bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ezh2-dependent epigenetic reprogramming controls a developmental switch between modes of gastric neuromuscular regulation
Authors: Syed Sabriya A. , Hayashi Yujiro , Lee Jeong-Heon , Yan Huihuang , Lorincz Andrea , Strege Peter R. , Gajdos Gabriella B. , Milosavljevic Srdjan , Nie Jinfu , Rumessen Jüri J. , Gibbons Simon J. , Horvath Viktor J. , Bardsley Michael R. , Redelman Doug D. , Klein Sabine , Saur Dieter , Farrugia Gianrico , Zhang Zhiguo , Urrutia Raul A. , Ordog Tamas 
Published: December 2018

SUMMARYPhysiological interconversion between specialized cell types has only been described in a few mammalian tissues and the mechanisms remain obscure. Using genetic lineage tracing during postnatal development and in-vitro models we demonstrate conversion of gastric interstitial cells of Cajal (ICC), regulatory cells that electrically pace phasic contractions and mediate nitrergic and cholinergic neural control of smooth muscle cells, into phenotypically distinct “fibroblast-like” interstitial cells (FLC), which only mediate purinergic signaling. Mechanistically, we find this transition to be epigenetically governed by H3K27 trimethylation of cell identity-related promoters whose susceptibility to repression is predicted by H3K27 acetylation patterns in ICC. The phenotypic switch was reversible by inhibition, knockdown or in-vivo genomic inactivation of the polycomb H3K27 methyl-transferase Ezh2. These results demonstrate a role for Ezh2-mediated epigenetic repression in physiological mammalian transdifferentiation and identify FLC as a reserve from which ICC can potentially be restored in common gastrointestinal disorders where ICC are depleted.GRAPHICAL ABSTRACTHIGHLIGHTSGastric pacemaker cells (ICC) transdifferentiate into quiescent cells (FLC) in vivoICC-to-FLC shift switches neural control from nitrergic/cholinergic to purinergicEzh2-mediated H3K27me3 represses cell-identity genes during ICC-to-FLC transitionEzh2 inhibition restores ICC numbers, phenotype and functioneTOC BLURBSyed et al. find aging to cause transdifferentiation of gastric pacemaker cells (interstitial cells of Cajal, ICC), which also communicate cholinergic and nitrergic neurotransmission to smooth muscle cells, into quiescent “fibroblast-like cells” (FLC), which only mediate purinergic signals. This switch is governed by Ezh2, whose inhibition can reverse ICC depletion.
Genome sequencing analysis identifies high-risk Epstein-Barr virus subtypes for nasopharyngeal carcinoma
Authors: Xu Miao , Yao Youyuan , Chen Hui , Zhang Shanshan , Xiang Tong , Cao Su-Mei , Zhang Zhe , Luo Bing , Liu Zhiwei , Li Zilin , He Guiping , Feng Qi-Sheng , Chen Li-Zhen , Guo Xiang , Jia Weihua , Chen Ming-Yuan , Zhao Bingchun , Zhang Xiao , Xie Shang-Hang , Peng Roujun , Chang Ellen T. , Pedergnana Vincent , Feng Lin , Bei Jin-Xin , Xu Ruihua , Zeng Mu Sheng , Ye Weimin , Adami Hans-Olov , Lin Xihong , Zhai Weiwei , Zeng Yi-Xin , Liu Jianjun 
Published: December 2018

