbic cortices. Most regions reached stability in the 30s but there was a second wave reaching stability in the 50s. Age at onset of decline was also bimodal: in some right hemisphere regions, the curve declined from the 60s, but in other left hemisphere regions, there was no significant decline from the stable plateau. These results are consistent with regionally heterogeneous waves of intracortical myelinogenesis and age-related demyelination.
Fairness in franchisor–franchisee relationship: an integrative perspective
Authors: Shaikh Ateeque , Sharma Dheeraj , Vijayalakshmi Akshaya , Yadav Rama Shankar 
Published: May 2018

PurposeThis paper aims to elucidate and extend the concept of power and fairness in the context of franchisor–franchisee relationship.Design/methodology/approachOn the basis of Dul and Hak’s (2007) recommendations, the conceptual model is developed from closely related domains (e.g. channel relationship) using pertinent theories. On the basis of this comprehensive analysis, new propositions about fairness in a franchisee–franchisor context are drawn. The primary purpose of this research is to conceptually and theoretically further the understanding of antecedents and consequences of fairness in a franchisor–franchisee relationship context by proffering a framework. Finally, this study examines the concept of fairness of its antecedents and moderators that have received scant attention in the context of franchising research.FindingsThis study contends that non-coercive power is perceived fairly. Also, coercive power that is legitimate is perceived fairly. However, coercive power that is illegitimate can be detrimental to relationships between franchisee and franchisor. Furthermore, a franchisee who perceives the relationship to be fair is likely to place more trust in relationship, is more satisfied with relationship and is less likely to be opportunistic. Finally, the study contends that these relationship outcomes are dependent on the franchisee’s personality traits.Research limitations/implicationsOne major limitation of this study is that the propositions have not been empirically tested. However, this paper cites several business cases that have been used to support the propositions proffered in the study. Our conceptual model supported by previous theoretical findings and industry cases suggests that it is important to focus on social dimensions along with economic costs of a franchisor–franchisee relationship. Future researchers may empirically examine the relationships posited in this study by using the primary industry data.Originality/valueThis paper takes a comprehensive view of various social constructs affecting a franchisor–franchisee relationship. It also highlights the role of individual personality factors in a franchisor–franchisee relationship, extends prior work on relational dimensions from channels to the franchising context and provides managerial conclusions.
Mutations in mevalonate pathway genes in patients with familial or sporadic porokeratosis
Authors: Leng Yunji , Yan Lulu , Feng Hongquan , Chen Chen , Wang Shusen , Luo Yang , Cao Lihua 
Published: May 2018

AbstractPorokeratosis comprises heterogeneous keratinization disorders that are characterized by one or more atrophic patches surrounded by a ridge‐like cornoid lamella. In this study, we evaluated seven families affected by porokeratosis and five sporadic patients of the disease in a Chinese population. We performed Sanger sequencing of exons and flanking intron–exon boundaries of mevalonate pathway genes (MVD, MVK, PMVK and FDPS) and of SLC17A9. In five familial and three sporadic patients, we detected six variations, including four novel mutations (MVD c.1A>G; p.Met1?, c.916G>A; p.Ala306Thr, c.1013+1G>A, and PMVK c.65A>G; p.Lys22Arg) and two recurrent mutations (MVD c.746T>C; p.Phe249Ser, and MVK c.1028T>C; p.Leu343Pro). We then applied I‐TASSER and iGEMDOCK to assess these variants for probable functional impacts. The findings of this study extend the mutation spectrum of porokeratosis and provide further evidence for the genetic basis of this disease.
Travel time computations using a compact eikonal equation for vertical transverse isotropic media
Authors: Moghaddam Peyman , Khajavi Reza , Keers Henk 
Published: May 2018

