bluuebunny/crossref_metadata_2025 huggingface dataset:
Reclassification of Hypertensive Outpatients According to New US Guidelines on High Blood Pressure
Authors: Tocci Giuliano , Presta Vivianne , Figliuzzi Ilaria , Miceli Francesca , Citoni Barbara , Coluccia Roberta , Paini Anna , Salvetti Massimo , Ferrucci Andrea , Muiesan Maria Lorenza , Volpe Massimo
Published: September 2018

BACKGROUND

US guidelines on high blood pressure (BP) have recently proposed a new BP stratification.

OBJECTIVE

To evaluate the redistribution of adult outpatients according to 2003 and 2017 US hypertension guidelines.

METHODS

We extracted data referred to individuals aged between 40 and 70 years with valid BP assessment from a national, cross-sectional database. The following systolic/diastolic BP strata were considered: (i) 2003 guidelines: 0 = normal (<120/180 mm Hg), 1 = prehypertension (≥120 and ≤139/≥80 and ≤89 mm Hg), 2 = stage 1 (≥140 and ≤159/≥90 and ≤99 mm Hg), 3 = stage 2 (≥160/≥100 mm Hg) and (ii) 2017 American College of Cardiology/American Heart Association guidelines: 0 = normal (<120/80 mm Hg), 1 = elevated (≥120 and ≤129/<80 mm Hg); 2 = stage 1 (≥130 and ≤139/≥80 and ≤89 mm Hg), 3 = stage 2 (≥140/≥90 mm Hg). Cardiovascular (CV) risk profile characterization was based on Framingham, 10-year risk of a first atherosclerotic cardiovascular disease and European score equations.

RESULTS

From an overall population sample of 10,012 individuals, we selected 8,911 (89.0%) with valid clinic BP data (44.4% female, age = 60.7 ± 6.6 years, body mass index = 28.2 ± 4.9 kg/m2, clinic BP = 136.8 ± 14.5/82.1 ± 8.3 mm Hg), among whom 339 (3.8%) were in the normal BP range. According to 2003 guidelines, 3,919 (44.0%) patients had prehypertension, 3,698 (41.5%) had stage-1 and 955 (10.7%) had stage-2 hypertension. According to 2017 guidelines, 635 (3.8%) patients had elevated BP, 3,284 (36.9%) had stage-1 and 4,653 (52.2%) had stage-2 hypertension. New BP classification moved 37% individuals from “pre-hypertension” to “stage 1” and 41% from “stage 1” to “stage 2” hypertension, respectively.

CONCLUSIONS

Redistribution of hypertensive patients according to 2017 US hypertension guidelines compared with previous ones may help to better identify uncontrolled hypertensive patients with high CV risk profile.
Inference and visualization of DNA damage patterns using a grade of membership model
Authors: Al-Asadi Hussein , Dey Kushal K , Novembre John , Stephens Matthew
Published: September 2018

Motivation

Quality control plays a major role in the analysis of ancient DNA (aDNA). One key step in this quality control is assessment of DNA damage: aDNA contains unique signatures of DNA damage that distinguish it from modern DNA, and so analyses of damage patterns can help confirm that DNA sequences obtained are from endogenous aDNA rather than from modern contamination. Predominant signatures of DNA damage include a high frequency of cytosine to thymine substitutions (C-to-T) at the ends of fragments, and elevated rates of purines (A & G) before the 5′ strand-breaks. Existing QC procedures help assess damage by simply plotting for each sample, the C-to-T mismatch rate along the read and the composition of bases before the 5′ strand-breaks. Here we present a more flexible and comprehensive model-based approach to infer and visualize damage patterns in aDNA, implemented in an R package aRchaic. This approach is based on a ‘grade of membership’ model (also known as ‘admixture’ or ‘topic’ model) in which each sample has an estimated grade of membership in each of K damage profiles that are estimated from the data.

Results

We illustrate aRchaic on data from several aDNA studies and modern individuals from 1000 Genomes Project Consortium (2012). Here, aRchaic clearly distinguishes modern from ancient samples irrespective of DNA extraction, lab and sequencing protocols. Additionally, through an in-silico contamination experiment, we show that the aRchaic grades of membership reflect relative levels of exogenous modern contamination. Together, the outputs of aRchaic provide a concise visual summary of DNA damage patterns, as well as other processes generating mismatches in the data.

Availability and implementation

aRchaic is available for download from https://www.github.com/kkdey/aRchaic.

Supplementary information

Supplementary data are available at Bioinformatics online.
Ambiguous splice sites distinguish circRNA and linear splicing in the human genome
Authors: Dehghannasiri Roozbeh , Szabo Linda , Salzman Julia
Published: September 2018

Motivation

Identification of splice sites is critical to gene annotation and to determine which sequences control circRNA biogenesis. Full-length RNA transcripts could in principle complete annotations of introns and exons in genomes without external ontologies, i.e., ab initio. However, whether it is possible to reconstruct genomic positions where splicing occurs from full-length transcripts, even if sampled in the absence of noise, depends on the genome sequence composition. If it is not, there exist provable limits on the use of RNA-Seq to define splice locations (linear or circular) in the genome.

