bluuebunny/crossref_metadata_2025 huggingface dataset:
Verified the effectiveness of AsCpf1 system in a variety of vertebrate species
Authors: Li Zhuo , Shi Zhaoying , Fan Nana , Chen Yongqiang , Guo Jing , Wu Jingchun , Song Hong , Chu Shilong , Mo Kunlun , Zhao Bentian , Ouyang Zhen , Tian Dandan , Zhao Shaoyang , Zhu Jieying , Chen Jiekai , Chen Yonglong , Lai Liangxue , Pei Duanqing
Published: February 2018

CRISPR/Cpf1 system is a novel genomic editing tool. Because of its more sophisticated components, and lower off-target rate, it has the potential to become a better gene-editing tool. Previous reports showed that CRISPR/Cpf1 could work effectively in multiple species. But our data show that AsCpf1 activity has a big difference in different vertebrates. Using in vitro experiments, we finally learned that the difference between species is due to temperature.
Predicting clinically promising therapeutic hypotheses using tensor factorization
Authors: Yao Jin , Hurle Mark R. , Nelson Matthew R. , Agarwal Pankaj
Published: February 2018

Determining which target to pursue is a challenging and error-prone first step in developing a therapeutic treatment for a disease, where missteps are potentially very costly given the long-time frames and high expenses of drug development. We identified examples of successes and failures of target-indication pairs in clinical trials across 875 targets and 574 disease indications to build a gold-standard data set of 6,140 known clinical outcomes. We used information from Open Targets and others databases that covered 17 different sources of evidence for target-indication association and represented the data as a matrix of 21,437×2,211×17 with over two million non-null values. We designed and executed three benchmarking strategies to examine the performance of multiple machine learning models: Logistic Regression, Elasticnet, Random Forest, Tensor Factorization and Gradient Boosting Machine. With ten-fold cross validation, tensor factorization achieved AUROC=0.82±0.02 and AUPRC=0.71±0.03. Across multiple validation schemes, this was comparable or better than other methods. Tensor factorization is a general form of matrix factorization that has been successfully exploited in recommendation systems that suggest items to users based on their existing preference on a small number of items. Our application, using Bayesian probabilistic modelling, extends the capacity of matrix factorization to model multiple relationships between and among targets and indications. We use the model to show that our predicted probabilities of success correlate with clinical phases, and within clinical phase we can predict which trials are most likely to succeed.
Variations in neuromodulatory chemical signatures define compartments in macaque cortex
Authors: Ward Nicholas J. , Zinke Wolf , Coppola Jennifer J. , Disney Anita A.
Published: February 2018

Subcortical neuromodulatory systems exhibit widespread projections that influence the output of cortical circuits. These modulatory systems have been portrayed as providing global signals to the entirety of cortex based on their widespread innervation. This innervation is not necessarily predictive of the levels of the neuromodulatory molecules that actually provide these signals to cortex. In the present study, we examine tissue concentrations of dopamine, noradrenaline, and serotonin to see how they locally vary across multiple areas of the macaque cortex. Our results indicate that different cortical areas exhibit varying levels of dopamine, noradrenaline, and serotonin. Using cluster analysis, we examine how similar cortical regions are to each other, finding that similarities in neurochemical content are shared by areas that exhibit similar functionality. Altogether, these findings demonstrate that neurochemical signatures vary across cortical regions and help define unique, local neuromodulatory signaling compartments.
Capturing the onset of PRC2-mediated repressive domain formation
Authors: Oksuz Ozgur , Narendra Varun , Lee Chul-Hwan , Descostes Nicolas , LeRoy Gary , Raviram Ramya , Blumenberg Lili , Karch Kelly , Rocha Pedro R. , Garcia Benjamin A. , Skok Jane A. , Reinberg Danny
Published: February 2018

Polycomb repressive complex 2 (PRC2) maintains gene silencing by catalyzing methylation of histone H3 at lysine 27 (H3K27me2/3) within chromatin. By designing a system whereby PRC2-mediated repressive domains were collapsed and then reconstructed in an inducible fashion in vivo, a two-step mechanism of H3K27me2/3 domain formation became evident. First, PRC2 is stably recruited by the actions of JARID2 and MTF2 to a limited number of spatially interacting “nucleation sites”, creating H3K27me3-forming polycomb foci within the nucleus. Second, PRC2 is allosterically activated via its binding to H3K27me3 and rapidly spreads H3K27me2/3 both in cis and in far-cis via long-range contacts. As PRC2 proceeds further from the nucleation sites, its stability on chromatin decreases such that domains of H3K27me3 remain proximal, and those of H3K27me2 distal, to the nucleation sites. This study demonstrates the principles of de novo establishment of PRC2-mediated repressive domains across the genome.
Assessing sufficiency and necessity of enhancer activities for gene expression and the mechanisms of transcription activation
Authors: Catarino Rui R. , Stark Alexander
Published: February 2018

