bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural neuroimaging correlates of alcohol and cannabis use in adolescents and adults
Authors: Thayer Rachel E. , YorkWilliams Sophie , Karoly Hollis C. , Sabbineni Amithrupa , Ewing Sarah Feldstein , Bryan Angela D. , Hutchison Kent E. 
Published: June 2017

AbstractBackground and AimsChronic alcohol use is associated with lower gray matter volume, and we reported recently that alcohol use showed negative associations with widespread gray matter (GM) volume even among young adults. The current study aimed to test the strength of association between (1) alcohol use and GM volume; (2) alcohol use and white matter (WM) integrity; (3) cannabis use and GM volume; and (4) cannabis use and WM integrity among adults and adolescents.Design and SettingGeneral linear models within large pooled cross‐sectional samples of adolescents and adults who had participated in studies collecting substance use and neuroimaging data in the southwestern United States.ParticipantsThe current analysis included adults aged 18–55 years (n = 853) and adolescents aged 14–18 years (n = 439) with a range of alcohol and cannabis use.MeasurementsThe dependent variable was GM volume or WM integrity, with key predictors of alcohol use [Alcohol Use Disorders Identification Test (AUDIT) score] and cannabis use (past 30‐day use).FindingsAlcohol use showed large clusters of negative associations (ηp2 = 0.028–0.145, P < 0.001) with GM volume among adults and to a lesser extent (one cluster; ηp2 = 0.070, P < 0.05) among adolescents. Large clusters showed significant associations (ηp2 = 0.050–0.124, P < 0.001) of higher alcohol use with poorer WM integrity, whereas adolescents showed no significant associations between alcohol use and WM. No associations were observed between structural measures and past 30‐day cannabis use in adults or adolescents.ConclusionsAlcohol use severity is associated with widespread lower gray matter volume and white matter integrity in adults, and with lower gray matter volume in adolescents.
Inhibition of JNK signalling mediates PPARα‐dependent protection against intrahepatic cholestasis by fenofibrate
Authors: Dai Manyun , Yang Julin , Xie Minzhu , Lin Jiao , Luo Min , Hua Huiying , Xu Gangming , Lin Hante , Song Danjun , Cheng Yuqing , Guo Bin , Zhao Jinshun , Gonzalez Frank J , Liu Aiming 
Published: June 2017

Background and PurposeFenofibrate, a PPARα agonist, is the most widely prescribed drug for treating hyperlipidaemia. Although fibrate drugs are reported to be beneficial for cholestasis, their underlying mechanism has not been determined.Experimental ApproachWild‐type mice and Pparα‐null mice were pretreated orally with fenofibrate for 3 days, following which α‐naphthylisothiocyanate (ANIT) was administered to induce cholestasis. The PPARα agonist WY14643 and JNK inhibitor SP600125 were used to determine the role of PPARα and the JNK pathway, respectively, in cholestatic liver injury. The same fenofibrate regimen was applied to investigate its beneficial effects on sclerosing cholangitis in a DDC‐induced cholestatic model.Key ResultsFenofibrate, 25 mg·kg−1 twice a day, totally attenuated ANIT‐induced cholestasis and liver injury as indicated by biochemical and histological analyses. This protection occurred in wild‐type, but not in Pparα‐null, mice. Alterations in bile acid synthesis and transport were found to be an adaptive response rather than a direct effect of fenofibrate. WY14643 attenuated ANIT‐induced cholestasis and liver injury coincident with inhibition of JNK signalling. Although SP600125 did not affect cholestasis, it inhibited liver injury in the ANIT model when the dose of fenofibrate used was ineffective. Fenofibrate was also revealed to have a beneficial effect in the sclerosing cholangitis model.Conclusions and ImplicationsThese data suggest that the protective effects of fenofibrate against cholestasis‐induced hepatic injury are dependent on PPARα and fenofibrate dose, and are mediated through inhibition of JNK signalling. This mechanism of fenofibrate protection against intrahepatic cholestasis may offer additional therapeutic opportunities for cholestatic liver diseases.
WMJ‐8‐B, a novel hydroxamate derivative, induces MDA‐MB‐231 breast cancer cell death via the SHP‐1‐STAT3‐survivin cascade
Authors: Chuang Yu‐Fan , Huang Shiu‐Wen , Hsu Ya‐Fen , Yu Meng‐Chieh , Ou George , Huang Wei‐Jan , Hsu Ming‐Jen 
Published: June 2017

