bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel dual‐action prodrug triggers apoptosis in glioblastoma cells by releasing a glutathione quencher and lysine‐specific histone demethylase 1A inhibitor
Authors: Engel Martin , Gee Yi Sing , Cross Dale , Maccarone Alan , Heng Benjamin , Hulme Amy , Smith Grady , Guillemin Gilles J. , Stringer Brett W. , Hyland Christopher J. T. , Ooi Lezanne 
Published: December 2018

AbstractTargeting epigenetic mechanisms has shown promise against several cancers but has so far been unsuccessful against glioblastoma (GBM). Altered histone 3 lysine 4 methylation and increased lysine‐specific histone demethylase 1A (LSD1) expression in GBM tumours nonetheless suggest that epigenetic mechanisms are involved in GBM. We engineered a dual‐action prodrug, which is activated by the high hydrogen peroxide levels associated with GBM cells. This quinone methide phenylaminecyclopropane prodrug releases the LSD1 inhibitor 2‐phenylcyclopropylamine with the glutathione scavenger para‐quinone methide to trigger apoptosis in GBM cells. Quinone methide phenylaminocyclopropane impaired GBM cell behaviours in two‐dimensional and three‐dimensional assays, and triggered cell apoptosis in several primary and immortal GBM cell cultures. These results support our double‐hit hypothesis of potentially targeting LSD1 and quenching glutathione, in order to impair and kill GBM cells but not healthy astrocytes. Our data suggest this strategy is effective at selectively targeting GBM and potentially other types of cancers.Open science badgesThis article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
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TACKLING FALSE POSITIVES IN BUSINESS RESEARCH: A STATISTICAL TOOLBOX WITH APPLICATIONS
Authors: Kim Jae H. 
Published: December 2018

AbstractSerious concerns have been raised that false positive findings are widespread in empirical research in business disciplines. This is largely because researchers almost exclusively adopt the ‘p‐value less than 0.05’ criterion for statistical significance; and they are often not fully aware of large‐sample biases which can potentially mislead their research outcomes. This paper proposes that a statistical toolbox (rather than a single hammer) be used in empirical research, which offers researchers a range of statistical instruments, including a range of alternatives to the p‐value criterion such as the Bayesian methods, optimal significance level, sample size selection, equivalence testing and exploratory data analyses. It is found that the positive results obtained under the p‐value criterion cannot stand, when the toolbox is applied to three notable studies in finance.
Compulsive internet use and the development of self‐esteem and hope: A four‐year longitudinal study
Authors: Donald James N. , Ciarrochi Joseph , Parker Philip D. , Sahdra Baljinder K. 
Published: December 2018

AbstractObjectiveCompulsive internet use (CIU) has been linked to decrements in mental health and well‐being. However, relatively little is known about how CIU relates to evaluations of the self, and in particular, whether CIU is antecedent to or is a consequence of negative evaluations of one’s social worth (self‐esteem) and general efficacy (hope). To examine this, we explored the longitudinal relations between CIU and the development of self‐esteem and hope among adolescents over a four‐year period.MethodTwo thousand eight hundred and nine adolescents completed measures yearly from Grade 8 (MAge = 13.7) to Grade 11. Autoregressive cross‐lagged structural equation models were used to test whether CIU influenced or was influenced by self‐esteem and hope.ResultsWe found consistent support for a CIU‐as‐antecedent model. CIU preceded reductions in trait hope, and small reductions in self‐esteem. In contrast, we did not find evidence for a CIU‐as‐consequence model: low self‐esteem and hope did not predict increases in CIU over time.ConclusionsOur findings suggest that CIU has negative consequences for young people’s feelings of goal‐efficacy, and that interventions that address the compulsive use of the internet are likely to strengthen hope and self‐esteem among young people.
Identifying an appropriate carrier for nonnutritive sweeteners in metabolic and controlled feeding investigations via sensory evaluation
Authors: Myers Emily A. , Duncan Susan E. , Wang Aili , Hedrick Valisa E. 
Published: December 2018