Enhancers are important genomic regulatory elements directing cell type-specific transcription. They assume a key role during development and disease, and their identification and functional characterization have long been the focus of scientific interest. The advent of next-generation sequencing and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-based genome editing has revolutionized the means by which we study enhancer biology. In this review, we cover recent developments in the prediction of enhancers based on chromatin characteristics and their identification by functional reporter assays and endogenous DNA perturbations. We discuss that the two latter approaches provide different and complementary insights, especially in assessing enhancer sufficiency and necessity for transcription activation. Furthermore, we discuss recent insights into mechanistic aspects of enhancer function, including findings about cofactor requirements and the role of post-translational histone modifications such as monomethylation of histone H3 Lys4 (H3K4me1). Finally, we survey how these approaches advance our understanding of transcription regulation with respect to promoter specificity and transcriptional bursting and provide an outlook covering open questions and promising developments.
SNPing away at mutant p53 activities
Authors: Ortiz Guadalupe J. , Lozano Guillermina
Published: February 2018

A delicate balance in the levels of proteins that regulate the p53 tumor suppressor pathway exists such that subtle changes alter p53 tumor suppressor activity and cancer risk. Many single-nucleotide polymorphisms (SNPs) in the p53 pathway alter p53 transcriptional activity and are associated with cancer risk. In addition, some SNPs influence the gain-of-function (GOF) activities of mutant p53 through unknown mechanisms. In this issue of Genes & Development, Basu and colleagues (pp. 230–243) provide direct evidence that the presence of an R72 polymorphism enhances the GOF invasive and metastatic properties of mutant p53 by regulating interactions with PGC-1α, an important regulator of mitochondrial biogenesis and oxidative phosphorylation. The study culminates with evidence that R72 is associated with worse outcomes in human breast cancer.
A rADAR defense against RNAi
Authors: Pasquinelli Amy E.
Published: February 2018

Adenosine deaminases that act on RNA (ADARs) convert adenosines (A) to inosines (I) in stretches of dsRNA. The biological purpose of these editing events for the vast majority of ADAR substrates is largely unknown. In this issue of Genes & Development, Reich and colleagues (pp. 271–282) demonstrate that in Caenorhabditis elegans, A-to-I editing in double-stranded regions of protein-coding transcripts protects these RNAs from targeting by the RNAi pathway. Disruption of this safeguard through loss of ADAR activity coupled with enhanced RNAi results in developmental abnormalities and profound changes in gene expression that suggest aberrant induction of an antiviral response. Thus, editing of cellular dsRNA by ADAR helps prevent host RNA silencing and inadvertent antiviral activity.
“Be here now” – service users’ experiences of a mindfulness group intervention
Authors: Dillon Aiveen , Wilson Charlotte , Jackman Catherine
Published: February 2018

Purpose

The purpose of this paper is to explore service users’ experiences of a mindfulness group intervention.

Design/methodology/approach

In total, 15 participants with a diagnosis of a mild or moderate intellectual disability and concurrent mental health difficulties were interviewed using semi-structured interviews about their experiences of attending the mindfulness group.

Findings

Thematic analysis was used to interpret the data. The three super ordinate themes that emerged were positive aspects of mindfulness, positive aspects of attending the group and negative aspects of attending the group. There were seven subthemes. The results highlighted that participants found the mindfulness group to be beneficial, partly due to specific aspects of the mindfulness intervention and partly due to the group process. The negative aspects of the group were harder to elicit, and were less specifically related to mindfulness.

Originality/value

Mindfulness-based interventions have emerged as a promising approach for individuals with intellectual disabilities with mental health difficulties. There is currently a lack of research exploring service users with intellectual disabilities about their experiences of mindfulness interventions.
Large-scale dynamic and static simulations of complex-shaped granular materials using parallel three-dimensional discrete element method (DEM) on DoD supercomputers
Authors: Yan Beichuan , Regueiro Richard
Published: March 2018

Purpose

The purpose of this paper is to extend complex-shaped discrete element method simulations from a few thousand particles to millions of particles by using parallel computing on department of defense (DoD) supercomputers and to study the mechanical response of particle assemblies composed of a large number of particles in engineering practice and laboratory tests.

Design/methodology/approach

Parallel algorithm is designed and implemented with advanced features such as link-block, border layer and migration layer, adaptive compute gridding technique and message passing interface (MPI) transmission of C++ objects and pointers, for high performance optimization; performance analyses are conducted across five orders of magnitude of simulation scale on multiple DoD supercomputers; and three full-scale simulations of sand pluviation, constrained collapse and particle shape effect are carried out to study mechanical response of particle assemblies.

Findings

The parallel algorithm and implementation exhibit high speedup and excellent scalability, communication time is a decreasing function of the number of compute nodes and optimal computational granularity for each simulation scale is given. Nearly 50 per cent of wall clock time is spent on rebound phenomenon at the top of particle assembly in dynamic simulation of sand gravitational pluviation. Numerous particles are necessary to capture the pattern and shape of particle assembly in collapse tests; preliminary comparison between sphere assembly and ellipsoid assembly indicates a significant influence of particle shape on kinematic, kinetic and static behavior of particle assemblies.

