bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitotic ER exit site dissociation and reassembly is regulated by TANGO1 phosphorylation status
Authors: Maeda Miharu , Komatsu Yukie , Saito Kota
Published: May 2019

Golgi fragmentation and ER exit site dissociation are considered as the leading causes of mitotic block of secretion from the ER. Although the mechanisms of Golgi fragmentation have been extensively characterized, ER exit block early in mitosis is not well-understood. We previously found that TANGO1 organizes ER exit sites by directly interacting with Sec16. Here, we showed that TANGO1 is phosphorylated by casein kinase 1 (CK1) during mitosis. Interestingly, the interaction with Sec16 was abrogated by phosphorylation of TANGO1, leading to dissociation of the ER exit sites. Moreover, a TANGO1 mutant deficient in phosphorylation inhibited the mitotic dissociation of ER exit sites. In contrast, a TANGO1 mutant mimicking CK1-mediated phosphorylation dissociated ER exit sites in interphase cells. Although CK1 activity remains constant throughout the cell cycle, PP1, a phosphatase for which activity decreases during mitosis, participates in the regulation of TANGO1 phosphorylation. This is the first report demonstrating the mechanisms of ER exit site dissociation during mitosis.
Efficient RNA-mediated reprogramming of human somatic cells to naïve pluripotency facilitated by tankyrase inhibition
Authors: Bredenkamp Nicholas , Yang Jian , Clarke James , Stirparo Giuliano Giuseppe , von Meyenn Ferdinand , Baker Duncan , Drummond Rosalind , li Dongwei , Wu Chuman , Rostovskaya Maria , Smith Austin , Guo Ge
Published: May 2019

In contrast to conventional human pluripotent stem cells (hPSC) that are related to post-implantation embryo stages, naïve hPSC exhibit features of pre-implantation epiblast. Naïve hPSC are established by resetting conventional hPSC, or are derived from dissociated embryo inner cell masses. Here we investigate conditions for transgene-free reprogramming of human somatic cells to naïve pluripotency. We find that tankyrase inhibition promotes RNA-mediated induction of naïve pluripotency. We demonstrate application to independent human fibroblast cultures and endothelial progenitor cells. We show that induced naïve hPSC can be clonally expanded with a diploid karyotype and undergo somatic lineage differentiation following formative transition. Induced naïve hPSC lines exhibit distinctive surface marker, transcriptome, and methylome properties of naïve epiblast identity. This system for efficient, facile, and reliable induction of transgene free naïve hPSC offers a robust platform, both for delineation of human reprogramming trajectories and for evaluating the attributes of isogenic naïve versus conventional hPSC.
Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac: the Aneurysm-Express Biobank Cohort
Authors: van Laarhoven Constance J.H.C.M. , van Setten Jessica , van Herwaarden Joost A. , de Kleijn Dominique P.V. , Pasterkamp Gerard , de Borst Gert J. , van der Laan Sander W.
Published: May 2019

Purpose

Abdominal aortic aneurysms (AAA) have a multifactorial pathology with both genetic and environmental risk factors. Recent genome-wide association studies (GWAS) have discovered ten genetic risk loci for AAA. To what extent these genetic loci contribute to the aneurysm pathology is yet unknown. This study aims to investigate whether genetic risk variants are associated with three clinical features: diameter of aneurysm sac, type of artery and symptoms.

Methods

We used aneurysm tissue from 415 patients included within the Aneurysm-Express biobank. A best fit polygenic risk score (PRS) based on previous GWAS effect size estimates was modeled for each clinical parameter by comparing model predictions across different p-value thresholds. Next, the established 10 risk variants for AAA were tested individually for association with selected clinical phenotypes. Models were corrected for age, sex, ancestral background, smoking status and diameter of the aneurysm sac or artery type if applicable, and data was normalized.

Results

The best fit PRS (including 272 SNPs with PT=0.01015) showed a significant correlation with diameter of the aneurysm sac (R2 = 0.019, p = 0.001). No association was found with clinical symptoms or type of artery. Individual variant analysis showed no clear associations with any of the clinical features.

Conclusions

Within the Aneurysm-Express Biobank Study, a weighted polygenic score of AAA susceptibility explained 1.9% of the phenotypic variation (p = 0.001) in aneurysm diameter. Individual risk variant analysis showed no clear associations. Given our limited sample size, future biobank collaborations need to confirm a potential causal role of individual SNPs on the pathology of aneurysms.
A microwell cell capture device reveals variable response to dobutamine in isolated cardiomyocytes
Authors: Clark J. A. , Weiss J. D. , Campbell S. G.
Published: May 2019

Isolated ventricular cardiomyocytes exhibit substantial cell-to-cell variability, even when obtained from the same small volume of myocardium. In this study, we investigated the possibility that cardiomyocyte responses to β-adrenergic stimulus are also highly heterogeneous. In order to achieve the throughput and measurement duration desired for these experiments, we designed and validated a novel microwell system that immobilizes and uniformly orients isolated adult cardiomyocytes. In this configuration, detailed drug responses of dozens of cells can be followed in parallel for intervals exceeding one hour. At the conclusion of an experiment, specific cells can also be harvested via a precision aspirator for single-cell gene expression profiling. Using this system, we followed changes in Ca2+ signaling and contractility of individual cells under sustained application of either dobutamine or omecamtiv mecarbil. Both compounds increased average cardiomyocyte contractility over the course of an hour, but responses of individual cells to dobutamine were significantly more variable. Surprisingly, some dobutamine-treated cardiomyocytes augmented Ca2+ release without increasing contractility. Other cells responded with increased contractility in spite of unchanged Ca2+ release. Single-cell gene expression analysis revealed a significant correlation between expression of PRKACA and cellular sensitivity to dobutamine, demonstrating that variable drug responses among cells are not merely experimental artifacts. By enabling direct comparison of the functional behavior of an individual cell and the genes it expresses, this new system constitutes a unique tool for interrogating cardiomyocyte drug responses and discovering the genes that modulate them.

