bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and metabolic effects of ripening mutations and vine detachment on tomato fruit quality
Authors: Osorio Sonia , Carneiro Raphael T. , Lytovchenko Anna , McQuinn Ryan , Sørensen Iben , Vallarino José G. , Giovannoni James J. , Fernie Alisdair R. , Rose Jocelyn K. C. 
Published: May 2019

SummaryTomato (Solanum lycopersicum) fruit ripening is regulated co‐operatively by the action of ethylene and a hierarchy of transcription factors, including RIPENING INHIBITOR (RIN) and NON‐RIPENING (NOR). Mutations in these two genes have been adopted commercially to delay ripening, and accompanying textural deterioration, as a means to prolong shelf life. However, these mutations also affect desirable traits associated with colour and nutritional value, although the extent of this trade‐off has not been assessed in detail. Here, we evaluated changes in tomato fruit pericarp primary metabolite and carotenoid pigment profiles, as well as the dynamics of specific associated transcripts, in the rin and nor mutants during late development and postharvest storage, as well of those of the partially ripening delayed fruit ripening (dfd) tomato genotype. These profiles were compared with those of the wild‐type tomato cultivars Ailsa Craig (AC) and M82. We also evaluated the metabolic composition of M82 fruit ripened on or off the vine over a similar period. In general, the dfd mutation resulted in prolonged firmness and maintenance of quality traits without compromising key metabolites (sucrose, glucose/fructose and glucose) and sectors of intermediary metabolism, including tricarboxylic acid cycle intermediates. Our analysis also provided insights into the regulation of carotenoid formation and highlighted the importance of the polyamine, putrescine, in extending fruit shelf life. Finally, the metabolic composition analysis of M82 fruit ripened on or off the vine provided insights into the import into fruit of compounds, such as sucrose, during ripening.
Urban bias and wage inequality
Authors: Pi Jiancai , Fan Yanwei 
Published: May 2019

AbstractThis paper explores how urban bias affects skilled–unskilled wage inequality through building several general equilibrium models. In the basic model, we find that an increase in the degree of urban bias will widen wage inequality if the unskilled sector is more capital intensive than the skilled sector and reduce wage inequality if the skilled sector is more capital intensive than the unskilled sector. In the extended models, we find that the conclusion obtained in the basic model almost still holds under different conditions.
Epoxyeicosatrienoic acids alleviate methionine‐choline‐deficient diet–induced non‐alcoholic steatohepatitis in mice
Authors: Wang Xiaojing , Li Lan , Wang Hongwu , Xiao Fang , Ning Qin 
Published: May 2019

AbstractThe epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxygenases and have recently been found to have an anti‐inflammatory activity. However, the role of EETs in non‐alcoholic steatohepatitis has not been fully understood. In this study, we investigated the protective role of EETs in methionine‐choline‐deficient (MCD) diet–induced non‐alcoholic steatohepatitis (NASH) in mice and the potential mechanisms. We used 1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl)urea(TPPU), a soluble epoxide hydrolase inhibitor, to increase the endogenous EET level in mice. Upon TPPU treatment, the liver steatosis and inflammatory damage were significantly ameliorated in mice with steatohepatitis, paralleled by the downregulation of pro‐inflammatory cytokines (TNF‐α, IL‐1β, IL‐6) as well as chemokines (CXCL1, MCP‐1). Compared with untreated NASH mice, mRNA levels of sterol regulatory element binding protein 1c (SREBP1c) and inflammation relevant adhesion molecules (ICAM‐1, VCAM‐1) were downregulated, whereas mRNA level of peroxisome proliferator–activated receptor α(PPAR‐α) was elevated in TPPU‐treated mice. In vitro, 11,12‐EET treatment remarkably attenuated free fatty acid (FFA)–induced inflammation in HepG2 and THP‐1 cells. Further, 11,12‐EET inhibited the activation of NF‐κB signalling pathway in macrophages from mice with steatohepatitis. Collectively, these results suggest that EETs play a protective role and alleviate the MCD diet–induced steatohepatitis in mice mainly by downregulating activation of NF‐κB pathway in macrophages.
Rural Arts Festivals as Contributors to Rural Development and Resilience
Authors: Mahon Marie , Hyyryläinen Torsti 
Published: May 2019