Originality/value

The high-performance parallel code enables the simulation of a wide range of dynamic and static laboratory and field tests in engineering applications that involve a large number of granular and geotechnical material grains, such as sand pluviation process, buried explosion in various soils, earth penetrator interaction with soil, influence of grain size, shape and gradation on packing density and shear strength and mechanical behavior under different gravity environments such as on the Moon and Mars.
Accomm: adaptive system for supply network operational planning
Authors: Morales-Alzate Luis Fernando , Solano-Vanegas Clara , Carrillo-Ramos Angela , Montoya-Torres Jairo , Fabregat Ramon , Pavlich-Mariscal Jaime A.
Published: February 2018

Purpose

This paper aims to presentAccomma software implementation ofÁgora-SN, a supply network (SN) customer-oriented model integrated with an Adaptation Model.Accommserves two purposes: as an experimental validation tool to measure the impact of Adaptation on an agribusinessSNmodel and as a logistic and marketing operations planning assistant.

Design/methodology/approach

The design ofAccommis based on the results of theÁgora-SNmodel that comprises the following tasks: to characterize theSNactors’ processes ( composed of multiple first-tier suppliers, a focal company and multiple first-tier customers), identifying the ones oriented to the customer; to integrate these processes into aSNmodel which incorporates a supplier cooperation model; and to provide an adaptation model that implements a customer profile and a context profile to improve order fulfillment.

Findings

To validate theÁgora-SNmodel, a prototypeAccommwas created referred to a real Colombian agribusiness sector company, specifically in the floriculture sector. This prototype was validated through two methods: a usability scale and a set of scenarios that compared the application’s behavior with and without adaptation and cooperation. The application provides a better response to demand when both adaptation and cooperation are enabled.

Research limitations/implications

This work was tested in an academic environment and was validated by different experts. Further tests in operational real-life environments are required to fully validate the approach.

Originality/value

The main contribution of this work is the integration of Adaptation into aSNmodel as a way to center theSNtoward the customer. As an additional contribution, the validation toolAccommis conceived as an operational planning tool for agribusinessSN.
Recently identified university students navigate dyslexia
Authors: Loveland-Armour Lorraine Anne
Published: February 2018

Purpose

The purpose of this paper is to capture students’ understandings of dyslexia as a component of identity. Specifically, the journey that students embarked on in order to contribute to self-understanding of learning and how dyslexia contributes to these experiences was examined.

Design/methodology/approach

This qualitative case study explored concepts of social identity theory, how students understood their dyslexia and whether or not labelling theory informed students’ identities through an arts-based phenomenological lens. Eight university students participated in a brief survey, a semi-structured interview and created artefacts representing their dyslexia, which facilitated dialogue about their individual experiences in a higher education context.

Findings

Interpretive phenomenological analysis revealed that student participants associated strongly with the identity of dyslexia; however they did not consider themselves to be part of a dyslexic group. They also discussed different routes that informed their decisions to undergo diagnostic assessments for dyslexia. Students did not report dyslexia identity as a label. Nonetheless, the students expressed that creating an artefact supported them to better understand and communicate their dyslexia.

Originality/value

Although visual methods are increasingly prevalent in educational research, they are not typical in the field of dyslexia in higher education. This research therefore engaged students in active self-reflection which provided valuable insight into the nature and diversity of the experiences that can emerge from identification of dyslexia at university.
Because access matters: an institutional case study
Authors: Peck Catherine , Bouilheres Frederique , Brown Melanie , Witney Carol
Published: February 2018

Purpose

The purpose of this paper is to overview an institution wide accessibility project undertaken at the Vietnam locations of a transnational Australian university, and the significance of this initiative in symbolising the organisation’s commitment to inclusion and diversity. The project implemented universal accessibility standards for learning materials across all courses delivered at the university. This facilitated an easier in-class and online learning experience for students with a broad range of print disabilities, visual or hearing impairments, and a range of other learning differences or disabilities.

Design/methodology/approach

The implementation of this project entailed three concurrent streams of activity which the authors describe in this paper. These included development of accessibility standards and processes for conversion of the existing learning materials, a sustained awareness raising campaign for staff and students, and integration of the accessibility standards into induction, support and development activities.

Findings

The process of establishing the technical foundations for inclusion through a focus on accessibility prompted rich dialogue with staff and students around inclusive practices. Many staff working in professional and non-teaching roles voluntarily adopted the standards to promote an inclusive workplace. Capability building activities for high school teachers were also conducted for the Vietnamese Department of Education & Training.

Originality/value

The approach outlined in this case is highly transferable, and provides a practical roadmap for achieving accessibility and promoting an inclusive environment. The strategies described through the lens of Kotter’s (1996) process for leading change in this paper can be applied by higher education institutions internationally.
Disability disclosure: categorical and cultural difficulties HETL Scotland 2017
Authors: Soorenian Armineh
Published: February 2018

Purpose

The purpose of this paper is to analyze a group of disabled students’ views and feelings on disclosing the nature of their impairments by applying via Universities and Colleges Admissions Service (UCAS, 2016), using a numerical coding system. The adequacy of “disability” categories on both university and UCAS forms, and related sensitive issues will be central to this paper.

Design/methodology/approach

Thus, the author will visit the debates surrounding the two contrasting models of “disability”, namely, the individual medical and the social model of “disability”. The associated advantages and disadvantages that are ensued will be examined.

Findings

This paper will conclude by offering inclusive solutions to disclosure, which are sensitive to both impairment and cultural-related issues and encourage disclosure from students with a wide range of impairments. The benefits of all-encompassing inclusive practice and the resulting wider implications for the student population at large will, therefore, be highlighted.