SIGNIFICANCE

We have created a microwell capture device that allows drug responses of dozens of isolated adult cardiomyocytes to be monitored for extended intervals. Using the device, we observed striking diversity in the Ca2+ handling and contractility responses of each cell to a β-adrenergic agonist. This included cells that responded to dobutamine by doubling the amplitude of Ca2+ release while decreasing contractility and vice-versa. We further show that these diverse responses can be linked to gene expression differences between cells. This work demonstrates the feasibility of linking the drug responses of individual cells with their gene expression. It opens the possibility of exploiting cell-to-cell variation to discover new genes that participate in and modulate regulatory cascades.
Deconvolution of Nucleic-acid Length Distributions: A Gel Electrophoresis Analysis Tool and Applications
Authors: Ziraldo Riccardo , Shoura Massa J. , Fire Andrew Z. , Levene Stephen D.
Published: May 2019

Next-generation DNA-sequencing (NGS) technologies, which are designed to streamline the acquisition of massive amounts of sequencing data, are nonetheless dependent on various preparative steps to generate DNA fragments of required concentration, purity, and average size (molecular weight). Current automated electrophoresis systems for DNA- and RNA-sample quality control, such as Agilent’s Bioanalyzer ®and TapeStation ® products, are costly to acquire and use; they also provide limited information for samples having broad size distributions. Here we describe a software tool that helps determine the size distribution of DNA fragments in an NGS library, or other DNA sample, based on gel-electrophoretic line profiles. The software, developed as an ImageJ plug-in, allows for straightforward processing of gel images, including lane selection and fitting of univariate functions to intensity distributions. The user selects the option of fitting either discrete profiles in cases where discrete gel bands are visible, or continuous profiles, having multiple bands buried under a single broad peak. The method requires only modest imaging capabilities and is a cost-effective, rigorous alternative characterization method to augment existing techniques for library quality control.
Choosing and learning: outcome valence differentially affects learning from free versus forced choices
Authors: Chambon Valérian , Théro Héloïse , Vidal Marie , Vandendriessche Henri , Haggard Patrick , Palminteri Stefano
Published: May 2019

Positivity bias refers to learning more from positive than negative events. This learning asymmetry could either reflect a preference for positive events in general, or be the upshot of a more general, and perhaps, ubiquitous, “choice-confirmation” bias, whereby agents preferentially integrate information that confirms their previous decision. We systematically compared these two theories with 3 experiments mixing free- and forced-choice conditions, featuring factual and counterfactual learning and varying action requirements across “go” and “no-go” trials. Computational analyses of learning rates showed clear and robust evidence in favour of the “choice-confirmation” theory: participants amplified positive prediction errors in free-choice conditions while being valence-neutral on forced-choice conditions. We suggest that a choice-confirmation bias is adaptive to the extent that it reinforces actions that are most likely to meet an individual’s needs, i.e. freely chosen actions. In contrast, outcomes from unchosen actions are more likely to be treated impartially, i.e. to be assigned no special value in self-determined decisions.
High-throughput propagation of human prostate tissue from induced-pluripotent stem cells
Authors: Hepburn AC , Curry EL , Moad M , Steele RE , Franco OE , Wilson L , Singh P , Crawford SE , Gaughan Luke , Mills IG , Hayward SW , Robson CN , Heer R
Published: May 2019

Primary culture of human prostate organoids is slow, inefficient and laborious. To overcome this, we demonstrate a new high-throughput model where rapidly proliferating and easily handled induced pluripotent stem cells, for the first time, enable generation of human prostate tissue in vivo and in vitro. Using a co-culture technique with urogenital sinus mesenchyme, we recapitulated the in situ prostate histology, including the stromal compartment and the full spectrum of epithelial differentiation. This approach overcomes major limitations in primary cultures of human prostate stem, luminal and neuroendocrine cells, as well as the stromal microenvironment. These models provide new opportunities to study prostate development, homeostasis and disease.
Modeling methylation dynamics with simultaneous changes in CpG islands
Authors: Grosser Konrad , Metzler Dirk
Published: May 2019

Motivation

Probabilistic models for methylation dynamics of CpG sites are usually based on sequence evolution models that assume indepedence between sites. In vertebrate genomes, CpG sites can be clustered in CpG islands, and the amount of methylation in a CpG island can change due to gene regulation processes. We propose a probabilistic model of methylation dynamics that accounts for simultaneous methylation changes in multiple CpG sites belonging to the same CpG island. We further propose a Markov-chain Monte-Carlo method to fit this model to methylation data from cell type phylogenies and apply this method to available data from murine haematopoietic cells.

