bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of triggering receptor expressed on myeloid cells‐1 in the population with obesity and insulin resistance
Authors: Subramanian Saravanan , Pallati Pradeep K. , Rai Vikrant , Sharma Poonam , Agrawal Devendra K. , Nandipati Kalyana C. 
Published: January 2017

ObjectiveTriggering receptor expressed on myeloid cells (TREM)−1 has recently been recognized as one of the potent amplifiers of acute and chronic inflammation. However, the exact role of TREM‐1 in regard to insulin insensitivity is unknown.MethodsmRNA transcripts and protein expression of TREM‐1, TREM‐2, and TREM‐1/TREM‐2 ratio were examined in the tissue biopsies (liver, omentum, and subcutaneous fat) and blood samples (neutrophils and monocytes) of subjects with obesity and diabetes (SO+ D+; n = 15), subjects with obesity but not diabetes (SO+ D−; n = 7), and subjects without obesity (BMI < 30) and diabetes (SO−D−; n = 5).ResultsThe immunofluorescence and RT‐PCR revealed significant increase in TREM‐1, decrease in TREM‐2, and increase in the TREM1/TREM2 ratio in SO+ D+ group compared with other groups. Overall, increased liver TREM‐1 expression and soluble‐TREM‐1 were found in SO+ D+ group compared with SO+ D− group (100% vs. 57.14%, r = 0.582; P = 0.023). TREM‐1 was significantly increased in all subjects with obesity and those with HOMA‐IR index of >2.ConclusionsTREM‐1 was found to be significantly higher in tissues biopsies and blood of subjects with obesity. Greater expression and activity of TREM‐1 suggest a possible role in the underlying pathophysiology of obesity and associated comorbidities.
Synthesis of C2‐Symmetric Diphosphormonoamidites and Their Use as Ligands in Rh‐Catalyzed Hydroformylation: Relationships between Activity and Hydrolysis Stability
Authors: Morales Torres Galina , Behrens Stephan , Michalik Dirk , Selent Detlef , Spannenberg Anke , Lühr Susan , Dyballa Katrin Marie , Franke Robert , Börner Armin 
Published: January 2017

AbstractA series of diphosphoramidites has been synthetized with a piperazine, homopiperazine, and an acyclic 1,2‐diamine unit in the backbone. New compounds were tested alongside related N‐acyl phosphoramidites as ligands in the Rh‐catalyzed hydroformylation of n‐octenes to investigate their influence on the activity and regioselectivity. A subsequent study of their hydrolysis stability revealed that the most stable ligands induced the highest activity in the catalytic reaction.
MDM4 is a rational target for treating breast cancers with mutant p53
Authors: Miranda Panimaya Jeffreena , Buckley Daniel , Raghu Dinesh , Pang Jia‐Min B , Takano Elena A , Vijayakumaran Reshma , Teunisse Amina FAS , Posner Atara , Procter Tahlia , Herold Marco J , Gamell Cristina , Marine Jean‐Christophe , Fox Stephen B , Jochemsen Aart , Haupt Sue , Haupt Ygal 
Published: January 2017

AbstractMutation of the key tumour suppressor p53 defines a transition in the progression towards aggressive and metastatic breast cancer (BC) with the poorest outcome. Specifically, the p53 mutation frequency exceeds 50% in triple‐negative BC. Key regulators of mutant p53 that facilitate its oncogenic functions are potential therapeutic targets. We report here that the MDM4 protein is frequently abundant in the context of mutant p53 in basal‐like BC samples. Importantly, we show that MDM4 plays a critical role in the proliferation of these BC cells. We demonstrate that conditional knockdown (KD) of MDM4 provokes growth inhibition across a range of BC subtypes with mutant p53, including luminal, Her2+ and triple‐negative BCs. In vivo, MDM4 was shown to be crucial for the establishment and progression of tumours. This growth inhibition was mediated, at least in part, by the cell cycle inhibitor p27. Depletion of p27 together with MDM4 KD led to recovery of the proliferative capacity of cells that were growth‐inhibited by MDM4 KD alone. Consistently, we identified low levels of p27 expression in basal‐like tumours corresponding to high levels of MDM4 and p53. This predicts a signature for a subset of tumours that may be amenable to therapies targeted towards MDM4 and mutant p53. The therapeutic potential of MDM4 as a target in BC with mutant p53 was shown in vitro by use of a small‐molecule inhibitor. Overall, our study supports MDM4 as a novel therapeutic target for BC expressing mutant p53. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Investigating the heterogeneity of alkylating agents’ efficacy and toxicity between sexes: A systematic review and meta‐analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study)
Authors: Fresneau Brice , Hackshaw A. , Hawkins D.S. , Paulussen M. , Anderson J.R. , Judson I. , Litière S. , Dirksen U. , Lewis I. , van den Berg H. , Gaspar N. , Gelderblom H. , Whelan J. , Boddy A.V. , Wheatley K. , Pignon J.P. , De Vathaire F. , Le Deley M.C. , Le Teuff G. 
Published: January 2017