Originality/value

There is an acute shortage of similar kinds of research conducted on disabled international students’ experiences of disclosure, which make the current work timely and original.
Firm‐Level Analysis Using the ABS’ Business Longitudinal Analysis Data Environment (BLADE)
Authors: Hansell David , Rafi Bilal
Published: March 2018

The Australian Bureau of Statistics’ (ABS) Business Longitudinal Analysis Data Environment (BLADE) is the most comprehensive firm‐level statistical asset in Australia. This short overview provides readers a window into what data sources are used, how they are integrated, current and future applications and how these can contribute to evidence‐based policy making in Australia. At present, direct access is limited to staff directly employed by the Australian Statistician or through secondment.
Of Lambkins And Piglets In Old English And Beyond
Authors: Stiles Patrick V.
Published: February 2018

It is suggested that the Old English adjectives ge‐ēan and ge‐cealf, each attested once in the same passage, could refer not only to pregnant livestock but also to mothers with their newborn young (as proposed by Osthoff in 1895). The twice occurring sequence gefearh sugu, which is usually taken to be a compound, is here analysed as consisting of a third such adjective used attributively before the noun; as the feminine nominative singular of a heavy‐syllabled adjective, it is endingless. This appears to be a return to an earlier view. A fourth example, ge‐fol, recorded once, is also discussed. The formation of these adjectives is briefly treated, as is the PGmc noun *auna‐ “lamb” presupposed by the first adjective, together with its presumed relationship to Latin agnus and further cognates. Evidence for the derived class II weak verb *aunôn (reflected in OEēanian*) in the Germanic languages is presented.
Management of distal radius fractures in the emergency department: A long‐term functional outcome measure study with the Disabilities of Arm, Shoulder and Hand (DASH) scores
Authors: Barai Avijit , Lambie Bruce , Cosgrave Conor , Baxter Joanne
Published: February 2018

Objective

Distal radius fracture (DRF) is a common presentation to the ED. However, little is known about the long‐term functional outcome of these patients following their initial management in the ED.

Methods

In order to evaluate the long‐term functional outcome of DRF, we collected the Disabilities of Arm, Shoulder and Hand (DASH) scores from the patients who attended our ED with DRF between January 2014 and June 2015. We divided the patients into two groups based on their overall management: (i) conservative group who did not have any surgical interventions; and (ii) open reduction internal fixation (ORIF) group who needed surgical interventions in the theatre. Multiple linear regression models were used to identify the statistically significant predictor variables.

Results

Out of the 229 patients whom we contacted, 128 patients responded. The response rate was 56%. The majority of the patients belonged to the conservative group (n = 87, 75%), while one‐quarter of the patients were in the ORIF group (n = 29, 25%). DASH score was higher in the ORIF group (median = 12.1, 95% confidence interval 5.6–25) than the conservative group (median = 6, 95% confidence interval 1.7–16.4). This difference between the groups was statistically significant (unadjusted P = 0.017, Wilcoxon test). Multiple linear regression models revealed that the management group and age of the patients were significant predictors for DASH score.

Conclusion

Conservative management had lower DASH scores signifying better functional outcomes. Further prospective multicentre studies may be suggested to assess the generalisability of the study.
A survey of tobacco dependence treatment guidelines content in 61 countries
Authors: Nilan Kapka , McNeill Ann , Murray Rachael L. , McKeever Tricia M. , Raw Martin
Published: February 2018

Aims

To assess tobacco dependence treatment guidelines content in accordance with Article 14 of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) and its guidelines, and association between content and country income level.

Design

Cross‐sectional study.

Setting

On‐line survey from March to July 2016.

Participants

Contacts in 77 countries, including 68 FCTC Parties, six Signatories and three non‐Parties which had indicated having guidelines in previous surveys, or had not been surveyed before.

Measurements

A nine‐item questionnaire on guidelines content, key recommendations, writing and dissemination.

Findings

We received responses from contacts in 63 countries (82%); 61 had guidelines. The majority are for doctors (93%), primary care (92%) and nurses (75%). All recommend brief advice, 82% recording tobacco use in medical notes, 98% nicotine replacement therapy (NRT), 61% quitlines, 31% text messaging and 87% intensive specialist support, and 54% stress the importance of health‐care workers not using tobacco. Only 57% have a dissemination strategy, and 62% have not been updated for 5 or more years. Compared with high‐income countries, quitlines are less likely to be recommended in upper middle‐income countries guidelines [odds ratio (OR) = 0.15, 95% confidence interval (CI) = 0.04–0.61] and intensive specialist support in lower middle‐income countries guidelines (OR = 0.01, 95% CI = 0.00–0.20). Guidelines updating is associated positively with country income level (P = 0.027).

