bluuebunny/crossref_metadata_2025_split huggingface dataset:
A population analysis of the DGAT1 inhibitor GSK3008356 and its effect on endogenous and meal‐induced triglyceride turnover in healthy subjects
Authors: Okour Malek , Brigandi Richard A. , Tenero David 
Published: February 2019

AbstractNon‐alcoholic steatohepatitis (NASH) is a liver disease in which fatty infiltration is accompanied by liver inflammation. GSK3008356 is under development as a selective inhibitor of diacylglycerol acyltransferase 1 (DGAT1), a key enzyme involved in the formation of triglyceride (TG). Decreased DGAT1 activity can reduce circulating TG and liver TG, and therefore could potentially prevent or treat NASH. The aim of the current study was to develop a population pharmacokinetic–pharmacodynamic (PKPD) model that characterizes the PK disposition of GSK3008356 and its relation to the changes in blood TG. Drug concentrations were measured in 104 healthy adults receiving various single (SD) and repeat doses (RD) in a first time in human (FiH) study. A 30% fat meal was given at hour 2 postdose, and blood postprandial TG concentrations were measured at various time points. The population PKPD model consists of several parts including a PK model, drug effect model, meal effect model, and a turnover model. The pharmacokinetic data were described using a 3‐compartment model. Drug effect was described by an inhibitory sigmoidal Emax model. Since TG levels change with the introduction of a meal, a bi‐exponential meal effect model was utilized. The total change in TG was fitted using a turnover model with drug and meal effects on the TG production rate. The current analysis presents a PKPD modeling strategy of time‐varying TG data coming from both endogenous and exogenous sources. In general, the presented model could be utilized in the model‐based drug development of drugs that influence TG levels in blood.
The structural features of Acetobacterium woodii F‐ATP synthase reveal the importance of the unique subunit γ‐loop in Na+ translocation and ATP synthesis
Authors: Bogdanović Nebojša , Trifunović Dragan , Sielaff Hendrik , Westphal Lars , Bhushan Shashi , Müller Volker , Grüber Gerhard 
Published: February 2019

The Na+translocating F1FO ATP synthase from Acetobacterium woodii shows a subunit stoichiometry of α3:β3:γ:δ:ε:a:b2:(c2/3)9:c1 and reveals an evolutionary path between synthases and pumps involving adaptations in the rotor c‐ring, which is composed of F‐ and vacuolar‐type c subunits in a stoichiometry of 9 : 1. This hybrid turbine couples rotation with Na+ translocation in the FO part and rotation of the central stalk subunits γ‐ε to drive ATP synthesis in the catalytic α3:β3 headpiece. Here, we isolated a highly pure recombinant A. woodii F‐ATP synthase and present the first projected structure of this hybrid engine as determined by negative‐stain electron microscopy and single‐particle analysis. The uniqueness of the A. woodii F‐ATP synthase is also reflected by an extra 17 amino acid residues loop (195TSGKVKITEETKEEKSK211) in subunit γ. Deleting the loop‐encoding DNA sequence (γΔ195–211) and purifying the recombinant F‐ATP synthase γΔ195–211 mutant provided a platform to study its effect in enzyme stability and activity. The recombinant F‐ATP synthase γΔ195–211 mutant revealed the same subunit composition as the wild‐type enzyme and a minor reduction in ATP hydrolysis. When reconstituted into proteoliposomes ATP synthesis and Na+ transport were diminished, demonstrating the importance of the γ195–211 loop in both enzymatic processes. Based on a structural model, a coupling mechanism for this enzyme is proposed, highlighting the role of the γ‐loop. Finally, the γ195–211 loop of A. woodii is discussed in comparison with the extra γ‐loops of mycobacterial and chloroplasts F‐ATP synthases described to be involved in species‐specific regulatory mechanisms.
Lower photorespiration in elevated CO2 reduces leaf N concentrations in mature Eucalyptus trees in the field
Authors: Wujeska‐Klause Agnieszka , Crous Kristine Y. , Ghannoum Oula , Ellsworth David S. 
Published: February 2019

