bluuebunny/crossref_metadata_2025_split huggingface dataset:
NRF2-dependent metabolic reprogramming is required for tumor recurrence following oncogene inhibition
Authors: Fox Douglas B. , Lupo Ryan , Noteware Laura C. , Newcomb Rachel , Liu Juan , Locasale Jason W. , Hirschey Matthew D. , Alvarez James V. 
Published: January 2019

SummaryOncogenic signaling pathways both directly and indirectly regulate anabolic metabolism, and this is required for tumor growth. Targeted therapies that inhibit oncogenic signaling have dramatic impacts on cellular metabolism. However, it is not known whether the acquisition of resistance to these therapies is associated with – or driven by – alterations in cellular metabolism. To address this, we used a conditional mouse model of Her2-driven breast cancer to study metabolic adaptations following Her2 inhibition, during residual disease, and after tumor recurrence. We found that Her2 downregulation caused widespread changes in cellular metabolism, culminating in oxidative stress. Tumor cells adapted to this metabolic stress by upregulation of the antioxidant transcription factor, NRF2. Constitutive NRF2 expression persisted during residual disease and tumor recurrence, and NRF2 was both sufficient to promote tumor recurrence, and necessary for recurrent tumor growth. These results are supported by clinical data showing that the NRF2 transcriptional program is activated in recurrent breast tumors, and that NRF2 is associated with poor prognosis in patients with breast cancer. Mechanistically, NRF2 signaling in recurrent tumors induced metabolic reprogramming to re-establish redox homeostasis and upregulate de novo nucleotide synthesis. Finally, this NRF2-driven metabolic state rendered recurrent tumor cells sensitive to glutaminase inhibition, suggesting that NRF2-high recurrent tumors can be therapeutically targeted. Together, these data provide evidence that NRF2-driven metabolic reprogramming is required for breast cancer recurrence following oncogene inhibition.SignificanceAlthough tumor recurrence is the leading cause of mortality in breast cancer, the cellular properties that allow tumor cells to evade therapy and form recurrent tumors remain largely uncharacterized. Similarly, very little is known about how tumor metabolism changes following therapy, or whether alterations in cellular metabolism drive tumor recurrence. In this study, we identify the antioxidant transcription factor NRF2 as a critical positive regulator of breast cancer recurrence. We find that NRF2-dependent metabolic reprogramming is both sufficient and required to promote tumor recurrence. Additionally, we demonstrate that the NRF2-driven metabolic state renders recurrent tumors sensitive to glutaminase inhibitors, suggesting a novel therapeutic approach for the treatment of recurrent breast cancer.
Acceptability of active case finding with a seed-and-recruit model to improve tuberculosis case detection and linkage to treatment in Cambodia: a qualitative study
Authors: Tuot Sovannary , Teo Alvin Kuo Jing , Cazabon Danielle , Sok Say , Ung Mengieng , Ly Sangky , Choub Sok Chamreun , Yi Siyan 
Published: January 2019

AbstractBackgroundWith support of the national tuberculosis (TB) program, KHANA has implemented an innovative approach using a seed-and-recruit model to actively find TB cases in the community. The intervention engaged community members including TB survivors to recruit people with TB symptoms in a ‘snowball’ approach for screening and linkage to treatment. This study aims to explore the acceptability of active case finding with the seed-and-recruit model in detecting new TB cases and determine the characteristics of successful seeds.MethodsThis qualitative study was conducted in four provinces (Banteay Meanchey, Kampong Chhnang, Siem Reap, and Takeo) in Cambodia in 2017. Fifty six in-depth interviews and ten focus group discussions were conducted to gain insights into the acceptability, strengths, and challenges in implementing the model. Transcripts were coded and content analyses were performed.ResultsThe seed-and-recruit active case finding model was generally well-received by the study participants. They saw the benefits of engaging TB survivors and utilize their social network to find new TB cases in the community. The social embeddedness of the model within the local community was one of the major strengths. The success of the model also hinges on the integration with existing health facilities. Having extensive social network, being motivated, and having good knowledge about TB were important characteristics of successful seeds. Study participants reported challenges in motivating the recruits for screening, logistic capacities, and high workload during implementation. However, there was a general consensus that the model ought to be expanded.ConclusionsThese findings indicate that the seed-and-recruit model should be fine-tuned and scaled up as part of the national TB Program to increase TB new case detection in Cambodia. Further studies are needed to more comprehensively evaluate the impacts and cost-effectiveness of the model in Cambodia as well as in other resource-limited settings.
Consideration of species-specific diatom indicators of anthropogenic stress in the Great Lakes
Authors: Reavie Euan D. , Cai Meijun 
Published: January 2019