AbstractThis article explores how two rural arts festivals, one in the town of Boyle (Boyle Arts Festival), in Western Ireland and the other in the municipality of Mäntyharju, (Salmela Festival) Eastern Finland, contribute to the development of their respective localities and communities via two different models of festival implementation. Both festivals have a major focus on visual art along with other events such as music and enjoy strong reputations for promoting quality artistic experiences. Drawing on the concepts of cultural capital, resilience and resourcefulness, the article investigates how the arts can work in providing wide‐ranging possibilities for engaging with local development activities and shaping local development agendas in diverse and changing rural contexts. The research is based on semi‐structured interviews with 15 festival contributors and individuals in institutional support roles. It finds that an emphasis on community‐focused, quality of life priorities that is a feature of the Boyle festival increasingly presents challenges to sourcing funding, and that an entrepreneurial approach applied in the case of the Salmela festival, while economically successful, does not provide the same scope for community participation. Both approaches have implications for the ways the festivals impact on local development processes.
Effects of resistance training on impulse above end‐test torque and muscle fatigue
Authors: de Menezes Bassan Natália , Denadai Benedito Sérgio , de Lima Leonardo Coelho Rabello , Caritá Renato Aparecido Corrêa , Abdalla Leonardo Henrique Perinotto , Greco Camila Coelho 
Published: May 2019

New Findings
What is the central question of this study?
What role do neuromuscular fatigue mechanisms play in resistance training‐induced adaptations of the impulse above end‐test torque (IET) after the training period?

What is the main finding and its importance?
IET and global and peripheral fatigue were increased after a short period of resistance training. Thus, resistance training‐induced adaptations in neuromuscular fatigue seem to contribute to enhanced IET after the training period.

AbstractShort‐term resistance training has a positive influence on the curvature constant of the power–duration relationship (W′). The physiological mechanism of W′ enhancement after resistance training is unclear. This study aimed to determine whether one‐leg maximal isometric resistance training influences (1) impulse above end‐test torque (IET; an analogue of W′) during a 5 min all‐out isometric test; and (2) exercise tolerance (limit of tolerance, Tlim) and neuromuscular fatigue during severe exercise (i.e. above end‐test torque; ET). Sixteen healthy active males participated in a 3‐week unilateral knee extensor resistance‐training programme, and 10 matched subjects participated as controls. The subjects were instructed to ramp up to 100% of maximal voluntary contraction (MVC) over 1 s, hold it for 3 s, and relax. Each repetition had a 2 s interval (10) and each set, a 2 min interval (3). MVC (18.6%) and muscle thickness (12.8%) were significantly improved after training. Significantly greater global (i.e. reduced MVC, 43.2 ± 13.5% vs. 58.9 ± 6.9%) and peripheral (51.7 ± 13.6% vs. 57.3 ± 15.3%) fatigue, IET (26%) and Tlim (92%) were obtained after resistance training. Moreover, both global (r = 0.57, P < 0.05) and peripheral fatigue (r = 0.55, P < 0.05) accrued during severe exercise were associated with IET. However, echo intensity, which reflects muscle quality, ET and central fatigue remained unchanged throughout the training period. No significant changes in the control group for any variable were observed. Resistance training‐induced adaptations in muscle size and neuromuscular fatigue seem to contribute to enhanced IET and Tlim after the training period.
Recruitment, retention, and training of people with type 2 diabetes as diabetes prevention mentors (DPM) to support a healthcare professional-delivered diabetes prevention program: the Norfolk Diabetes Prevention Study (NDPS)
Authors: Garner Nikki J , Pascale Melanie , France Kalman , Ferns Clare , Clark Allan , Auckland Sara , Sampson Michael 
Published: May 2019