SummaryEpstein-Barr virus (EBV) infection is ubiquitous worldwide and associated with multiple cancers including nasopharyngeal carcinoma (NPC). The role of EBV viral genomic variation in NPC development and its striking endemicity in southern China has been poorly explored. Through large-scale genome sequencing and association study of EBV isolates from China, we identified two non-synonymous EBV variants withinBALF2strongly associated with NPC risk (conditionalPvalue 1.75×10-6for SNP162476_C and 3.23×10-13for SNP163364_T), whose cumulative effects contributed to 83% of the overall risk in southern China. Phylogenetic analysis of the risk variants revealed a unique origin in southern China followed by clonal expansion. EBVBALF2haplotype carrying the risk variants were shown to reduce viral lytic DNA replication, as a result potentially promoting viral latency. Our discovery has not only provided insight to the unique endemic pattern of NPC occurrence in southern China, but also paved the way for the identification of individuals at high risk of NPC and effective intervention program to reduce the disease burden in southern China.
SapM mutation to improve the BCG vaccine: genomic, transcriptomic and preclinical safety characterization
Authors: Festjens Nele , Vandewalle Kristof , Houthuys Erica , Plets Evelyn , Vanderschaeghe Dieter , Borgers Katlyn , Hecke Annelies Van , Tiels Petra , Callewaert Nico 
Published: December 2018

AbstractThe Mycobacterium bovis Bacille Calmette Guérin (BCG) vaccine shows variable efficacy in protection against adult tuberculosis (TB). Earlier, we have described a BCG mutant vaccine with a transposon insertion in the gene coding for the secreted acid phosphatase SapM, which led to enhanced long-term survival of vaccinated mice challenged with TB infection. To facilitate development of this mutation as part of a future improved live attenuated TB vaccine, we have now characterized the genome and transcriptome of this sapM::Tn mutant versus parental BCG Pasteur. Furthermore, we show that the sapM::Tn mutant had an equal low pathogenicity as WT BCG upon intravenous administration to immunocompromised SCID mice, passing this important safety test. Subsequently, we investigated the clearance of this improved vaccine strain following vaccination and found a more effective innate immune control over the sapM::Tn vaccine bacteria as compared to WT BCG. This leads to a fast contraction of IFNγ producing Th1 and Tc1 cells after sapM::Tn BCG vaccination. These findings corroborate that a live attenuated vaccine that affords improved long-term survival upon TB infection can be obtained by a mutation that further attenuates BCG. These findings suggest that an analysis of the effectiveness of innate immune control of the vaccine bacteria could be instructive also for other live attenuated TB vaccines that are currently under development, and encourage further studies of SapM mutation as a strategy in developing a more protective live attenuated TB vaccine.
The impact of the genetic background on gene deletion phenotypes inSaccharomyces cerevisiae
Authors: Galardini Marco , Busby Bede P. , Vieitez Cristina , Dunham Alistair S. , Typas Athanasios , Beltrao Pedro 
Published: December 2018

AbstractLoss-of-function (LoF) mutations associated with disease don’t manifest equally in different individuals, a phenomenon known as incomplete penetrance. The impact of the genetic background on incomplete penetrance remains poorly characterized. Here, we systematically assessed the changes in gene deletion phenotypes for 3,786 gene knockouts in fourSaccharomyces cerevisiaestrains and 38 conditions. We observed 16% to 42% of deletion phenotypes changing between pairs of strains with a small fraction conserved in all strains. Conditions causing higher WT growth differences and the deletion of pleiotropic genes showed above average changes in phenotypes. We further illustrate how these changes affect the interpretation of the impact of genetic variants across 925 yeast isolates. These results show the high degree of genetic background dependencies for LoF phenotypes.
Gut microbiome communication with bone marrow regulates susceptibility to amebiasis
Authors: Burgess Stacey L. , Leslie Jhansi L. , Uddin Md. Jashim , Oakland Noah , Gilchrist Carol , Brett Moreau G. , Watanabe Koji , Saleh Mahmoud , Simpson Morgan , Thompson Brandon A. , Auble David T. , Turner Stephen D. , Giallourou Natasa , Swann Jonathan , Pu Zhen , Ma Jennie Z. , Haque Rashidul , Petri William A. 
Published: December 2018

