bluuebunny/crossref_metadata_2025 huggingface dataset:
GeneWeld: a method for efficient targeted integration directed by short homology
Authors: Wierson Wesley A. , Welker Jordan M. , Almeida Maira P. , Mann Carla M. , Webster Dennis A. , Torrie Melanie E. , Weiss Trevor J. , Vollbrecht Macy K. , Lan Merrina , McKeighan Kenna C. , Levey Jacklyn , Ming Zhitao , Wehmeier Alec , Mikelson Christopher S. , Haltom Jeffrey A. , Kwan Kristen M. , Chien Chi-Bin , Balciunas Darius , Ekker Stephen C. , Clark Karl J. , Webber Beau R. , Moriarity Branden , Solin Staci L. , Carlson Daniel F. , Dobbs Drena L. , McGrail Maura , Essner Jeffrey J.
Published: October 2018

Choices for genome engineering and integration involve high efficiency with little or no target specificity or high specificity with low activity. Here, we describe a targeted integration strategy, called GeneWeld, and a vector series for gene tagging, pGTag (plasmids forGeneTagging), which promote highly efficient and precise targeted integration in zebrafish embryos, pig fibroblasts, and human cells utilizing the CRISPR/Cas9 system. Our work demonstrates thatin vivotargeting of a genomic locus of interest with CRISPR/Cas9 and a donor vector containing as little as 24 to 48 base pairs of homology directs precise and efficient knock-in when the homology arms are exposed with a double strand breakin vivo. Our results suggest that the length of homology is not important in the design of knock-in vectors but rather how the homology is presented to a double strand break in the genome. Given our results targeting multiple loci in different species, we expect the accompanying protocols, vectors, and web interface for homology arm design to help streamline gene targeting and applications in CRISPR and TALEN compatible systems.
Do Cells use Passwords in Cell-State Transitions? Is Cell Signaling sometimes Encrypted?
Authors: Root Alex
Published: October 2018

Organisms must maintain proper regulation including defense and healing. Life-threatening problems may be caused by pathogens or by a multicellular organism’s own cells through cancer or auto-immune disorders. Life evolved solutions to these problems that can be conceptualized through the lens of information security, which is a well-developed field in computer science. Here I argue that taking an information security view of cells is not merely semantics, but useful to explain features of signaling, regulation, and defense. An information security perspective also offers a conduit for cross-fertilization of advanced ideas from computer science, and the potential for biology to inform computer science. First, I consider whether cells use passwords, i.e., initiation sequences that are required for subsequent signals to have effects, by analyzing the concept of pioneer transcription factors in chromatin regulation and cellular reprogramming. Second, I consider whether cells may encrypt signal transduction cascades. Encryption could benefit cells by making it more difficult for pathogens or oncogenes to hijack cell networks. By using numerous molecules cells may gain a security advantage in particular against viruses, whose genome sizes are typically under selection pressure. I provide a simple conceptual argument for how cells may peform encryption through post-translational modifications, complex formation, and chromatin accessibility. I invoke information theory to provide a criterion of an entropy spike to assess whether a signaling cascade has encryption-like features. I discuss how the frequently invoked concept of context-dependency may over-simplify more advanced features of cell signaling networks, such as encryption. Therefore, by considering that biochemical networks may be even more complex than commonly realized we may be better able to understand defenses against pathogens and pathologies.
Application of Long Read Sequencing to Determine Expressed Antigen Diversity inTrypanosoma BruceiInfections
Authors: Jayaraman Siddharth , Harris Claire , Paxton Edith , Donachie Anne-Marie , Vaikkinen Heli , McCulloch Richard , Hall James P. J. , Kenny John , Lenzi Luca , Hertz-Fowler Christiane , Cobbold Christina , Reeve Richard , Michoel Tom , Morrison Liam J.
Published: October 2018