Results

We provide a formal definition of splice site ambiguity due to the genomic sequence by introducing equivalent junction, which is the set of local genomic positions resulting in the same RNA sequence when joined through RNA splicing. We show that equivalent junctions are prevalent in diverse eukaryotic genomes and occur in 88.64% and 78.64% of annotated human splice sites in linear and circRNA junctions, respectively. The observed fractions of equivalent junctions and the frequency of many individual motifs are statistically significant when compared against the null distribution computed via simulation or closed-form. The frequency of equivalent junctions establishes a fundamental limit on the possibility of ab initio reconstruction of RNA transcripts without appealing to the ontology of “GT-AG” boundaries defining introns. Said differently, completely ab initio is impossible in the vast majority of splice sites in annotated circRNAs and linear transcripts.

Availability and implementation

Two python scripts generating an equivalent junction sequence per junction are available at: https://github.com/salzmanlab/Equivalent-Junctions.

Supplementary information

Supplementary data are available at Bioinformatics online.
German senior citizens’ capabilities for physical activity: a qualitative study
Authors: Sauter Alexandra , Curbach Janina , Rueter Jana , Lindacher Verena , Loss Julika
Published: September 2018

Sen’s capability approach (CA) has found its way into health promotion over the last few years. The approach takes both individual factors as well as social and environmental conditions into account and therefore appears to have great potential to explore opportunities for (‘capabilities’) and barriers to active lifestyles. Thus, our objective in this study was to investigate which capabilities senior citizens perceive to have available to them in order to be physically active. In Southern Germany, we conducted 26 semi-standardized interviews with senior citizens aged 66–97, as well as 9 interviews with key persons who have close contact to senior citizens in their work life. We identified 11 capabilities which the interviewees considered as important in leading an active lifestyle. They could be grouped into four domains: (1) individual resources, (2) social interactions and norms, (3) living conditions and (4) organizational environment. Results highlight the need for health-promoting interventions that widen the range of capabilities on social and environmental levels in a way that individuals can freely choose to be as physically active as they like. The results make clear that interventions should not only target and involve older adults themselves, but also their families, nursing home staff or community representatives, because these groups are important in shaping older adults’ capabilities for an active lifestyle.
Internal dynamics of the Large Magellanic Cloud from Gaia DR2
Authors: Vasiliev Eugene
Published: September 2018

We use the proper motions (PM) of half a million red giant stars in the Large Magellanic Cloud measured by Gaia to construct a 2D kinematic map of mean PM and its dispersion across the galaxy, out to 7 kpc from its centre. We then explore a range of dynamical models and measure the rotation curve, mean azimuthal velocity, velocity dispersion profiles, and the orientation of the galaxy. We find that the circular velocity reaches ∼90 km s−1 at 5 kpc, and that the velocity dispersion ranges from ∼30–40 km s−1 in the galaxy centre to ∼15–20 km s−1 at 7 kpc.
The Predictive Validity of Physical Performance Measures in Determining Markers of Preclinical Disability in Community-Dwelling Middle-Aged and Older Adults: A Systematic Review
Authors: Cavanaugh Ellen J , Richardson Jenna , McCallum Christine A , Wilhelm Mark
Published: September 2018

Background

Identification of preclinical disability in middle-aged and older adults might allow early identification of and treatment for functional mobility deficits.

Purpose

This study aimed to determine which physical performance measures (PPMs) were effective in identifying preclinical disability in individuals at risk for future disability.

Data Sources

CINHAL, PubMed, Scopus, and Web of Science databases were searched until September 2017 using key words.

Study Selection

Two individuals screened peer-reviewed prospective longitudinal studies that assessed healthy individuals > 45 years old using PPMs at baseline. Eight studies met inclusion criteria.

Data Extraction

Two individuals extracted data on participant demographics, PPMs, predictive validity effect size, and disability outcomes. Risk of bias was assessed using the Quality Assessment Tool for Cohort Studies II (Q-Coh II).

Data Synthesis

Four constructs were used to guide data synthesis: functional mobility, activities of daily living disability, fall(s), and hospitalization. Multiple sit-to-stands from a chair, standing balance, and gait speed were found to have some merit in identifying preclinical disability across all 4 disability constructs. All studies were scored as good-quality studies using the Q-Coh II.

Limitations

The heterogeneity in follow-up times and reporting of risk prediction statistics made it difficult to compare results across studies, PPMs, and constructs. The 4 constructs used as markers of preclinical disability potentially do not fully capture the progression of disability.