AbstractThe gut microbiome provides resistance to infection. However, the mechanisms for this are poorly understood. Colonization with the intestinal bacteriumClostridium scindensprovided protection from the parasiteEntamoeba histolyticavia innate immunity. Introduction ofC. scindensinto the gut microbiota epigenetically altered and expanded bone marrow granulocyte-monocyte-progenitors (GMPs) and provided neutrophil-mediated protection against subsequent challenge withE. histolytica. Adoptive transfer of bone-marrow fromC. scindenscolonized-mice into naïve-mice protected against ameba infection and increased intestinal neutrophils. Because of the known ability ofC. scindensto metabolize the bile salt cholate, we measured deoxycholate and discovered that it was increased in the sera ofC. scindenscolonized mice, as well as in children protected from amebiasis. Administration of deoxycholate alone (in the absence ofC. scindens) increased the epigenetic mediator JMJD3 and GMPs and provided protection from amebiasis. In conclusion the microbiota was shown to communicate to the bone marrow via microbially-metabolized bile salts to train innate immune memory to provide antigen-nonspecific protection from subsequent infection. This represents a novel mechanism by which the microbiome protects from disease.One Sentence SummaryIntroduction of the human commensal bacteriaClostridium scindensinto the intestinal microbiota epigenetically alters bone marrow and protects from future parasite infection.
Widespread PERK-dependent repression of ER targets in response to ER stress
Authors: Gonen Nir , Sabath Niv , Burge Christopher B. , Shalgi Reut 
Published: December 2018

AbstractThe UPR (Unfolded Protein Response) is a well-orchestrated response to ER protein folding and processing overload, integrating both transcriptional and translational outputs. Its three arms in mammalian cells, the PERK translational response arm, together with the ATF6 and IRE1-XBP1-mediated transcriptional arms, have been thoroughly investigated.Using ribosome footprint profiling, we performed a deep characterization of gene expression programs involved in the early and late ER stress responses, within WT or PERK -/- Mouse Embryonic Fibroblasts (MEFs). We found that both repression and activation gene expression programs, affecting hundreds of genes, are significantly hampered in the absence of PERK. Specifically, PERK -/- cells do not show global translational inhibition, nor do they specifically activate early gene expression programs upon short exposure to ER stress. Furthermore, while PERK -/- cells do activate/repress late ER-stress response genes, the response is substantially weaker. Importantly, we highlight a widespread PERK-dependent repression gene expression program, consisting of ER targeted proteins, including transmembrane proteins, glycoproteins, and proteins with disulfide bonds. This phenomenon occurs in various different cell types, and has a major translational regulatory component. Moreover, we revealed a novel interplay between PERK and the XBP1-ATF6 arms of the UPR, whereby PERK attenuates the expression of a specific subset of XBP1-ATF6 targets, further illuminating the complexity of the integrated ER stress response.
The combination of different open innovations: a longitudinal case study
Authors: Yuan Xiaodong , Li Xiaotao 
Published: December 2018

Purpose
The purpose of this paper is to explore how an organization can combine different types of open innovations and what are the key factors that may influence the combination of different open innovations.

Design/methodology/approach
The basic methodology of this paper is the longitudinal inductive analysis within the conceptual framework of the open innovation proposed by Dahlander and Gann (2010). In this case study of Xiaomi Tech Inc., the open innovation combination is investigated through examining 25 new products created between August 2010 and December 2016 in terms of four general types: acquiring, sourcing, selling and revealing open innovation.

Findings
In practice, the combination of different types of open innovations can be realized. A firm may combine different open innovations at three levels: a single product level, a related product cluster level and a company level. In addition, different open innovations can be combined in diverse modes. The purpose of combining different types of open innovations is to overcome the disadvantages of each type and to exploit the advantages of all different types. Many factors may affect a firm’s option of how to combine open innovations. At different development stages, a firm may make and implement corresponding strategic direction based on its innovation capacity and internal resource. For a given strategy, the firm needs to create profits and manage intellectual property in the implementation of open innovations. These factors are interacted each other, rather than isolated.