Abstract

Antigenic variation is employed by many pathogens to evade the host immune response, andTrypanosoma bruceihas evolved a complex system to achieve this phenotype, involving sequential use of variant surface glycoprotein (VSG) genes encoded from a large repertoire of ∼2,000 alleles.T. bruceiexpress multiple, sometimes closely related, VSGs in a population at any one time, and the ability to resolve and analyse this diversity has been limited. We applied long read sequencing (PacBio) to VSG amplicons generated from blood extracted from batches of mice sacrificed at time points (days 3, 6, 10 and 12) post-infection with T. brucei TREU927. The data showed that long read sequencing is reliable for resolving allelic differences between VSGs, and demonstrated that there is significant expressed diversity (449 VSGs detected across 20 mice) and across the timeframe of study there was a clear semi-reproducible pattern of expressed diversity (median of 27 VSGs per sample at day 3 post infection (p.i.), 82 VSGs at day 6 p.i., 187 VSGs at day 10 p.i. and 132 VSGs by day 12 p.i.). There was also consistent detection of one VSG dominating expression across replicates at days 3 and 6, and emergence of a second dominant VSG across replicates by day 12. The innovative application of ecological diversity analysis to VSG reads enabled characterisation of hierarchical VSG expression in the dataset, and resulted in a novel method for analysing such patterns of variation. Additionally, the long read approach allowed detection of mosaic VSG expression from very few reads – this was observed as early as day 3, the earliest that such events have been detected. Therefore, our results indicate that long read analysis is a reliable tool for resolving diverse allele expression profiles, and provides novel insights into the complexity and nature of VSG expression in trypanosomes, revealing significantly higher diversity than previously shown and identifying mosaic gene formation unprecedentedly early during the infection process.
Genetic risk for coronary heart disease alters the influence of Alzheimer’s genetic risk on mild cognitive impairment
Authors: Elman Jeremy A. , Panizzon Matthew S. , Logue Mark W. , Gillespie Nathan A. , Neale Michael C. , Reynolds Chandra A. , Gustavson Daniel E. , Andreassen Ole A. , Dale Anders M. , Franz Carol E. , Lyons Michael J. , Kremen William S.
Published: October 2018

BACKGROUND

Alzheimer’s disease (AD) is under considerable genetic influence. However, known susceptibility loci only explain a modest proportion of variance in disease outcomes. This small proportion could occur if the etiology of AD is heterogeneous. We previously found that an AD polygenic risk score (PRS) was significantly associated with mild cognitive impairment (MCI), an early stage of AD. Poor cardiovascular health is also associated with increased risk for AD and has been found to interact with AD pathology. Conditions such as coronary artery disease (CAD) are also heritable, and may contribute to heterogeneity if there are interactions of genetic risk for these conditions as there is phenotypically. However, case-control designs based on prevalent cases of a disease with relatively high case-fatality rate such as CAD may be biased toward individuals who have long post-event survival times and may therefore also identify loci with protective effects.

METHODS

We compared interactions between an AD-PRS and two CAD-PRSs, one based on a GWAS of incident cases and one on prevalent cases, on MCI status in 1,209 individuals.

RESULTS

As expected, the incidence-based CAD-PRS interacts with the AD-PRS to further increase MCI risk. Conversely, higher prevalence-based CAD-PRSs reduced the effect of AD genetic risk on MCI status.

CONCLUSIONS

These results demonstrate: i) the utility of including multiple PRSs and their interaction effects; ii) how genetic risk for one disease may modify the impact of genetic risk for another; and iii) the importance of considering ascertainment procedures of GWAS being used for genetic risk prediction.
In silico results of ϰ-Opioid receptor antagonists as ligands for the second bromodomain of the Pleckstrin Homology Domain Interacting Protein
Authors: El Assal Lemmer R. P.
Published: October 2018

Pleckstrin Homology Domain Interacting Protein (PHIP) is a member of the BRWD1-3 Family (Bromodomain and WD repeat-containing proteins). PHIP (BRWD2, WDR11) contains a WD40 repeat (methyl-lysine binder) and 2 bromodomains (acetyl-lysine binder). It was discovered through interactions with the pleckstrin homology domain of Insulin Receptor Signalling (IRS) proteins and has been shown to mediate transcriptional responses in pancreatic islet cells and postnatal growth. An initial hit for the second bromodomain of PHIP (PHIP(2)) was discovered in 2012, with consecutive research yielding a candidate with a binding affinity of 68μM. PHIP(2) is an atypical category III bromodomain with a threonine (THR1396) where an asparagine residue would usually be. In the standard case, this pocket holds four water molecules, but in the case of PHIP(2), there is room for one extra water molecule - also known as “PHIP water”, able to mediate interaction between THR1396 and the typical water network at the back of the binding pocket. We present first ever results of two ϰ-Opioid receptor (KOR) antagonists with distinct pharmacophores having an estimated binding affinity in the nM to μM range, as well as higher binding affinities for every currently discovered PHIP(2) ligand towards KOR. Finally, we also demonstrate selectivity of LY-255582 and LY-2459989 towards PHIP(2) over other bromodomains.
Gene fitness landscape of group A streptococcus during necrotizing myositis
Authors: Zhu Luchang , Olsen Randall J. , Beres Stephen B. , Eraso Jesus M. , Saavedra Matthew Ojeda , Kubiak Samantha L. , Cantu Concepcion C. , Jenkins Leslie , Charbonneau Amelia R. L. , Waller Andrew S. , Musser James M.
Published: October 2018