ObjectiveIntensive lifestyle interventions reduce the risk of type 2 diabetes in populations at highest risk, but staffing levels are usually unable to meet the challenge of delivering effective prevention strategies to a very large at-risk population. Training volunteers with existing type 2 diabetes to support healthcare professionals deliver lifestyle interventions is an attractive option.MethodsWe identified 141 973 people at highest risk of diabetes in the East of England, screened 12 778, and randomized 1764 into a suite of type 2 diabetes prevention and screen detected type 2 diabetes management trials. A key element of the program tested the value of volunteers with type 2 diabetes, trained to act as diabetes prevention mentors (DPM) when added to an intervention arm delivered by healthcare professionals trained to support participant lifestyle change.ResultsWe invited 9951 people with type 2 diabetes to become DPM and 427 responded (4.3%). Of these, 356 (83.3%) were interviewed by phone, and of these 131 (36.8%) were interviewed in person. We then appointed 104 of these 131 interviewed applicants (79%) to the role (mean age 62 years, 55% (n=57) male). All DPMs volunteered for a total of 2895 months, and made 6879 telephone calls to 461 randomized participants. Seventy-six (73%) DPMs volunteered for at least 6 months and 66 (73%) for at least 1 year.DiscussionIndividuals with type 2 diabetes can be recruited, trained and retained as DPM in large numbers to support a group-based diabetes prevention program delivered by healthcare professionals. This volunteer model is low cost, and accesses the large type 2 diabetes population that shares a lifestyle experience with the target population. This is an attractive model for supporting diabetes prevention efforts.
Assessing risks to paediatric patients: conversation analysis of situation awareness in huddle meetings in England
Authors: Hayes Jacqueline , Lachman Peter , Edbrooke-Childs Julian , Stapley Emily , Wolpert Miranda , Deighton Jessica 
Published: May 2019

ObjectivesTo analyse the language and conversation used in huddles to gain a deeper understanding of exactly how huddles proceed in practice and to examine the methods by which staff members identify at-risk patients.SettingPaediatric wards in four English hospitals, which were part of a 12-hospital cohort participating in the Situation Awareness for Everyone programme. Wards varied by geographical region and type of hospital.ParticipantsPaediatric staff on wards in four English hospitals.DesignEthnomethodology and conversation analysis of recorded safety huddles.MethodsThis study represents the first analysis of huddle interaction. All huddle meetings taking place on four wards across four different hospitals were audio recorded and transcribed. The research question examined was: how are staff identifying at-risk patients in huddles? The ethnomethodological conversation analytic approach was used to analyse the transcripts.ResultsHuddlers made use of categories that allowed them to efficiently identify patients for each other as needing increased attention. Lexicon included the use of ‘no concerns’, ‘the one to watch’, ‘watcher’ and ‘acute concerns’. Huddlers used the meetings to go beyond standardised indicators of risk to identify relative risk and movement in patients towards deterioration, relative to the last huddle meeting and to their usual practices. An implicit category, termed here ‘pre-concerns’, was used by staff to identify such in-between states. Sequential analysis also highlighted the conversational rights that were held implicitly by staff in different clinical roles.ConclusionPractical implications and recommendations for huddlers are considered. These included that for increased situation awareness, it is recommended that all staff are active in the huddle conversation and not only the most senior team members.
SAFE, a new therapeutic intervention for families of children with autism: study protocol for a feasibility randomised controlled trial
Authors: McKenzie Rebecca , Dallos Rudi , Stedmon Jacqui , Hancocks Helen , Vickery Patricia Jane , Ewings Paul , Barton Andy , Vassallo Tara , Myhill Craig 
Published: May 2019

IntroductionIncidence of autistic traits, mental health problems, stress and poor coping is high among family members of children with autism. These problems are coupled with challenging behaviour among children with autism. Current treatment for these families is disjointed and costly. The need for whole family support is supported by the National Institute for Health and Care Excellence recommendations, developments regarding children’s service provision, research and requests by families of children with autism. Despite evidence that family therapies can provide benefits to these families, efficacy has not been subject to a randomised controlled trial. Systemic Autism-related Family Enabling (SAFE) is a new family therapy intervention designed specifically for families of children with autism. We aim to establish the feasibility of running a fully powered randomised controlled trial to evaluate SAFE.Methods and analysisFamilies of children with autism aged 3–16 years will be invited to participate. Consenting participants will be randomised 2:1 to either SAFE+support as usual or support as usual alone. The proposed primary outcome measure for the main trial will be the Systemic CORE 15. Participants will also complete proposed secondary outcome measures, indexing changes in child behaviour, child-parent attachment, anxiety and depression. Generic health economic outcome measures (EuroQol 5 dimensions and Child Health Utility 9 Dimensions) will also provide data on the feasibility of cost-effectiveness analysis. Questionnaires will be completed at baseline and 32 weeks post-allocation. Data on ability to identify, recruit, randomise, retain and collect data from families, acceptability of outcome measures, adherence of therapists and families to the intervention, appropriateness of resource use questionnaires and effectiveness of training will be collected for feasibility analysis. Qualitative data will also explore acceptability of SAFE and reasons for declining and withdrawing from the study.Ethics and disseminationThe current trial protocol received ethical approval from the South West-Exeter Research Ethics Committee (Ref: 17/SW/0192). The findings of the trial will be disseminated in collaboration with our Family Consultation Group and other partners. Findings will be shared locally, nationally and internationally through events, conferences and published papers.Trial registration numberISCTRN83964946 (Pre-results) IRAS 213527
User-testing an interactive option grid decision aid for prostate cancer screening: lessons to improve usability
Authors: Scalia Peter , Durand Marie-Anne , Faber Marjan , Kremer J A , Song Julia , Elwyn Glyn 
Published: May 2019

