bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model
Authors: Ono Hanako , Arai Yasuhito , Furukawa Eisaku , Narushima Daichi , Matsuura Tetsuya , Nakamura Hiromi , Shiokawa Daisuke , Nagai Momoko , Imai Toshio , Mimori Koshi , Okamoto Koji , Hippo Yoshitaka , Shibata Tatsuhiro , Kato Mamoru
Published: April 2019

Intra-tumor heterogeneity (ITH) encompasses cellular differences in tumors and is related to clinical outcomes, such as drug resistance. However, little is known about the dynamics of ITH, owing to the lack of time-series analysis at the single-cell level. We performed single-cell exome and transcriptome sequencing of 200 cells and investigated how ITH is generated from one single cell in a mouse colorectal cancer model. The ITH of the transcriptome increased after transplantation from cultured organoids, while that of the exome decreased. Mutations generated in the culture did not greatly change at the transplantation at the bulk-cell level. The RNA ITH increase was due to the emergence of new transcriptional subpopulations. In contrast to the initial cells expressing mesenchymal-marker genes, new subpopulations repressed these genes at transplantation. Analyses of colorectal cancer data from The Cancer Genome Atlas revealed a high proportion of metastatic cases in human subjects with expression patterns similar to the new cell subpopulations in mouse. These results suggest that the birth of transcriptional subpopulations may be a key for adaptation to drastic micro-environmental changes when cancer cells have sufficient genetic alterations at later tumor stages. This study revealed an evolutionary dynamics of single-cell RNA and DNA changes in tumor progression, giving insights into the mesenchymal-epithelial transformation of tumor cells at metastasis in colorectal cancer.
Impaired alanine transport or exposure to D-cycloserine increases the susceptibility of MRSA to β-lactam antibiotics
Authors: Gallagher Laura A. , Shears Rebecca K. , Fingleton Claire , Alvarez Laura , Waters Elaine M. , Clarke Jenny , Bricio-Moreno Laura , Campbell Christopher , Yadav Akhilesh K. , Razvi Fareha , O’Neill Eoghan , O’Neill Alex J. , Cava Felipe , Fey Paul D. , Kadioglu Aras , O’Gara James P.
Published: April 2019

Prolonging the clinical effectiveness of β-lactams, which remain first-line antibiotics for many infections, is an important part of efforts to address antimicrobial resistance. We report here that inactivation of the predicted D-cycloserine (DCS) transporter genecycAre-sensitized MRSA to β-lactam antibiotics. ThecycAmutation also resulted in hyper-susceptibility to DCS, an alanine analogue antibiotic that inhibits alanine racemase and D-alanine ligase required for D-alanine incorporation into cell wall peptidoglycan (PG). Alanine transport was impaired in thecycAmutant and this correlated with increased susceptibility to oxacillin and DCS. ThecycAmutation or exposure to DCS were both associated with the accumulation of muropeptides with tripeptide stems lacking the terminal D-ala-D-ala and reduced PG crosslinking, prompting us to investigate synergism between β-lactams and DCS. DCS re-sensitised MRSA to β-lactamsin vitroand significantly enhanced MRSA eradication by oxacillin in a mouse bacteraemia model. These findings reveal alanine transport as a new therapeutic target to enhance the susceptibility of MRSA to β-lactam antibiotics.
A convolutional neural network for fast upsampling of undersampled tomograms in X-ray CT time-series using a representative highly sampled tomogram
Authors: Bellos Dimitrios , Basham Mark , Pridmore Tony , French Andrew P.
Published: April 2019

X-ray computed tomography and, specifically, time-resolved volumetric tomography data collections (4D datasets) routinely produce terabytes of data, which need to be effectively processed after capture. This is often complicated due to the high rate of data collection required to capture at sufficient time-resolution events of interest in a time-series, compelling the researchers to perform data collection with a low number of projections for each tomogram in order to achieve the desired `frame rate'. It is common practice to collect a representative tomogram with many projections, after or before the time-critical portion of the experiment without detrimentally affecting the time-series to aid the analysis process. For this paper these highly sampled data are used to aid feature detection in the rapidly collected tomograms by assisting with the upsampling of their projections, which is equivalent to upscaling the θ-axis of the sinograms. In this paper, a super-resolution approach is proposed based on deep learning (termed an upscaling Deep Neural Network, or UDNN) that aims to upscale the sinogram space of individual tomograms in a 4D dataset of a sample. This is done using learned behaviour from a dataset containing a high number of projections, taken of the same sample and occurring at the beginning or the end of the data collection. The prior provided by the highly sampled tomogram allows the application of an upscaling process with better accuracy than existing interpolation techniques. This upscaling process subsequently permits an increase in the quality of the tomogram's reconstruction, especially in situations that require capture of only a limited number of projections, as is the case in high-frequency time-series capture. The increase in quality can prove very helpful for researchers, as downstream it enables easier segmentation of the tomograms in areas of interest, for example. The method itself comprises a convolutional neural network which through training learns an end-to-end mapping between sinograms with a low and a high number of projections. Since datasets can differ greatly between experiments, this approach specifically develops a lightweight network that can easily and quickly be retrained for different types of samples. As part of the evaluation of our technique, results with different hyperparameter settings are presented, and the method has been tested on both synthetic and real-world data. In addition, accompanying real-world experimental datasets have been released in the form of two 80 GB tomograms depicting a metallic pin that undergoes corruption from a droplet of salt water. Also a new engineering-based phantom dataset has been produced and released, inspired by the experimental datasets.
The self-built city: theorizing urban design of informal settlements
Authors: Pojani Dorina
Published: April 2019