AbstractBackgroundA marginal interaction between sex and the type of alkylating agent was observed for event‐free survival in the Euro‐EWING99‐R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data meta‐analysis of RCTs assessing cyclophosphamide versus ifosfamide in any type of cancer.MethodsA literature search produced two more eligible RCTs (EICESS92 and IRS‐IV). The endpoints were progression‐free survival (PFS, main endpoint) and overall survival (OS). The hazard ratios (HRs) of the treatment‐by‐sex interaction and their 95% confidence interval (95% CI) were assessed using stratified multivariable Cox models. Heterogeneity of the interaction across age categories and trials was explored. We also assessed this interaction for severe acute toxicity using logistic models.ResultsThe meta‐analysis comprised 1,528 pediatric and young adult sarcoma patients from three RCTs: Euro‐EWING99‐R1 (n = 856), EICESS92 (n = 155), and IRS‐IV (n = 517). There were 224 PFS events in Euro‐EWING99‐R1 and 200 in the validation set (EICESS92 + IRS‐IV), and 171 and 154 deaths in each dataset, respectively. The estimated treatment‐by‐sex interaction for PFS in Euro‐EWING99‐R1 (HR = 1.73, 95% CI = 1.00–3.00) was not replicated in the validation set (HR = 0.97, 95% CI = 0.55–1.72), without heterogeneity across trials (P = 0.62). In the pooled analysis, the treatment‐by‐sex interaction was not significant (HR = 1.31, 95% CI = 0.89–1.95, P = 0.17), without heterogeneity across age categories (P = 0.88) and trials (P = 0.36). Similar results were observed for OS. No significant treatment‐by‐sex interaction was observed for leucopenia/neutropenia (P = 0.45), infection (P = 0.64), or renal toxicity (P = 0.20).ConclusionOur meta‐analysis did not confirm the hypothesis of a treatment‐by‐sex interaction on efficacy or toxicity outcomes.
Respiratory muscle training improves respiratory muscle endurance but not exercise tolerance in children with cystic fibrosis
Authors: Bieli Christian , Summermatter Selina , Boutellier Urs , Moeller Alexander 
Published: January 2017

SummaryBackgroundRespiratory muscle endurance (RME) training has been shown to increase exercise endurance and lung function in adults with cystic fibrosis (CF). We conducted an interventional study to investigate the effectiveness of RME training on CF‐related health outcomes in children.MethodsIn a crossover trial, 22 children, aged 9–18 years, with CF performed 8 weeks of RME training and standard chest physiotherapy in a randomized sequence separated by a 1 week washout period. All children underwent training sessions using the RME training device before beginning the study. The primary outcomes were RME (in minutes) and exercise endurance (in minutes). Data were analyzed according to the intention‐to‐treat principle.ResultsSixteen of 22 children (73%) completed the study. Study dropouts tended to be older with more advanced lung disease. After RME training, respiratory muscle endurance significantly increased by 7.03 ± 8.15 min (mean ± standard deviation, P < 0.001), whereas exercise endurance was unchanged by RME training (0.80 ± 2.58 min, P = 0.169). No significant improvement in secondary outcomes (lung function, CF quality of life, and CF clinical score) were observed. The small sample size and short intervention time have to be acknowledged as limitations of our study.ConclusionsRME training led to a significant increase in respiratory muscle endurance in children with CF. However, RME training did not improve exercise endurance or other CF‐related health outcomes. Thus, our results do not support the routine use of RME training in the care of children with CF. Future studies in larger populations and with prolonged intervention time may overcome the limitations of our study. Pediatr Pulmonol. 2017;52:331–336. © 2017 Wiley Periodicals, Inc.
High resolution crystal structures of human kynurenine aminotransferase‐I bound to PLP cofactor, and in complex with aminooxyacetate
Authors: Nadvi Naveed A. , Salam Noeris K. , Park Joohong , Akladios Fady N. , Kapoor Vimal , Collyer Charles A. , Gorrell Mark D. , Church William Bret 
Published: January 2017