ObjectiveTo user-test a web-based, interactive Option Grid decision aid ‘prostate-specific antigen (PSA) test: yes or no?’ to determine its usability, acceptability and feasibility with men of high and low health literacy.DesignA semi-structured interview study.SettingInterviews were conducted at a senior centre, academic hospital or college library in New Hampshire and Vermont.ParticipantsIndividuals over 45 years of age with no history of prostate cancer who voluntarily contacted study authors after viewing local invitations were eligible for inclusion. Twenty interviews were conducted: 10 participants had not completed a college degree, of which eight had low health literacy, and 10 participants had high health literacy.InterventionAn interactive, web-based Option Grid patient decision aid for considering whether or not to have a PSA test.ResultsUsers with lower health literacy levels were able to understand the content in the tool but were not able to navigate the Option Grid independent of assistance. The tool was used independently by men with high health literacy. In terms of acceptability, the flow of questions and answers embedded in the tool did not seem intuitive to some users who preferred seeing more risk information related to age and family history. Users envisioned that the tool could be feasibly implemented in clinical workflows.ConclusionMen in our sample with limited health literacy had difficulty navigating the Option Grid, thus suggesting that the tool was not appropriately designed to be usable by all audiences. The information provided in the tool is acceptable, but users preferred to view personalised risk information. Some participants could envision using this tool prior to an encounter in order to facilitate a better dialogue with their clinician.Ethics approvalThe study received ethical approval from the Dartmouth College Committee for the Protection of Human Subjects (STUDY00030116).
Contemporary occurrence and aetiology of chronic leg ulcers in Africa: a systematic review and meta-analysis protocol
Authors: Danwang Celestin , Tochie Joel Noutakdie , Mazou Temgoua Ngou , Nzalie Rolf Nyah Tuku , Bigna Jean Joel 
Published: May 2019

IntroductionChronic leg ulcers are known as a major and snowballing threat to public health and the global economy. In Africa, there is controversy on the dearth of studies reporting the epidemiology of chronic leg ulcers. The present systematic review and meta-analysis aim at synthesising the prevalence, incidence and aetiologies of this ailment in this continent from contemporary data.Methods and designWe will include cohort studies, case–control, cross-sectional studies and case series with more than 30 participants. Electronical databases including African Journals Online, MEDLINE, Excerpta Medica Database and Web of knowledge, and grey literature will be searched for relevant abstracts of studies published and unpublished between 1 January, 2000, and 28 February, 2019, without language restriction. The review will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Each study included in this review will be assessed for methodological quality. Clinically homogenous studies will be pooled using random-effects meta-analysis. Visual inspection of funnel-plots and the Egger’s test will be used to investigate publication bias. Meta-regression and subgroup analyses will be performed to investigate the possible sources of heterogeneity.Ethics and disseminationThe present study will be based on published data; therefore, ethical approval is not required. Result of the review will be presented at conferences, to relevant health authorities and will be published in a biomedical peer-reviewed journal.Protocol registration numberCRD42018108250.
Applying the five-pillar matrix to the decade of action for road safety in Qatar: identifying gaps and priorities
Authors: Consunji Rafael , Mekkodathil Ahammed , Abeid Aisha , El-Menyar Ayman , Al-Thani Hassan , Sekayan Tsoler , Peralta Ruben 
Published: May 2019