AbstractRobust inferences of environmental condition come from bioindicators that have strong relationships with stressors and are minimally confounded by extraneous environmental variables. These indicator properties are generally assumed for assemblage-based indicators such as diatom transfer functions that use species abundance data to infer environmental variables. However, failure of assemblage approaches necessitates the interpretation of individual dominant taxa when making environmental inferences. To determine whether diatom species from Laurentian Great Lakes sediment cores have the potential to provide unambiguous inferences of anthropogenic stress, we evaluated fossil diatom abundance against a suite of historical environmental gradients: human population, agriculture, mining, atmospheric nutrient deposition, atmospheric temperature and ice cover. Several diatom species, such asStephanodiscus parvus, had reliable relationships with anthropogenic stress such as human population. However, many species had little or no indicator value or had confusing relationships with multiple environmental variables, suggesting one should be careful when using those species to infer stress in the Great Lakes. Recommendations for future approaches to refining diatom indicators are discussed, including accounting for the effects of broad species geographic distributions to minimize region-specific responses that can weaken indicator power.
What drives phenotypic divergence among coral clonemates?
Authors: Baums Iliana B , Devlin-Durante Meghann K , Williams Dana W , Kemp Dustin 
Published: January 2019

AbstractEvolutionary rescue of populations depends on their ability to produce phenotypic variation that is heritable and adaptive. DNA mutations are the best understood mechanisms to create phenotypic variation, but other, less well-studied mechanisms exist. Marine benthic foundation species provide opportunities to study these mechanisms because many are dominated by isogenic stands produced through asexual reproduction. For example, Caribbean acroporid corals are long lived and reproduce asexually via breakage of branches. Fragmentation is often the dominant mode of local population maintenance. Thus, large genets with many ramets (colonies) are common. Here, we observed phenotypic variation in stress response within genets following the coral bleaching events in 2014-and 2015 caused by high water temperatures. This was not due to genetic variation in their symbiotic dinoflagellates (Symbiodinium ‘fitti’) because each genet of this coral species typically harbors a single strain of S. ‘fitti’. Characterization of the microbiome via 16S tag sequencing did not provide evidence for a central role of microbiome variation in determining bleaching response. Instead, epigenetic changes were significantly correlated with the host’s genetic background, the position of the sampled polyps within the colonies (e.g. branch versus base of colony), and differences in the colonies’ condition during the bleaching event. We conclude that microenvironmental differences in growing conditions led to long-term changes in the way the ramets methylated their genomes contributing to, but not fully explaining, the differential bleaching response. This research provides novel data to understanding intra-genet variability in stress phenotypes of sessile marine species.
Efficacy and Safety of Immunosuppressive Treatment in IgA Nephropathy: A Meta-analysis of Randomized Controlled Trials
Authors: Zhang Zheng , Yang Yue , Jiang Shi-min , Li Wen-ge 
Published: January 2019

AbstractBackgroundThere is some controversy regarding the efficacy and safety of immunosuppressive agents for the treatment of kidney diseases. The recent STOP-IgAN and TESTING studies have focused attention on the application of immunosuppressive agents in IgA nephropathy (IgAN). This study investigated the benefits and risks of immunosuppressive agents in IgAN.MethodsMEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) comparing immunosuppressive agents with any other non-immunosuppressive agents for treating IgAN. A meta-analysis was performed on the outcomes of proteinuria, creatinine (Cr), estimated glomerular filtration rate (eGFR), and adverse events in patients with IgAN, and trial sequential analyses were also performed for outcomes.ResultsTwenty-nine RCTs (1957 patients) that met our inclusion criteria were identified. Steroids (weighted mean difference [WMD] −0.70, 95% confidence interval [CI] −1.2 to −0.20), non-steroidal immunosuppressive agents (NSI) (WMD −0. 43, 95% CI −0.55 to −0.31), and combined steroidal and non-steroidal immunosuppressive agents (S&NSI) (WMD −1.46, 95% CI −2.13 to −0.79) therapy significantly reduced proteinuria levels in patients with IgAN. Steroid treatment significantly reduced the risk for end-stage renal disease (ESRD) (relative risk [RR] 0.39, CI 0.19 to 0.79). The immunosuppressive therapy group showed significant increases in gastrointestinal, hematological, dermatological, and genitourinary side effects, as well as impaired glucose tolerance or diabetes. Hyperkalemia was more common in the control group.ConclusionImmunosuppressive therapy can significantly reduce proteinuria and ESRD risk in patients with IgAN, but with a concomitant increase in adverse reactions. Therefore, care is required in the application of immunosuppressive agents in IgAN.
Immigration and establishment of urban Trypanosoma cruzi populations
Authors: Berry Alexander S.F. , Salazar-Sánchez Renzo , Castillo-Neyra Ricardo , Borrini-Mayorí Katty , Chipana-Ramos Claudia , Vargas-Maquera Melina , Ancca-Juarez Jenny , Náquira-Velarde César , Levy Michael Z. , Brisson Dustin ,   Chagas Disease Working Group in Arequipa
Published: January 2019