Originality/value
The findings of this paper are helpful for better understanding how and why an organization can combine different types of open innovations. From a managerial point of view, an organization may combine different types of open innovations to leverage advantages and avoid disadvantages of each certain type of open innovation. An appropriate combination of different open innovations can effectively improve new product development.
Critical perspectives on international pharmaceutical innovation
Authors: Callaghan Christian William 
Published: December 2018

Purpose
This paper aims to argue that certain insights offered by Kuhn and Foucault may be of use to those seeking to resist a global paradigm of inequality in access to the outcomes of pharmaceutical development. It is further argued that these relationships are not independent of certain power relationships. This critical review seeks to highlight certain of these power relationships, and to suggest how they might be better managed to ensure more equitable outcomes for those in society that are most vulnerable to innovation failure.

Design/methodology/approach
This research takes the form of a critical review paper, seeking to develop theory though a synthesis of literature.

Findings
Unlike market incentives, it might be the research process itself that is most vulnerable to stakeholder resistance to slow and unequal delivery of life-saving pharmaceutical development. Given that a lack of responsiveness to societal needs can itself be considered unethical, Kuhnian theory predicting pharmaceutical innovation failure is related to what Foucault describes as a system of oppression, whereby power relationships disadvantage those most vulnerable and powerless.

Research limitations/implications
Given the rise of movements like citizen science and participant-led research, as well as new ethical frameworks premised on increasing accountability in science, Foucault’s principles are considered to echo a general trend towards the democratisation of science, and towards increasing the responsiveness of pharmaceutical development to societal needs.

Originality/value
A novel synthesis of literature is undertaken, offering useful theoretical insights into how social actors might contribute to enabling a more responsive system of international healthcare business.
More product, more process: metadata in digital image collections
Authors: Therrell Grace 
Published: December 2018

Purpose
The purpose of this paper is to discuss the implications of current theories that advocate for minimal levels of description in digital collections. Specifically, this paper looks at the archival theory of “More Product, Less Process” and its encouragement of collection-level description. The purpose of the study was to analyze how levels of description impact resource retrieval.

Design/methodology/approach
This study analyzed 35 images from a New York Public Library (NYPL) digital collection present on the NYPL website and on Flickr. The methodology was designed to reflect users’ information seeking behavior for image collections. There were two research questions guiding this study: what are the descriptive terms used to describe items in digital collections? and what is the success rate of retrieving resources using assigned descriptive terms?

Findings
The results of this study revealed that the images from the NYPL collection were more difficult to find on the institution’s website as compared with Flickr. These findings suggest that lesser levels of description in digital collections hinder resource retrieval.

Research limitations/implications
These findings suggest that lesser description levels hurt the findability of resources. In the wake of theories such as “More Product, Less Process”, information professionals must find ways to assign metadata to individual materials in digital image collections.

Originality/value
Recent research concerning description levels of digital collections is several years old and focuses mostly on the usefulness of collection-level metadata as a supplement to or substitute for item-level metadata. Few, if any, studies exist that explore the implications of description levels on resource retrievability and findability. This study is also unique in that it discusses these implications in the context of less-is-more theories of archival processing.
Implementation of RFID in university libraries of Bangladesh
Authors: Rahman Md. Habibur , Islam Md. Shiful 
Published: December 2018

PurposeThe purpose of this paper is to describe the present status of implementing innovative radio frequency identification (RFID) technology in university libraries of Bangladesh. The main obstacles of implementing this technology among university libraries and ways to overcome the obstacles are also described.Design/methodology/approachThis study uses both qualitative and quantitative approaches along with review of related literature. The present scenario of RFID implementation status of Bangladesh is shown by a survey with a structured questionnaire and reviewing related literature.FindingsThe findings show that RFID is being used in the university libraries to reduce staff stress, increase efficiency, track and locate items quickly, book drop support at any time, easier circulation, promote self-check-in check-out activities, etc. This study identifies the challenges in libraries of Bangladesh which are lack of adequate funding, unavailability of RFID accessories, lack of skilled manpower, unwillingness, erratic power supply, etc. Also, it suggests some suitable ways such as creating positive impression and attitudes, arrangement of proper training, appointment of skilled manpower and allocation of sufficient budget to overcome the existing challenges of RFID.Originality/valueThe study describes the benefits of RFID technology for libraries, and some recommendations are proposed for extensive use of this technology.
Pakistani prison libraries: an assessment of services and challenges
Authors: Hussain Tauseef , Batool Syeda Hina , Soroya Saira Hanif , Warraich Nosheen Fatima 
Published: December 2018