Purpose

While a substantial amount of study of informal settlements has been undertaken, they remain largely unstudied in terms of urban form. In this analysis, the purpose of this paper is to set forth a conceptual framework, which considers the context in which informality takes place, the settlement itself, the houses contained therein, the dwellers of those houses and the process through which a settlement is designed and transformed over time.

Design/methodology/approach

This is a literature review.

Findings

This framework aims to be sufficiently flexible to be deployed across diverse national settings. Its formulation is important because informal settlements are a permanent fixture of the global urban landscape, and are increasing in scale.

Originality/value

Any sustainable strategies to improve informal settlements depend on a better understanding of their urban space, as well as of the producers of this space – the residents themselves. Finally, professional designers may be able to learn from this contemporary urban vernacular grammar – perhaps the only one left in the era of sanitized, contrived and prosaic urban design.
Moderating role of LMX and proactive coping in the relationship between learning value of the job and employability enhancement among academic staff employees
Authors: Van der Heijden Beatrice , Spurk Daniel
Published: April 2019

Purpose

Building upon a competence-based employability model and a social exchange and proactive perspective, the purpose of this paper is to investigate the relationship between learning value of the job and employability among academic staff employees. Moreover, this study also examined whether this relationship was moderated by leader–member exchange (LMX) and a proactive coping style.

Design/methodology/approach

An online self-report questionnaire with thoroughly validated measures was distributed among academic staff employees (n=139).

Findings

The results partially supported the specific study assumptions. Concrete, learning value of the job was positively related to anticipation and optimization, corporate sense and balance. LMX moderated the relationship between learning value of the job, on the one hand, and all employability dimensions, on the other hand. However, proactive coping only moderated the relationship with anticipation and optimization, flexibility and balance. In all cases, under the condition of high moderator variable levels, the relationship became stronger.

Originality/value

This study extends past employability research by applying an interactionist perspective (person: proactive coping style, context: LMX and learning value of the job) approach for explaining employability enhancement. The results of this scholarly work provide useful insights for stimulating future career development and growth, which is of upmost importance in nowadays’ labor markets.
Can the integration of a tax-compliant transfer pricing system into the management control system be successful?
Authors: Hummel Katrin , Pfaff Dieter , Bisig Benedikt
Published: April 2019

Purpose

This paper aims to draw on Adler and Borys’ (1996) concept of an enabling use of bureaucracy to examine how the integration of a single-book tax-compliant transfer pricing system into the management control system is related to the perceived success of that transfer pricing system.

Design/methodology/approach

Based on survey data from Swiss multinational firms, the authors test a structural equation model. In addition, the authors conduct interviews with executives from three multinational enterprises.

Findings

The authors find that the integration of a tax-compliant transfer pricing system into the management control system may be perceived to be successful in achieving both tax compliance and internal (control) purposes. This is particularly true when the transfer pricing system is transparent and can be amended in the case of fundamental management control problems.

Research limitations/implications

The typical shortcomings of a survey-based research apply to this study. Future research could build on this model and more closely investigate the relationship between transfer pricing system integration and an enabling use of the transfer pricing system.

Practical implications

Based on this study’s findings, the authors recommend that a strong integration of tax-compliant transfer prices into the management control system should be accompanied by internal transparency and the ability to repair the transfer pricing system.

Originality/value

Prior research on the integration between transfer pricing and management control systems has either been analytical or based on case studies. This cross-sectional analysis provides reliable insights into different levels of integration, use and the success of transfer pricing systems.
Post-contract material management and waste minimization
Authors: Saka Abdullahi Babatunde , Olaore Fatai Oladayo , Olawumi Timothy Oluwatosin
Published: April 2019

Purpose

This paper aims to assess the level of awareness of quantity surveyors in material management and their key roles in waste minimization during the post-contract stage of the project with a view of achieving value for money in their roles.

Design/methodology/approach

This involves administering a questionnaire survey to registered members of the Nigerian Institute of Quantity Surveyors, the only recognized professional body of quantity surveyors in Nigeria, within Lagos state. The empirical questionnaire survey succeeds a literature review that isolates the key strategies used by quantity surveyors in material management and waste minimization at the post-contract stage. The validity of the questionnaire was carried out by two experienced construction industry researchers and three experienced professional quantity surveyors to ensure that the questionnaire was not ambiguous and that it consists of the right questions in tandem with the research. The respondents were grouped into consultant’s QS and contractor’s QS.