AbstractChanging environmental conditions, including those caused by human activities, reshape biological communities through both loss of native species and establishment of non-native species in the altered habitats. Dynamic interactions with the abiotic environment impact both immigration and initial establishment of non-native species into these altered habitats. The repeated emergence of disease systems in urban areas worldwide highlights the importance of understanding how dynamic migratory processes affect the current and future distribution and abundance of pathogens in urban environments. In this study, we examine the pattern of invasion of Trypanosoma cruzi—the causative agent of human Chagas disease—in the city of Arequipa, Peru. Phylogenetic analyses of 136 T. cruzi isolates from Arequipa and other South American locations suggest that only one T. cruzi immigrant established a population in Arequipa as all T. cruzi isolated from vectors in Arequipa form a recent monophyletic group within the broader South American phylogeny. We discuss several hypotheses that may explain the limited number of established T. cruzi lineages despite multiple introductions of the parasite.Author SummaryHuman-associated pests and pathogens, who benefit from the abundance of humans and human-associated hosts or vectors, commonly invade environments altered by human activities. As the number and size of human-disturbed environments increase, so does the importance of identifying ecological and environmental factors that affect the probability that disease systems immigrate to, subsequently establish populations in, urban environments. We examined the number and timing of immigration and establishment events of Trypanosoma cruzi, the causative agent of Chagas disease, in a currently endemic area. Phylogenetic analyses of 136 T. cruzi isolates suggests that the current population descended from a single, recent immigration event. We discuss historical and ecological hypotheses that can explain the limited T. cruzi diversity in this region.
Experimental study of the solubility and diffusivity of CO2 and O2 in RP-3 jet fuel
Authors: Li Chaoyue , Feng Shiyu , Shao Lei , Pan Jun , Liu Weihua 
Published: January 2019

Purpose
This study aims to get the essential data of the solubility and diffusion coefficient of gas in jet fuel for appropriately designing a kind of on-board inert gas generation system.

Design/methodology/approach
A test apparatus based on pressure–decay method was constructed to measure solubility and diffusion coefficient of gas in liquid. The test apparatus and method were verified via measurement of solubility and diffusion of CO2 in the pure water.

Findings
The solubility of CO2 and O2 in RP-3 jet fuel with the temperature from 253 to 313 K under three various pressures were measured and compared with theoretical value calculated by a relative density method provided in the standard of ASTM D2780-92, and the deviation is within 10 per cent. The diffusion coefficients of CO2 and O2 in RP-3 jet fuel are determined by monitoring the gas pressure in a hermetic cell versus time with the temperature from 253 to 333 K. The measured diffusivity-temperature relation can be well fitted through the Arrhenius equation for engineering applications. The obtained correlation can be used to predict the diffusion coefficient of CO2 and O2 in RP-3 jet fuel under a wide temperature range.

Practical implications
The semi-empirical correlation of solubility and diffusion coefficient in RP-3 jet fuel obtained from the experimental data could be used to support the design of an inert gas generation system.

Originality/value
There are no essential data of solubility and diffusion of CO2 and O2 in RP-3 jet fuel; therefore, it is fatal if the quantity and rate of mass transfer of CO2 and O2 in RP-3 jet fuel must be assessed, e.g. during the design of green on-board inert gas generation system.
Participatory autism research with students at a UK university: evidence from a small-scale empirical project
Authors: Searle Kenneth Andrew , Ellis Liz , Kourti Marianthi , MacLeod Andrea , Lear Caroline , Duckworth Callum , Irvine Davide , Jones Harry , King Michaela , Ling Jessica , Simpson John 
Published: January 2019

Purpose
The purpose of this paper is to address the benefits of a participatory approach to autism research, demonstrating the positive effects of giving autistic project assistants (PAs) the opportunity to design and undertake a project researching the experiences of autistic university students.

Design/methodology/approach
A participatory approach was implemented, engaging autistic university students as research assistants. All the research team except project co-ordinators were autistic. Undergraduate autistic students developed and conducted a set of semi-structured interviews, with two autistic alumni responsible for data analysis and both scheduling and moderating focus groups. Participation in dissemination of the findings was open to all.