Background and PurposeHistone deacetylase (HDAC) inhibitors have been demonstrate to have broad‐spectrum anti‐tumour properties and have attracted lots of attention in the field of drug discovery. However, the underlying anti‐tumour mechanisms of HDAC inhibitors remain incompletely understood. In this study, we aimed to characterize the underlying mechanisms through which the novel hydroxamate‐based HDAC inhibitor, WMJ‐8‐B, induces the death of MDA‐MB‐231 breast cancer cells.Experimental ApproachEffects of WMJ‐8‐B on cell viability, cell cycle distribution, apoptosis and signalling molecules were analysed by the MTT assay, flowcytometric analysis, immunoblotting, reporter assay, chromatin immunoprecipitation analysis and use of siRNAs. A xenograft model was used to determine anti‐tumour effects of WMJ‐8‐B in vivo.Key ResultsWMJ‐8‐B induced survivin reduction, G2/M cell cycle arrest and apoptosis in MDA‐MB‐231 cells. STAT3 phosphorylation, transactivity and its binding to the survivin promoter region were reduced in WMJ‐8‐B‐treated cells. WMJ‐8‐B activated the protein phosphatase SHP‐1 and when SHP‐1 signalling was blocked, the effects of WMJ‐8‐B on STAT3 phosphorylation and survivin levels were abolished. However, WMJ‐8‐B increased the transcription factor Sp1 binding to the p21 promoter region and enhanced p21 levels. Moreover, WMJ‐8‐B induced α‐tubulin acetylation and disrupted microtubule assembly. Inhibition of HDACs was shown to contribute to WMJ‐8‐B′s actions. Furthermore, WMJ‐8‐B suppressed the growth of MDA‐MB‐231 xenografts in mammary fat pads in vivo.Conclusions and ImplicationsThe SHP‐1‐STAT3‐survivin and Sp1‐p21 cascades are involved in WMJ‐8‐B‐induced MDA‐MB‐231 breast cancer cell death. These results also indicate the potential of WMJ‐8‐B as a lead compound for treatment of breast cancer and warrant its clinical development.
Tofacitinib restores the inhibition of reverse cholesterol transport induced by inflammation: understanding the lipid paradox associated with rheumatoid arthritis
Authors: Pérez‐Baos S , Barrasa J I , Gratal P , Larrañaga‐Vera A , Prieto‐Potin I , Herrero‐Beaumont G , Largo R 
Published: June 2017

Background and PurposePatients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The JAK inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analysed the effect of tofacitinib on the lipid profile of hyperlipidaemic rabbits with chronic arthritis (CA) and on the changes in reverse cholesterol transport (RCT) during chronic inflammation.Experimental ApproachCA was induced in previously immunized rabbits, fed a high‐fat diet, by administering four intra‐articular injections of ovalbumin. A group of rabbits received tofacitinib (10 mg·kg−1·day−1) for 2 weeks. Systemic and synovial inflammation and lipid content were evaluated. For in vitro studies, THP‐1‐derived macrophages were exposed to high lipid concentrations and then stimulated with IFNγ in the presence or absence of tofacitinib in order to study mediators of RCT.Key ResultsTofacitinib decreased systemic and synovial inflammation and increased circulating lipid levels. Although it did not modify synovial macrophage density, it reduced the lipid content within synovial macrophages. In foam macrophages in culture, IFNγ further stimulated intracellular lipid accumulation, while the JAK/STAT inhibition provoked by tofacitinib induced lipid release by increasing the levels of cellular liver X receptor α and ATP‐binding cassette transporter (ABCA1) synthesis.Conclusions and ImplicationsActive inflammation could be associated with lipid accumulation within macrophages of CA rabbits. JAK inhibition induced lipid release through RCT activation, providing a plausible explanation for the effect of tofacitinib on the lipid profile of RA patients.
The hydrophobic side chain of oseltamivir influences type A subtype selectivity of neuraminidase inhibitors
Authors: Lin Xiong , Qin‐Hua Chen , Peng Li , Chun‐Lei Li , Guang‐De Yang 
Published: June 2017