Conclusions

Physical therapists should consider using PPMs on healthy adult populations to gather baseline data during annual health screens for use in identifying preclinical disability.
Galleria mellonellaas an infection model for the multi-host pathogenStreptococcus agalactiaereflects hypervirulence of ST283
Authors: Six Anne , Kranjangwong Sakranmanee , Crumlish Margaret , Zadoks Ruth , Walker Daniel
Published: September 2018

Streptococcus agalactiae, or group B streptococcus (GBS), infects diverse hosts including humans, economically important livestock and fishes. In the context of human health, GBS is a major cause of neonatal infections and an emerging cause of invasive disease in adults. Here we show that GBS is able to establish a systemic infection inG. mellonellalarvae that is associated with extensive bacterial replication and dose dependent larval survival. This infection model is suitable for use with GBS isolates from both homeothermic and poikilothermic hosts and a hypervirulent sequence type (ST) associated with invasive human disease, ST283, shows increased virulence in this model, indicating it may be useful in studying GBS virulence determinants. In addition, we demonstrate that larval survival can be afforded by antibiotic treatment and so the model may also be useful in the development of novel anti-GBS strategies. The use ofG. mellonellain GBS research has the potential to provide a low cost infection model that could reduce the number of vertebrates used in the study of GBS infection.
Sex differences in post-stroke aphasia rates are caused by age. A meta-analysis and database query
Authors: Wallentin Mikkel
Published: September 2018

Background

Studies have suggested that aphasia rates are different in men and women following stroke. One hypothesis says that men have more lateralized language function than women. Given unilateral stroke, this would lead to a prediction of men having higher aphasia rates than women. Another line of observations suggest that women are more severely affected by stroke, which could lead to a higher aphasia rate among women. An additional potential confounding variable could be age, given that women are typically older at the time of stroke.

Methods & Procedures

This study consists of two parts. First, a meta-analysis of the available reports of aphasia rates in the two sexes was conducted. A comprehensive literature search yielded 25 studies with sufficient information about both aphasia and gender. These studies included a total of 48,362 stroke patients for which aphasia rates were calculated. Second, data were extracted from an American health database (with 1,967,038 stroke patients), in order to include age and stroke severity into a regression analysis of sex differences in aphasia rates.

Outcomes & Results

Both analyses revealed significantly larger aphasia rates in women than in men (1.1-1.14 ratio). This speaks against the idea that men should be more lateralized in their language function. When age and stroke severity were included as covariates, sex failed to explain any aphasia rate sex difference above and beyond that which is explained by age differences at time of stroke.
Structural instability of IкB kinase β promotes autophagic degradation through enhancement of Keap1 binding
Authors: Kanamoto Mayu , Tsuchiya Yoshihiro , Nakao Yuki , Suzuki Takafumi , Motohashi Hozumi , Yamamoto Masayuki , Kamata Hideaki
Published: September 2018

IKKβ, an essential kinase of NF-кB signaling, is composed of an N-terminal kinase domain (KD) and a C-terminal scaffolding domain, containing a ubiquitin-like domain (ULD). The Hsp90 chaperon has special responsibility for folding of protein kinases including IKKβ. Here, we found that Hsp90 inhibition induced IKKβ degradation, which is partially mediated by Keap1. Geldanamycin (GA), a Hsp90 inhibitor, enhances association of IKKβ with Keap1 through the binding site in KD, and translocates IKKβ to detergent-insoluble fractions leading its autophagic degradation. An electrophile tBHQ suppressed Keap1-mediated proteasomal Nrf2 degradation but not autophagic IKKβ degradation. Substitution mutation of Leu353 to Ala in the ULD destabilizes IKKβ, enhances its association with Keap1, translocates it to detergent-insoluble fractions, and causes its autophagic degradation. These results suggest that Keap1 is involved in the degradation of structural destabilized IKKβ and negative regulation of NF-кB under proteotoxic stress.
A Flexible Model of Working Memory
Authors: Bouchacourt Flora , Buschman Timothy J.
Published: September 2018

Working memory is fundamental to cognition, allowing one to hold information ‘in mind’ and use it to guide behavior. A defining characteristic of working memory is its flexibility: we can hold anything in mind. However, typical models of working memory rely on finely tuned, content-specific, attractors to persistently maintain neural activity and therefore do not allow for the flexibility observed in behavior. Here we present a flexible model of working memory that maintains representations through random recurrent connections between two layers of neurons: a structured ‘sensory’ layer and a randomly connected, unstructured, layer. As the interactions are untuned with respect to the content being stored, the network is able to maintain any arbitrary input. However, this flexibility comes at a cost: the random connections overlap, leading to interference between representations and limiting the memory capacity of the network. Additionally, our model captures several other key behavioral and neurophysiological characteristics of working memory.
USP21 and OTUD3 Antagonize Regulatory Ribosomal Ubiquitylation and Ribosome-Associated Quality Control
Authors: Garshott Danielle M. , Sundaramoorthy Elayanambi , Leonard Marilyn , Bennett Eric J.
Published: September 2018

Defects within mRNAs or nascent chains that halt ribosomal progression can trigger ribosome-associated quality control (RQC) pathways that facilitate mRNA and nascent polypeptide destruction as well as ribosome recycling. Failure to remove defective mRNAs or nascent chains can lead to the accumulation of cytotoxic protein aggregates and proteotoxic stress. We previously established that the E3 ligase ZNF598 catalyzes regulatory ribosomal ubiquitylation of specific 40S ribosomal proteins required for downstream RQC events. Utilizing an optical RQC reporter we identify OTUD3 and USP21 as deubiquitylating enzymes that antagonize ZNF598-mediated 40S ubiquitylation and facilitate ribosomal deubiquitylation following RQC activation. Overexpression of either USP21 or OTUD3 enhances readthrough of stall-inducing sequences as compared to knock-in cells lacking individual RRub sites suggesting that combinatorial ubiquitylation of RPS10 (eS10) and RPS20 (uS10) is required for optimal resolution of RQC events and that deubiquitylating enzymes can limit RQC activation.
How good are pathogenicity predictors in detecting benign variants?
Authors: Niroula Abhishek , Vihinen Mauno
Published: September 2018