IntroductionRoad traffic injuries (RTIs) are the leading cause of preventable death in Qatar; consequently, the country has participated in the Decade of Action for Road Safety (DoARS) coordinated by the United Nations Road Safety Collaboration (UNRSC). Its goal is to reduce the number of road traffic deaths and injuries by 50% by 2020, by implementing road safety activities, in the areas of road safety management, safer roads, safer vehicles, safer road users and postcrash response, the five pillars. This study will evaluate the initiatives and programs implemented in Qatar, during the initial period of the DoARS.MethodsA retrospective process evaluation of the compliance of national road safety activities in Qatar, with global indicators for the DoARS set by the UNRSC was conducted. A web-based online and electronic media search, in both official languages of Qatar: Arabic and English, for data and information on completed or ongoing road safety initiatives and activities implemented in Qatar, from January 1, 2011 to December 31, 2016, was supplemented by personal consultation with relevant stakeholders in the road safety field.ResultsThere was complete compliance for Pillars 1 (Road Safety Management) and 2 (Safer Roads), whereas Pillars 4 (Safer Road Users) and 5 (Postcrash Response) met most of the DoARS indicators, and Pillar 3 (Safer Vehicles) complied with none.ConclusionQatar must continue to implement its present road safety activities within the Action Plan for the DoARS to achieve its goals by 2020. It must, however, implement more new efforts to require safer vehicles and make road users safer, especially those at the highest risk, that is, young drivers, occupants and workers.Level of EvidenceLevel IV.
Fermion-current basis and correlation functions for the integrable spin-1 chain
Authors: Babenko C. , Smirnov F. 
Published: May 2019

We use the fermion-current basis in the space of local operators for the computation of the expectation values for the integrable spin chain of spins 1. Our main tool consists in expressing a given local operator in the fermion-current basis. For this, we use the same method as in the spin-1/2 case which is based on the arbitrariness of the Matsubara data.
Tumor-Localized Costimulatory T-Cell Engagement by the 4-1BB/HER2 Bispecific Antibody-Anticalin Fusion PRS-343
Authors: Hinner Marlon J. , Aiba Rachida Siham Bel , Jaquin Thomas J. , Berger Sven , Dürr Manuela Carola , Schlosser Corinna , Allersdorfer Andrea , Wiedenmann Alexander , Matschiner Gabriele , Schüler Julia , Moebius Ulrich , Rothe Christine , Matis Louis , Olwill Shane Anthony 
Published: May 2019

Abstract

Purpose:
4-1BB (CD137) is a key costimulatory immunoreceptor and promising therapeutic target in cancer. To overcome limitations of current 4-1BB–targeting antibodies, we have developed PRS-343, a 4-1BB/HER2 bispecific molecule. PRS-343 is designed to facilitate T-cell costimulation by tumor-localized, HER2-dependent 4-1BB clustering and activation.

Experimental Design:
PRS-343 was generated by the genetic fusion of 4-1BB–specific Anticalin proteins to a variant of trastuzumab with an engineered IgG4 isotype. Its activity was characterized using a panel of in vitro assays and humanized mouse models. The safety was assessed using ex vivo human cell assays and a toxicity study in cynomolgus monkeys.

Results:
PRS-343 targets 4-1BB and HER2 with high affinity and binds both targets simultaneously. 4-1BB–expressing T cells are efficiently costimulated when incubated with PRS-343 in the presence of cancer cells expressing HER2, as evidenced by increased production of proinflammatory cytokines (IL2, GM-CSF, TNFα, and IFNγ). In a humanized mouse model engrafted with HER2-positive SK-OV-3 tumor cells and human peripheral blood mononuclear cells, PRS-343 leads to tumor growth inhibition and a dose-dependent increase of tumor-infiltrating lymphocytes. In IND-enabling studies, PRS-343 was found to be well tolerated, with no overt toxicity and no relevant drug-related toxicologic findings.

Conclusions:
PRS-343 facilitates tumor-localized targeting of T cells by bispecific engagement of HER2 and 4-1BB. This approach has the potential to provide a more localized activation of the immune system with higher efficacy and reduced peripheral toxicity compared with current monospecific approaches. The reported data led to initiation of a phase I clinical trial with this first-in-class molecule.
See related commentary by Su et al., p. 5732