Neuraminidase, which plays a critical role in the influenza virus life cycle, is a target for new therapeutic agents. The study of structure–activity relationships revealed that the C‐5 position amino group of oseltamivir was pointed to 150‐cavity of the neuraminidase in group 1. This cavity is important for selectivity of inhibitors against N1 versus N2 NA. A serial of influenza neuraminidase inhibitors with the oseltamivir scaffold containing lipophilic side chains at the C‐5 position have been synthesized and evaluated for their influenza neuraminidase inhibitory activity and selectivity. The results indicated that compound 13o (H5N1 IC50 = 0.1 ± 0.04 μm, H3N2 IC50 = 0.26 ± 0.18 μm) showed better inhibitory activity and selectivity against the group 1 neuraminidase. This study may provide a clue to design of better group 1 neuraminidase inhibitors.
A habitat‐based approach to predict impacts of marine protected areas on fishers
Authors: Teixeira João B. , Moura Rodrigo L. , Mills Morena , Klein Carissa , Brown Christopher J. , Adams Vanessa M. , Grantham Hedley , Watts Matthew , Faria Deborah , Amado‐Filho Gilberto M. , Bastos Alex C. , Lourival Reinaldo , Possingham Hugh P. 
Published: June 2017

AbstractAlthough marine protected areas can simultaneously contribute to biodiversity conservation and fisheries management, the global network is biased toward particular ecosystem types because they have been established primarily in an ad hoc fashion. The optimization of trade‐offs between biodiversity benefits and socioeconomic values increases success of protected areas and minimizes enforcement costs in the long run, but it is often neglected in marine spatial planning (MSP). Although the acquisition of spatially explicit socioeconomic data is perceived as a costly or secondary step in MSP, it is critical to account for lost opportunities by people whose activities will be restricted, especially fishers. We developed an easily reproduced habitat‐based approach to estimate the spatial distribution of opportunity cost to fishers in data‐poor regions. We assumed the most accessible areas have higher economic and conservation values than less accessible areas and their designation as no‐take zones represents a loss of fishing opportunities. We estimated potential distribution of fishing resources from bathymetric ranges and benthic habitat distribution and the relative importance of the different resources for each port of total catches, revenues, and stakeholder perception. In our model, we combined different cost layers to produce a comprehensive cost layer so that we could evaluate of trade‐offs. Our approach directly supports conservation planning, can be applied generally, and is expected to facilitate stakeholder input and community acceptance of conservation.
Towards “cognitively complex” problem‐solving: Six models of public service reform
Authors: McCourt Willy 
Published: June 2017

AbstractThis article proposes “cognitively complex problem‐solving” as a refinement of the recent problem‐solving approach to public service reform, and as an addition to existing political and institutional explanations for the frequent failure of reform. It substantiates the new problem‐solving model by identifying and selectively reviewing six models of reform that have been practised in developing countries over the past half‐century: public administration, decentralization, pay and employment reform, New Public Management, integrity and corruption reforms and “bottom‐up” reforms. A short case study of Myanmar is presented to illustrate the problem‐solving approach in practice.
Who bears the burden of bribery? Evidence from public service delivery in Kenya
Authors: Mbate Michael 
Published: June 2017

AbstractThis article empirically examines how an individual's economic, social and political capital affects their propensity to make bribe payments in exchange for public services. Using an individual‐level survey on bribes, the econometric results suggest that the burden of bribery is borne by the poor, but substantially decreases when institutions that constrain bureaucratic corruption are strong and effective. The results also show that the incidence of bribery decreases when social capital is high but increases when political networks are prevalent. These findings support the need to combine anti‐corruption reforms with poverty reduction strategies and social policies in order to foster equity in public services provision in Kenya.
The impact of higher education expansion on intergenerational mobility
Authors: Li Zhi , Zhong Hai 
Published: June 2017

AbstractThe persistent correlations between parents and children's outcomes have long been investigated. From a policy perspective, it is important to understand the underlying causes of those correlations. Educational policy changes may have significant impacts on intergenerational mobility. The last several decades have witnessed a remarkable expansion of higher education around the world. In this paper, we examine the effect of higher education expansion on intergenerational mobility in China. We find that the higher education expansion in China has weakened the advantage of cadres’ children in higher education participation, and has strengthened the intergenerational educational correlation. One explanation for these results might be that, along with the process of economic reform started in 1979, the cadre selection mechanism has placed more and more weight on candidate's education and abilities.
Congenital unilateral facial nerve paralysis in a Warmblood filly
Authors: Schön S. , Wehrli Eser M. , Kircher P. R. , Sydler T. , Augsburger H. , Ohlerth S. , Beckmann K. , Fürst A. E. 
Published: June 2017