Computational tools are widely used for interpreting variants detected in sequencing projects. The choice of computational tools is critical for reliable variant impact interpretation for precision medicine and should be based on systematic performance assessment. The performance of the methods varies widely in different performance assessments, for example due to the sizes of test datasets. To address this issue, we obtained 63,160 common amino acid substitutions (allele frequency ≥1% and <25%) from the Exome Aggregation Consortium (ExAC) database, which contains variants from 60,706 genomes or exomes. We evaluated the specificity, the capability to detect benign variants, for 10 variant interpretation tools. In addition to overall specificity of the tools, we tested their performance for variants in six geographical populations. PON-P2 had the best performance (95.5%) followed by FATHMM (86.4%) and VEST (83.5%). While these tools had excellent performance, the poorest method predicted more than one third of the benign variants to be disease-causing. The results allow choosing reliable methods for benign variant interpretation, for both research and clinical purposes, as well as provide a benchmark for method developers.

AUTHOR SUMMARY

In precision/personalized medicine of many conditions it is essential to investigate individual’s genome. Interpretation of the observed variation (mutation) sets is feasible only with computational approaches. We assessed the performance of variant pathogenicity/tolerance prediction programs on benign variants. Variants were obtained from high-quality ExAC database and selected to have minor allele frequency between 1 and 25%. We obtained 63,160 such cases and investigated 10 widely used predictors. Specificities of the methods showed large differences, from 0.64 to 0.96%, thus users of these methods have to be careful when choosing the one(s) they will use. We investigated further the performances on different populations, allele frequencies, separately for males and females, chromosome wise and for population unique and non-unique variants. The ranking of the tools remained the same in all these scenarios, i.e. the best methods were the best irrespective on how the data is filtered and grouped. This is to our knowledge the first evaluation of method performance on benign variants.
Photon-separation to enhance the spatial resolution in pulsed STED microscopy
Authors: Tortarolo Giorgio , Sun Yuansheng , Teng Kai-Wen , Ishitsuka Yuji , Lanzanó Luca , Selvin Paul R. , Barbieri Beniamino , Diaspro Alberto , Vicidomini Giuseppe
Published: September 2018

Stimulated emission depletion microscopy (STED) is one of the pivotal super-resolution techniques. It overcomes the spatial resolution limit imposed by the diffraction by using an additional laser beam, the STED beam, whose intensity is directly related to the achievable resolution. Despite achieving nanometer resolution, much effort in recent years has been devoted to reduce the STED beam intensity because it may lead to photo-damaging effects. Exploring the temporal dynamics of the detected fluorescence photons and accessing the encoded spatial information has proven to be a powerful strategy, and has contributed to the separation by lifetime tuning (SPLIT) technique. The SPLIT technique uses the phasor analysis to efficiently distinguish photons emitted from the center and the periphery of the excitation spot. It thus improves the resolution without increasing the STED beam intensity. This method was proposed for architectures based on STED beam running in continuous wave (CW-STED microscopy). Here, we extend it to architectures based on pulsed STED beam (pSTED microscopy). We show, through simulated and experimental data, that the SPLIT-pSTED method reduces the detection volume of the pSTED microscope without significantly reducing the signal-to-noise ratio of the final image, thus effectively improving the resolution without increasing the STED beam intensity.
Estimating HLA disease associations using similarity trees
Authors: Dorp Christiaan H. van , Keşmir Can
Published: September 2018

The human leukocyte antigen (HLA) is associated with many (infectious) disease outcomes. These associations are perhaps best documented for HIV-1. For example, the HLA-B*58:01 allele is associated with control of the virus, while HLA-B*18:01 is considered detrimental. In HLA disease association studies, it is often ignored that certain HLA molecules are functionally very similar to others. For instance, HLA-B*18:03 differs “only” at 3 positions in its peptide binding site from HLA-B*18:01, and not surprisingly, HLA-B*18:03 is also associated with fast progression to AIDS. Here, we present a Bayesian method that takes functional HLA similarities into account to find HLA associations with quantitative traits such as HIV-1 viral load. The method is based on the so-called phylogenetic mixed model (a model for the evolution of a quantitative trait on the branches of a phylogeny), and can easily be modified to study a wide range of research questions, like the role of the heterozygote advantage, or KIR ligands on disease outcomes. We show that in the case of HIV-1, our model is significantly better at predicting set-point virus load than a model that ignores HLA similarities altogether. Furthermore, our method provides a comprehensible visualization of HLA associations. The software is available online at www.github.com/chvandorp/MHCshrubs
OSCA/TMEM63 are an Evolutionarily Conserved Family of Mechanically Activated Ion Channels
Authors: Murthy Swetha E. , Dubin Adrienne E. , Whitwam Tess , Jojoa-Cruz Sebastian , Cahalan Stuart M. , Mosavi Seyed Ali Reza , Ward Andrew B. , Patapoutian Ardem
Published: September 2018