Necrotizing fasciitis and myositis are devastating infections characterized by high mortality. Group A streptococcus (GAS) is a common cause of these infections, but the molecular pathogenesis is poorly understood. We report a genome-wide analysis using serotype M1 and M28 strains that identified novel GAS genes contributing to necrotizing myositis in nonhuman primates (NHP), a clinically relevant model. Using transposon directed insertion-site sequencing (TraDIS) we identified 126 and 116 GAS genes required for infection by serotype M1 and M28 organisms, respectively. For both M1 and M28 strains, more than 25% of the GAS genes required for necrotizing myositis encode known or putative transporters. Thirteen GAS transporters contributed to both M1 and M28 strain fitness in NHP myositis, including putative importers for amino acids, carbohydrates, and vitamins, and exporters for toxins, quorum sensing peptides, and uncharacterized molecules. Targeted deletion of genes encoding five transporters confirmed that each isogenic mutant strain was significantly impaired in causing necrotizing myositis in NHPs. qRT-PCR analysis showed that these five genes are expressed in infected NHP and human skeletal muscle. Certain substrate-binding lipoproteins of these transporters, such as Spy0271 and Spy1728, were previously documented to be surface-exposed, suggesting that our findings have translational research implications.
A target enrichment bait set for studying relationships among ostariophysan fishes
Authors: Faircloth Brant C. , Alda Fernando , Hoekzema Kendra , Burns Michael D. , Oliveira Claudio , Albert James S. , Melo Bruno F. , Ochoa Luz E. , Roxo Fábio F. , Chakrabarty Prosanta , Sidlauskas Brian L. , Alfaro Michael E.
Published: October 2018

Target enrichment of conserved nuclear loci has helped reconstruct evolutionary relationships among a wide variety of species. While there are preexisting bait sets to enrich a few hundred loci across all fishes or a thousand loci from acanthomorph fishes, no bait set exists to enrich large numbers (>1000 loci) of ultraconserved nuclear loci from ostariophysans, the second largest actinopterygian superorder.

In this manuscript, we describe how we designed a bait set to enrich 2,708 ultraconserved nuclear loci from ostariophysan fishes by combining an existing genome assembly with low coverage sequence data collected from two ostariophysan lineages.

We perform a series of enrichment experiments using this bait set across the ostariophysan Tree of Life, from the deepest splits among the major groups (>150 MYA) to more recent divergence events that have occured during the last 50 million years.

Our results demonstrate that the bait set we designed is useful for addressing phylogenetic questions from the origin of crown ostariophysans to more recent divergence events, and our in silico results suggest that this bait set may be useful for addressing evolutionary questions in closely related groups of fishes, like Clupeiformes.
Reductions in prefrontal activation predict off-topic utterances during speech production
Authors: Hoffman Paul
Published: October 2018

The ability to speak coherently is essential for effective communication but declines with age: older people more frequently produce tangential, off-topic speech. Little is known, however, about the neural systems that support coherence in speech production. Here, fMRI was used to investigate extended speech production in healthy older adults. Computational linguistic analyses were used to quantify the coherence of utterances produced in the scanner, allowing identification of the neural correlates of coherence for the first time. Highly coherent speech production was associated with increased activity in bilateral inferior prefrontal cortex (BA45), an area implicated in selection of task-relevant knowledge from semantic memory, and in bilateral rostrolateral prefrontal cortex (BA10), implicated more generally in planning of complex goal-directed behaviours. These findings demonstrate that neural activity during spontaneous speech production can be predicted from formal analysis of speech content, and that multiple prefrontal systems contribute to coherence in speech.
An anti-Gn glycoprotein antibody from a convalescent patient potently inhibits the infection of severe fever with thrombocytopenia syndrome virus
Authors: Kim Ki Hyun , Kim Jinhee , Ko Meehyun , Chun June Young , Kim Hyori , Kim Seungtaek , Min Ji-Young , Park Wan Beom , Oh Myoung-don , Chung Junho
Published: October 2018

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 reported SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates.