Findings

Key roles of quantity surveyors during the material management process are proper material storage, and material inventory and accounting are the most important material management and waste minimization practices during the institute stage. It revealed that there is a lack of material waste documentation practices during the construction stage. In addition, there is no statistically significant difference in the responses of the two groups. This may be because there is no clear compartmentalization between the practices of the two groups. In addition, these two groups had the same education training, as there is no difference between the educational training of the consultant’s QS and contractor’s QS.

Originality/value

This study assessed the quantity surveyors’ roles with regard to material management and waste minimization. It would add to the scanty research work in this area. The study has also successfully revealed the strategies that are to be adopted by the quantity surveyors to achieve value for money during the post-contract stage.
Tackling protein–energy under‐nutrition among resource‐limited people living with HIV/AIDS in Malawi using soybean‐enriched maize‐based stiff porridge (nsima): A pilot study
Authors: Bhima Karen , Mtimuni Beatrice , Matumba Limbikani
Published: April 2019

Aim

The Ministry of Health in Malawi has scaled‐up antiretroviral therapy (ART) for HIV infection. However, the majority of Malawians heavily depend on maize‐based stiff porridge (nsima), a protein‐deficient staple, a practice that exacerbates wasting and ultimately compromises the success of ART programming. This pilot study was conducted to evaluate the efficacy of utilising soybean‐enriched nsima as a strategy for managing HIV‐related wasting among resource‐poor people.

Methods

A before and after designed study involving 25 wasted (<18.5 BMI (body mass index)) to normal (18.5–24.9 BMI) HIV‐positive rural women (21–40 years) taking ART and provided with soybean–maize flour (20 kg/month for 3 months) prepared from hydrothermally treated soybeans and maize in the ratio of 1:4 (wt/wt). Anthropometry was performed at baseline and every month for the 3‐month study period. Paired sample t‐tests were used to test for changes in body mass and BMI between baseline and the subsequent months.

Results

Statistically significant (P < 0.001) cumulative mean weight gain for the first, second and third month of the study were 1.6, 2.1 and 2.9 kg, respectively. The number of participants with low BMI reduced from 6/25 at baseline to 2/25 after 3 months, and the mean BMI improved from 19.3 to 21.1 kg/m2.

Conclusions

Nsima prepared from a blend of maize and hydrothermally treated soybeans could feasibly be used to prevent and manage wasting among resource‐poor people living with HIV/AIDS in sub‐Saharan Africa who rely on maize as a major staple.
Functional assessment of hydrophilic domains of late embryogenesis abundant proteins from distant organisms
Authors: Liu Yingying , Zhang Heng , Han Jiahui , Jiang Shijie , Geng Xiuxiu , Xue Dong , Chen Yun , Zhang Chen , Zhou Zhengfu , Zhang Wei , Chen Ming , Lin Min , Wang Jin
Published: April 2019

Late embryogenesis abundant (LEA) proteins play a protective role during desiccation and oxidation stresses. LEA3 proteins are a major group characterized by a hydrophilic domain (HD) with a highly conserved repeating 11‐amino acid motif. We compared four different HD orthologs from distant organisms: (i) DrHD from the extremophilic bacterium Deinococcus radiodurans; (ii) CeHD from the nematode Caenorhabditis elegans; (iii) YlHD from the yeast Yarrowia lipolytica; and (iv) BnHD from the plant Brassica napus. Circular dichroism spectroscopy showed that all four HDs were intrinsically disordered in phosphate buffer and then folded into α‐helical structures with the addition of glycerol or trifluoroethanol. Heterologous HD expression conferred enhanced desiccation and oxidation tolerance to Escherichia coli. These four HDs protected the enzymatic activities of lactate dehydrogenase (LDH) by preventing its aggregation under desiccation stress. The HDs also interacted with LDH, which was intensified by the addition of hydrogen peroxide (H2O2), suggesting a protective role in a chaperone‐like manner. Based on these results, the HDs of LEA3 proteins show promise as protectants for desiccation and oxidation stresses, especially DrHD, which is a potential ideal stress‐response element that can be applied in synthetic biology due to its extraordinary protection and stress resistance ability.
Estrogen receptor α promotes Cav1.2 ubiquitination and degradation in neuronal cells and in APP/PS1 mice
Authors: Lai Yu‐Jie , Zhu Bing‐Lin , Sun Fei , Luo Dong , Ma Yuan‐Lin , Luo Bio , Tang Jing , Xiong Ming‐Jian , Liu Lu , Long Yan , Hu Xiao‐Tong , He Ling , Deng Xiao‐Juan , Zhang John H. , Yang Jian , Yan Zhen , Chen Guo‐Jun
Published: April 2019