AbstractIn this study, we report two high‐resolution structures of the pyridoxal 5′ phosphate (PLP)‐dependent enzyme kynurenine aminotransferase‐I (KAT‐I). One is the native structure with the cofactor in the PLP form bound to Lys247 with the highest resolution yet available for KAT‐I at 1.28 Å resolution, and the other with the general PLP‐dependent aminotransferase inhibitor, aminooxyacetate (AOAA) covalently bound to the cofactor at 1.54 Å. Only small conformational differences are observed in the vicinity of the aldimine (oxime) linkage with which the PLP forms the Schiff base with Lys247 in the 1.28 Å resolution native structure, in comparison to other native PLP‐bound structures. We also report the inhibition of KAT‐1 by AOAA and aminooxy‐phenylpropionic acid (AOPP), with IC50s of 13.1 and 5.7 μM, respectively. The crystal structure of the enzyme in complex with the inhibitor AOAA revealed that the cofactor is the PLP form with the external aldimine linkage. The location of this oxime with the PLP, which forms in place of the native internal aldimine linkage of PLP of the native KAT‐I, is away from the position of the native internal aldimine, with the free Lys247 substantially retaining the orientation of the native structure. Tyr101, at the active site, was observed in two conformations in both structures.
Systems, Networks, and Policy
Authors: Johnson Jeffrey , Fortune Joyce , Bromley Jane 
Published: January 2017

AbstractSystems theory is fundamental to understanding the dynamics of the complex social systems of concern to policy makers. A system is defined as: (1) an assembly of components, connected together in an organised way; (2) the components are affected by being in the system and the behaviour of the systems is changed if they leave it; (3) the organised assembly of components does something; and (4) the assembly has been identified as being of particular interest. Feedback is central to system behaviour at all levels, and can be responsible for systems behaving in complex and unpredictable ways. Systems can be represented by networks and there is a growing literature that shows how the behaviour of individuals is highly dependent on their social networks. This includes copying or following the advice of others when making decisions. Network theory gives insights into social phenomena such as the spread of information and the way people form social groups which then constrain their behaviour. It is emerging as a powerful way of examining the dynamics of social systems. Most systems relevant to policy have many levels, from the individual to local and national and international organisations and institutions. In many social systems the micro, meso and macrolevel dynamics are coupled, meaning that they cannot be studied or modified in isolation. Systems and network science allow computer simulations to be used to investigate possible system behaviour. This science can be made available to policy makers through policy informatics which involves computer-based simulation, data, visualisation, and interactive interfaces. The future of science-based policy making is seen to be through Global Systems Science which combines complex systems science and policy informatics to inform policy makers and facilitate citizen engagement. In this context, systems theory and network science are fundamental for modelling far-from-equilibrium systems for policy purposes.
A phase 1 study of the pharmacokinetics of nucleoside analog trifluridine and thymidine phosphorylase inhibitor tipiracil (components of TAS-102) vs trifluridine alone
Authors: Cleary James M. , Rosen Lee S. , Yoshida Kenichiro , Rasco Drew , Shapiro Geoffrey I. , Sun Weijing 
Published: January 2017