Results

Branch lengths in cell phylogenies show the amount of changes in methylation in the development of one cell type from another. We show that accounting for CpG island wide methylation changes has a strong effect on the inferred branch lengths and leads to a significantly better model fit for the methylation data from murine haematopoietic cells.

Availability

An implementation of the methods presented in this article is freely available as C++ source code onhttps://github.com//statgenlmu//IWEPoissonPaperunder the terms of the GNU general public license (GPLv3).
Kinetics of cytokine receptor trafficking determine signaling and functional selectivity
Authors: Martinez-Fabregas J. , Wilmes S. , Wang L. , Hafer M. , Pohler E. , Lokau J. , Garbers C. , Cozzani A. , Piehler J. , Kazemian M. , Mitra S. , Moraga I.
Published: May 2019

Cytokines activate downstream signaling networks via assembly of cell surface receptors, but it is unclear whether modulation of cytokine-receptor binding parameters can modify biological outcomes. We have engineered variants of IL-6 with different affinities to the gp130 receptor chain to investigate how cytokine receptor binding kinetics influence functional selectivity. Engineered IL-6 variants showed a range of signaling amplitudes, from minimal to full agonist, and induced biased signaling, with changes in receptor binding kinetics affecting more profoundly STAT1 than STAT3 phosphorylation. We show that this differential signaling arises from defective translocation of ligand-gp130 complexes to the endosomal compartment and competitive STAT1/STAT3 binding to phospho-tyrosines in gp130, and results in unique patterns of STAT3 binding to chromatin. This, in turn, leads to a graded gene expression response and substantial differences in ex vivo differentiation of Th17, Th1 and Treg cells. These results provide a molecular understanding of signaling biased by cytokine receptors, and demonstrate that manipulation of signaling thresholds is a useful strategy to decouple cytokine functional pleiotropy.
Group B rotavirus encodes a functional fusion-associated small transmembrane (FAST) protein
Authors: Diller Julia R. , Parrington Helen M. , Patton John T. , Ogden Kristen M.
Published: May 2019

Rotavirus is an important cause of diarrheal disease in young mammals. Group A rotavirus (RVA) causes most human rotavirus diarrheal disease and primarily affects infants and young children. Group B rotavirus (RVB) has been associated with sporadic outbreaks of human adult diarrheal disease. RVA and RVB are predicted to encode mostly homologous proteins but differ significantly in the proteins encoded by the NSP1 gene. In the case of RVB, the NSP1 gene encodes two putative protein products of unknown function, NSP1-1 and NSP1-2. We demonstrate that human RVB NSP1-1 mediates syncytia formation in cultured human cells. Based on sequence alignment, NSP1-1 from groups B, G, and I contain features consistent with fusion-associated small transmembrane (FAST) proteins, which have previously been identified in otherReoviridaeviruses. Like some other FAST proteins, RVB NSP1-1 is predicted to have an N-terminal myristoyl modification. Addition of an N-terminal FLAG peptide disrupts NSP1-1-mediated fusion, consistent with a role for this fatty-acid modification in NSP1-1 function. NSP1-1 from a human RVB mediates fusion of human cells but not hamster cells and, thus, may serve as a species tropism determinant. NSP1-1 also can enhance RVA replication in human cells, both in single-cycle infection studies and during a multi-cycle time course in the presence of fetal bovine serum, which inhibits rotavirus spread. These findings suggest potential yet untested roles for NSP1-1 in RVB species tropism, immune evasion, and pathogenesis.

IMPORTANCE

While group A rotavirus is commonly associated with diarrheal disease in young children, group B rotavirus has caused sporadic outbreaks of adult diarrheal disease. A major genetic difference between group A and B rotaviruses is the NSP1 gene, which encodes two proteins for group B rotavirus. We demonstrate that the smaller of these proteins, NSP1-1, can mediate fusion of cultured human cells. Comparison with viral proteins of similar function provides insight into NSP1-1 domain organization and fusion mechanism. Our findings are consistent with an important role for a fatty acid modification at the amino terminus of the protein in mediating its function. NSP1-1 from a human virus mediates fusion of human cells, but not hamster cells, and enhances rotavirus replication in culture. These findings suggest potential, but currently untested, roles for NSP1-1 in RVB species tropism, immune evasion, and pathogenesis.
How does task-technology fit influence cloud-based e-learning continuance and impact?
Authors: Cheng Yung-Ming
Published: May 2019

Purpose

According to expectation–confirmation model (ECM) and task-technology fit (TTF) model, the purpose of this paper is to examine the role of TTF in students’ cloud-based e-learning continuance and evaluate whether TTF affects students’ perceived impact on learning of the cloud-based e-learning system within the educational institution.

Design/methodology/approach

Sample data for this study were collected from students enrolled in a comprehensive university in Taiwan. A total of 500 questionnaires were distributed in the campus, and 391 (78.2 percent) usable questionnaires were analyzed using structural equation modeling in this study.

Findings

This study’s results verified that both task characteristics and technology characteristics affected students’ perceived TTF, which significantly contributed to their perceived usefulness, confirmation and satisfaction with the cloud-based e-learning system, and these in turn directly or indirectly led to their continuance intention of the system and perceived impact on learning; essentially, the results strongly supported the research model integrating ECM and TTF model via positioning key constructs as the drivers with all hypothesized links being significant.