Cav1.2 is the pore‐forming subunit of L‐type voltage‐gated calcium channel (LTCC) that plays an important role in calcium overload and cell death in Alzheimer's disease. LTCC activity can be regulated by estrogen, a sex steroid hormone that is neuroprotective. Here, we investigated the potential mechanisms in estrogen‐mediated regulation of Cav1.2 protein. We found that in cultured primary neurons, 17β‐estradiol (E2) reduced Cav1.2 protein through estrogen receptor α (ERα). This effect was offset by a proteasomal inhibitor MG132, indicating that ubiquitin–proteasome system was involved. Consistently, the ubiquitin (UB) mutant at lysine 29 (K29R) or the K29‐deubiquitinating enzyme TRAF‐binding protein domain (TRABID) attenuated the effect of ERα on Cav1.2. We further identified that the E3 ligase Mdm2 (double minute 2 protein) and the PEST sequence in Cav1.2 protein played a role, as Mdm2 overexpression and the membrane‐permeable PEST peptides prevented ERα‐mediated Cav1.2 reduction, and Mdm2 overexpression led to the reduced Cav1.2 protein and the increased colocalization of Cav1.2 with ubiquitin in cortical neurons in vivo. In ovariectomized (OVX) APP/PS1 mice, administration of ERα agonist PPT reduced cerebral Cav1.2 protein, increased Cav1.2 ubiquitination, and improved cognitive performances. Taken together, ERα‐induced Cav1.2 degradation involved K29‐linked UB chains and the E3 ligase Mdm2, which might play a role in cognitive improvement in OVX APP/PS1 mice.
Ethanol induces maladaptive impulse control and decreased seeking behaviors in mice
Authors: Starski Phillip , Hong Sa‐Ik , Peyton Lee , Oliveros Alfredo , Wininger Katheryn , Hutchison Colleen , Kang Seungwoo , Karpyak Victor , Choi Doo‐Sup
Published: April 2019

Waiting impulsivity is a risk factor for many psychiatric disorders including alcohol use disorder (AUD). Highly impulsive individuals are vulnerable to alcohol abuse. However, it is not well understood whether chronic alcohol use increases the propensity for impulsive behavior. Here, we establish a novel experimental paradigm demonstrating that continuous binge‐like ethanol exposure progressively leads to maladaptive impulsive behavior. To test waiting impulsivity, we employed the 5‐choice serial reaction time task (5‐CSRTT) in C57BL/6J male mice. We assessed premature responses in the fixed and variable intertrial interval (ITI) 5‐CSRTT sessions. We further characterized our ethanol‐induced impulsive mice using Open Field, y‐maze, two‐bottle choice, and an action‐outcome task. Our results indicate that continuous binge‐like ethanol exposure significantly increased premature responses when mice were tested in variable ITI sessions even during a prolonged abstinent period. Ethanol‐induced impulsive mice exhibited anxiety‐like behavior during chronic exposures. This behavior was also observed in a separate cohort that was subjected to 20 days of abstinence. Ethanol‐treated mice were less motivated for a sucrose reward compared with air‐exposed control mice, while also demonstrating reduced responding during action‐outcome testing. Overall, ethanol‐treated mice demonstrated increased impulsive behavior, but a reduced motivation for a sucrose reward. Although waiting impulsivity has been hypothesized to be a trait or risk factor for AUD, our findings indicate that maladaptive impulse control can also be potentiated or induced by continuous chronic ethanol exposure in mice.
Exploring the Consequences of Competing Uses of Budgets
Authors: Henri Jean‐François , Massicotte Steeve , Arbour Dominique
Published: April 2019

The purpose of this paper is to revisit the impact of budgets within organisations by combining the notions of simultaneity and tension between budget uses and by introducing the notion of predominance. More specifically, we first intend to empirically examine the combination of budget uses in an organisational setting. Second, our aim is to examine to what extent the simultaneous use of budgets for the purpose of performance evaluation or forecasting gives rise to satisfactory or unsatisfactory consequences of budgets. Using survey data collected from a large sample of manufacturing firms, the results suggest that more satisfactory budget consequences, in terms of budget value, arise in two situations: (a) whereby budgets are predominately used for performance evaluation, or (b) whereby budgets are predominately used for forecasting. Those firms displaying no predominant budget use show less satisfactory budget consequences.
A longitudinal analysis of urological chronic pelvic pain syndrome flares in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network
Authors: Sutcliffe Siobhan , Gallop Robert , Henry Lai Hing Hung , Andriole Gerald L. , Bradley Catherine S. , Chelimsky Gisela , Chelimsky Thomas , Quentin Clemens James , Colditz Graham A. , Erickson Bradley , Griffith James W. , Kim Jayoung , Krieger John N. , Labus Jennifer , Naliboff Bruce D. , Rodriguez Larissa V. , Sutherland Suzette E. , Taple Bayley J. , Landis John Richard
Published: April 2019

Objective

To describe the frequency, intensity and duration of urological chronic pelvic pain syndrome symptom exacerbations (‘flares’), as well as risk factors for these features, in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Epidemiology and Phenotyping longitudinal study.

Participants and Methods

Current flare status (‘urological or pelvic pain symptoms that are much worse than usual’) was ascertained at each bi‐weekly assessment. Flare characteristics, including start date, and current intensity of pelvic pain, urgency and frequency (scales of 0–10), were assessed for participants’ first three flares and at three randomly selected times when they did not report a flare. Generalized linear and mixed effects models were used to investigate flare risk factors.