Introduction

Mechanotransduction, the conversion of mechanical cues into biochemical signals, is crucial for many biological processes in plants and animals1,2. In mammals, some mechanosensory processes such as touch sensation and vascular development are mediated by the PIEZO family of mechanically activated (MA) ion channels3-5. In plants, the impact of gravity or soil properties on root development, wind on stem growth, and turgor pressure on plant-cell size and shape are proposed to involve activation of MA ion channels6,7. Homologues of the bacterial MA channel MscS (MSLs) exist in plants, and MSL8 is shown to be involved in pollen hydration8; however, the identity of the MA channels required for most mechanotransduction processes in plants have remained elusive9. Here, we identify various members of the 15 OSCA proteins from Arabidopsis thaliana (previously reported as hyperosmolarity sensors10,11) as MA ion channels. Purification and reconstitution of OSCA1.2 in liposomes induced stretch-activated currents, suggesting that OSCAs are inherently mechanosensitive, pore-forming ion channels. This conclusion is confirmed by a high-resolution electron microscopy structure of OSCA1.2 described in a companion paper12. Beyond plants, we present evidence that fruit fly, mouse, and human TMEM63 family of proteins, homologues of OSCAs, induce MA currents when expressed in naïve cells. Our results suggest that OSCA/TMEM63 proteins are the largest family of MA ion channels identified, and are conserved across eukaryotes. We anticipate that further characterization of OSCA isoforms which have diverse biophysical properties, will help gain substantial insight on the molecular mechanism of MA ion channel gating and permeation. OSCA1.1 mutant plants have impaired leaf and root growth under stress, potentially linking this ion channel to a mechanosensory role11. We expect future studies to uncover novel roles of OSCA/TMEM63 channels in mechanosensory processes across plants and animals.
Genetics and biology of prostate cancer
Authors: Wang Guocan , Zhao Di , Spring Denise J. , DePinho Ronald A.
Published: September 2018

Despite the high long-term survival in localized prostate cancer, metastatic prostate cancer remains largely incurable even after intensive multimodal therapy. The lethality of advanced disease is driven by the lack of therapeutic regimens capable of generating durable responses in the setting of extreme tumor heterogeneity on the genetic and cell biological levels. Here, we review available prostate cancer model systems, the prostate cancer genome atlas, cellular and functional heterogeneity in the tumor microenvironment, tumor-intrinsic and tumor-extrinsic mechanisms underlying therapeutic resistance, and technological advances focused on disease detection and management. These advances, along with an improved understanding of the adaptive responses to conventional cancer therapies, anti-androgen therapy, and immunotherapy, are catalyzing development of more effective therapeutic strategies for advanced disease. In particular, knowledge of the heterotypic interactions between and coevolution of cancer and host cells in the tumor microenvironment has illuminated novel therapeutic combinations with a strong potential for more durable therapeutic responses and eventual cures for advanced disease. Improved disease management will also benefit from artificial intelligence-based expert decision support systems for proper standard of care, prognostic determinant biomarkers to minimize overtreatment of localized disease, and new standards of care accelerated by next-generation adaptive clinical trials.
Alternative pre-mRNA splicing switch controls hESC pluripotency and differentiation
Authors: Agosto Laura M. , Lynch Kristen W.
Published: September 2018

Alternative splicing (AS) of pre-mRNAs is a ubiquitous process in mammals that is tightly regulated in a cell type- and cell state-dependent manner. However, the details of how splicing is regulated to impact specific cell fate decisions remains incompletely understood. A study by Yamazaki and colleagues (pp. 1161–1174) in this issue of Genes & Development provides exciting new insight into the role and regulation of splicing in the maintenance of pluripotency of human embryonic stem cells (hESCs). In brief, they show that AS of several genes is robustly regulated upon differentiation of hESCs. One of these genes, T-cell factor 3 (TCF3), is regulated at least in part through the activity of heterogeneous nuclear ribonucleoproteins H1 and F (hnRNP H/F) to control the mutually exclusive expression of the encoded E12 and E47 transcription regulators. The investigators demonstrate that reduced expression of hnRNP H/F favors expression of E47, which in turn decreases E-cadherin expression to promote hESC differentiation. In contrast, high levels of hnRNP H/F induce expression of E12 to maintain pluripotency. Thus, this work provides at least one new link between AS and control of human stem cell fate and suggests a broader role of splicing in pluripotency.
Polymerase Chain Reaction (PCR) Detection of 3C Ligation Products Present in 3C, ChIP-Loop, and Control Libraries: Library Titration and Interaction Frequency Analysis
Authors: Kim Tae Hoon , Dekker Job
Published: September 2018