AbstractRising atmospheric CO2 concentrations is expected to stimulate photosynthesis and carbohydrate production, while inhibiting photorespiration. By contrast, nitrogen (N) concentrations in leaves generally tend to decline under elevated CO2 (eCO2), which may reduce the magnitude of photosynthetic enhancement. We tested two hypotheses as to why leaf N is reduced under eCO2: (a) A “dilution effect” caused by increased concentration of leaf carbohydrates; and (b) inhibited nitrate assimilation caused by reduced supply of reductant from photorespiration under eCO2. This second hypothesis is fully tested in the field for the first time here, using tall trees of a mature Eucalyptus forest exposed to Free‐Air CO2 Enrichment (EucFACE) for five years. Fully expanded young and mature leaves were both measured for net photosynthesis, photorespiration, total leaf N, nitrate () concentrations, carbohydrates and reductase activity to test these hypotheses. Foliar N concentrations declined by 8% under eCO2 in new leaves, while the fraction and total carbohydrate concentrations remained unchanged by CO2 treatment for either new or mature leaves. Photorespiration decreased 31% under eCO2 supplying less reductant, and in situ reductase activity was concurrently reduced (−34%) in eCO2, especially in new leaves during summer periods. Hence, assimilation was inhibited in leaves of E. tereticornis and the evidence did not support a significant dilution effect as a contributor to the observed reductions in leaf N concentration. This finding suggests that the reduction of reductase activity due to lower photorespiration in eCO2 can contribute to understanding how eCO2‐induced photosynthetic enhancement may be lower than previously expected. We suggest that large‐scale vegetation models simulating effects of eCO2 on N biogeochemistry include both mechanisms, especially where is major N source to the dominant vegetation and where leaf flushing and emergence occur in temperatures that promote high photorespiration rates.
Wild halophytic species as forage sources: Key aspects for plant breeding
Authors: Marinoni Lorena del Rosario , Zabala Juan Marcelo , Taleisnik Edith Liliana , Schrauf Gustavo Enrique , Richard Geraldina Alicia , Tomas Pablo Andrés , Giavedoni Julio Alberto , Pensiero José Francisco 
Published: February 2019

AbstractThe use of wild halophytic species as forage resources in saline environments has gained increasing attention. Argentina ranks third in area of saline soils in the world, with a third of its territory showing various degrees of salinity, sodicity and/or alkalinity. On this type of soils, rangelands are the main forage resource for livestock production. Many wild species have forage potential and can also be used for the rehabilitation of rangelands and for intercropping. Information about these species, as well as on the physiological and genetic bases associated with salinity tolerance, provides relevant tools for efficient selection methods. This study addresses Argentine wild halophyte species with forage potential and describes selection criteria with an emphasis on the following taxa: (a) Poaceae: subfamily Chloridoideae and tribes Paniceae and Triticeae, (b) Fabaceae and (c) Amaranthaceae (formerly known as Chenopodiaceae). The review is intended to contribute to the general discussion on strategies for the improvement of wild plant genetic resources, using forage species naturally growing in saline soils in Argentina as a case study.
Clinical outcomes of kidney transplantation in older end‐stage renal disease patients: A nationwide cohort study
Authors: Ko Eun Jeong , Yang Jaeseok , Ahn Curie , Kim Myoung Soo , Han Duck Jong , Kim Sung Joo , Yang Chul Woo , Chung Byung Ha ,   the Korean Organ Transplantation Registry Study Group
Published: February 2019

AimThe aim of the present study was to investigate the clinical outcomes of kidney transplantation (KT) in elderly recipients compared with those in young recipients.MethodsWe compared the incidence of biopsy‐proven acute rejection, death‐censored allograft survival and all‐cause mortality, and also compared the impact of high sensitization or desensitization on the clinical outcomes of elderly and young recipients.ResultsA total of 4966 KT recipients from the Korean Organ Transplantation Registry were included. The definition of elderly recipients was based on age >60 years (n = 356), and recipients aged <60 years were defined as young recipients (n = 4610). The incidence of biopsy‐proven acute rejection did not differ between the two groups irrespective of the donor type; however, the impact of high sensitization was significant only in young recipients. Being an elderly recipient was an independent risk factor for death‐censored allograft failure in terms of overall and living donor KT, but not with deceased donor KT. In regard to patient death, being an elderly recipient was a significant predictor in general and in the two subgroups, and desensitization showed a significant interaction with death in the elderly recipients in the living donor KT group.ConclusionsIn conclusion, KT in elderly recipients might be associated with poor allograft or patient survival in general, and especially, desensitization therapy carried out in these patients might increase the risk of patient mortality. Geriatr Gerontol Int 2019; 19: 392–398.
Maritime labour, transnational political trajectories and decolonization from below: the opposition to the 1935 British Shipping Assistance Act
Authors: FEATHERSTONE DAVID 
Published: February 2019