Results

Of the 385 eligible participants, 24.2% reported no flares, 22.9% reported one flare, 28.3% reported 2–3 flares, and 24.6% reported ≥4 flares, up to a maximum of 18 during the 11‐month follow‐up (median incidence rate = 0.13/bi‐weekly assessment, range = 0.00–1.00). Pelvic pain (mean = 2.63‐point increase) and urological symptoms (mean = 1.72) were both significantly worse during most flares (60.6%), with considerable within‐participant variability (26.2–37.8%). Flare duration varied from 1 to 150 days (94.3% within‐participant variability). In adjusted analyses, flares were more common, symptomatic, and/or longer‐lasting in women and in those with worse non‐flare symptoms, bladder hypersensitivity, and chronic overlapping pain conditions.

Conclusion

In this foundational flare study, we found that pelvic pain and urological symptom flares were common, but variable in frequency and manifestation. We also identified subgroups of participants with more frequent, symptomatic, and/or longer‐lasting flares for targeted flare management/prevention and further study.
Attention! Cosmopolitans ahead – They may not be as creative as they think!
Authors: Vogelgesang Lester Gretchen , Clapp‐Smith Rachel , Yunlu Dilek , James Adrian
Published: April 2019

Research on cosmopolitanism and creativity has received significant attention in recent years; however, the connections between these constructs are still ill‐defined. This study uses the creative cognition model to explore the relationship between cosmopolitanism and creativity using both self‐report and expert ratings of a qualitative task. Quantitative data support the assertion that cosmopolitanism is significantly and positively related to self‐expectations of creativity and creative work involvement. However, creative performance on a productive solutions task coded by creativity experts failed to replicate the self‐reported findings. We describe the practical and theoretical implications of these results for future research into cosmopolitanism and creativity.
Individual motivation among entrepreneurs in the creative and cultural industries: A self‐determination perspective
Authors: Cnossen Boukje , Loots Ellen , van Witteloostuijn Arjen
Published: April 2019

We aim to shed light on the deep mechanisms that keep individual entrepreneurs in the creative and cultural industries motivated in this insecure and fast‐paced environment. We collect data through a survey of entrepreneurs working in the Dutch creative and cultural industries (CCI) and examine what motivates these professionals to work in an environment characterized by tough competition. Specifically, we analyse our respondents' self‐perceived (creative and entrepreneurial) competences and needs (for autonomy and relatedness) in relation to their motivation to execute creative work. We suggest a reading of our results through the lens of self‐determination theory. Our results show that the need for competence is a consistent predictor of an individual's motivation to work in the CCI. Furthermore, we find that although intrinsic motivation is very high among entrepreneurs working in the creative and cultural industries, those who have a relatively high esteem of their creative capabilities do expect external rewards as well. Our study suggests the existence of a trade‐off between autonomy and commercial viability rather than one between intrinsic and extrinsic motivations.
Nonconvex/nonsmooth economic load dispatch using modified time‐varying particle swarm optimization
Authors: Parouha Raghav Prasad
Published: April 2019

In this paper, a modified time‐varying particle swarm optimization (MTVPSO) is proposed for solving nonconvex economic load dispatch problems. It is a variant of the traditional particle swarm optimization (PSO) algorithm. In an MTVPSO, novel acceleration coefficients for cognitive and social components are presented as linear time‐varying parameters in the velocity update equation of the PSO algorithm. In the early stages of the optimization process, it improves the global search capability of particles and directs the global optima at the end stage. Additionally, a linearly decreased inertia weight is introduced in an MTVPSO, instead of a fixed constant value, which helps improve the diversity of the population. Through this modification mechanism in PSO, the proposed algorithm has a higher probability of avoiding local optima, and it is likely to find global optima more quickly. Six complex benchmark functions have been used to validate the effectiveness of the proposed algorithm. Furthermore, to demonstrate its efficiency, feasibility, and fastness, six different cases (3‐, 6‐, 13‐, 15‐, and 40‐unit systems and one large‐scale Korean power 140‐unit system) of the economic load dispatch problem are solved by an MTVPSO. The results of the proposed algorithm have been compared with state‐of‐the‐art algorithms. It was found that the proposed MTVPSO can deliver better results in terms of solution quality, convergence characteristics, and robustness.
LncRNA TRERNA1 facilitates hepatocellular carcinoma metastasis by dimethylating H3K9 in the CDH1 promoter region via the recruitment of the EHMT2/SNAI1 complex
Authors: Song Wei , Gu Yuejun , Lu Sen , Wu Huazhang , Cheng Zhenxing , Hu Jiaojiao , Qian Yanyan , Zheng Ying , Fan Hong
Published: April 2019

Objectives

Long non‐coding RNAs (LncRNAs) play an important role in hepatocellular carcinoma development, however, as a crucial driver of hepatocellular carcinoma (HCC) metastasis, their functions in tumour metastasis remain largely unknown.

Materials and methods

The lncRNA TRERNA1 expression levels were detected in HCC by quantitative real‐time PCR (qPCR). The function of TRERNA1 was examined by wound‐healing assays, transwell assays and tail vein injection experiments. The potential regulatory mechanisms of TRERNA1 on its target genes were explored by ChIP, RIP, IP and WB assays.