ABSTRACTEikonal solvers often have stability problems if the velocity model is mildly heterogeneous. We derive a stable and compact form of the eikonal equation for P‐wave propagation in vertical transverse isotropic media. The obtained formulation is more compact than other formulations and therefore computationally attractive. We implemented ray shooting for this new equation through a Hamiltonian formalism. Ray tracing based on this new equation is tested on both simple as well as more realistic mildly heterogeneous velocity models. We show through examples that the new equation gives travel times that coincide with the travel time picks from wave equation modelling for anisotropic wave propagation.
Determination of the relationship between oxalate degradation and exopolysaccharide production by different Lactobacillus probiotic strains
Authors: Sönmez Şule , Önal Darilmaz Derya , Beyatli Yavuz 
Published: May 2018

The aim of this study was to evaluate the protective effects of exopolysaccharide (EPS) production on resistance to gastrointestinal digestive conditions and oxalate by probiotic strains of the species Lactobacillus rhamnosus, Lactobacillus fermentum and Lactobacillus brevis. The oxalate‐degrading ability of the strains was determined using an enzymatic assay. The correlation between oxalate degradation rate and EPS production was not significant (P > 0.05); however, the high‐EPS‐producing L. fermentumIP5 and L. brevisYG7 strains showed high oxalate‐degrading activity, whereas the low‐EPS‐producing strain L. fermentumBP5 demonstrated low oxalate‐degrading activity. The present findings suggest that dietary supplementation with the probiotic strain L. fermentumIP5 could be a promising strategy for the prevention of oxalate stone disease.
Observational pre–post study showed that a quality improvement project reduced paediatric antibiotic prescribing rates in primary care
Authors: Di Mario Simona , Gagliotti Carlo , Buttazzi Rossella , Cisbani Luca , Di Girolamo Chiara , Brambilla Antonio , Moro Maria Luisa ,   the regional working group “Progetto ProBA‐Progetto Bambini e Antibiotici‐2014”
Published: May 2018

AbstractAimThis study assessed the effectiveness of a quality improvement project that aimed to promote more considered antibiotic prescribing in paediatric primary care.MethodThis was an observational pre–post study that used patient‐level prescribing data from the Emilia‐Romagna region of Italy to monitor indicators from 2005 to 2016. Multilevel interventions and activities were started in 2007 and these included developing guidelines and updates, disseminating evidence, audits and feedback, public information campaigns, engaging health managers and performance incentives. The primary outcomes were total antibiotic prescription rates for children aged 0–13 years and the rates for specific drugs.ResultsThe intervention was associated with a significant reduction in the antibiotic prescribing rate, from 1307 per 1000 children in 2005 to 881 prescriptions in 2016 (p for trend <0.001), and a significant increase in the ratio of amoxicillin to amoxicillin–clavulanic acid, from 0.6 to 1.1 (p for trend = 0.001). Prescriptions of other second‐choice antibiotics also declined significantly. In contrast, antibiotic prescribing rates remained high in the rest of Italy.ConclusionThe intervention was effective in promoting a more considered use of antibiotic in paediatric primary care in an Italian region. Further studies are needed to confirm its effectiveness in other settings.
High prevalence and low spontaneous eradication rate of Helicobacter pylori infection among schoolchildren aged 7–12 years
Authors: Zhou Ying , Ye Ziqing , Huang Jie , Huang Ying , Yan Weili , Zhang Yi 
Published: May 2018

AbstractAimHelicobacter pylori infections mainly occur during childhood and may cause chronic diseases and persist for life unless they are treated. The aim of this study was to identify the prevalence and infection status of H. pylori infection among schoolchildren.MethodsWe conducted a cross‐sectional study of 867 children (52% male) aged 7–12 years in a primary school in the Minhang District of Shanghai, China, in 2014, and a one‐year follow‐up study of 352 subjects. The 13C‐urea breath test was used to identify the H. pylori infection at baseline and one year later. A parental questionnaire provided information regarding the children's socioeconomic status and household environment.ResultsThe overall prevalence of the H. pylori infection was 24.1% (209/867), with a 95% confidence interval of 21.3% to 27.0%. The one‐year follow‐up study of 352 subjects found that 33.5% were positive for the infection at baseline and 66.5% were negative. We found that 27.1% of the positive cases recovered and 8.9% of the negative cases acquired the infection during the year. The spontaneous eradication rate was only 2.9% over the one‐year period.ConclusionThe prevalence of the H. pylori infection among Chinese schoolchildren aged 7–12 was high and spontaneous eradication was low.
Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders
Authors: Gill P. A. , van Zelm M. C. , Muir J. G. , Gibson P. R. 
Published: May 2018