Originality/value

This study contributes to an understanding of the TTF in explaining students’ cloud-based e-learning continuance that is difficult to explain with only their utilitarian perception of the cloud-based e-learning system, and further places considerably more emphasis upon students’ perceived impact on learning greatly driven by their TTF in the system. Thus, this study’s empirical evidence on incorporating ECM and TTF model can shed light on the outcome for cloud-based e-learning continuance and enhance better understanding of a richer post-adoption model.
The health challenges of families experiencing homelessness
Authors: Annor Bridget Osei Henewaah , Oudshoorn Abe
Published: May 2019

Purpose

The purpose of this paper is to report the findings of a scoping review on the health challenges of families experiencing homelessness. There is a bi-directional relationship between health and homelessness in that poor health can increase the risk of housing loss, and experiencing homelessness is bad for one’s health. The experience of homelessness differs between populations and this review focuses on families as one of the fastest growing segments of the homeless population. While research has been integrated on the causes of homelessness for families, this same integration has not been conducted looking at health challenges of families experiencing homelessness.

Design/methodology/approach

A scoping review methodology is utilized in the paper. As the goal of this work is to ultimately develop interventions for a Canadian context, primacy is given to Canadian sources, but other relevant literature is also included.

Findings

A clear distinction is seen in the literature between health challenges of children of homeless families and health challenges of parents. These themes are explored separately, and preliminary recommendations are made for potential points of intervention as personal, program and policy levels.

Originality/value

This review of current evidence is an important first step in building a foundation for interventions to improve health outcomes for those experiencing housing loss.
Illuminating undergraduate experiential and situated learning in podiatry clinical placement provision at a UK school of podiatric medicine
Authors: Hayes Catherine , Bussey Sonia , Graham Yitka
Published: May 2019

Purpose

Situated and experiential learning methodologies are largely underresearched in relation to student experience and satisfaction. The purpose of this paper is to illuminate the perspectives of students studying on a BSc (Hons) Podiatry degree programme to establish perceptions of their experience in practice.

Design/methodology/approach

Using an interpretivist methodological framework, Free Association Narrative Interviewing was used to provide an insight into the perceived impact that experiential learning in clinical placements had on undergraduate podiatry students.

Findings

Students perceived that what could not be taught but what could be experienced, contributed much to the confidence that students had gained during their training and which they anticipated would be further developed during the initial years of their training in practice, particularly in the context of the NHS.

Research limitations/implications

This is a study from which it is acknowledged that within the underpinning research design and methodology there is no scope for generalisability.

Practical implications

The study highlights an appreciation for the implication and recognition of “tacit” knowledge, currently recognised in medical curricula as an asset which can aid a move towards higher order critical thinking skills.

Social implications

Student acknowledgement of the need for emphasis on “soft skills” can be posited, in the context of this small-scale study as an appreciation for affective domain learning in the context of podiatric academic and clinical curricula.

Originality/value

Limited information from the extant literature is available in relation to the illumination of podiatry student placement experiences, so this research contributes to an effectively underresearched field.
Family-to-work spillover effects of family incivility on employee sabotage in the service industry
Authors: Cheng Bao , Zhou Xing , Guo Gongxing
Published: May 2019

Purpose

This study aims to explore family incivility as a source of stress originating in the family domain and empirically examine its spillover effects on the workplace.

Design/methodology/approach

Through integrating the work–family interface model with conservation of resources (COR) theory, this study investigated the effect of family incivility as perceived by employees of the service industry on service sabotage, along with the mediating role of family-to-work conflict (FWC) and the moderating role of work–family centrality.

Findings

The results of a three-wave survey of 335 employees in China and 62 of their immediate supervisors demonstrated that family incivility was positively related to service sabotage, and FWC also mediated this relationship. Moreover, work–family centrality was found to strengthen the effect of family incivility on FWC, as well as the mediating effect of FWC on the relationship between family incivility and service sabotage.

Research limitations/implications

This study not only enriched the work–family interface literature but also suggested new insights into sabotage behaviors by focusing on antecedents in the family domain.

Practical implications

By realizing that family incivility has detrimental effects on service employee behaviors, enterprises and managers should provide greater support for employees in managing family incivility and help them to maintain a better balance between work and family life.

Originality/value

This study appears to be the first empirical evidence linking a family stressor (i.e. family incivility) with a workplace behavioral outcome in the service industry (i.e. service sabotage).
Does country-of-origin matter in the era of globalisation? Evidence from cross sectional data in Uzbekistan
Authors: Karimov Farhod , El-Murad Jaafar
Published: May 2019

Purpose

The purpose of this paper is to examine the consistency over time of customer attitude towards country-of-origin in a transitional economy.

Design/methodology/approach

A single cross-sectional study in Uzbekistan was carried out, with n=527, consisting of 374 street and 153 online surveys, replicating a study carried out 20 years earlier.

Findings

Whilst consumers still perceive products from advanced countries to have higher quality, quality perception in relation to country-of-origin information is dynamic and transitional countries can improve the perception of consumers towards their national brands.