Results

Elevated TRERNA1 levels promoted HCC cell migration and invasion in vitro and in vivo. TRERNA1 recruited EHMT2 to dimethylate H3K9 in the CDH1 promoter region. Furthermore, EHMT2 bound to SNAI1 to suppress CDH1 expression in HCC cells. After inhibiting TRERNA1, the expression level of CDH1 was restored and was involved in the regulation of the EHMT2/SNAI1 complex. The level of TRERNA1 was positively correlated with tumour metastasis and was negatively correlated with the expression of CDH1 in HCC tissues.

Conclusions

For the first time, the current study reveals that TRERNA1 promotes cell metastasis and the invasion of HCC via the recruitment of EHMT2 and/or the EHMT2/SNAI1 complex to suppress CDH1. These data identify a novel mechanism that regulates TRERNA1 in metastatic HCC and provides a potential targeted therapy for HCC patients.
Objectifying trustworthiness: Market formation in the transport policy field
Authors: Ek Österberg Emma
Published: April 2019

This paper addresses market formation in the public sector, particularly questions of how and why market arrangements for public services change, and what it means in terms of governance. The paper presents an in‐depth empirical study of a case in the Swedish transport sector, building on sociological research into market formation, particularly the work of Callon, Méadel, and Rabeharisoa on the qualification of products. Given the demand for process‐oriented research into market relations, especially in the public sector, this study empirically illustrates how and why roles, relations, and objects are maintained and transformed, and how these features are cocreated in practice. Although previous research has paid relatively little attention to product qualification, this paper demonstrates that it is useful to put this process at the center of the analysis. The present findings emphasize that how products came to be objectified, in terms of provider qualities rather than technical specifications, was the compromise that enabled various logics to be at stake simultaneously. The paper also contributes by demonstrating that NPM reforms of marketization can accommodate far‐reaching attempts by public organizations to influence the market, which is especially relevant in markets in which public‐sector organizations are dominant purchasers.
Paternal Support and Involvement in Unmarried Fragile Families: Impacts on Long‐Term Maternal Mental Health
Authors: Mallette Jacquelyn K. , Futris Ted G. , Oshri Assaf , Brown Geoffrey L.
Published: April 2019

Fragile families are defined as those that include unmarried or romantically unstable parents who have children and are socioeconomically disadvantaged. Mothers in fragile families may experience risk factors that lead to increased depressive symptoms that inhibit their ability to bounce back after stressful events. Risk factors for poorer maternal mental health may include declines in father involvement and a lack of coparenting support. This study examined the connected nature of coparenting and father involvement over time among continuously unmarried mothers from the Fragile Families and Child Wellbeing Study. A bidirectional latent growth curve analysis demonstrated that early father involvement was associated with a more gradual decline in coparenting support over the child's first 5 years, while early coparenting support also predicted a slower decline in father involvement over time. Steeper declines in coparenting support and father involvement over time were linked with more maternal depression and lower maternal life satisfaction when their child was nine. Results demonstrate a clear need for targeted intervention with both parents in fragile families to promote involved fathering behavior and enhance coparental relationships.
Foliar water uptake in Amazonian trees: Evidence and consequences
Authors: Binks Oliver , Mencuccini Maurizio , Rowland Lucy , da Costa Antonio C. L. , de Carvalho Claudio José Reis , Bittencourt Paulo , Eller Cleiton , Teodoro Grazielle Sales , Carvalho Eduardo Jorge Maklouf , Soza Azul , Ferreira Leandro , Vasconcelos Steel Silva , Oliveira Rafael , Meir Patrick
Published: April 2019

The absorption of atmospheric water directly into leaves enables plants to alleviate the water stress caused by low soil moisture, hydraulic resistance in the xylem and the effect of gravity on the water column, while enabling plants to scavenge small inputs of water from leaf‐wetting events. By increasing the availability of water, and supplying it from the top of the canopy (in a direction facilitated by gravity), foliar uptake (FU) may be a significant process in determining how forests interact with climate, and could alter our interpretation of current metrics for hydraulic stress and sensitivity. FU has not been reported for lowland tropical rainforests; we test whether FU occurs in six common Amazonian tree genera in lowland Amazônia, and make a first estimation of its contribution to canopy–atmosphere water exchange. We demonstrate that FU occurs in all six genera and that dew‐derived water may therefore be used to “pay” for some morning transpiration in the dry season. Using meteorological and canopy wetness data, coupled with empirically derived estimates of leaf conductance to FU (kfu), we estimate that the contribution by FU to annual transpiration at this site has a median value of 8.2% (103 mm/year) and an interquartile range of 3.4%–15.3%, with the biggest sources of uncertainty being kfu and the proportion of time the canopy is wet. Our results indicate that FU is likely to be a common strategy and may have significant implications for the Amazon carbon budget. The process of foliar water uptake may also have a profound impact on the drought tolerance of individual Amazonian trees and tree species, and on the cycling of water and carbon, regionally and globally.
A spatiotemporal assessment of field residues of rice, maize, and wheat at provincial and county levels in China
Authors: Lin Tao , Xu Jialu , Shen Xiqiang , Jiang Hao , Zhong Renhai , Wu Sensen , Du Zhenhong , Rodriguez Luis , Ting K. C.
Published: April 2019