Author summary

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea. This tick-borne virus has infected more than 5,000 humans with a 6.4% to 20.9% fatality rate. Currently, there are no prophylactic or therapeutic measures against this virus. Historically, antibodies from patients who recovered from viral infection have been used to treat new patients. Until now, one recombinant monoclonal antibody was approved for the prophylaxis of respiratory syntial virus infection. We selected 10 antibodies from a patient who recovered from SFTS and found that one antibody potently inhibited SFTS viral infection in both test tube and animal studies. We determined the binding site of this antibody to SFTS virus, which allowed us to predict that this antibody could bind 247 out of 272 SFTS virus isolates reported up to now. We anticipate that this antibody could be developed into a therapeutic measure against SFTS.
Productivity benefits of employer-sponsored training
Authors: Chhetri Prem , Gekara Victor , Manzoni Alex , Montague Alan
Published: October 2018

Purpose

The purpose of this paper is to examine the impact of employer-sponsored workforce training on employee productivity in the Australian transport and logistics industry. It challenges the quantitative notion of the ratio of input–output per labour hour as the single most important measure of productivity.

Design/methodology/approach

The study utilised a mixed-method approach, involving online and on-site survey questionnaires and on-site semi-structured interviews of employers, employees and students within the industry. Survey questionnaires were administered to Vocational Education and Training (VET) learners to determine the dimensions of productivity gains, while qualitative interviews were conducted specifically to capture employers’ perceptions and expectations of the benefits of training.

Findings

Results show that the relationship between employer-sponsored training and workforce productivity is multi-dimensional where, ideally, all essential dimensions must be fulfilled to effectively achieve sustainable productivity level. One dimension is the quantitative measure of increased performance as an outcome of enhanced knowledge, skills and competencies. Another relates to the increased self-confidence, job satisfaction and pride. The third dimension is the cost savings that come with increasing employees’ overall awareness and appreciation of occupational health and safety. The results show that, aside from the dominant theories on training and labour productivity, the perception of the benefits of training on workplace productivity is not merely limited to the conventional understanding of productivity as a simplistic relationship between resource inputs and tangible outputs.

Practical implications

Firms should consider redefining the benefits of training to include employee well-being and individual contribution to common team and organisational goals. Organisations therefore should broaden the notion of productivity to incorporate intangible benefits.

Originality/value

The use of multi-method approach to investigate the views and perceptions of employees, employers and trainers about the productivity benefits of training and key concerns and challenges for the industry.
Peer mentoring in entrepreneurship education: towards a role typology
Authors: Kubberød Elin , Fosstenløkken Siw M. , Erstad Per Olav
Published: October 2018

Purpose

The purpose of this paper is to explore the contributions of peer mentoring as a learning support for mentee students in higher entrepreneurship education.

Design/methodology/approach

This paper presents a single embedded case study focussing on mentee students’ perceptions of peer mentors’ support of their entrepreneurial learning during an experiential master’s course. Employing an abductive approach, the researchers conducted cross-sectional, thematic analyses of individual mentee interviews complemented by data from joint reflection sessions, reflection reports and observations during the course timeline.

Findings

The peer mentors contributed to the mentee students’ learning through various forms of support, which were categorised into mentor roles, mentor functions and intervention styles. The analysis found that peer mentors fulfil three coexisting roles: learning facilitator, supportive coach and familiar role model. These roles constitute the pillars of a typology of entrepreneurial peer mentoring.

Research limitations/implications

This study contributes theoretical and empirical insights on peer mentoring in entrepreneurship education. It represents a first benchmark of best practices for future studies.

Practical implications

The case study suggests that adding peer mentoring represents more efficient support for entrepreneurial learning than a teacher alone is able to provide. The typology can also be used for training peer mentors.