Research limitations/implications

This study was carried out in Tashkent, the capital of Uzbekistan, the most populous of the Central Asian republics. Researchers may wish to extend it by examining COO effects in other transitional economies, and additionally to examine the effect of country-of-brand origin.

Practical implications

Customer perceptions and attitudes take a long-time to evolve. This cross-sectional study showed that the COO perception of China has improved significantly and the perception towards the products produced locally in Uzbekistan has also slightly improved across all categories. Strong brands can contribute to the image of the country. Transition countries need to take appropriate marketing actions to cultivate positive perception through innovation and branding.

Originality/value

Prior research has been extended by adding new product categories such as mobile phones, computers, washing machines and air conditioners. This research shows that government officials and exporters in developing countries should prioritise strengthening their country’s image to help domestic marketers export and attract foreign investors. The authors provide insights for marketers to understand the impact of product country-of-origin on customer purchase intention and its antecedents in transitional economies, such as Uzbekistan.
Blockchain technology: implications for operations and supply chain management
Authors: Cole Rosanna , Stevenson Mark , Aitken James
Published: May 2019

Purpose

This paper aims to encourage the study of blockchain technology from an operations and supply chain management (OSCM) perspective, identifying potential areas of application, and to provide an agenda for future research.

Design/methodology/approach

An explanation and analysis of blockchain technology is provided to identify implications for the field of OSCM.

Findings

The hype around the opportunities that digital ledger technologies offer is high. For OSCM, a myriad of ways in which blockchain could transform practice are identified, including enhancing product safety and security; improving quality management; reducing illegal counterfeiting; improving sustainable supply chain management; advancing inventory management and replenishment; reducing the need for intermediaries; impacting new product design and development; and reducing the cost of supply chain transactions. The immature state of practice and research surrounding blockchain means there is an opportunity for OSCM researchers to study the technology in its early stages and shape its adoption.

Research limitations/implications

The paper provides a platform for new research that addresses gaps in knowledge and advances the field of OSCM. A research agenda is developed around six key themes.

Practical implications

There are many opportunities for organisations to obtain an advantage by making use of blockchain technology ahead of the competition, enabling them to enhance their market position. But it is important that managers examine the characteristics of their products, services and supply chains to determine whether they need or would benefit sufficiently from the adoption of blockchain. Moreover, it is important that organisations build human capital expertise that allows them to develop, implement and exploit applications of this technology to maximum reward.

Originality/value

This is one of the first papers in a leading international OSCM journal to analyse blockchain technology, thereby complementing a recent article on digital supply chains that omitted blockchain.
Virtual social enterprise: modeling sustainability of an enterprise by digital intervention
Authors: Javed Asad , Yasir Muhammad
Published: May 2019

Purpose

Social enterprises (SEs) have emerged as a tool to sustainable development. SEs create a social value along with an economic value. However, the aspect of SEs still missing from literature is the process of virtualization. The purpose of this paper is to introduce international social entrepreneurship as an emerging form of social entrepreneurship that is using information and communication technology (ICT)-enabled innovation and networking with international partners as virtual enterprise network, to create social and economic values across the borders.

Design/methodology/approach

In this paper, qualitative research paradigm is adopted to study the internationalization of SEs. To identify the drivers of internationalization, in-depth literature review was conducted. Articles from six databases and Google Scholar were searched to propose a comprehensive model for internationalization of SEs.

Findings

There is limited academic work on the use and impact of digital intervention (ICTs) on SEs and, especially, on the virtualization of SEs as there is no paper explaining virtualization of SEs. This paper proposes a model for the internationalization of SEs, named virtual social enterprise.

Research limitations/implications

The conceptual models and discussions on the virtualization of SEs are very limited in the extant literature. Very few articles could be found that studied the process of internationalization of SEs. Thus, the paper would have far-reaching implications for social enterprise theory and practice.

Originality/value

This is first study of its kind proposing a comprehensive theoretical model for internationalization of SEs. This model could be used by SEs for networking across international boundaries to control the flow of information and to market their products.
Switching on the light: using metagenomic shotgun sequencing to characterize the intestinal microbiome of Atlantic cod
Authors: Riiser Even Sannes , Haverkamp Thomas H.A. , Varadharajan Srinidhi , Borgan Ørnulf , Jakobsen Kjetill S. , Jentoft Sissel , Star Bastiaan
Published: May 2019

Atlantic cod (Gadus morhua) is an ecologically important species with a wide‐spread distribution in the North Atlantic Ocean, yet little is known about the diversity of its intestinal microbiome in its natural habitat. No geographical differentiation in this microbiome was observed based on 16S rRNA amplicon analyses, yet such finding may result from an inherent lack of power of this method to resolve fine‐scaled biological complexity. Here, we use metagenomic shotgun sequencing to investigate the intestinal microbiome of 19 adult Atlantic cod individuals from two coastal populations in Norway–located 470 km apart. Resolving the species community to unprecedented resolution, we identify two abundant species, Photobacterium iliopiscarium and Photobacterium kishitanii, which comprise over 50% of the classified reads. Interestingly, the intestinal P. kishitanii strains have functionally intact lux genes, and its high abundance suggests that fish intestines form an important part of its ecological niche. These observations support a hypothesis that bioluminescence plays an ecological role in the marine food web. Despite our improved taxonomical resolution, we identify no geographical differences in bacterial community structure, indicating that the intestinal microbiome of these coastal cod is colonized by a limited number of closely related bacterial species with a broad geographical distribution.
Evaluating the stoichiometric trait distributions of cultured bacterial populations and uncultured microbial communities
Authors: Manzella Michael , Geiss Roy , Hall Ed K.
Published: May 2019