Conclusions

Although most tobacco dependence treatment guidelines in the 61 countries assessed in 2016 follow the World Health Organization's Framework Convention on Tobacco Control Article 14 recommendations and do not differ significantly by income level, improvements are needed in keeping guidelines up‐to‐date, applying good writing practices and developing a dissemination strategy.
Desiring Self‐Determination in Research and Beyond: Parental Consent Requirements and Situated Ethics for Migrant Young People Living amid Changing Family Dynamics
Authors: Shaw Jennifer E.
Published: February 2018

How are procedural research ethics complicit in homogenising and paternalising young people? Through a youth‐centred ethnographic study completed in Canada, I illustrate how migrant young people's complex experiences of family separation, responsibility, and autonomy sit in relation to parental consent requirements for research. By complicating notions of childhood and critically discussing capacity to consent, I elucidate how procedural ethics can negate diversity among young people and perpetuate the structural barriers some face in determining their lives. More flexible ethical procedures and responses could reduce barriers and better accommodate young people's inclusion by recognising their specific circumstances, desires and competencies through heightened contextual awareness.
Characteristic findings of cervical Papanicolaou tests from transgender patients on androgen therapy: Challenges in detecting dysplasia
Authors: Adkins B. D. , Barlow A. B. , Jack A. , Schultenover S. J. , Desouki M. M. , Coogan A. C. , Weiss V. L.
Published: February 2018

Introduction

The characteristic features of Papanicolaou (Pap) tests collected from female‐to‐male (FTM) transgender patients on androgen therapy have not been well defined in the literature. FTM transgender patients require cervical cancer screening with the same recommended frequency as cis‐gender females. Dysplasia remains challenging to differentiate from atrophy. Without pertinent history, the atrophic findings in younger transgender patients can be misinterpreted as high‐grade dysplasia.

Methods

A review of all cervical Pap tests of transgender patients receiving androgen therapy (2010‐2017) was performed. Bethesda diagnosis, cytomorphological features, HPV testing and cervical biopsy results were reviewed.

Results

Eleven transgender patients receiving androgen therapy were identified with 23 cervical Pap tests, 11 HPV tests and five cervical biopsies performed. A review of the Pap tests demonstrated: 57% negative for intraepithelial lesion; 13% unsatisfactory; 13% atypical squamous cells of undetermined significance; 13% atypical squamous cells – cannot exclude high‐grade squamous intraepithelial lesion; and 4% high‐grade squamous intraepithelial lesion. The rates of abnormal tests were higher than our age‐matched cis‐gender atrophic cohort rates of unsatisfactory (0.5%), atypical squamous cells of undetermined significance (7%), atypical squamous cells—cannot exclude high‐grade squamous intraepithelial lesion (0%) and high‐grade squamous intraepithelial lesion (0.5%). The cytological findings from liquid‐based preparations included dispersed and clustered parabasal‐type cells, scattered degenerated cells, smooth evenly dispersed chromatin, and occasional mild nuclear enlargement and irregularity. Dysplastic cells had larger nuclei, hyperchromatic clumped chromatin, and more irregular nuclear contours.

Conclusions

The evaluation of dysplasia can be challenging on Pap tests from transgender patients on androgen therapy. The cohort evaluated had higher rates of unsatisfactory and abnormal Pap tests. Pathologists should be familiar with the distinctive cytomorphological changes in the Pap tests from patients on androgen therapy to evaluate them appropriately.
The Solace of an Uncertain Future: Acute Illness, the Self, and Self‐Care
Authors: Weingarten Kaethe , Worthen Miranda
Published: March 2018

“Take care of yourself” may be one of the most ubiquitous phrases spoken to people who are ill or to their caretakers. Yet few people who offer it as a balm consider what the self experience is of the person to whom the injunction is offered. We unravel some of the paradoxes inherent in the phrase, illustrating complexities that arise in the context of a life‐threatening diagnosis. To illustrate the relational nature of the self, we analyze a partial transcript of an interview conducted in 1988 with the authors—a family therapist mother who had recently undergone surgery for breast cancer and her then 9‐year‐old daughter. We also examine the role of time in the interview. We propose that unlike PTSD when the past invades the present, in life‐threatening illness the future is foreclosed, leading to distortions in current perception and behavior. The second author presents a follow‐up to the interview and relates it to her current experience as a mother with chronic health issues. We close with suggestions for clinicians.
The effect of grazing intensity on the performance of high‐yielding dairy cows
Authors: Dale A. J. , Laidlaw A. S. , McGettrick S. , Gordon A. , Ferris C. P.
Published: February 2018

The study evaluated the impact of High, Moderate and Low grazing intensities throughout the grazing season, within a rotational stocking system, on the performance of high‐yielding dairy cows receiving a high level of concentrates. Sixty‐three Holstein‐Friesian dairy cows, 21 at each grazing intensity, were rotationally grazed. Average paddock size, post‐grazing sward heights and seasonal grazing stocking rates within the High, Moderate and Low grazing intensities were 0.143, 0.167 and 0.200 hectares, 5.2, 6.1 and 6.8 cm and 7.8, 6.7 and 5.6 cows ha−1respectively. Grazing intensity had no effect on milk fat and protein content, end‐of‐study body condition score or end‐of‐study live weight although the latter tended towards significance (p = .057). Average daily milk yield per cow was higher within the Low grazing intensity (33.2 kg day−1) than High grazing intensity (30.5 kg day−1), and average daily fat‐plus‐protein yield was higher for Low and Moderate than High. Milk output per hectare was higher for the High grazing intensity than Low grazing intensity (33,544 and 26,215 kg ha−1respectively). Grazing intensity had no effect on grazing bite number, blood metabolites or concentrations of milk fatty acids or on sward morphological components, although dead matter increased with time across all grazing intensities. Herbage utilization efficiency (above 1,600 kg DM ha−1) was 52%, 74% and 87% for Low, Moderate and High respectively. It is concluded that high‐producing dairy cows can graze at high levels of utilization when they are receiving high rates of concentrates. Although cow performance will be reduced, milk yield per ha will increase.
Hereditary palmoplantar keratodermas. Part I. Non‐syndromic palmoplantar keratodermas: classification, clinical and genetic features
Authors: Guerra L. , Castori M. , Didona B. , Castiglia D. , Zambruno G.
Published: February 2018