Originality/value

The researchers construct a new typology for entrepreneurial learning support, which contributes to theory development within the field of entrepreneurship education.
Control dimensions, job demands and job satisfaction: does ownership matter?
Authors: Lindfors Petra , Hansen Niklas
Published: October 2018

Purpose

New ownership types in health care of welfare states raise concerns regarding psychosocial work conditions including different control dimensions. The purpose of this paper is to investigate how job demands, control over work and control within work (CWW) were related to job satisfaction in publicly administered, private non-profit and private for-profit hospitals.

Design/methodology/approach

Questionnaire data came from employees at three hospitals; a publicly administered (n=774), a private non-profit (n=1,481) and a private for-profit (n=694) hospital. Mean-level analyses and hierarchical regressions with multiple group tests were conducted.

Findings

Demands including workload were significantly lower at the publicly administered hospital while the control dimension CWW was significantly higher. Background factors and their associations with job satisfaction differed slightly between ownership types. Attitudes to privatization were not associated with job satisfaction within any ownership type. Overall, psychosocial work characteristics, including job demands and control, were significantly associated with job satisfaction while their interactions showed no consistent associations with job satisfaction. As for the strength of the associations, no consistent differences emerged between ownership types.

Research limitations/implications

Using self-reports only, the associations between psychosocial work characteristics and job satisfaction seemed comparable across ownership types.

Practical implications

Associations between psychosocial work characteristics and job satisfaction seem comparable across ownership types. This may relate to societal demands on the structuring of costs, work and production efficiency being similar for all.

Originality/value

Contributions include researching different occupations and their attitudes to privatization and two control dimensions considered important for different ownership types.
Sustainability adoption in project management practices within a social enterprise case
Authors: Shah Satya , Naghi Ganji Elmira
Published: October 2018

Purpose

The purpose of this paper is to present the preliminary findings on the use of sustainable project management practices within social enterprise projects. The research gaps within this field have proposed the authors to address the challenges rising from lack of sustainable infrastructures in social-based projects both within for-profit and non-profit organisations. On the other side, behavioural needs and sustainable awareness of different stakeholders will be examined.

Design/methodology/approach

Secondary research consists of conducting a literature review clarifying the existing knowledge of the research topic within the body of literature. The stakeholders’ behavioural needs towards acting and implementing sustainable practices led to the adoption of sustainable practices within projects which are managed across profit and non-profit organisations.

Findings

The lack of sustainable behaviour and its adoption within organisations is also highlighted. The limitation of the research is the importance of integration of sustainable development (SD) within social projects. Such projects were identified as the drivers towards educating the society towards future generations’ sustainability awareness. However, if the adoption of sustainable practices is well established in some sectors (such as construction), literature tends to demonstrate a lack of information regarding other sectors, especially within social enterprises.

Originality/value

The novelty of the research is to develop an early understanding regarding linkages between sustainable practices and project management programmes within the social projects. The particular focus is given to corporate social responsibility and the comparative analysis has been made among for-profit and non-profit organisations in terms of SD metrics. The study results would be beneficial to the researchers and practitioners exploring within the same field.
Occasional long distance dispersal increases spatial synchrony of population cycles
Authors: Hopson Jessica , Fox Jeremy W.
Published: October 2018

Spatially separated populations of the same species often exhibit correlated fluctuations in abundance, a phenomenon known as spatial synchrony. Dispersal can generate spatial synchrony. In nature, most individuals disperse short distances with a minority dispersing long distances. The effect of occasional long distance dispersal on synchrony is untested, and theoretical predictions are contradictory. Occasional long distance dispersal might either increase both overall synchrony and the spatial scale of synchrony, or reduce them.

We conducted a protist microcosm experiment to test whether occasional long distance dispersal increases or decreases overall synchrony and the spatial scale of synchrony.

We assembled replicate 15‐patch ring metapopulations of the protist predator Euplotes patella and its protist prey Tetrahymena pyriformis. All metapopulations experienced the same dispersal rate, but differed in dispersal distance. Some metapopulations experienced strictly short distance (nearest neighbour) dispersal, others experienced a mixture of short‐ and long distance dispersal.

Occasional long distance dispersal increased overall spatial synchrony and the spatial scale of synchrony for both prey and predators, though the effects were not statistically significant for predators. As predicted by theory, dispersal generated spatial synchrony by entraining the phases of the predator–prey cycles in different patches, a phenomenon known as phase locking.