PurposeThe purpose of the paper is to examine the current status of prison libraries, their role, services and collection in Pakistani context. It also attempts to highlight the main problems faced by selected libraries.Design/methodology/approachThe qualitative research approach was adopted to achieve the study objectives. Data were collected using face-to-face interviews to find out respondents’ views about libraries in prison.FindingsFindings of the study confirmed that inmates’ library queries are mostly related to the legal matters, and it is quite natural. One of the significant services of the Pakistani prison libraries is to help prisoners in their education. The main role of the library caretaker was to educate and offer rehabilitation programs. Unavailability of library space, lack of professional staff, limited collections, poor budgetary situation and censorship issues are the major challenges that Pakistani prison libraries are facing.Social implicationsThe study findings further implicate that open libraries and access to books would promote positivity within society and reduce criminal and immoral acts.Originality/valueIt is the first of its kind and unique study that presents the current situation of prison libraries in the Pakistani context. The study has practical implications for policymakers to give importance to prison libraries in terms of finance, professional staff and the availability of information sources.
Improving outcomes for homeless inpatients in mental health
Authors: Khan Zana , Koehne Sophie , Haine Philip , Dorney-Smith Samantha 
Published: December 2018

Purpose
The purpose of this paper is to describe the delivery of the first clinically led, inter-professional Pathway Homeless team in a mental health trust, within the King’s Health Partners hospitals in South London. The Kings Health Partners Pathway Homeless teams have been operating since January 2014 at Guy’s and St Thomas’ (GStT) and Kings College Hospital and expanded to the South London and Maudsley in 2015 as a charitable pilot, now continuing with short-term funding.

Design/methodology/approach
This paper outlines how the team delivered its key aim of improving health and housing outcomes for inpatients. It details the service development and integration within a mental health trust incorporating the experience of its sister teams at Kings and GStT. It goes on to show how the service works across multiple hospital sites and is embedded within the Trust’s management structures.

Findings
Innovations including the transitional arrangements for patients’ post-discharge are described. In the first three years of operation the team saw 237 patients. Improved housing status was achieved in 74 per cent of patients with reduced use of unscheduled care after discharge. Early analysis suggests a statistically significant reduction in bed days and reduced use of unscheduled care.

Originality/value
The paper suggests that this model serves as an example of person centred, value-based health that is focused on improving care and outcomes for homeless inpatients in mental health settings, with the potential to be rolled-out nationally to other mental health Trusts.
Introducing MathQA: a Math-Aware question answering system
Authors: Schubotz Moritz , Scharpf Philipp , Dudhat Kaushal , Nagar Yash , Hamborg Felix , Gipp Bela 
Published: December 2018

Purpose
This paper aims to present an open source math-aware Question Answering System based on Ask Platypus.

Design/methodology/approach
The system returns as a single mathematical formula for a natural language question in English or Hindi. These formulae originate from the knowledge-based Wikidata. The authors translate these formulae to computable data by integrating the calculation engine sympy into the system. This way, users can enter numeric values for the variables occurring in the formula. Moreover, the system loads numeric values for constants occurring in the formula from Wikidata.

Findings
In a user study, this system outperformed a commercial computational mathematical knowledge engine by 13 per cent. However, the performance of this system heavily depends on the size and quality of the formula data available in Wikidata. As only a few items in Wikidata contained formulae when the project started, the authors facilitated the import process by suggesting formula edits to Wikidata editors. With the simple heuristic that the first formula is significant for the paper, 80 per cent of the suggestions were correct.

Originality/value
This research was presented at the JCDL17 KDD workshop.