The term palmoplantar keratoderma (PPK) indicates any form of persistent thickening of the epidermis of palms and soles and includes genetic as well as acquired conditions. We review the nosology of hereditary PPKs that comprise an increasing number of entities with different prognoses, and a multitude of associated cutaneous and extracutaneous features. On the basis of the phenotypic consequences of the underlying genetic defect, hereditary PPKs may be divided into the following: (i) non‐syndromic, isolated PPKs, which are characterized by a unique or predominant palmoplantar involvement; (ii) non‐syndromic PPKs with additional distinctive cutaneous and adnexal manifestations, here named complex PPKs; (iii) syndromic PPKs, in which PPK is associated with specific extracutaneous manifestations. To date, the diagnosis of the different hereditary PPKs is based mainly on clinical history and features combined with histopathological findings. In recent years, the exponentially increasing use of next‐generation sequencing technologies has led to the identification of several novel disease genes, and thus substantially contributed to elucidate the molecular basis of such a heterogeneous group of disorders. Here, we focus on hereditary non‐syndromic isolated and complex PPKs. Syndromic PPKs are reviewed in the second part of this 2‐part article, where other well‐defined genetic diseases, which may present PPK among their phenotypic manifestations, are also listed and diagnostic and therapeutic approaches for PPKs are summarized.
A Rewriting Experiment of Modernity from the Perspective of Connected Histories: Taiwan as a Laboratory of Modernity
Authors: Tang Chih‐Chieh
Published: February 2018

This paper aims at a new understanding of modernity from the perspective of connected history. It demonstrates that with the case of Taiwan, so‐called ‘modernity’ emerged from the interactions and connections among the various regions, cultures, and civilizations. Thus, modernity has been entangled since its birth, and has had diverse variants. When we combine this reconceptualization of modernity with the concept of functional differentiation as the most essential structural condition of modernity, a theoretical escape from the trap of Eurocentrism emerges; additionally, we are able to integrate sociological theoretical reflections with the advancements of world history study.
Sex‐based differences in bleeding and long‐term adverse events after percutaneous coronary intervention in older patients with coronary artery disease
Authors: Xu Na , Tang Xiao‐Fang , Zhao Xue‐Yan , Chen Jue , Gao Zhan , Qiao Shu‐bin , Yang Yue‐jin , Gao Run‐Lin , Xu Bo , Yuan Jin‐Qing
Published: February 2018

Objectives

Differences in outcomes for women and men after percutaneous coronary intervention (PCI) in older patients remain controversial. Herein, we compared 2‐year outcomes by sex in Chinese older patients undergoing PCI.

Methods

A total of 4926 consecutive patients (33.6% women, age ≥60 years, mean age 67.4 ± 5.7 years) who underwent PCI at a single center in China from January 2013 to December 2013 were included in this study. The primary endpoint was 2‐year risk of bleeding according to the Bleeding Academic Research Consortium definitions. The secondary endpoints included 2‐year risk of major adverse cardiovascular and cerebrovascular events (MACCE). Hazard ratios were generated using multivariable Cox regression.

Results

Compared with men, women had significantly higher rates of in‐hospital all‐cause mortality (0.8% vs 0.2%, P = 0.001), cardiac death (0.5% vs 0.1%, P = 0.006), MACCE (2.4% vs 1.5%, P = 0.017), and bleeding (0.4% vs 0.1%, P = 0.015). At 2‐year follow up, there were no differences between men and women for all‐cause mortality (1.9% vs 1.8%, P = 0.839) and 2‐year MACCE (13.1% vs 11.8%, P = 0.216). However, women had a higher risk of 2‐year bleeding (9.2% vs 6.2%, P < 0.001), which persisted after adjusting for baseline differences and treatment characteristics (hazard ratio 1.35, 95% confidence interval 1.06‐1.71; P = 0.014).

Conclusion

We found that older women undergoing PCI were at increased risk of 2‐year bleeding compared with men. Further dedicated studies are needed to confirm these findings.
Do the Health Benefits of Marriage Depend on the Likelihood of Marriage?
Authors: Tumin Dmitry , Zheng Hui
Published: March 2018

Marriage promotion initiatives presume substantial health benefits of marriage. Current literature, however, has provided inconsistent results on whether these benefits would be shared by people unlikely to marry. We investigate whether the physical and mental health benefits of marriage depend on the likelihood of marriage. Whereas prior studies have compared health benefits of marriage across a single predictor of marriage chances, we define the likelihood of marriage as a composite of demographic, economic, and health characteristics. Using the National Longitudinal Survey of Youth 1979, we find that married adults are only modestly healthier than unmarried adults in both physical and mental dimensions. People with a higher likelihood of marriage generally do not reap greater health benefits from marriage than their counterparts. The only exception is that continuous marriage is more strongly associated with improved mental health among men who are more likely to be married.
Vitamin D levels and risk for periodontal disease: A systematic review
Authors: Pinto J. P. N. S. , Goergen J. , Muniz F. W. M. G. , Haas A. N.
Published: March 2018

Objective

To evaluate the existing evidence supporting or refuting the following questions: (i) Do patients with lower vitamin D levels have higher risk for periodontal disease? (ii) Are periodontal treatment outcomes improved by the adjuvant supplementation of vitamin D or by elevated serum vitamin D levels?