China has a huge resource potential for biomass‐based renewable energy development, but the resources of field residues are still not effectively used. Rice, maize, and wheat made up 89% of staple crop production in China in 2009. A comprehensive assessment of field residues of these three crops is necessary for the development of biomass‐based industries. This research was based on multiyear county‐level data of crop production, area and yield, as well as the crop phenology information from agrometeorological stations. Spatial and temporal analyses were conducted to quantify the spatial patterns, seasonal variations, and temporal trends of the three major field residues. The mean amount of field residue of rice, maize, and wheat was 470.8 Mt/year from 2002 to 2009. Rice residue topped the field residues at 188.5 Mt/year, followed by maize (152.6 Mt/year) and wheat (129.8 Mt/year). The resource supply of field residues varied temporally throughout the season, where peak months are May, June, September, and October. The resources of all three field residues increased from 2002 to 2009, topped by maize residues at a rate of 10.0 Mt/year. Spatially, high production counties had the fast growth rate and a strong positive spatial autocorrelation. The results showed that the intersection area of East and South Central regions has a spatially concentrated residue density and a stable supply for 5 months. The region can be considered as a suitable region for bioenergy development. A better understanding of spatial and temporal distribution of crop residues could facilitate strategic and tactical bioenergy planning.
Facilitators and barriers to co‐research by people with dementia and academic researchers: Findings from a qualitative study
Authors: Waite Jacob , Poland Fiona , Charlesworth Georgina
Published: April 2019

Background

Public and patient involvement (PPI) is now established in dementia research. Barriers and facilitators to engagement from family carers and people in early stages of dementia have been explored. However, specific barriers and facilitators to co‐research with people with dementia have not previously been investigated.

Objective

To discover the facilitators of, and barriers to, involving people with dementia as co‐researchers, from the perspectives of people with dementia, gatekeepers (family caregivers, ethics committee members, service providers) and researchers.

Design

Thematic analysis of data from individual interviews about the co‐research experience.

Results

Four themes emerged from interviews with 19 participants (five people with dementia): “getting one's head round it” (assumptions about research and dementia; different forms of language); practicalities (eg transport; accessibility of communication); “this feeling of safety” (perceptions of danger, protectiveness and opportunities for building trust); and motivations (“making a difference” and “keeping doing”).

Conclusions

Findings both replicate and extend previous knowledge on PPI in dementia. Cognitive capacity of potential co‐researchers with dementia is only a part of the picture, with attitudes and expectations of researchers, gatekeepers and people with dementia also forming barriers. Researcher education, adequate resourcing, and both creativity and flexibility are needed to support recruitment of co‐researchers with dementia and to enable meaningful co‐research.
Atypical intraductal proliferation detected in prostate needle biopsy is a marker of unsampled intraductal carcinoma and other adverse pathological features: a prospective clinicopathological study of 62 cases with emphasis on pathological outcomes
Authors: Shah Rajal B , Nguyen Jane K , Przybycin Christopher G , Reynolds Jordan P , Cox Roni , Myles Jonathan , Klein Eric , McKenney Jesse K
Published: April 2019

Aims

Intraductal proliferations of the prostate with more complexity and/or cytological atypia than high‐grade prostate intra‐epithelial neoplasia (HGPIN), but falling short of intraductal carcinoma (IDC‐P), are described as ‘atypical intraductal proliferation’ (AIP). When present in needle biopsy (NBX) without IDC‐P, the clinical significance is not known.

Methods and results

Sixty‐two NBX cases were diagnosed as AIP over 7 years with estimated incidence of 1%. AIP was characterised by loose cribriform architecture (90%) or non‐cribriform architecture exhibiting significant nuclear atypia that fell short of IDC‐P. Fifty patients had concomitant PCa (20% grade group (GG) 1, 48% GG2, 14% GG3, 8% GG4 and 10% GG 5), and 12 had AIP alone. Of 40 patients who were candidates for no therapy (AIP alone) or active surveillance (AIP with GG1 or GG2 PCa without cribriform pattern 4), 20 had subsequent follow‐up pathology [seven NBXs and 13 radical prostatectomy (RP)]. Of the 12 AIP only patients, six had a subsequent biopsy diagnosis of: benign prostate (two), IDC‐P with PCa (one) and PCa (three). One or more adverse pathological features at subsequent RP were present in 93% of patients with AIP and GG1 or GG2 PCa, defined as: GG ≥ 3 (15%), IDC‐P (77%), cribriform Gleason pattern 4 (69%), pT3a (77%) or pT3b (8%).