Our results are consistent with theoretical models predicting that occasional long distance dispersal increases spatial synchrony. However, our results also illustrate that the spatial scale of synchrony need not match the spatial scale of the processes generating synchrony. Even strictly short distance dispersal maintained high spatial synchrony for many generations at spatial scales much longer than the dispersal distance, thanks to phase locking.
Multiple density‐dependent processes shape the dynamics of a spatially structured amphibian population
Authors: Cayuela Hugo , Schmidt Benedikt R. , Weinbach Avril , Besnard Aurélien , Joly Pierre
Published: October 2018

Understanding the mechanisms that regulate the dynamics of spatially structured populations (SSP) is a critical challenge for ecologists and conservation managers. Internal population processes such as births and deaths occur at a local level, while external processes such as dispersal take place at an inter‐population level. At both levels, density dependence is expected to play a critical role. At a patch scale, demographic traits (e.g., survival, breeding success) and the population growth rate can be influenced by density either negatively (e.g., competition effect) or positively (e.g., Allee effects). At the scale of an SSP, although positive density‐dependent dispersal has been widely reported, an increasing number of studies have highlighted negative density‐dependent dispersal.

While many studies have investigated the effects of density on population growth or on dispersal, few have simultaneously examined density‐dependent effects at the scale of both the local population and the entire SSP. In this study, we examine how density is related to demographic processes at both the pond level (survival and population growth) and the SSP level (between‐pond dispersal) in a pond‐breeding amphibian, the great crested newt (Triturus cristatus). The study was based on 20 years of individual capture–recapture (CR) data (from 1996 to 2015) gathered from an SSP made up of 12 experimental ponds (“patches”).

We first used a CR multievent model to estimate both survival and dispersal rates in specific ponds as a function of distance between ponds. Then, using a second CR multievent model, we examined whether survival and recapture rates were influenced by population density in a pond. Lastly, we used state‐space time series models to investigate whether density affected population growth in each pond.

Our results found a positive density‐dependent effect on survival and a negative density‐dependent effect on departure. In addition, the findings indicate that population growth was negatively related to density in all 12 ponds.

These results support the hypothesis that in SSPs, density may have multiple and contrasting effects on demographic parameters and growth rates within local populations as well as on dispersal. This study underlines the need to better understand how density dependence may influence potential trade‐offs between life‐history strategies and life‐history stages.
Predicting tubal factor infertility by using markers of humoral and cell‐mediated immune response against Chlamydia trachomatis
Authors: Rantsi Tiina , Öhman Hanna , Puolakkainen Mirja , Bloigu Aini , Paavonen Jorma , Surcel Heljä‐Marja , Tiitinen Aila , Joki‐Korpela Päivi
Published: October 2018

Problem

The accuracy of Chlamydia trachomatis antibody test in predicting tubal factor infertility (TFI) is limited, and more accurate methods are needed. Cell‐mediated immune response (CMI) is crucial in the resolution of pathogen, but it may play an important role in the pathogenesis of C trachomatis‐associated tubal damage. We studied whether combining the markers of C trachomatis‐induced CMI to humoral immune response improves the accuracy of serology in TFI prediction.

Method of study

Our prospective study consists of 258 subfertile women, of whom 22 (8.5%) had TFI. Women with other causes for subfertility served as a reference group. Serum C trachomatis major outer membrane protein (MOMP) and chlamydial heat‐shock protein 60 (cHSP60) IgG antibodies were measured by ELISA. CMI was studied by lymphocyte proliferation assay in vitro.

Results

Serological markers were more prevalent in women with TFI than in other subfertile women (40.9% vs 12.3% for MOMP IgG and 27.3% vs 10.2% for cHSP60 IgG). The best test combination for TFI was C. trachomatis MOMP and cHSP60 antibody with an accuracy of 90.3%, sensitivity of 22.7% and specificity of 96.6%. Positive post‐test probability of this combination was 54.2%, and negative post‐test probability was 12.4%. Adding of the markers of CMI did not significantly improve the accuracy of serology in TFI prediction.

Conclusion

The accuracy of TFI prediction increases when the combination of C trachomatis MOMP and cHSP60 antibody tests is used. C trachomatis‐induced CMI was common in our study population, but the markers of CMI did not predict TFI.
Proteomic analysis of posterior capsular plaques in congenital unilateral cataract
Authors: Van Looveren Jan , Van Gerwen Veerle , Schildermans Karin , Laukens Kris , Baggerman Geert , Tassignon Marie‐José
Published: October 2018

Purpose

To obtain insights on the protein composition of posterior capsular plaques (PCP) in congenital unilateral cataract with anterior vitreolenticular interface dysgenesis (AVLID).