We measured the stoichiometric trait distribution of cultured freshwater bacterial populations under different resource conditions and compared them to natural microbial communities sampled from three lakes. Trait distributions showed population differences among growth phases and community differences among lakes that would have been masked by only reporting the mean biomass value. The stoichiometric trait distribution of the environmental isolates changed with P availability, growth phase and genotype, with P availability having the strongest effect. The distribution of biomass ratios within each isolate growth experiment were the most constrained during the stages of rapid growth and commonly had unimodal distributions. In contrast to the population distributions, the distribution of N:P and C:P for a similar number of cells from each of the lake communities had narrower stoichiometric distributions and more commonly exhibited multiple modes. © 2019 Society for Applied Microbiology and John Wiley & Sons Ltd
A Tale of Two Inquiries: Sans Everything and Ely
Authors: Hilton Claire
Published: May 2019

The government acknowledged scandalously poor care of long‐stay patients in National Health Service (NHS) hospitals in 1969. This followed the Ely Hospital inquiry, which emerged in the aftermath of revelations of abuse at seven hospitals described in Barbara Robb's book Sans Everything: A Case to Answer (1967). Allegations in Sans Everything and at Ely were similar. However, the inquiry committees which investigated, ‘disproved’ those in Sans Everything and upheld those at Ely. The Ely inquiry became pivotal to NHS policy reform for long‐stay mental illness and mental handicap hospitals, and for giving patients and their families a greater voice if they had concerns about inadequacies. This paper explains the relationship between Sans Everything and ‘Ely’ and analyses the impact of Robb's work—her high‐profile press campaign, networking, and determination to achieve improvement—which triggered revelations at Ely and elsewhere, and helped shape the course and constructive outcome of the Ely inquiry.
Economic performance of state‐owned enterprises under the Chinese Communist Party's supervision: Some reflection on China's economic reform
Authors: Hu Len‐Kuo , Lee Daniel C.
Published: May 2019

This study examines the economic behaviour of state‐owned enterprises in China with special emphasis on the role of the state's sole party as either an agent (management) or supervisor in the enterprises. It is found that with the construction of an incentive‐compatible compensation design and the Chinese Communist Party orchestrating an appropriate objective guideline for its members to follow, state or socialist capitalism could still achieve efficient economic performance. If party members did not behave prudently or pursued their personal interests instead of the state's overall welfare, there could be grave consequences, including corruption, nepotism or even the breakdown of the system.
Tax Deferral and Mutual Fund Inflows: Evidence from a Quasi‐Natural Experiment
Authors: Cappelletti Giuseppe , Guazzarotti Giovanni , Tommasino Pietro
Published: May 2019

We propose a new method to identify the impact of a change in the tax burden on mutual fund inflows. We use quasi‐experimental data from Italy where, starting from July 2011, the tax regime for domestic mutual funds was changed from an accruals basis to a realisation basis, while the taxation of foreign funds remained on a realisation basis. We find that the reform has had a positive effect on net inflows of Italian funds (the treated group) with respect to foreign funds (the control group). The effect is both economically and statistically significant. Moreover, there is no evidence that the increase in the demand for Italian funds came at the expense of foreign funds.
Comparison of ankylosing spondylitis and non‐radiographic axial spondyloarthritis in a multi‐ethnic Asian population of Singapore
Authors: Hong Cassandra , Kwan Yu Heng , Leung Ying‐Ying , Lui Nai Lee , Fong Warren
Published: May 2019

Objectives

To compare clinical characteristics, disease activity, patient‐reported outcomes and associated comorbidities between patients with ankylosing spondylitis (AS) and non‐radiographic axial spondyloarthitis (nr‐axSpA) in a multi‐ethnic Asian population of Singapore.

Methods

We used data from the PREcision medicine in SPONdyloarthritis for Better Outcomes and Disease Remission (PRESPOND) registry in Singapore General Hospital. All patients fulfilled 2009 Assessment in AS International Working Group classification criteria for axial SpA (axSpA). Of these, all AS patients fulfilled the 1984 modified New York criteria. Baseline characteristics, medications, disease activity, patient‐reported outcomes and inflammatory markers were recorded using standardized questionnaires.