SummaryBackground Trifluridine, a thymidine-based chemotherapeutic, has limited bioavailability after clinical administration as it is rapidly degraded via thymidine phosphorylase. An oral combination tablet combines trifluridine with a potent thymidine phosphorylase inhibitor, tipiracil hydrochloride. This study’s objective was to evaluate whether trifluridine/tipiracil (TAS-102) administration increases trifluridine exposure vs trifluridine alone. Methods This open-label pharmacokinetic study randomly assigned patients with advanced solid tumors into two groups. On the morning of day 1, one group received a single 35 mg/m2 dose of trifluridine/tipiracil and the other group received a single 35-mg/m2 dose of trifluridine. Both groups received trifluridine/tipiracil 35 mg/m2 on the evening of day 1, then twice daily on days 2–5 and 8–12 in a 28-day cycle. Results Twenty patients received an initial one-time dose of trifluridine alone and 19 other patients received an initial dose of trifluridine/tipiracil. Trifluridine area under the curve (AUC0-last) and maximum observed plasma concentrations (Cmax) were approximately 37- and 22-fold higher, respectively, with trifluridine/tipiracil vs trifluridine alone. Plasma concentrations of the major metabolite of trifluridine were lower following the administration of trifluridine/tipiracil vs trifluridine alone. Conclusion Tipiracil administered in combination with trifluridine significantly increased exposure to trifluridine compared with trifluridine alone.
Intracohort cannibalism and methods for its mitigation in cultured freshwater fish
Authors: Duk Karolina , Pajdak Joanna , Terech-Majewska Elżbieta , Szarek Józef 
Published: January 2017

Abstract Cannibalism is a common phenomenon that occurs in over 30 fish families. Most of the species are valuable objects of aquaculture and cannibalism is highly undesirable. Cannibalism is an aggressive behaviour, which can be caused by stress induced by various population and environmental factors and can occur in two main forms: early larval and late juvenile (or adult). Each of these forms can lead to severe losses of stock. Losses are caused not only by fish eating each other, but also by an increase in the number of infections (the result of body surface damage). It is important to understand the phenomenon of cannibalism in order to properly prevent, diagnose and reduce it. The main aim of this study was to present and examine some of the well-examined methods of cannibalism mitigation. Most of the methods consist of creating rearing conditions similar to natural conditions and to reduce stress. Moreover, because of large interspecies differences, similar methods can result in different effects depending on the species. Additional studies are needed to better understand the biology of each cultured species with particular emphasis on the impact of domestication, as well as to improve fish rearing conditions.
Hegel and Husserl: Two Phenomenological Reactions to Kant
Authors: Rockmore Tom 
Published: January 2017

AbstractThe widespread tendency to understand phenomenology on a Husserlian model makes it incomparable with other views. I will use the term ‘phenomenology’ in a wider sense to refer to approaches to cognition based on phenomena. From the latter angle of vision, ’phenomenology’ includes not only Husserl and the Husserlians but also a wider selection of thinkers stretching back to early Greece. Although this will enlarge the scope of what counts as phenomenology, I will not be claiming that everyone is a phenomenologist. I will, however, be arguing that Kant, Hegel and Husserl are phenomenologists, or again phenomenological thinkers, and that Hegel and Husserl can be understood through their different reactions to Kantian phenomenology.
Cross-stream stereoscopic particle image velocimetry of a modified turbulent boundary layer over directional surface pattern
Authors: Kevin Kevin , Monty J. P. , Bai H. L. , Pathikonda G. , Nugroho B. , Barros J. M. , Christensen K. T. , Hutchins N. 
Published: January 2017

A turbulent boundary layer developed over a herringbone patterned riblet surface is investigated using stereoscopic particle image velocimetry in the cross-stream plane at$Re_{\unicode[STIX]{x1D70F}}\approx 3900$. The three velocity components resulting from this experiment reveal a pronounced spanwise periodicity in all single-point velocity statistics. Consistent with previous hot-wire studies over similar-type riblets, we observe a weak time-average secondary flow in the form of$\unicode[STIX]{x1D6FF}$-filling streamwise vortices. The observed differences in the surface and secondary flow characteristics, compared to other heterogeneous-roughness studies, may suggest that different mechanisms are responsible for the flow modifications in this case. Observations of instantaneous velocity fields reveal modified and rearranged turbulence structures. The instantaneous snapshots also suggest that the time-average secondary flow may be an artefact arising from superpositions of much stronger instantaneous turbulent events enhanced by the surface texture. In addition, the observed instantaneous secondary motions seem to have promoted a free-stream-engulfing behaviour in the outer layer, which would indicate an increase turbulent/non-turbulent flow mixing. It is overall demonstrated that the presence of large-scale directionality in transitional surface roughness can cause a modification throughout the entire boundary layer, even when the roughness height is 0.5 % of the layer thickness.
The jaguar's spots are darker than they appear: assessing the global conservation status of the jaguarPanthera onca
Authors: de la Torre J. Antonio , González-Maya José F. , Zarza Heliot , Ceballos Gerardo , Medellín Rodrigo A. 
Published: January 2017