SummaryBackgroundButyrate, propionate and acetate are short chain fatty acids (SCFA), important for maintaining a healthy colon and are considered as protective in colorectal carcinogenesis. However, they may also regulate immune responses and the composition of the intestinal microbiota. Consequently, their importance in a variety of chronic inflammatory diseases is emerging.AimsTo review the physiology and metabolism of SCFA in humans, cellular and molecular mechanisms by which SCFA may act in health and disease, and approaches for therapeutic delivery of SCFA.MethodsA PubMed literature search was conducted for clinical and pre‐clinical studies using search terms: ‘dietary fibre’, short‐chain fatty acids’, ‘acetate’, ‘propionate’, ‘butyrate’, ‘inflammation’, ‘immune’, ‘gastrointestinal’, ‘metabolism’.ResultsA wide range of pre‐clinical evidence supports roles for SCFA as modulators of not only colonic function, but also multiple inflammatory and metabolic processes. SCFA are implicated in many autoimmune, allergic and metabolic diseases. However, translating effects of SCFA from animal studies to human disease is limited by physiological and dietary differences and by the challenge of delivering sufficient amounts of SCFA to the target sites that include the colon and the systemic circulation. Development of novel targeted approaches for colonic delivery, combined with postbiotic supplementation, may represent desirable strategies to achieve adequate targeted SCFA delivery.ConclusionsThere is a large array of potential disease‐modulating effects of SCFA. Adequate targeted delivery to the sites of action is the main limitation of such application. The ongoing development and evaluation of novel delivery techniques offer potential for translating promise to therapeutic benefit.
Futility of current urine salbutamol doping control
Authors: Heuberger Jules A. A. C. , van Dijkman Sven C. , Cohen Adam F. 
Published: May 2018

AimsSalbutamol is used in the management of obstructive bronchospasm, including that of some elite athletes. It is claimed that high salbutamol (oral) doses may also have an anabolic effect. Therefore, inhalation of salbutamol is restricted by the World Anti‐Doping Agency (WADA) to a maximal daily dose. Urine is tested for violations, but recent cases have resulted in a debate regarding the validity of this approach. It was our aim to determine whether current approaches are sufficiently able to differentiate approved usage from violations.MethodsWe extracted pharmacokinetic parameters from literature for salbutamol and its sulphated metabolite. From these parameters, a semi‐physiological pharmacokinetic model of inhaled and orally administered salbutamol was synthesized, validated against literature data, and used to perform clinical trial simulations (n = 1000) of possible urine concentrations over time resulting from WADA‐allowed and oral unacceptable dosages.ResultsThe synthesized model was able to predict the literature data well. Simulations showed a very large range of salbutamol concentrations, with a significant portion of virtual subjects (15.4%) exceeding the WADA threshold limit of 1000 ng ml−1 at 1 h post‐dose.ConclusionsThe observed large variability in urine concentrations indicates that determining the administered dose from a single untimed urine sample is not feasible. The current threshold inadvertently leads to incorrect assumptions of violation, whereas many violations will go unnoticed, especially when samples are taken long after drug administration. These issues, combined with the dubious assertion of its anabolic effect, leads us to conclude that the large effort involved in testing should be reconsidered.
The opioid oxycodone use‐dependently inhibits the cardiac sodium channel NaV1.5
Authors: Meents Jannis E , Juhasz Krisztina , Stölzle‐Feix Sonja , Peuckmann‐Post Vera , Rolke Roman , Lampert Angelika 
Published: May 2018