AbstractThis article uses a discussion of struggles over attempts by the National Union of Seamen to exclude seafarers from the maritime labour market in the inter‐war period to contribute to debates at the intersection of maritime spaces and transnational labour geographies (cf. Balachandran 2012; Høgsbjerg 2013). By focusing on struggles engendered by the British Shipping (Assistance) Act of 1935, I explore some of the transnational dynamics through which racialized forms of trade unionism were contested. I argue that the political trajectories, solidarities and organizing spaces constructed by the alliances formed to oppose the effects of the act shaped articulations of ‘decolonization from below’ (James 2015). In this way, engaging with the political trajectories and activities of activists from organizations like the Colonial Seamen's Association can reveal new ways of understanding the spatial politics of decolonization and new accounts of who or how such processes were articulated and contested. I conclude the article by arguing that engagement with these struggles can help assert the importance of forms of subaltern agency in shaping processes of decolonization.
Effects of calcium application on the salt tolerance and sodium excretion from salt glands in zoysiagrass (Zoysia japonica)
Authors: Maeda Yoshiyuki 
Published: February 2019

AbstractZoysiagrass (Zoysia japonica Steud.), a native grass in Japan, is a warm‐season turfgrass displaying high salt tolerance, mainly derived from salt excretion through salt glands. The present study focused on how external calcium (Ca) affects sodium (Na) excretion from salt glands to relieve salt stress, including response to oxidative stress, and discussed the physiological mechanisms possibly involved. Treatments using 0, 25, 50, 75, 100, 125 and 150 mmol/L sodium chloride (NaCl), with or without applying 2 or 10 mmol/L calcium chloride (CaCl2), were conducted for seven days. Growth inhibition and an abrupt increase in Na excretion from salt glands occurred above 100 mmol/L NaCl treatment, while Na concentrations in shoot and root tissues increased with increasing NaCl concentration from 0 to 75 mmol/L treatment. Above 100 mmol/L NaCl treatment, pectic acid‐binding Ca and glycinebetaine concentrations decreased in shoot and root tissues, but free proline concentration and the activities of plasmalemma ATPase, catalase (CAT) and ascorbate peroxidase (APX) increased. Calcium application alleviated growth inhibition when added to high level of NaCl treatments (over 100 mmol/L NaCl). Compared to the treatment without Ca, Na concentration in shoot and root tissues and ATPase activity in the root decreased, but Na exclusion from salt glands, pectic acid‐binding Ca concentration in shoot and root tissues, and ATPase, CAT and APX activities in the shoot increased. Thus, Na excretion through salt glands seems to occur when Na concentration in the plant exceeds its accumulation limit, and this salt tolerance reaction involving salt glands proceeds in two steps: the grass absorbs and accumulates Na in the shoot and root up to a threshold, above which Na is removed through salt glands. Calcium application promoted Na excretion through salt glands, especially under growth‐inhibiting Na concentrations, which might be induced by the increase in extracellular excretion of Na by plasmalemma ATPase.
Early use of PEPA dialyzer for light chains removal and for the recovery from myeloma cast nephropathy: A case report
Authors: Donati Gabriele , Zappulo Fulvia , Croci Chiocchini Anna Laura , Comai Giorgia , Zamagni Elena , La Manna Gaetano 
Published: February 2019

AbstractChemotherapy and extracorporeal treatment reduce serum free light chains (FLCs) allowing the recovery of acute kidney injury (AKI) caused by myeloma cast nephropathy (MCN). We report the first case of recovery from AKI in a patient with MCN who underwent the removal of FLCs using the PEPA filter, with an undisclosed cut‐off, combined with chemotherapy for multiple myeloma (MM).
Beyond citizen and subject: New perspectives on political thought, “tribe,” and “indirect rule” in Africa
Authors: Visana Vikram 
Published: February 2019