Material and Methods

MEDLINE,SCOPUS,EMBASEand Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched up to September 2017. Studies were included if they had measured serum vitamin D levels or vitamin D intake and any periodontal parameter.

Results

Overall, 27 studies were included (13 cross‐sectional studies, 6 case‐control studies, 5 cohort studies, 2 randomized clinical trials and 1 case series study). Sixty‐five percent of the cross‐sectional studies reported significant associations between low vitamin D levels and poor periodontal parameters. None of the observational longitudinal studies found that periodontal disease progression could be attributed to lower vitamin D levels. No interventional studies that evaluated the use of vitamin D supplementation as a solely adjuvant to periodontal treatment was found. No meta‐analysis was performed due to high variability across studies.

Conclusion

The data to support or refute the association between vitamin D levels and periodontal disease are inconclusive at the moment. More rigorously designed longitudinal studies with standardized definitions of periodontal disease and vitamin D are necessary.
Intra‐operative high‐resolution mapping of slow wave propagation in the human jejunum: Feasibility and initial results
Authors: Angeli T. R. , O'Grady G. , Vather R. , Bissett I. P. , Cheng L. K.
Published: March 2018

Background

Bioelectrical slow waves are a coordinating mechanism of small intestine motility, but extracellular human studies have been restricted to a limited number of sparse electrode recordings. High‐resolution (HR) mapping has offered substantial insights into spatiotemporal intestinal slow wave dynamics, but has been limited to animal studies to date. This study aimed to translate intra‐operative HR mapping to define pacemaking and conduction profiles in the human small intestine.

Methods

Immediately following laparotomy, flexible‐printed‐circuit arrays were applied around the serosa of the proximal jejunum (128‐256 electrodes; 4‐5.2 mm spacing; 28‐59 cm2). Slow wave propagation patterns were mapped, and frequencies, amplitudes, downstroke widths, and velocities were calculated. Pacemaking and propagation patterns were defined.

Key Results

Analysis comprised nine patients with mean recording duration of 7.6 ± 2.8 minutes. Slow waves occurred at a frequency of 9.8 ± 0.4 cpm, amplitude 0.3 ± 0.04 mV, downstroke width 0.5 ± 0.1 seconds, and with faster circumferential velocity than longitudinal (10.1 ± 0.8 vs 9.0 ± 0.7 mm/s; P = .001). Focal pacemakers were identified and mapped (n = 4; mean frequency 9.9 ± 0.2 cpm). Disordered slow wave propagation was observed, including wavefront collisions, conduction blocks, and breakout and entrainment of pacemakers.

Conclusions & Inferences

This study introduces HR mapping of human intestinal slow waves, and provides first descriptions of intestinal pacemaker sites and velocity anisotropy. Future translation to other intestinal regions, disease states, and postsurgical dysmotility holds potential for improving the basic and clinical understanding of small intestine pathophysiology.
Electroacupuncture for patients with refractory functional dyspepsia: A randomized controlled trial
Authors: Zheng H. , Xu J. , Sun X. , Zeng F. , Li Y. , Wu X. , Li J. , Zhao L. , Chang X.‐R. , Liu M. , Gong B. , Li X.‐Z. , Liang F.‐R.
Published: February 2018

Background

To test the efficacy of electroacupuncture for patients with refractory functional dyspepsia (FD).

Methods

A 24‐week, 2‐arm, single‐blind, randomized controlled trial was conducted at three hospitals in China. Patients with refractory FD were randomly assigned to receive 20 sessions of authentic or sham electroacupuncture in a treatment duration of 4 weeks. The primary outcome was complete absence of dyspeptic symptoms at 16 weeks after initiation of acupuncture (week 16). The secondary outcomes included adequate relief of dyspeptic symptoms, Leeds Dyspepsia Questionnaire (LDQ), Nepean Dyspepsia Index (NDI), and adverse events. Intention‐to‐treat analysis was performed.

Key Results

Two hundred patients were included, of which 196 (98%) completed follow‐up data at week 24. At week 16, 17 (17%) patients in the authentic electroacupuncture group vs 6 (6%) patients in the sham group achieved the primary outcome (P = .014). Sixty‐two (62%) patients had adequate relief in the authentic electroacupuncture group, as compared to 22 (22%) in the sham group (P = .001). The scores of LDQ and NDI were significantly improved in both groups at week 16, and patients in the authentic electroacupuncture group have more improvements (LDQ, mean difference, −2.2, 95% confidence interval, −2.3 to −2.1, P < .001; NDI, −7.3, −10.5 to −4.2, P < .001). Results were similar for all the outcomes assessed at week 24. No serious adverse events were reported in both groups.