Findings
The results included in this paper reflect a portion of the overall findings, specifically regarding the participatory approach. The findings of the study indicate the perceptions of respondents being interviewed by autistic researchers in relation to their shared understanding, facilitating positive feelings and a sense of rapport in the interview process. The PAs were able to improve their research skills through the project, which contributed constructively to their CV and allowed them to feel more positive about being autistic, and specifically about being an autistic researcher.

Originality/value
This paper is one of the first to discuss the challenges and benefits of including autistic participant researchers at all stages of the research project, including research design, data collection, analysis and dissemination, being co-written by both project co-ordinators and autistic project researchers.
Silent deaths: a commentary on new mortality data relating to volatile substance abuse in Great Britain
Authors: Leigh Victoria , MacLean Sarah 
Published: January 2019

Purpose
The purpose of this paper is to provide a commentary on new information from the Office for National Statistics (ONS) on deaths caused by volatile substance abuse (VSA) in Great Britain which occurred between 2001 and 2016.

Design/methodology/approach
Comparing the new study with previous mortality data, the authors consider the strengths and some limitations of the analysis provided by ONS.

Findings
By utilising a broader range of codes and collating additional information from death certificates, the new report provides a more comprehensive measure of VSA mortality than was previously available, showing increasing prevalence of deaths. The age profile of people dying is older than in previous studies. Most deaths were associated with inhalation of gases and almost three-quarters of deaths involved volatile substances alone.

Practical implications
Understanding VSA mortality is essential for service planning. It is important that we identify why so many people whose deaths are associated with VSA are not accessing treatment, with particular concern about treatment access for those who only use volatiles. Training to support drug and alcohol and other health service staff to respond to VSA is essential. In future reports, data to identify socioeconomic correlations of VSA deaths would enable targeted responses. Additionally, information on whether deaths occur in long term rather than episodic or one-off users could enable risk reduction education.

Originality/value
This paper shows how data on VSA deaths may inform for policy and service planning.
Wealth measurement and the role of built asset investment: an empirical comparison
Authors: Ruddock Les , Ruddock Steven 
Published: January 2019

Purpose
The purpose of this paper is to assess the role of investment in built assets in the achievement of economic growth as part of a wealth measurement approach and to undertake an analysis of the relative importance of such investment as part of a country’s overall capital asset portfolio.

Design/methodology/approach
Panel data on capital asset investment are used to compare groups of countries at different stages of development. Data sets on investment and capital levels from the Penn World Tables 9.0 are used. Population and gross domestic product data are taken from the same source and the UN Statistics Division. World Bank reports provide data on countries’ income group classification.

Findings
There is confirmation of the view that, as economies grow, a pattern of investment based on developing a different structure of capital asset portfolio occurs. Investment patterns similar to those found in advanced countries arise as low income countries move to higher income classification groups even though built assets remain the most valuable capital asset group.

Originality/value
The study provides time series evidence on the nature of changing capital investment patterns in countries’ economies and demonstrates the value of a wealth measurement approach.
“Tea girl and garden boy” bankers: exploring substantive equality in bankers’ narratives
Authors: Canham Hugo 
Published: January 2019

Purpose
The purpose of this paper is to explore what narratives of inequality tell us about societal inequality both inside and outside of workplaces. It illuminates the intertwined fates of social agents and the productive potential of seeing organisational actors as social beings in order to advance resistance and substantive equality.

Design/methodology/approach
This research empirically examines narratives of inequality and substantive empowerment among a group of 25 black bankers within a major bank in Johannesburg, South Africa. Data were gathered through one-on-one interviews. The data were analysed using narrative analysis.

Findings
The findings indicate that narratives of organisational agents always contain fragments of personal and societal narratives. An intersectional lens of how people experience inequality allows us to work towards a more substantive kind of equality. Substantive equality of organisational actors is closely tied to the recognition and elimination of broader societal inequality.

Research limitations/implications
The implications for teaching and research are for scholars to methodically centre the continuities between the personal, organisational and societal in ways that highlight the productive tensions and possibilities for a more radical form of equality. Moreover, teaching, research and policy interventions should always foreground how the present comes to be constituted historically.

Practical implications
Policy and inclusivity interventions would be better served by using substantive empowerment as a theoretical base for deeper changes beyond what we currently conceive of as empowerment. At base, this requires policy makers and diversity practitioners to see all oppression and inequality as interconnected. Individuals are simultaneously organisational beings and societal agents.

Social implications
Third world approaches to diversity and inclusion need to be vigilant against globalised western notions of equity that are not contextually and historically informed. The failure of equity initiatives in SA means that alternative ideas and approaches are necessary.

Originality/value
The paper illustrates how individual narratives become social scripts of resistance. It develops a way for attaining substantive empowerment through the use of narrative approaches. It allows us to see that employees are also social agents.