AbstractDespite the extensive literature on “tribe” and “indirect rule” in colonial Africa, historians have tended to confine their analyses to the economic and administrative pragmatism of empire‐builders, the domination of colonial knowledge, and the mediation of these factors by African culture‐brokers who brandished local “tradition” in order to satisfy a range of local material interests. This essay shows that these arguments replicate colonial views that bifurcated Africa into incommensurable spheres of “modern” European agency and “traditional” African response. Placing the existing scholarship of African colonial history in dialogue with Indian intellectual history and African film studies, I propose that dyadic understandings of “tribe” and “indirect‐rule” can be overcome in order to reposition Africa and its institutions at the heart of a global narrative of “modernisation.” In considering this new perspective, the essay invites students and scholars of African history and political science to recognise that—for some—“tribe” was a constituent part of a uniquely African vision of future progress rather than a premodern anachronism or a tool of Western epistemological dominance.
Anaplastic lymphoma kinase expression in small‐cell lung cancer
Authors: Kondoh Chiaki , Horio Yoshitsugu , Hayashi Yuko , Ebi Hiromichi , Hida Toyoaki , Hasegawa Yoshinori , Yatabe Yasushi 
Published: February 2019

AimsAnaplastic lymphoma kinase (ALK) immunohistochemistry has shifted from being a screening tool to being a sole determinant for ALK‐targeted therapy. Recent articles have referred to small‐cell lung cancer (SCLC) transformation as a resistance mechanism after ALK inhibitor treatments, but few reports have addressed ALK expression in treatment‐naive SCLC in a comprehensive manner. Therefore, we examined ALK expression and the mechanisms in treatment‐naive SCLCs.Methods and resultsWe examined ALK expression in a consecutive series of SCLC tumours, and the expression mechanism was analysed regarding gene rearrangement, copy number changes, and point mutations. We also examined whether SCLC with ALK expression can be suppressed by crizotinib treatment in vitro. Immunohistochemical results revealed that ALK was expressed in 16 of 142 (11.3%) SCLCs. The expression was focal and less intense, which is in contrast to strong and uniform expression in adenocarcinoma with ALK rearrangement. Two combined SCLCs showed a positive reaction restricted to the SCLC component. None of the known genetic alterations, including rearrangement, amplification, copy number gain, or point mutations, were associated with ALK expression. A SCLC cell line, SKLC2, which expressed ALK without known genetic alterations, was not inhibited by a practically achievable serum concentration of crizotinib.ConclusionsAnaplastic lymphoma kinase immunohistochemistry for treatment‐naive SCLCs should not be used as a predictive biomarker for ALK inhibitor therapy, because the positive reactions were due to intrinsic expression of normal ALK transcript.
Self-rated health and medicine beliefs among older hospital outpatients in Hong Kong
Authors: Wan Bosco , Ball Patrick , Jackson David , Maynard Gregg 
Published: February 2019

Abstract

Objectives
(1) To identify any demographic characteristics, which predict medicines adherence by reporting Necessity-Concern Differential (NCD) and Self-Reported Health (SRH) scores among Hong Kong hospital outpatients. (ii) To investigate any association between SRH and NCD in this cultural group.

Methods
A total of 709 outpatients completed a questionnaire consisting demographic information, SRH and Belief about Medicines Questionnaire. Findings were analysed statistically.

Key findings
Descriptive statistics suggested that older participants (mean age &gt; 64 years) tended to report low SRH, but high NCD compared to younger respondents (mean age &lt; 53 years). Males were more likely to return high SRH and NCD scores than females (56.9 versus 42.2% and 74.8 versus 64.6%, respectively). Chi-squared tests demonstrated that socio-economic status was not significantly associated with SRH and NCD reporting (P &gt; 0.05). Logistic regressions indicated gender and age groups (young-old and old-old) were significant predictors of SRH reporting (P &lt; 0.001). Moreover, patients with high SRH were more likely to report high NCD than those with low SRH (P = 0.02; OR = 1.53; 95%CI 1.07–2.20). This indicates that regular administration of the SRH item followed by specific questioning could enhance early identification of potential medicine non-believers and, subsequently, non-adherent patients who may require urgent interventions or monitoring.