Methods

Posterior capsular plaque's were collected during surgery in children presenting with congenital unilateral cataract. Surgeries were analysed focusing on the type of cataract, the integrity of the posterior capsule after peeling the PCP and the presence of vitreolenticular adherences when performing primary posterior capsulorhexis. Proteome analysis was performed on the collected PCPs.

Results

Posterior capsular plaques collection and proteome analysis were feasible from four children presenting with unilateral idiopathic congenital cataract and AVLID. A large portion of the proteins found in the PCPs was similar to the proteins known to be present in lens epithelial cells and fibres. Proteins like vimentin, fibronectin, collagen type I, collagen type VI and lumican were also found, which typically are present in mesenchymal tissue but not in lens tissue or capsule.

Conclusion

Posterior capsular plaques in cases of unilateral idiopathic congenital cataract of the AVLID type present a protein composition of mainly proteins found in lens epithelial cells and fibres. Some proteins however are a specific for lens tissue and are typically seen in mesenchymal tissue.
Understanding an emerging treatment population: Protocol for and baseline characteristics of a prospective cohort of people receiving treatment for pharmaceutical opioid dependence
Authors: Nielsen Suzanne , Lintzeris Nicholas , Murnion Bridin , Degenhardt Louisa , Bruno Raimondo , Haber Paul , Johnson Jennifer , Hardy Mark , Ling Stephen , Saddler Craig , Dunlop Adrian , Demirkol Apo , Silsbury Catherine , Phung Nghi , Houseman Jennie , Larance Briony
Published: October 2018

Introduction and Aims

Despite large increases in pharmaceutical opioid dependence and related mortality, few studies have focused on the characteristics and treatment experiences of those with pharmaceutical opioid dependence. We describe the formation of a prospective cohort of people receiving treatment for pharmaceutical opioid dependence and describe their baseline characteristics.

Design and Methods

People who had entered treatment for pharmaceutical opioid dependence (n = 108) were recruited through drug treatment services in New South Wales, Australia. We describe baseline characteristics of those that commenced pharmaceutical opioids for pain or other reasons and conducted a thematic analysis of responses regarding their treatment experience.

Results

Mean age was 41 years (SD 11), half were male (48%). Just over half reported lifetime heroin use (57%). Oxycodone (49%) and codeine (29%) were the most common opioids reported. Most (85%) reported past‐year problematic pain, 38% reported chronic pain. Half (52%) reported moderate to severe depression symptoms. Most (66%) commenced opioids for pain, and this group were older, less likely to report a previous overdose and less likely to report use of illicit drugs compared to those commencing for other reasons. Five themes related to treatment expectations: (i) stigma; (ii) the restrictive nature of treatment; (iii) knowledge; (iv) pain; and (v) positive experience with buprenorphine.

Discussion and Conclusions

This study describes the complexities in an important emerging treatment population of pharmaceutical opioid‐dependent people. Findings highlights that addressing knowledge and perceptions around treatment may be critical to address the rising mortality associated with pharmaceutical opioid dependence.
Association between diabetic eye disease and other complications of diabetes: Implications for care. A systematic review
Authors: Pearce Ian , Simó Rafael , Lövestam‐Adrian Monica , Wong David T. , Evans Marc
Published: October 2018

The aim of this systematic review was to examine the associations between diabetic retinopathy (DR) and the common micro‐ and macrovascular complications of diabetes mellitus, and how these could potentially affect clinical practice. A structured search of the PubMed database identified studies of patients with diabetes that assessed the presence or development of DR in conjunction with other vascular complications of diabetes. From 70 included studies, we found that DR is consistently associated with other complications of diabetes, with the severity of DR linked to a higher risk of the presence of, or of developing, other micro‐ and macrovascular complications. In particular, DR increases the likelihood of having or developing nephropathy and is also a strong predictor of stroke and cardiovascular disease, and progression of DR significantly increases this risk. Proliferative DR is a strong risk factor for peripheral arterial disease, which carries a risk of lower extremity ulceration and amputation. Additionally, our findings suggest that a patient with DR has an overall worse prognosis than a patient without DR. In conclusion, this analysis highlights the need for a coordinated and collaborative approach to patient management. Given the widespread use of DR screening programmes that can be performed outside of an ophthalmology office, and the overall cost‐effectiveness of DR screening, the presence and severity of DR can be a means of identifying patients at increased risk for micro‐ and macrovascular complications, enabling earlier detection, referral and intervention with the aim of reducing morbidity and mortality among patients with diabetes. Healthcare professionals involved in the management of diabetes should encourage regular DR screening.
The role of the cerebellum in drug‐cue associative memory: functional interactions with the medial prefrontal cortex
Authors: Gil‐Miravet Isis , Guarque‐Chabrera Julian , Carbo‐Gas Maria , Olucha‐Bordonau Francisco , Miquel Marta
Published: October 2018