In all 3C-based assays, the aim is to measure the frequency with which two loci interact within cells. This is achieved by determining the relative abundance of ligation products formed during the 3C protocol that carry sequences from both loci. Individual 3C ligation products that are present in a 3C library, the ChIP-loop library, or the control library can be detected by polymerase chain reaction (PCR) using locus-specific primers. The following protocol outlines the procedure to measure relative abundances of ligation products in these libraries using PCR. The first part of the protocol—library titration—is required only once to determine the linear range of PCR detection. Once the linear range of PCR detection is known for a given ligation product library, follow the second part—interaction analysis—to measure the abundance of ligation products of interest in that library. Specific issues regarding determining the relative abundance of ligation products, designing PCR primers, and quantifying interaction frequencies are also described.
Dynamic multi-attribute decision-making method with three-parameter interval grey number based on the prospect theory
Authors: Li Ye , Zhang Dongxing
Published: September 2018

Purpose

The purpose of this paper is to propose a dynamic multi-attribute decision-making method based on the prospect theory for dealing with the dynamic multi-attribute decision-making problem with three-parameter interval grey number.

Design/methodology/approach

First, the kernel and comparison rule of three-parameter interval grey numbers are defined, which are the basis of collecting and sorting grey numbers. Next, the prospect value function is determined in view of the decision-making information with different time points as the reference points. Then, an optimal model for solving the attribute weight and time weight is constructed based on the grey entropy principle.

Findings

The paper provides a dynamic grey interrelation decision method based on the prospect theory with three-parameter interval grey number, and the example analysis shows that the method proposed in this paper has validity and rationality.

Research limitations/implications

If we have a better understanding of the weights of different reference points, it is possible to receive a more reasonable expression for the comprehensive prospect utility value function.

Practical implications

The paper provides a grey interrelation decision method based on the prospect theory, which can help the decision maker deal with the dynamic multi-attribute decision-making problems under the uncertain environment.

Originality/value

The paper proposes the kernel and ranking method of three-parameter interval grey number, and uses different time points as the reference points to define the prospect value function. Furthermore, this paper structures a dynamic grey interrelation decision method with three-parameter interval grey number based on the prospect theory.
Micropolitical Dynamics of Interlingual Translation Processes in an MNC Subsidiary
Authors: Ciuk Sylwia , James Philip , Śliwa Martyna
Published: September 2018

Drawing on a deep single case study of a Polish subsidiary of a US‐headquartered pharmaceutical multinational company (MNC), the paper contributes to the study of power and politics in international business (IB) by advancing understanding of the interactional and processual dynamics of micropolitics in MNCs, which supplements the current dominant actor‐centred approach. The paper advances understanding of translation in IB by demonstrating how interlingual translation can be deliberately used as a management tool to pre‐empt resistance and promote managerially desired attitudes and behaviours at the subsidiary level. It highlights how hitherto largely ignored processes of interlingual translation provide an important internal forum for the exercise of power and micropolitics. The paper puts forward an emergent model of the micropolitical dynamics of interlingual translation and demonstrates how subsidiary managers can use interlingual translation to support and oppose the views of both corporate and local managerial colleagues, and thereby influence how HQ‐level decisions will be received by subsidiary‐level employees.
Circulating tumor cell levels and carcinoembryonic antigen: An improved diagnostic method for lung adenocarcinoma
Authors: Ding Cheng , Zhou Xiaofei , Xu Chun , Chen Jun , Ju Shen , Chen Tengfei , Liang Zhipan , Cui Zihan , Li Chang , Zhao Jun
Published: September 2018

Background

The aim of this study was to determine a correlation between benign and malignant lung solitary pulmonary nodules (SPN), and analyze the association between circulating tumor cell (CTC) levels and different subtypes of lung adenocarcinoma.

Methods

A total of 200 patients (80 with SPNs and 120 diagnosed with lung cancer) were included in the study. The CTC levels were quantified by identifying the folate receptor on the surface of tumor cells; clinical tumor specific markers were detected by biochemical immunization. The content of peripheral blood CTCs in benign and malignant lung SPN patients was detected and the differences in preoperative CTC levels in different pathological subtypes were analyzed. Based on the collected data, receiver operating characteristic curves were calculated and the rate of lung cancer was predicted.

Results

The peripheral blood CTC levels in patients with malignant lung SPNs were higher than in patients with benign SPNs. The maximum nodule diameter, carcinoembryonic antigen, and CTC levels were independent risk factors for malignant lung SPNs. The peripheral blood CTC levels in patients with stage III–IV lung adenocarcinoma were higher than in stage I–II patients. The peripheral blood CTC levels in patients with microinvasive and invasive adenocarcinoma were higher than in adenocarcinoma in situ patients. The CTC levels in the peripheral blood of patients with maximum tumor diameter > 2 cm were higher than in patients with tumors < 2 cm.