Conclusions
Demographic characteristics and significant association between SRH and NCD reporting support our claim that SRH opens new opportunities for prompt identification of potentially non-adherent patients. However, further interviews to determine the cause(s) of non-adherence are necessary to validate such findings.
Transparent CaF2 surface crystallized CaO–2B2O3 glass possessing efficient photocatalytic and antibacterial properties
Authors: Singh Gurpreet , Kumar Sandeep , Sharma Moolchand , Vaish Rahul 
Published: February 2019

AbstractThis study aims to fabricate surface crystallized transparent calcium borate glass (CaO–2B2O3) for photocatalytic and antibacterial applications. The CaO–2B2O3 glass was fabricated by using the conventional melt‐quenching technique. Instead of using traditional high temperature and longer soaking time heat‐treatment, the acid etching method was adopted to get surface crystallization. Surface etching of as‐quenched glass was performed at room temperature by using three different concentrations of hydrogen fluoride in order to attain the different amount of calcium fluoride crystals at the surface. The characterization of surface crystallized glass was performed with an X‐ray diffraction pattern and scanning electron microscope‐EDS mapping system. Sufficient transparency (65%) was retained even at highest crystallization of glass surface. Surface crystallization with CaF2 induces hydrophilicity and photocatalytic character in glasses which was evaluated with contact angle measurements and smart resazurin (Rz) ink test. Around 68% of methylene blue (MB) dye degradation was also displayed by the crystallized glass. Crystallized glasses portrayed good antibacterial property against Escherichia coli (gram‐negative bacteria). Ninety‐nine per cent of bacterial depletion was recorded in 3 hours exposure time with surface crystallized glass without any external intervention. Interesting morphological changes were observed in bacterial shape and physical appearance under field emission scanning electron microscope after exposure to crystallized glasses.
Work engagement and perceived work ability: An evidence‐based model to enhance nurses’ well‐being
Authors: Tomietto Marco , Paro Eleonora , Sartori Riccardo , Maricchio Rita , Clarizia Luciano , De Lucia Paola , Pedrinelli Giuseppe , Finos Rosanna ,   PN Nursing Group
Published: February 2019

AbstractAimsThe study aims are (a) to test a model developed to estimate the impact of work engagement on work ability as it is perceived by nurses; (b) to test the parameters between work ability and job satisfaction and between job satisfaction and turnover intention.DesignCross‐sectional.MethodsThis study involved 1,024 nurses from January ‐ May 2018. The response rate was 70.7%. The Work Ability Index and the Utrecht Work Engagement Scale were used. Path analysis was performed, both in the whole sample and in age categories (<45yy–≥45yy). Model's parameters and fit indexes were estimated.ResultsThe comprehensive model was validated through the multi‐group approach. Fit indexes were adequate in the general model and in the multi‐group testing. Parameters confirmed the association between work engagement and work ability and between work ability and job satisfaction and turnover intention. Parameters highlighted different age‐dependent patterns.ConclusionThis study states the contribution of work engagement to enhance work ability in nursing profession. Findings contribute in understanding motivational dynamics in nurses and they suggest the use of tailored strategies for different age categories. Further research could address the model to deepen generational patterns in work engagement, work ability, and organizational outcomes.ImpactThe study highlights how to address nursing management to improve nurses’ motivation and work ability and to improve organizational outcomes. Main findings point out different age‐dependent patterns to tailor managerial strategies. Healthcare organizations have new elements to design human resources management and to improve job satisfaction and nurses’ retention.
Support staff’s perceptions of discontinuing antipsychotics in people with intellectual disabilities in residential care: A mixed‐method study
Authors: Kleijwegt Bas , Pruijssers Addy , de Jong‐Bakker Lydie , de Haan Koos , van Os‐Medendorp Harmieke , van Meijel Berno 
Published: February 2019

AbstractBackgroundAlthough there is little evidence on their efficacy regarding challenging behaviour, antipsychotics are the most used psychotropic drugs in residential intellectually disabled people. Discontinuation is possible for some residential clients with intellectual disabilities. This study aimed to gain insight into support staff's perceptions of discontinuing antipsychotics in residential clients with intellectual disabilities.MethodFour focus groups were conducted in this mixed‐methods study, followed by a survey.ResultsA large majority of support staff perceive antipsychotics to be effective in controlling challenging behaviour. Support staff regarded themselves as willing to contribute to the discontinuation of antipsychotics, but were more confident about achieving reductions.ConclusionsThe attitude of the majority of support staff towards discontinuation provides a good basis for regularly reviewing antipsychotics use. A reduction plan should include preliminary steps, methods of monitoring and evaluating the process, and establishing measures for dealing with possible crises.