AbstractTo strengthen metabolic study designs on nonnutritive sweeteners (NNS), sensory characteristics of NNS combined with different carriers should be better understood. The research objective was to determine an appropriate carrier (water or applesauce) for a high dose of specific NNS types (aspartame, sucralose, or stevia) to inform future metabolic and controlled feeding study designs. Adult participants (n = 67) sampled six sweetener‐carrier combinations (water and applesauce containing high concentrations of aspartame [30 g/oz], sucralose [8.25 g/oz], and stevia [6.75 g/oz]). Participants completed Check‐All‐That‐Apply emotional terminology questionnaires, affective attribute questionnaires, and paired preference questionnaires. Applesauce was preferred (sucralose = 83.6%; aspartame = 79.1%; stevia = 74.6%) significantly more than water for all sweetener types (p < .001) and mean acceptability scores were significantly higher for all applesauce samples. Participants preferred NNS delivered in applesauce rather than water. Applesauce is likely a more appropriate and tolerable carrier for high‐dose NNS, which may contribute to designing effective intervention studies with greater participant compliance.Practical applicationsThis investigation will allow researchers to understand which carrier (applesauce or water) is more tolerable for participants consuming high doses of NNS and to design future research studies to determine health outcomes associated with NNS consumption. Applesauce is likely a more appropriate and tolerable carrier for high‐dose NNS in research studies. Using an acceptable carrier for delivery of high doses of NNS to research participants may contribute to designing effective intervention studies, with greater participant compliance. An acceptable method for delivering NNS to research participants will be valuable for designing intervention studies aimed at examining how NNS consumption impacts health outcomes.
The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat
Authors: Lux Sebastian , Lobos Nicolas , Lespay-Rebolledo Carolyne , Salas-Huenuleo Edison , Kogan Marcelo J , Flores Christian , Pinto Mauricio , Hernandez Alejandro , Pelissier Teresa , Constandil Luis 
Published: December 2018

Abstract

Objectives
To study the antinociceptive effect of single and repeated doses of resveratrol in a bone cancer pain model, and whether this effect is prevented by the Silent Information Regulator 1 (SIRT1) inhibitor selisistat.

Methods
The femoral intercondylar bone of BALB/c mice was injected with 1 000 000 BJ3Z cancer cells. Bone resorption and tumour mass growth (measured by in vivo X-ray and fluorescence imaging), as well as mechanical nociceptive thresholds (von Frey device) and dynamic functionality (rotarod machine), were evaluated during the following 4 weeks. Acute resveratrol (100 mg/kg i.p.) and/or selisistat (10 mg/kg s.c.) were administered on day 14. Chronic resveratrol (100 mg/kg i.p., daily) and/or selisistat (0.5 μg/h s.c., Alzet pump) were administered between days 14 and 20.

Key findings
Tumour growth gradually incremented until day 31, while mechanical hyperalgesia started on day 3 after cancer cell injection. Acute resveratrol increased the mechanical threshold of pain (peaking at 1.5 h), while the dynamic functionality decreased. Chronic resveratrol produced a sustained antinociceptive effect on mechanical hyperalgesia and improved the loss of dynamic functionality induced by the bone cancer tumour. Selisistat prevented all the effects of resveratrol.

Conclusions
Acute and chronic resveratrol induces antinociceptive effect in the model of metastatic osseous oncological pain, an effect that would be mediated by SIRT1 molecular signalling.
“Someone's generosity has formed a bond between us”: Interpersonal relationships in Internet‐facilitated peer‐to‐peer milk sharing
Authors: Gribble Karleen 
Published: December 2018