Conclusion

The detection of CTCs can be used as a biomarker for screening SPNs and diagnosing early‐stage lung cancer. Using the combination of CTC levels and CEA significantly improves the efficacy of lung adenocarcinoma diagnosis.
Dividend payout and executive compensation: theory and evidence from New Zealand
Authors: Anderson Warwick , Bhattacharyya Nalinaksha , Morrill Cameron , Roberts Helen
Published: September 2018

Using a model based on Bhattacharyya (2007), we predict a positive (negative) relationship between the earnings retention ratio (dividend payout ratio) and managerial compensation. We use tobit regression to analyse data for New Zealand firms' dividend payouts over the period 1997–2015 and find results consistent with Bhattacharyya (2007). These results hold when the definition of payout is modified to incorporate both common dividends and common share repurchases. Our results indicate that corporate dividend policy among New Zealand firms is perhaps best understood by considering the dividend payout ratio, rather than the level of, or changes in, cash dividends alone.
Choroidal structural analysis and vascularity index in retinal dystrophies
Authors: Wei Xin , Mishra Chitaranjan , Kannan Naresh Babu , Holder Graham E. , Khandelwal Neha , Kim Ramasamy , Agrawal Rupesh
Published: September 2018

Purpose

To assess choroidal structural changes in patients with retinal dystrophies using choroidal vascularity index (CVI), a novel optical coherence tomography (OCT) based tool.

Methods

This retrospective study included 26 patients with retinal dystrophies (17 with retinitis pigmentosa, four with Stargardt disease, three with cone‐rod dystrophy, one each with Best disease and Bietti crystalline dystrophy) and 32 healthy controls. Subfoveal OCT images were used for analysis. Mean CVI was compared between retinal dystrophy and control group, as well as among the retinal dystrophy subgroups.

Results

Mean CVI in eyes with retinal dystrophies was 52 ± 9% and it was significantly lower compared to that in normal eyes (70 ± 3%, p < 0.001). The differences among subgroups of retinal dystrophy were not statistically significant (p = 0.084). All types of retinal dystrophy were associated with lower CVI (all p < 0.001), after adjusting for age, gender, visual acuity and duration of symptoms. Older age was also shown to be independently associated with lower CVI (p = 0.012). Gender, visual acuity (VA) and duration of symptoms did not significantly affect CVI.

Conclusion

Decreased choroidal vascularity was seen in eyes with retinal dystrophies. (CVI) may be a helpful tool in monitoring choroidal involvement in retinal dystrophies.
Review article: the relationship between obesity, bariatric surgery, and inflammatory bowel disease
Authors: Cañete Fiorella , Mañosa Míriam , Clos Ariadna , Cabré Eduard , Domènech Eugeni
Published: September 2018

Background

The convoluted relationship between obesity, bariatric surgery and inflammatory bowel disease (IBD) is of increasing interest.

Aim

To analyse evidence regarding the role of bariatric surgery in the development of de novo IBD and its impact on clinical outcomes and safety in patients with established IBD.

Methods

A PubMed/Medline search was performed to identify studies reporting the development of IBD after bariatric surgery and the outcomes of IBD patients after bariatric surgery.

Results

Eighty patients were reported to have developed de novo IBD after bariatric surgery (21% ulcerative colitis [UC], 75% Crohn's disease [CD]), mostly females. Roux‐en‐Y gastric bypass was the most frequent bariatric technique (80%). Symptoms related to IBD occurred within 1 month and 16 years after surgery. Regarding patients with known IBD undergoing bariatric surgery, 60 patients (35 CD, 24 UC, and 1 unclassified colitis) have been reported. Sleeve gastrectomy was the most frequent bariatric procedure, particularly in CD patients. Acute flares after surgery were observed in only four UC patients. In addition, two retrospective population‐based studies described perioperative outcomes of bariatric surgery on IBD patients, demonstrating only a significant increase in small bowel obstruction in these patients.

Conclusions

Bariatric surgery in carefully selected patients with established IBD is technically feasible and probably safe. Development of de novo IBD should be taken into account in individuals with previous bariatric surgery who develop diarrhoea, anaemia or excessive weight loss.
Child protection and fathering where there is domestic violence: Contradictions and consequences
Authors: Smith Joanie , Humphreys Cathy
Published: September 2018

Children live in different contexts of protection and vulnerability when exposed to domestic violence. The negative impacts for many children are consistent and widely acknowledged. However, the implication that this requires men who use violence to address their fathering has been slower to emerge. This article draws from 69 in‐depth qualitative interviews with men, women, and workers across four men's behaviour change programmes in rural Victoria, Australia. Particular attention is given to men's attitudes to their fathering and the formal and informal consequences they experienced as a result of their violence and its impact on their fathering. Although most men came to recognize that their violence impacted their children, they failed to make the connection that the involvement of statutory child protection services in their lives was a direct consequence of their abusive behaviour. This article explores this disconnection by fathers who use violence, their attitude to the involvement of statutory child protection services, and identifies the implications for social work practitioners in addressing this issue.
Unspoken Rules: Resolving Underdetermination With Closure Principles
Authors: Nichols Shaun , Gaus Jerry
Published: September 2018

When people learn normative systems, they do so based on limited evidence. Many of the possible actions that are available to an agent have never been explicitly permitted or prohibited. But people will often need to figure out whether those unspecified actions are permitted or prohibited. How does a learner resolve this incompleteness? The learner might assume if an action‐type is not expressly forbidden, then acts of that type are permitted. This closure principle is one of Liberty. Alternatively, the learner might assume that if an action‐type is not expressly permitted, then acts of that type are prohibited. This closure principle would be one of Residual Prohibition (Mikhail, 2011). On the basis of principles of pedagogical sampling (e.g., Shafto, Goodman, & Griffiths, ), we predicted that participants would infer the Liberty Principle (LP) when trained on prohibitions, and they would infer the Residual Prohibition Principle when trained on permissions. This is exactly what we found across several experiments. We also found a bias in favor of Liberty insofar as participants trained on both a prohibition and a permission rule tended still to infer the LP. However, we also found that if an action is potentially harmful, this diminishes the tendency to infer the LP.
From understanding tooth development to bioengineering of teeth
Authors: Thesleff Irma
Published: September 2018