Conclusions

AIP in NBX may be a marker of unsampled IDC‐P and/or other adverse pathological features in suspected low‐ to intermediate‐risk PCa. AIP should be considered distinct from HGPIN for risk assessment and warrant consideration for further work‐up to detect unsampled high‐risk PCa.
Osteoarthritis‐alleviating effects in papain‐induced model rats of chicken cartilage hydrolysate and its peptide fractions
Authors: Yang Jingyi , Sun‐Waterhouse Dongxiao , Xiao Yu , He Weiwei , Zhao Mouming , Su Guowan
Published: April 2019

This study aims to discover natural bioactive substances as alternative therapies to current medical and surgical treatments for osteoarthritis (OA). Chicken cartilage hydrolysate (CCH) was produced using trypsin and separated via ultrafiltration into CCH‐I (molecular weight (MW) > 10 kDa) and CCH‐II (MW <10 kDa). Results showed that CCH and its fractions (CCH‐I and CCH‐II) could relieve OA with different extents, and the outcome using these treatments depended on their especial composition. CCH‐II (a fraction rich in low MW peptides with no chondroitin sulphate (CS) and low in sugar) exhibited desired OA‐alleviating effect in papain‐induced rat and highest in vitro antioxidant activities. CCH‐I (a fraction rich in CS and in high MW peptides) might have an adverse effect on renal function. Therefore, it is industrially feasible to produce anti‐inflammatory and antioxidative CCH, especially CCH‐II, with the therapeutic potential for alleviating or treating OA. Further separation of CS from CCH‐I may lead to a commercial pure CS product for treating OA.
Eating behaviour and oxytocin in patients with childhood‐onset craniopharyngioma and different grades of hypothalamic involvement
Authors: Daubenbüchel Anna M. , Özyurt Jale , Boekhoff Svenja , Warmuth‐Metz Monika , Eveslage Maria , Müller Hermann L.
Published: April 2019

Background

Patients with childhood‐onset craniopharyngioma (CP) often suffer from tumour or treatment‐related hypothalamic lesions (HL). These lesions may alter production of oxytocin, which plays a major role in the regulation of eating behaviour and body composition.

Objective

In CP with different degrees of HL, we investigated associations between HL, eating behaviour/eating attitudes, and oxytocin saliva concentrations (OSC).

Methods

In a cross‐sectional case‐control study on 34 CP and 73 healthy controls, OSC were measured before, and 60 minutes after breakfast by immunoassay. Eating behaviour, attitudes, and habits were assessed by standardized questionnaires.

Results

CP with anterior + posterior HL presented with more adverse eating behaviours/symptoms of eating disorders than CP without HL, CP with anterior HL, and controls. Eating behaviour in CP with anterior HL was similar to controls, except for their tendency towards high dietary restraints. Decreases in postprandial compared with fasting OSC were associated with adverse eating behaviour in CP and controls and with higher BMI in CP.

Conclusions

CP with anterior HL and CP with anterior + posterior HL present with distinct patterns of eating behaviour. Reduced postprandial compared with fasting OSC is associated with weight problems in CP and with adverse eating behaviour and symptoms of eating disorders in both CP and controls.
Inventor Chief Executive Officers and Firm Innovation
Authors: Bostan Ibrahim , Mian G. Mujtaba
Published: April 2019

Using a novel, manually collected dataset, we find that firms whose chief executive officer (CEO) is an inventor experience significantly better innovation outcomes, as measured by patents and future citations. We obtain these results in models with firm fixed effects, in difference‐in‐difference analysis of transitioning CEOs that controls for the CEO fixed effects, and among firms with founder CEOs. Firms led by an inventor CEO also exhibit greater tolerance for failure as indicated by a greater number of both highly cited and uncited patents, and engage more in explorative search strategies that exploit new technological trajectories. Stock market, however, seems unable to fully capture the positive impact of inventor CEOs on future innovation: firms whose CEO transitions to be an inventor experience positive abnormal stock returns, especially during the early years following the transition.
Essential global health competencies for baccalaureate nursing students in the United States: A mixed methods Delphi study
Authors: Torres‐Alzate Herica M. , Wilson Lynda Law , Harper Doreen C. , Ivankova Nataliya V. , Heaton Karen , Shirey Maria R.
Published: April 2019

Aims

To reach consensus among experts on global health competencies for baccalaureate nursing students in the USA.

Design

A three‐round modified Delphi study using a mixed methods research approach.

Methods

In the first round, the original list of competencies (Wilson et al., 2012, Journal of Professional Nursing, 28, 213–222) was revised based on prior research, a review of literature and the Nursing Global Health Competencies Framework developed by the fist author. Nine global health domains and 52 competencies were identified in Round One. In Round Two, two surveys were conducted for validation of the revised list of global health competencies using a group of six nurses with expertise in global health and baccalaureate nursing education, which produced modifications in the competencies used for the third phase of the study. In Round Three, 41 participants completed a survey to rate the extent to which they thought the competencies obtained in Round Two were essential for baccalaureate nursing education in the United States. Data collection took place from May 2017 ‐ January 2018.

Results

A group of experts in global health and baccalaureate nursing education from the United States achieved consensus that 40 global health competencies were essential for baccalaureate nursing education in the United States.

Conclusion and Impact

The domains and competencies derived in this study can be used to guide undergraduate nursing curriculum development in global health and provide a framework for both clinical instruction and evaluation of global health student experiences.