SummaryA 17‐month‐old Warmblood filly was referred to our clinic for evaluation of congenital facial nerve (FN) paralysis. Clinical examination revealed a right‐sided facial paralysis with mild masticatory muscle atrophy, mild dysphagia and exposure keratitis. Apart from the FN deficits, neurological examination of the remaining cranial nerves showed no abnormalities. Magnetic resonance imaging (MRI) examination using a 3.0 Tesla scanner showed that in comparison to the left FN, the intracranial section of the right FN between the pons and internal acoustic canal was thinner, whereas it appeared indistinct and thickened within the internal acoustic canal and facial canal. Signs of meningitis or encephalitis were not present on MRI. Cerebrospinal fluid analysis showed mild pleocytosis. The owner of the filly requested euthanasia due to the guarded prognosis. At necropsy, the intracranial section of the right FN was macroscopically thinner than the left side and within the facial canal, a 5 mm tissue stump could be identified with an absent extracranial part of the right FN. Histological examination of the brain stem showed different architecture of the left and right motor nuclei of the FN: in the left nucleus, motor neurons of a normal size and well stainable Nissl bodies were present, whereas in the right nucleus, neurons with Nissl bodies were decreased in number and size. Further, a cytoplasmic rich cell population with a nucleus size compatible with normal neurons was present. These cells were suspected to be atrophic neurons. The tissue stump within the facial canal was histologically identified as connective tissue. Unilateral malformation of the FN has not previously been described in the horse. This filly showed a right‐sided, intracranial hypoplasia accompanied by an extracranial aplasia of the FN causing complete, congenital facial nerve paralysis, which corresponded to a difference in the architecture of the affected motor nucleus of the FN.
Aryepiglottic lymphoma in a 19‐year‐old Paint gelding treated with excision and adjunctive radiotherapy
Authors: Pezzanite L. M. , Leary D. M. , LaRue S. M. , Hackett E. S. 
Published: June 2017

SummaryThis case report describes the diagnosis and treatment of an aryepiglottic tumour in a 19‐year‐old Paint gelding. Diagnostic work‐up included physical examination, endoscopic evaluation of the upper airway, and histopathology of the mass following removal. Treatment consisted of surgical excision of the aryepiglottic mass under endoscopic guidance followed by a 100 Gy dose of radiation delivered with strontium‐90 plesiotherapy to the surgical bed at 72 h post‐operatively. The radiation applicator was passed through the left nostril and the application area was confirmed via endoscopic evaluation. Histopathology, including immunohistochemistry, confirmed that the aryepiglottic tumour was T cell lymphoma. Recheck examination, including physical examination and upper airway endoscopy, was performed 1, 3 and 6 months following treatment and local recurrence was not observed. Local control with minimal morbidity can be achieved with surgical excision of equine lymphoma followed by strontium‐90 plesiotherapy.
Progress in Nd3+, Er3+, and Yb3+ doped laser glasses at Shanghai Institute of Optics and Fine Mechanics
Authors: Zhang Liyan , Hu Lili , Jiang Shibin 
Published: June 2017

AbstractThis paper reviews the progress made on Nd3+, Er3+, and Yb3+ doped laser glasses at SIOM, China. Key properties of Nd: phosphate and Nd: fluorophosphate (FP) laser glasses are presented and compared with the commercial laser glasses from Hoya and Schott. Also reviewed are properties of four types of Er: phosphate glasses. The development of a continuous, large‐scale melting platform producing high‐quality Nd: phosphate laser glass at SIOM is briefly described. Our study on the Stark splitting of Yb3+: 2F7/2 level indicates that mixed‐glass formers can significantly improve the Stark splitting, resulting enhancement of lasing performance of Yb: phosphate glass.
Vaccine candidate discovery for the next generation of malaria vaccines
Authors: Tuju James , Kamuyu Gathoni , Murungi Linda M. , Osier Faith H. A. 
Published: June 2017