AbstractBackground and PurposeOxycodone is a potent semi‐synthetic opioid that is commonly used for the treatment of severe acute and chronic pain. However, treatment with oxycodone can lead to cardiac electrical changes, such as long QT syndrome, potentially inducing sudden cardiac arrest. Here, we investigate whether the cardiac side effects of oxycodone can be explained by modulation of the cardiac Nav1.5 sodium channel.Experimental ApproachHeterologously expressed human Nav1.5, Nav1.7 (HEK293 cells) or Nav1.8 channels (mouse N1E‐115 cells) were used for whole‐cell patch‐clamp electrophysiology. A variety of voltage‐clamp protocols were used to test the effect of oxycodone on different channel gating modalities. Human stem cell‐derived cardiomyocytes were used to measure the effect of oxycodone on cardiomyocyte beating.Key ResultsOxycodone inhibited Nav1.5 channels, concentration and use‐dependently, with an IC50 of 483 μM. In addition, oxycodone slows recovery of Nav1.5 channels from fast inactivation and increases slow inactivation. At high concentrations, these effects lead to a reduced beat rate in cardiomyocytes and to arrhythmia. In contrast, no such effects could be observed on Nav1.7 or Nav1.8 channels.Conclusions and ImplicationsOxycodone leads to an accumulation of Nav1.5 channels in inactivated states, with a slow time course. Although the concentrations needed to elicit cardiac arrhythmias in vitro are relatively high, some patients under long‐term treatment with oxycodone as well as drug abusers and addicts might suffer from severe cardiac side effects induced by the slowly developing effects of oxycodone on Nav1.5 channels.
A novel cross‐species inhibitor to study the function of CatSper Ca2+ channels in sperm
Authors: Rennhack Andreas , Schiffer Christian , Brenker Christoph , Fridman Dmitry , Nitao Elis T , Cheng Yi‐Min , Tamburrino Lara , Balbach Melanie , Stölting Gabriel , Berger Thomas K , Kierzek Michelina , Alvarez Luis , Wachten Dagmar , Zeng Xu‐Hui , Baldi Elisabetta , Publicover Stephen J , Kaupp U Benjamin , Strünker Timo 
Published: May 2018

Background and PurposeSperm from many species share the sperm‐specific Ca2+ channel CatSper that controls the intracellular Ca2+ concentration and, thereby, the swimming behaviour. A growing body of evidence suggests that the mechanisms controlling the activity of CatSper and its role during fertilization differ among species. A lack of suitable pharmacological tools has hampered the elucidation of the function of CatSper. Known inhibitors of CatSper exhibit considerable side effects and also inhibit Slo3, the principal K+ channel of mammalian sperm. The compound RU1968 was reported to suppress Ca2+ signaling in human sperm by an unknown mechanism. Here, we examined the action of RU1968 on CatSper in sperm from humans, mice, and sea urchins.Experimental ApproachWe resynthesized RU1968 and studied its action on sperm from humans, mice, and the sea urchin Arbacia punctulata by Ca2+ fluorimetry, single‐cell Ca2+ imaging, electrophysiology, opto‐chemistry, and motility analysis.Key ResultsRU1968 inhibited CatSper in sperm from invertebrates and mammals. The compound lacked toxic side effects in human sperm, did not affect mouse Slo3, and inhibited human Slo3 with about 15‐fold lower potency than CatSper. Moreover, in human sperm, RU1968 mimicked CatSper dysfunction and suppressed motility responses evoked by progesterone, an oviductal steroid known to activate CatSper. Finally, RU1968 abolished CatSper‐mediated chemotactic navigation in sea urchin sperm.Conclusion and ImplicationsWe propose RU1968 as a novel tool to elucidate the function of CatSper channels in sperm across species.
On‐the‐job‐search, wage dispersion and trade liberalization
Authors: Rodrigue Joel , Tsuyuhara Kunio 
Published: May 2018