Results

Two hundred and sixty‐two axSpA patients (82% Chinese, 79% male) were included. Mean age (SD) at diagnosis was 32.4 (13.1) years, which was similar between AS and nr‐axSpA patients. AS patients were older (mean age 42.7 [13.5] vs 37.4 [13.8] years, P = 0.02), had longer disease duration (mean disease duration 10.9 [8.7] vs 6.4 [4.8] years, P < 0.01), higher Bath Ankylosing Spondylitis Metrology Index (BASMI) (mean BASMI 3.1 [2.3] vs 1.5 [1.5], P < 0.01), more frequently human leukocyte antigen (HLA)‐B27 positive (82% vs 68%, P = 0.03), associated with uveitis (33% vs 17%, P = 0.03), and hypertensive (17% vs 0%, P < 0.01) compared to nr‐axSpA, respectively. Nr‐axSpA patients had higher Bath Ankylosing Spondylitis Global Score (BAS‐G) (mean BAS‐G 46.9 [16.8] vs 38.6 [20.6], P < 0.01), Bath Ankylosing Spondylitis Disease Activity Index (mean [SD] 4.2 [1.6] vs 3.5 [1.9], P = 0.02) and AS quality of life (ASQoL) (mean ASQoL 4.9 [4.8] vs 3.5 [4.1], P = 0.04) scores compared to AS patients respectively at baseline. Patient global assessment, Bath Ankylosing Spondylitis Functional Index, AS Disease Activity Score – C‐reactive protein (CRP), Health Assessment Questionnaire, Short‐Form 36 physical component summary and mental component summary were similar in both groups at baseline, as were medications used and mean erythrocyte sedimentation rate and CRP.

Conclusions

In our multi‐ethnic Asian cohort, patients with AS are more likely to be HLA‐B27 positive, have uveitis, hypertensive, and have poorer spinal mobility, while nr‐axSpA patients tend to experience poorer well‐being and quality of life.
Phase II APEC trial: The impact of primary tumor side on outcomes of first‐line cetuximab plus FOLFOX or FOLFIRI in patients with RAS wild‐type metastatic colorectal cancer
Authors: Price Timothy , Shen Lin , Ma Brigette , Esser Regina , Chen Wenfeng , Gibbs Peter , Lim Robert , Cheng Ann‐Lii
Published: May 2019

Aim

The open‐label, nonrandomized, phase II APEC study enrolled 167 patients with RAS wild‐type (wt) metastatic colorectal cancer (mCRC) to investigate the safety and efficacy of first‐line, every‐2‐weeks cetuximab plus investigator's choice of FOLFIRI or FOLFOX in this patient population.

Methods

A subgroup analysis of the APEC study population by primary tumor location was performed.

Results

A total of 130 patients (81.8%) had left‐sided and 29 (18.2%) had right‐sided mCRC. Median progression‐free survival (PFS), overall survival (OS) and overall response rate (ORR) were 14.0 months, 30.6 months and 68.5% for patients with left‐sided tumors and 8.9 months, 24.6 months and 51.7% for patients with right‐sided mCRC, concurring with pivotal phase III trial results. In patients with right‐sided tumors, median PFS was 15.4 months vs 8.3 months with cetuximab plus FOLFIRI vs cetuximab plus FOLFOX, respectively; median OS was 32.1 months vs 21.8 months with cetuximab plus FOLFIRI vs cetuximab plus FOLFOX, respectively.

Conclusion

The APEC tumor‐location subgroup analysis results were largely consistent with available literature regarding the equivalent efficacy of cetuximab plus FOLFIRI/FOLFOX in patients with left‐sided RAS wt mCRC. A trend toward improved efficacy with cetuximab plus FOLFIRI compared with cetuximab plus FOLFOX was observed in patients with right‐sided tumors; however, a direct comparison between groups cannot be made due to the nonrandomized study design. Nevertheless, the similar ORR observed with either chemotherapy backbone in patients with right‐sided RAS wt mCRC suggests a potential role for both regimens in this patient population when cytoreduction is a treatment goal.
EUFOREA consensus on biologics for CRSwNP with or without asthma
Authors: Fokkens Wytske J. , Lund Valerie , Bachert Claus , Mullol Joaquim , Bjermer Leif , Bousquet Jean , Canonica Giorgio W. , Deneyer Lauren , Desrosiers Martin , Diamant Zuzana , Han Joseph , Heffler Enrico , Hopkins Claire , Jankowski Roger , Joos Guy , Knill Andrew , Lee Jivianne , Lee Stella E. , Mariën Gert , Pugin Benoit , Senior Brent , Seys Sven F. , Hellings Peter W.
Published: May 2019

Novel therapies such as type 2 targeting biologics are emerging treatment options for patients with chronic inflammatory respiratory diseases, fulfilling the needs of severely uncontrolled patients. The majority of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and over half of patients with asthma show a type 2 inflammatory signature in sinonasal mucosa and/or lungs. Importantly, both chronic respiratory diseases are frequent comorbidities, ensuring alleviation of both upper and lower airway pathology by systemic biological therapy. Type 2‐targeting biologics such as anti‐IgE, anti‐IL4Rα, anti‐IL5, and anti‐IL5Rα have entered the market for selected pheno/endotypes of asthma patients and may soon also become available for CRSwNP patients. Given the high prevalence of chronic respiratory diseases and the high cost associated with biologics, patient selection is crucial in order to implement such therapies into chronic respiratory disease care pathways.

The European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) organized a multidisciplinary Expert Board Meeting to discuss the positioning of biologics into the care pathways for CRSwNP patients with and without comorbid asthma.
Dramatically deteriorated quality of life in men with prostatitis‐like symptoms
Authors: Mändar R. , Korrovits P. , Rahu K. , Rahu M. , Sibul E.‐L. , Mehik A. , Punab M.
Published: May 2019

Background

Despite widespread occurrence and poor comprehension, prostatitis has been largely under‐researched.