SummaryAlthough epidemiological observations, IgG passive transfer studies and experimental infections in humans all support the feasibility of developing highly effective malaria vaccines, the precise antigens that induce protective immunity remain uncertain. Here, we review the methodologies applied to vaccine candidate discovery for Plasmodium falciparum malaria from the pre‐ to post‐genomic era. Probing of genomic and cDNA libraries with antibodies of defined specificities or functional activity predominated the former, whereas reverse vaccinology encompassing high throughput in silico analyses of genomic, transcriptomic or proteomic parasite data sets is the mainstay of the latter. Antibody‐guided vaccine design spanned both eras but currently benefits from technological advances facilitating high‐throughput screening and downstream applications. We make the case that although we have exponentially increased our ability to identify numerous potential vaccine candidates in a relatively short space of time, a significant bottleneck remains in their validation and prioritization for evaluation in clinical trials. Longitudinal cohort studies provide supportive evidence but results are often conflicting between studies. Demonstration of antigen‐specific antibody function is valuable but the relative importance of one mechanism over another with regards to protection remains undetermined. Animal models offer useful insights but may not accurately reflect human disease. Challenge studies in humans are preferable but prohibitively expensive. In the absence of reliable correlates of protection, suitable animal models or a better understanding of the mechanisms underlying protective immunity in humans, vaccine candidate discovery per se may not be sufficient to provide the paradigm shift necessary to develop the next generation of highly effective subunit malaria vaccines.
Interferon‐β regulates dendritic cell activation and migration in experimental autoimmune encephalomyelitis
Authors: Pennell Leesa M. , Fish Eleanor N. 
Published: June 2017

SummaryCD11c+ dendritic cells (DCs) exert a critical role as antigen‐presenting cells in regulating pathogenic T cells in multiple sclerosis (MS). To determine whether the therapeutic benefit of interferon‐β (IFN‐β) treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DCs derived from IFN‐β+/+ and IFN‐β−/− mice using a myelin oligodendrocyte glycoprotein (MOG) peptide‐induced mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our earlier work identified that IFN‐β−/− mice exhibit earlier onset and more rapid progression of neurological impairment compared with IFN‐β+/+ mice. In this study we show that lipopolysaccharide‐/MOG peptide‐stimulated IFN‐β−/− DCs secrete cytokines associated with pathological T helper type 17 rather than regulatory T‐cell polarization and exhibit increased CD80 and MHCII expression when compared with stimulated IFN‐β+/+ DCs. IFN‐β−/− DCs from mice immunized to develop EAE induce greater proliferation of MOG‐transgenic CD4+ T cells and promote interleukin‐17 production by these T cells. Adoptive transfer of MOG peptide‐primed IFN‐β−/− DCs into IFN‐β+/+ and IFN‐β−/− mice immunized to develop EAE resulted in their rapid migration into the central nervous system of recipient mice, before onset of disease, which we attribute to failed signal transducer and activator of transcription 1‐mediated inhibition of CCR7. Taken together, our data support immunoregulatory roles for IFN‐β in the activation and migration of DCs during EAE.
Views of mental health consumers about being involved in nursing handover on acute inpatient units
Authors: Olasoji Michael , Plummer Virginia , Reed Fiona , Jacob Sini , Shaw Liam , Shanti Michelle , Cross Wendy 
Published: June 2017

AbstractThe involvement of consumers in handover with nurses has been identified as reducing miscommunication and a reduction in adverse events in generalist nursing settings. Mental health (MH) care is complex, and handover practices need to fit with the philosophy of recovery‐focussed practice. Recovery‐focussed practice recognizes the person at the centre of care as an expert in their own treatment and decision‐making. The aim of the present study was to explore the views of consumers with a mental illness, without prior involvement in nursing handover, about their need to be involved in nursing handover on an acute mental health inpatient unit. Using an exploratory descriptive, qualitative design (n = 11), participants who were receiving care in an acute inpatient unit were recruited using purposive convenience sampling. Data were collected using semistructured interviews and analysed using thematic analysis. Participants' diagnoses were schizophrenia (n = 6), bipolar affective disorder (n = 4), and depression (n = 1). Two themes emerged from the interviews: (i) behind closed doors; and (ii) being involved. Several subthemes were also identified. The first theme, behind closed doors, had two subthemes: (i) it is about us; and (ii) knowing their thoughts. The second theme had three subthemes: (i) clarifying issues; (ii) setting expectations; and (iii) when and how. Nursing handover on the acute inpatient unit offers a good opportunity for consumers to take an active role in the delivery of nursing care. There is a need to rethink the way nursing handover occurs to include consumers.