AbstractThe IUCN Red List is widely used to guide conservation policy and practice. However, in most cases the evaluation of a species using IUCN Red List criteria takes into account only the global status of the species. Although subpopulations may be assessed using the IUCN categories and criteria, this rarely occurs, either because it is difficult to identify subpopulations or because of the effort involved. Using the jaguarPanthera oncaas a model we illustrate that wide-ranging species that are assigned a particular category of threat based on the IUCN Red List criteria may display considerable heterogeneity within individual taxa in terms of the level of risk they face. Using the information available on the conservation status of the species, we evaluated the jaguar's current geographical range and its subpopulations. We identified the most threatened subpopulations, using the extent of occurrence, area of occupancy, population size and the level of threat to each subpopulation. The main outcome of this analysis was that although a large subpopulation persists in Amazonia, virtually all others are threatened because of their small size, isolation, deficient protection and the high human population density. Based on this approach, future conservation efforts can be prioritized for the most threatened subpopulations. Based on our findings we recommend that for future Red List assessments assessors consider the value of undertaking assessments at the subpopulation level. For the jaguar, sub-global assessments should be included on the Red List as a matter of urgency.
Implication of reward alterations in the expression of negative symptoms in 22q11.2 deletion syndrome: a behavioural and DTI study
Authors: Dubourg L. , Schneider M. , Padula M. C. , Chambaz L. , Schaer M. , Eliez S. 
Published: January 2017

BackgroundAlterations of the reward system have been proposed as one of the core mechanisms underlying the expression of negative symptoms in schizophrenia. Specifically, deficits in specific reward components and white matter (WM) integrity of the reward system have been highlighted. The putative link between negative symptoms and the hedonic experience, or structural connectivity of the reward system has never been examined in the 22q11.2 deletion syndrome (22q11DS), a condition with increased risk for psychosis.MethodAnticipatory and consummatory dimensions of pleasure were assessed in participants with 22q11DS (N= 54) and healthy controls (N= 55). In patients with 22q11DS, the association between pleasure scores and positive or negative symptoms was investigated. Furthermore, WM integrity of the accumbofrontal tract was quantified using diffusion tensor imaging (DTI). Associations between DTI measures, pleasure dimensions and negative symptoms were examined.ResultsPatients with 22q11DS showed reduced anticipatory and consummatory pleasure compared to controls. Furthermore, anticipatory pleasure scores were negatively correlated to negative and positive symptoms in 22q11DS. WM microstructural changes of the accumbofrontal tract in terms of increased fractional anisotropy and reduced radial anisotropy were also identified in patients. However, no significant correlation between the DTI measures and pleasure dimensions or psychotic symptoms was observed.ConclusionsThis study revealed that participants with 22q11DS differed in their experience of pleasure compared to controls. The anticipatory pleasure component appears to be related to negative and positive symptom severity in patients. Alterations of WM integrity of the accumbofrontal tract seem to be related to myelination abnormalities in 22q11DS patients.
Meanings of ‘lifecycle robust neighbourhoods’: constructing versus attaching to places
Authors: VAN HEES SUSAN , HORSTMAN KLASIEN , JANSEN MARIA , RUWAARD DIRK 
Published: January 2017

ABSTRACTIn Western welfare states, notions of age-friendly communities and ageing-in-place are increasingly important in new health policies. In the Netherlands, care reforms are modifying the former welfare state to be more participatory; local governments are seeking collaborative solutions. Municipalities and housing, care and welfare organisations in the southern part of the country developed the concept of ‘lifecycle robust neighbourhoods’, envisioned as places where older people can age-in-place. Although many scholars have used the concept ageing-in-place in their studies of neighbourhoods, we aim to unravel this concept further by exploring how this particular ageing policy plays out in practice. This paper explores what the development of ‘lifecycle robust neighbourhoods’ means in relation to notions of ageing-in-place and age-friendly communities. We used ethnography (interviews, observations and focus groups) to reveal how, on the one hand, the policy makers, housing, care and welfare directors and representatives of older people, as developers of ‘lifecycle robust neighbourhoods’ and, on the other hand, older people, give meaning to places to age-in-place. It becomes clear that ageing-in-place has a different meaning in policy discourses than in practice. While developers mainly considered place as something construable, older people emotionally attached to place through lived experiences.