AbstractThis paper builds a dynamic, general equilibrium, open economy model that allows for ex ante homogeneous workers to experience different wage growth before and after trade liberalization. Key features of our model include a product market composed of heterogeneous firms and a labour market characterized by directed, on‐the‐job‐search and dynamic contracts. We characterize the complementarity of these two sources of wage dispersion in an open economy setting where trade liberalization affects the endogenous equilibrium set of producers and the structure of wages. We find that worker job‐to‐job transitions, through on‐the‐job search, increases the impact of trade liberalization on wage dispersion by 4%.RésuméRecherche d’emploi en cours d’emploi, dispersion des salaires et libéralisation du commerce. Ce mémoire construit un modèle dynamique d’équilibre général d’une économie ouverte qui permet à des travailleurs ex ante homogènes de faire l’expérience de croissance différente des salaires avant et après la libéralisation du commerce. Les caractéristiques importantes du modèle incluent un marché du produit composé de firmes hétérogènes et un marché du travail caractérisé par une recherche dirigée d’emploi en cours d’emploi et des contrats de salaires dynamiques. On caractérise la complémentarité de ces deux sources de dispersion des salaires dans une économie ouverte où la libéralisation du commerce affecte l’équilibre endogène de l’ensemble des producteurs et la structure des salaires. On découvre que les transitions d’emploi à emploi des travailleurs, via la recherche d’emploi en cours d’emploi, accroîssent l’impact de la libéralisation du commerce sur la dispersion des salaires de 4 %.
Modulation of forebrain function by nucleus incertus and relaxin‐3/RXFP3 signaling
Authors: Olucha‐Bordonau Francisco E. , Albert‐Gascó Héctor , Ros‐Bernal Francisco , Rytova Valeria , Ong‐Pålsson Emma K. E. , Ma Sherie , Sánchez‐Pérez Ana M. , Gundlach Andrew L. 
Published: May 2018

SummaryThe nucleus incertus (NI) in the pontine tegmentum sends ascending projections to the midbrain, hypothalamus, amygdala, basal forebrain, hippocampus, and prefrontal cortex, and has a postulated role in modulating several forebrain functions. A substantial population of GABAergic NI neurons expresses the neuropeptide, relaxin‐3, which acts via the Gi/o‐protein‐coupled receptor, RXFP3, present throughout the forebrain target regions. Broad and specific manipulations of these systems by activation or inhibition of the NI or modulating RXFP3 signaling have revealed key insights into the likely influence of the NI/relaxin‐3/RXFP3 system on modalities including arousal, feeding, stress responses, anxiety and addiction, and attention and memory. This range of actions corresponds to a likely impact of NI/(relaxin‐3) projections on multiple integrated circuits, but makes it difficult to draw conclusions about a generalized function for this network. This review will focus on the key physiological process of oscillatory theta rhythm and the neural circuits that promote it during behavioral activation, highlighting the ability of NI and relaxin‐3/RXFP3 signaling systems to modulate these circuits. A better understanding of these mechanisms may provide a way to therapeutically adjust malfunction of forebrain activity present in several pathological conditions.
Investigating cumulative effects across ecological scales
Authors: Hodgson Emma E. , Halpern Benjamin S. 
Published: May 2018

AbstractSpecies, habitats, and ecosystems are increasingly exposed to multiple anthropogenic stressors, fueling a rapidly expanding research program to understand the cumulative impacts of these environmental modifications. Since the 1970s, a growing set of methods has been developed through two parallel, sometimes connected, streams of research within the applied and academic realms to assess cumulative effects. Past reviews of cumulative effects assessment (CEA) methods focused on approaches used by practitioners. Academic research has developed several distinct and novel approaches to conducting CEA. Understanding the suite of methods that exist will help practitioners and academics better address various ecological foci (physiological responses, population impacts, ecosystem impacts) and ecological complexities (synergistic effects, impacts across space and time). We reviewed 6 categories of methods (experimental, meta‐analysis, single‐species modeling, mapping, qualitative modeling, and multispecies modeling) and examined the ability of those methods to address different levels of complexity. We focused on research gaps and emerging priorities. We found that no single method assessed impacts across the 4 ecological foci and 6 ecological complexities considered. We propose that methods can be used in combination to improve understanding such that multimodel inference can provide a suite of comparable outputs, mapping methods can help prioritize localized models or experimental gaps, and future experiments can be paired from the outset with models they will inform.