AbstractInternet‐facilitated peer‐to‐peer milk sharing enables the giving and receiving of human milk between individuals previously unknown to one another. However, the process of milk sharing allows for milk sharing partners to develop relationships with one another. The development of relationships between 41 milk recipients and 97 milk donors in Internet‐facilitated peer‐to‐peer milk sharing was explored via a questionnaire. Thirty‐seven recipient respondents and 55 donor respondents placed some level of importance on developing a relationship with their milk sharing partner. Thirty‐four recipient respondents and 48 donor respondents had developed a relationship with at least one milk sharing partner, from acquaintanceship to close friendship. Respondents also described milk kinship relationships. Friendships were commonly noted as a positive repercussion of milk sharing. Milk sharing stigma was the only commonly reported negative repercussion of milk sharing. Peer‐to‐peer milk recipients and donors are forced by circumstance and encouraged by the process of milk sharing and by their similarity to one another to trust each another, which acts as a catalyst to friendship development. Peer‐to‐peer milk sharing is a type of cooperative mothering wherein milk recipients are assisted in parenting their children via the gift of milk. However, reciprocity is evident as milk donors benefit from good feelings from helping another mother and child, pleasure through seeing the recipient infant grow, and often friendship with their milk recipient. Although Internet‐facilitated peer‐to‐peer milk sharing is instigated by the impersonal medium of the Interweb, each milk sharing connection has the potential to become a real relationship.
The genetic architecture underlying diapause termination in a planktonic crustacean
Authors: Czypionka Till , Fields Peter D. , Routtu Jarkko , van den Berg Edwin , Ebert Dieter , De Meester Luc 
Published: December 2018

AbstractDiapause is a feature of the life cycle of many invertebrates by which unfavourable environmental conditions can be outlived. The seasonal timing of diapause allows organisms to adapt to seasonal changes in habitat suitability and thus is key to their fitness. In the planktonic crustacean Daphnia, various cues can induce the production of diapause stages that are resistant to heat, drought or freezing and contain one to two embryos in developmental arrest. Daphnia is a keystone species of many freshwater ecosystems, where it acts as the main link between phytoplankton and higher trophic levels. The correct seasonal timing of diapause termination is essential to maintain trophic interactions and is achieved via a genetically based interpretation of environmental cues like photoperiod and temperature. Field monitoring and modelling studies raised concerns on whether populations can advance their seasonal release from diapause to advances in spring phenology under global change, or if a failure to adapt will cause trophic mismatches negatively affecting ecosystem functioning. Our capacity to understand and predict the evolution of diapause timing requires information about the genetic architecture underlying this trait. In this study, we identified eight quantitative trait loci (QTLs) and four epistatic interactions that together explained 66.5% of the variation in diapause termination in Daphnia magna using QTL mapping. Our results suggest that the most significant QTL is modulating diapause termination dependent on photoperiod and is involved in three of the four detected epistatic interactions. Candidate genes at this QTL could be identified through the integration with genome data and included the presynaptic active zone protein bruchpilot. Our findings contribute to understanding the genomic control of seasonal diapause timing in an ecological relevant species.
Early‐life telomere length predicts lifespan and lifetime reproductive success in a wild bird
Authors: Eastwood Justin R. , Hall Michelle L. , Teunissen Niki , Kingma Sjouke A. , Hidalgo Aranzamendi Nataly , Fan Marie , Roast Michael , Verhulst Simon , Peters Anne 
Published: December 2018

AbstractPoor conditions during early development can initiate trade‐offs that favour current survival at the expense of somatic maintenance and subsequently, future reproduction. However, the mechanisms that link early and late life‐history are largely unknown. Recently it has been suggested that telomeres, the nucleoprotein structures at the terminal end of chromosomes, could link early‐life conditions to lifespan and fitness. In wild purple‐crowned fairy‐wrens, we combined measurements of nestling telomere length (TL) with detailed life‐history data to investigate whether early‐life TL predicts fitness prospects. Our study differs from previous studies in the completeness of our fitness estimates in a highly philopatric population. The association between TL and survival was age‐dependent with early‐life TL having a positive effect on lifespan only among individuals that survived their first year. Early‐life TL was not associated with the probability or age of gaining a breeding position. Interestingly, early‐life TL was positively related to breeding duration, contribution to population growth and lifetime reproductive success because of their association with lifespan. Thus, early‐life TL, which reflects growth, accumulated early‐life stress and inherited TL, predicted fitness in birds that reached adulthood but not noticeably among fledglings. These findings suggest that a lack of investment in somatic maintenance during development particularly affects late life performance. This study demonstrates that factors in early‐life are related to fitness prospects through lifespan, and suggests that the study of telomeres may provide insight into the underlying physiological mechanisms linking early‐ and late‐life performance and trade‐offs across a lifetime.
Familial neuronal intranuclear inclusion disease complicated by subcortical hemorrhage
Authors: Mitsutake Akihiko , Tamai Tomohisa , Kamisawa Aya , Sugiyama Yusuke , Sato Tatsuya , Katsumata Junko , Seki Tomonari , Maekawa Risa , Hideyama Takuto , Saito Yuko , Shiio Yasushi 
Published: December 2018