Remarkable breakthroughs in the fields of developmental biology and stem cell biology during the last 15 yr have led to a new level of understanding regarding how teeth develop and how stem cells can be programmed. As a result, the possibilities of growing new teeth and of tooth bioengineering have been explored. Currently, a great deal is known about how signaling molecules and genes regulate tooth development, and modern research using transgenic mouse models has demonstrated that it is possible to induce the formation of new teeth by tinkering with the signaling networks that govern early tooth development. A breakthrough in stem cell biology in 2006 opened up the possibility that a patient′s own cells can be programmed to develop into pluripotent stem cells and used for building new tissues and organs. At present, active research in numerous laboratories around the world addresses the question of how to program the stem and progenitor cells to develop into tooth‐specific cell types. Taken together, the remarkable progress in developmental and stem cell biology is now feeding hopes of growing new teeth in the dental clinic in the not‐too‐distant future.
The oral microbiome – friend or foe?
Authors: Kilian Mogens
Published: September 2018

The microbiome and the human body constitute an integrated superorganism, which is the result of millions of years of coevolution with mutual adaptation and functional integration, and confers significant benefits for both parties. This evolutionary process has resulted in a highly diverse oral microbiome, which covers the full spectrum of acidogenic, aciduric, inflammatory, and anti‐inflammatory properties. The relative proportions of members of the microbiome are affected by factors associated with modern life, such as general diet patterns, sugar consumption, tobacco smoking, oral hygiene, use of antibiotics and other antimicrobials, and vaccines. A perturbed balance in the oral microbiome may result in caries, periodontal disease, or candidiasis, and oral bacteria passively transferred to normally sterile parts of the body may cause extra‐oral infections. Nevertheless, it should never be our goal to eliminate the oral microbiome, but rather we have to develop ways to re‐establish a harmonious coexistence that is lost because of the modern lifestyle. With regard to oral diseases, this goal can normally be achieved by optimal oral hygiene, exposure to fluoride, reduction of sucrose consumption, stimulation of our innate immune defense, smoking cessation, and control of diabetes.
Prevention of dental caries as a non‐communicable disease
Authors: Twetman Svante
Published: September 2018

Today, dental caries is regarded as a preventable non‐communicable disease (NCD) that affects a majority of the population across their lifespan. As such, it shares a number of behavioural, socio‐economic, and lifestyle factors with other NCDs, such as overweight and diabetes, and should be subjected to a similar model of chronic disease management. Caries prevention has traditionally relied on fluoride exposure, diet control, thorough oral hygiene, and antibacterial measures. Prevention of caries as an NCD does certainly not disqualify these methods, but brings them into a new context. This conference paper provides a brief review on how common preventive measures can interfere with the drivers of dysbiosis and promote the growth of health‐associated clusters in the oral microbiome. Besides the established routines of regular toothbrushing with fluoride products, there is an opportunity for additional technologies, based on ecological principles, to address and modify the oral biofilm. Methods to reduce dietary sugar intake, slow down plaque metabolism, and support saliva functions should be further developed and investigated in terms of efficacy, compliance, and cost‐effectiveness. Furthermore, biofilm engineering through pre‐ and probiotics early in life to support microbial diversity seem promising in order to obtain a sustained caries‐preventive effect.
Pricing joint use of municipal services: Theoretical perspectives and regulatory issues
Authors: Valkama Pekka , Bailey Stephen J.
Published: September 2018

This paper analyses price regulation of inter‐municipal contracts in Finland to demonstrate interpretative problems of regulatory rules specifying full‐cost or market prices and, by so doing, deepen understanding of the theoretical underpinnings for pricing collaborative municipal services. It considers how to price inter‐municipal services taking into account the specific socio‐economic nature of inter‐municipal cooperation, including both financial and non‐financial objectives, through a new joint‐use pricing model of municipal services that challenges the supremacy of full‐cost pricing requirements in cases of inter‐municipal collaborative contracting. Acknowledging limitations and benefits, it concludes European Single Market rules militate against municipal discretion and localism.
Young Women's Perceptions of Traditional and Contemporary Female Beauty Ideals in China
Authors: Jung Jaehee
Published: September 2018

This study examined cultural standards of the female ideal beauty as perceived by young women in China using a qualitative approach. Twenty‐three female Chinese students enrolled in Donghua University in Shanghai were recruited for focus groups. Being fat and a round face were mentioned as traditional characteristics of female beauty, while contemporary characteristics included a slim body and a small face. Women in contemporary China seem to endorse many Western standards for the female beauty ideal. These standards have been pervasive in media images in the context of rapid and disruptive social change, in particular for changing gender roles for women.