Objective

To compare complaints, general and sexual health, co‐morbidities, risk factors, and lifestyle in men with and without prostatitis‐like symptoms (PLS).

Material and methods

The cross‐sectional study included 20‐ to 59‐year‐old male residents of Estonia. Questionnaire data of 82 men with PLS and of 711 men without PLS were compared.

Results and discussion

A third of men with PLS considered their health poor, with more frequently diagnosed renal diseases, benign prostate hyperplasia, STDs, chronic nervous system diseases, and depression in them than in controls. They reported more cystitis and gynecological inflammations in their partners, and more prostatitis in their close relatives. This familial predisposition indicates possible genetic and immunologic background of PLS that may be associated also with susceptibility to respiratory tract infections revealed for the first time in our study. By the personality type, the men in the PLS group were less calm but more worrying. Hard drinks, antidepressants, sedative, and sleeping pills were more frequently consumed, and nightshift working and continuous stress were more commonly seen among men with than without PLS. PLS disturbed the sexual life as well as everyday activities.

Conclusions

The men with PLS are characterized by remarkable complex of co‐morbidities, habits, and attitudes. PLS possess substantial negative impact on quality of life. Successful work‐up of these patients needs multidimensional treatment modalities that take into consideration major factors of syndrome. Genetic factors and central nervous system imbalance but also partner's genital tract microbiota as the potential contributing and/or perpetuating factors to PLS need more scientific attention.
Resectable recurrent colorectal liver metastasis: can radiofrequency ablation replace repeated metastasectomy?
Authors: Mao Rui , Zhao Jian‐Jun , Bi Xin‐Yu , Zhang Ye‐Fan , Han Yue , Li Zhi‐Yu , Zhao Hong , Cai Jian‐Qiang
Published: May 2019

Background

Percutaneous radiofrequency ablation (RFA) is used as a first‐line treatment for colorectal liver metastases that recur after first liver resection in our institution. We aim to evaluate its therapeutic efficacy compared to repeated surgical resection.

Methods

A retrospective review was performed in 104 patients treated with curative intent for resectable recurrent colorectal liver metastases.

Results

Sixty‐one patients underwent RFA and 43 patients underwent surgery. The overall recurrence rates were 82% in the RFA group and 65.1% in the resection group (P = 0.05). The local recurrence rate on a lesion‐basis was markedly higher after RFA than that after resection (16.7% versus 7.3%, P = 0.04). The difference remained significant in patients with a maximum lesion diameter >3 cm (24.5% versus 7.6%, P = 0.01). RFA treatment was independently associated with recurrence on multivariate analyses (P = 0.01). 69.7% of RFA patients and 42.6% of surgery patients with intrahepatic recurrence were amenable to repeated local treatment (P = 0.05), leading to the equivalent actuarial 3‐year progression free survival rates (RFA: 29.1% versus Resection: 33.1%, P = 0.48) and 5‐year overall survival rates in the two treatment groups (RFA: 33% versus Resection: 28.4%, P = 0.36).

Conclusions

Surgery remains the treatment of choice for resectable recurrence. RFA may offer similar benefit in selected patients.
Selective laser trabeculoplasty in exfoliative glaucoma eyes with prior argon laser trabeculoplasty
Authors: Ilveskoski Lotta , Taipale Claudia , Tuuminen Raimo
Published: May 2019

Purpose

To explore the efficacy of selective laser trabeculoplasty (SLT) within eyes with exfoliative glaucoma and history of prior argon laser trabeculoplasty (ALT).

Methods

A single‐centre trial consisting of 47 patients (47 eyes) with uncontrolled exfoliative glaucoma. The main outcome measure was intraocular pressure (IOP) reduction 3 and 9 months afterSLT. Treatment success was defined as reduction from the preoperativeIOPby 20% and 2 mmHg (<12 mmHg), 3 mmHg (12‐16 mmHg) or 4 mmHg (>16 mmHg) depending on the baselineIOP.

Results

Patient age was 79.3 ± 7.6 years (mean ± SD) and gender distribution 15 males and 32 females. The mean pre‐SLT IOPwas 15.6 ± 5.1 (range 9–28) mmHg, and mean number of glaucoma drugs 2.0 ± 1.2. The mean interval between priorALTandSLTwas 44.0 ± 36.9 (range 11–137) months. AfterSLT, the meanIOPchange was −2.7 ± 4.2 mmHg (−14.8 ± 23.5%) at 3 months, and −2.8 ± 3.5 mmHg (−16.3 ± 19.4%) at 9 months. Pre‐SLT IOPcorrelated with theIOPreduction at 3 months (r = 0.530, p < 0.001) and at 9 months (r = 0.432, p = 0.007). The overall success rate was 50% at 3 months, and 42% at 9 months. At both 3 and at 9 months, the cut‐off level for treatment success was achieved when preoperativeIOPwas 18 mmHg and above.IOPlowering effect ofSLTdid not correlate with the number of glaucoma drugs, age, gender or use of prostaglandin inhibitors. Neither postoperative iritis nor other adverse effects were documented during the follow‐up.

Conclusions

Selective laser trabeculoplasty is a safe and noteworthy treatment option to reduceIOPin exfoliative glaucoma eyes, especially with pre‐SLT IOPover 18 mmHg.