AbstractAn 80‐year‐old woman presented with loss of appetite. At age 78, she was diagnosed as familial neuronal intranuclear inclusion disease (NIID) based on (i) leukoencephalopathy with hyperintensities along the corticomedullary junction on diffusion‐weighted imaging (DWI) revealed by brain magnetic resonance imaging (MRI), (ii) skin biopsy samples showing ubiquitin‐positive intranuclear inclusions in adipocytes, and (iii) family history. Her cognitive function was preserved while apathy was apparent. However, on this admission, her cognitive function got worse. Afterward, the patient developed subcortical hemorrhage, and the risk for the hemorrhage was not identified. NIID might be associated with intracranial hemorrhage. In addition, brain MRI after the bleeding showed the rapid expansion of hyperintense lesions on DWI even in the frontal lobe where bleeding was irrelevant. Intracranial hemorrhage might have affected the enlarged hyperintense lesions.
Analyzing clinical characteristics of patients with myasthenia gravis through repetitive nerve stimulation testing
Authors: Tsugawa Jun , Ogura Hiromutsu , Mera Hidekazu , Fukae Jiro , Tsuboi Yoshio 
Published: December 2018

AbstractBackgroundThe diagnosis of Myasthenia gravis (MG) is confirmed by clinical features with the presence of MG‐specific antibodies or the effect of intravenous edrophonium (Tensilon) administration. Diagnosis of MG is difficult in cases with negative serologic and Tensilon testing. Electrophysiological tests can support the diagnosis in such cases. Repetitive nerve stimulation testing (RNST) is one such electrophysiological test, and it is usually performed on several muscles.AimThe probability of RNST‐positivity varies between muscles, so we aimed to elucidate the relationship between muscle‐specific RNST‐positivity and patients’ clinical characteristics.MethodsWe included 46 patients and examined RNST results for the abductor digiti minimi (ADM), trapezius, and frontalis muscles. We classified muscles as RNST‐positive or RNST‐negative and compared RNST‐positive and RNST‐negative muscles for various clinical characteristics.ResultsWe observed RNST‐positivity in 11 out of 40 (27.5%) ADM muscles, 20 out of 35 (57.1%) trapezius muscles, and 14 out of 29 (48.3%) frontalis muscles. The trapezius muscle's RNST‐positivity rate was the highest in the 21 patients who underwent RNST for all 3 muscles and was significantly higher than the ADM's RNST‐positivity rate. RNST‐positivity in any muscle was significantly associated with higher serum antiacetylcholine receptor antibody (AChR‐Ab) titers. Frontalis muscle RNST‐positivity was significantly associated with higher Quantitative Myasthenia Gravis scores.ConclusionWhen diagnosing MG, physicians should recognize that the trapezius has the highest RNST‐positivity rate and that patients with low AChR‐Ab titers may exhibit negative RNST results. Furthermore, patients with frontalis muscle RNST‐positivity may present severe symptoms.
A simple model to bridge Hardin's tragedy and Ostrom's comity
Authors: Soedomo Sudarsono 
Published: December 2018

AbstractTriggered by the article titled “The tragedy of the commons” by Hardin, a collectively‐managed resource (CMR) emerges and becomes a highly fruitful discussion topic. Furthermore, Ostrom augments the topic and demonstrates that the utilization of a CMR should not always result in a tragedy. However, the theory used to justify Hardin's tragedy differs from the one used to justify Ostrom's comity; Hardin's tragedy is justified by one‐shot prisoners' dilemma (PD), while Ostrom's comity is justified by infinitely repeated PD. The discussion in this study shows that Hardin's tragedy and Ostrom's comity can be supported by the same theory. An infinitely repeated PD complemented with a likelihood of making an error is used to reach the conclusion that the occurrences of Hardin's tragedy and Ostrom's comity are just a matter of probability.Recommendations for Resource Managers
To avoid as far as possible placing divisible resources under the common property regime.
To develop effective monitoring systems for resource management under the common property regime to stop deviations as early as possible.
To facilitate resource users involved in resource utilization under the common property regime to meet and to communicate regularly to increase mutual trust.
Community care for severely frail older people: Developing explanations of how, why and for whom it works
Authors: Lhussier Monique , Dalkin Sonia , Hetherington Ross 
Published: December 2018