Conclusion

Acupuncture efficaciously improves dyspeptic symptoms in patients with refractory FD.
Disarming the Red Queen: plant invasions, novel weapons, species coexistence, and microevolution
Authors: Espeland Erin K.
Published: February 2018

This article is a Commentary on Huang et al., 218: 357–369.
Changes in maxillofacial morphology due to improvement of nasal obstruction in rats
Authors: Sato T. , Yamaguchi M. , Murakami Y. , Horigome Y. , Negishi S. , Kasai K.
Published: March 2018

Structured Abstract

Objectives

To investigate the effect of release of experimentally introduced nasal obstruction on maxillofacial morphology and percutaneous arterial oxygen saturation (SpO2) in rats.

Materials and Methods

Six‐week‐old male Wistar rats (n = 36) were divided into a control group (n = 6) and a nasal obstruction group (n = 30). In the nasal obstruction group, the right nostril was occluded with silicon, which was subsequently removed after a given experimental period (days 7, 21, 35, 49 and 63). These animals were then divided into groups D7, D21, D35, D49 and D63 (each n = 6), according to the day at which the obstruction was released. The SpO2 was measured in rats with nasal obstruction at five experimental points. The maxillofacial morphology in rats on the first day and 63 days after the start of the experiment was evaluated by microcomputed tomography.

Results

The SpO2 was still lower at 2 weeks after the improvement of the nasal obstruction in the D49 group than in the control group. In addition, the height of the nasal maxillary complex of the D35, D49 and D63 groups was significantly decreased compared with the control group.

Conclusions

The results of this study suggest that long‐term unilateral nasal obstruction in growing rats may affect the growth of the nasomaxillary complex and reduce the SpO2 permanently. Therefore, early improvement of nasal obstruction in rats during the growth period may improve the SpO2 and cranial development and promote normal growth and development.
MicroRNA‐622 is a novel mediator of tumorigenicity in melanoma by targeting Kirsten rat sarcoma
Authors: Dietrich Peter , Kuphal Silke , Spruss Thilo , Hellerbrand Claus , Bosserhoff Anja K.
Published: March 2018

The network of molecular players is similar when comparing neural crest‐derived, actively migrating melanoblasts to melanoma cells. However, melanoblasts are sensitive to differentiation‐initiating signals at their target site (epidermis), while melanoma cells maintain migratory and undifferentiated features. We aimed at identifying downregulated genes in melanoma that are particularly upregulated in melanoblasts. Loss of such genes could contribute to stabilization of a dedifferentiated, malignant phenotype in melanoma. We determined that microRNA‐622 (miR‐622) expression was strongly downregulated in melanoma cells and tissues compared to melanocytes and melanoblast‐related cells. miR‐622 expression correlated with survival of patients with melanoma. miR‐622 re‐expression inhibited clonogenicity, proliferation, and migration in melanoma. Inhibition of miR‐622 in melanocytes induced enhanced migration. Kirsten rat sarcoma (KRAS) was identified as a major functional target of miR‐622 in melanoma. We conclude that miR‐622 is a novel tumor suppressor in melanoma and identify the miR‐622‐KRAS axis as potential therapeutic target.
Role of Potassic Alteration for Porphyry Cu Mineralization: Implication for the Absence of Porphyry Cu Deposits in Japan
Authors: Watanabe Yasushi , Sato Ryuya , Sulaksono Adi
Published: February 2018

The role of potassic alteration and associated quartz veins for porphyry Cu mineralization in two representative porphyry systems (El Salvador, Chile, and Grasberg, Indonesia) was examined to evaluate the potential of porphyry Cu mineralization in Japan. The reactions between the aqueous magmatic–hydrothermal fluids and host rocks during potassic alteration at El Salvador and Grasberg includes (i) reduction of SO42− in the aqueous fluids due to oxidation of ferrous iron in mafic minerals and (ii) disproportionation of SO2 in the fluids by elevated concentrations of Ca2+ leached by the fluids from igneous plagioclase and hornblende. These reactions resulted in an increase of reduced S species (H2S) in the fluids and promoted Cu sulfide precipitation during the potassic or subsequent chlorite–sericite alteration in the temperature range of 600–400°C.

Although numerous magnetite‐series, calc‐alkaline intrusive stocks of dioritic or granodioritic composition are exposed in the Sanin belt of the Cretaceous–Paleogene Southwestern Japan arc and late Miocene Northeast Japan arc, potassic alteration represented by abundant hydrothermal biotite, magnetite, and K‐feldspar is uncommon in these rocks. However, the intrusive rocks may have undergone molybdenite mineralization in association with phyllic alteration, represented by quartz, sericite and pyrite, or chalcopyrite in chlorite–sericite alteration in the subepithermal and epithermal environments at <400°C. The absence of porphyry Cu deposits in the Japanese islands in petrochemically and compositionally favorable intrusive rocks is ascribed to the lack of early quartz veins and poor development of potassic alteration that prevented Cu sulfide precipitation at high temperatures. The lack of early quartz veins and scarcity of potassic‐altered intrusive rocks in Japan is explained by the noncompressional stress field throughout the Japanese islands, which was incapable of maintaining lithostatic pressures during fluid exsolution from the intrusive magmas.