AbstractBackgroundA Community Wellness Team was implemented in North East England in 2014, in line with national policy directives to support frail older people in the community. The service provides a comprehensive and integrated care package, which aims to reduce avoidable admissions, inappropriate service use and enable patients to stay at home.DesignA realist design combining a review of the literature and primary data collection from service providers and patients was used to develop programme theories explaining the links between the Team interventions and expected outcomes.ResultsFive programme theories were developed, detailing: trust development and relationship building; risk minimisation in the home environment; advice on self‐management; referral to preventative services; and coordination of services.DiscussionThe programme theories explain the role and impact of the Community Wellness Team. These programme theories are interrelated and impact one another; a hypothesised progression of programme theories indicating how the Community Wellness Team “works” is discussed. Of particular importance was the comprehensive initial assessment, which leads to the alteration of the social and physical environment within which older people live.ConclusionSeverely frail older people present cases that are complex socially, medically, financially and environmentally. In order to meet these needs, the Team coordinators are adopting a complex and flexible person‐centred approach.Implications for PracticeThis study paves the way for further research into the care networks surrounding severely frail older people living in the community, and how they can most effectively be implemented.
An unusual case of Sinusitis – foreign body in the maxillary antrum
Authors: Tanna N. , Awal D. , Eyeson J. 
Published: December 2018

AbstractWe report a diagnostic challenge relating to a 9‐year persistent oroantral fistula and subsequent insertion of foreign body in the maxillary antrum. An oroantral communication initially occurred following the removal of a maxillary molar. This persisted to form an oroantral fistula which the patient cleaned daily with a cotton wool bud. This ultimately led to a large volume of foreign body being implanted into the maxillary antrum. The patient was largely asymptomatic in the early stages and only attended the dentist when experiencing discomfort. This case is unusual for a number of reasons; first, due to the chronicity of the fistula and second, the method of self‐management that the patient utilised which involved daily cleaning of the fistula with a cotton bud. There are likely to have been a number of factors contributing to the delay in presentation including a lack of symptoms, preconceptions about visiting the dentist and a lack of understanding regarding the expected post‐operative healing process. This case highlights the crucial role of dentists in providing clear and comprehensive post‐operative instructions, while ensuring patients understand the need for appropriate follow‐up. Dentists should recognise that patients will often have pre‐conceived ideas or anxieties about dental treatment and may only attend if in pain, preferring to self‐manage their symptoms if possible. This case also considers difficulties in diagnosing oral pathology with unusual aetiology. Foreign body was not initially considered, and it highlights the importance of detailed history taking and thinking laterally when formulating a differential diagnosis.
Autotransplantation of an impacted maxillary canine with complete root formation in a young female – a case report
Authors: Boschini L. , Tepedino M. , Melillo M. , Mastrangelo F. , Laurenziello M. , Chimenti C. , Lo Muzio L. , Ciavarella D. 
Published: December 2018

AbstractMaxillary canines are the second most frequently impacted teeth after third molars. In some cases, the position of the impacted tooth makes orthodontic traction too risky or even impossible. Autotransplantation can be a viable treatment option, and has been proven to have an acceptable success rate. The case reports a young female with a complex impaction solved using autotransplantation together with orthodontic alignment, with a 5‐year follow‐up.
Anesthetist‐delivered intraoperative transesophageal echocardiography in pediatric cardiac surgery
Authors: Murphy Tim 
Published: December 2018

SummaryThis article reviews the evidence for anesthetist‐delivered perioperative transesophageal echocardiography for children undergoing cardiac surgery. It addresses the additional issues of training, developing practice, accreditation, and the requirement for collaboration with pediatric cardiologists, surgeons and other members of the perioperative team. Finally an overview of the potential structure of an anesthetist‐delivered perioperative transesophageal echocardiography service is presented.