Drug‐induced Pavlovian memories are thought to be crucial for drug addiction because they guide behaviour towards environments with drug availability. Drug‐related memory depends on persistent changes in dopamine‐glutamate interactions in the medial prefrontal cortex (mPFC), basolateral amygdala, nucleus accumbens core and hippocampus. Recent evidence from our laboratory indicated that the cerebellum is also a relevant node for drug‐cue associations. In the present study, we tested the role that specific regions of the cerebellum and mPFC play in the acquisition of cocaine‐induced preference conditioning. Quinolinic acid was used to manage a permanent deactivation of lobule VIII in the vermis prior to conditioning. Additionally, lidocaine was infused into the prelimbic and infralimbic (IL) cortices for reversible deactivation before every training session. The present findings show, for the first time, that the cerebellum and mPFC might act together in order to acquire drug‐cue Pavlovian associations. Either a dorsal lesion in lobule VIII or an IL deactivation encouraged cocaine‐induced preference conditioning. Moreover, simultaneous IL‐cerebellar deactivation prevented the effect of either of the separate deactivations. Therefore, similar to the IL cortex, neural activity in the cerebellum may be crucial for ensuring inhibitory control of the expression of cocaine‐related memories.
Improving Volatility Forecasts Using Market‐Elicited Ambiguity Aversion Information
Authors: So Raymond H.Y. , Driouchi Tarik
Published: October 2018

Distinguishing between risk and uncertainty, this paper proposes a volatility forecasting framework that incorporates asymmetric ambiguity shocks in the (exponential) generalized autoregressive conditional heteroskedasticity‐in‐mean conditional volatility process. Spanning 25 years of daily data and considering the differential role of investors' ambiguity attitudes in the gain and loss domains, our models capture a rich set of information and provide more accurate volatility forecasts both in‐sample and out‐of‐sample when compared to ambiguity‐free or risk‐based counterparts. Ambiguity‐based volatility‐timing trading strategies confirm the economic significance of our proposed framework and indicate that an annualized excess return of 3.2% over the benchmark could be earned from 1995 to 2014.
Influence of CTNNB1 rs2953 polymorphism on schizophrenia susceptibility in Chinese Han population through modifying miR‐485 binding to CTNNB1
Authors: Guo Xiaojing , Yang Jialei , Huang Jiao , Chen Zhaoxia , Wu Xulong , Zhu Lulu , Huang Guifeng , Long Jianxiong , Su Li
Published: October 2018

Schizophrenia (SCZ) and bipolar disorder (BD) are two major neuropsychiatric diseases that are the most substantial causes of disability and mortality worldwide. CTNNB1 encodes beta‐catenin, an important protein in canonical Wnt signaling. We aimed to investigate the association between the rs2953 of CTNNB1 and the risk of SCZ and BD and to further explore the function of rs2953. A total of 1658 samples (548 SCZ cases, 512 BD cases, and 598 controls) were examined in terms of the genotype of CTNNB1 rs2953. The mRNA expression level of CTNNB1 significantly increased in the SCZ and BD groups compared with that in the control group. Significant association remained between CTNNB1 3′‐untranslated region (UTR) variant rs2953 and SCZ susceptibility (additive and dominant model) after gender and age were adjusted. rs2953 disrupted the binding of CTNNB1 and miR‐485. miR‐485 significantly suppressed the luciferase activity of CTNNB1‐T vector by binding to the CTNNB1 3′‐UTR containing the T allele of rs2953. The mRNA expression of CTNNB1 can be used as a biomarker for the diagnosis of SCZ and BD. The 3′‐UTR variant rs2953 in CTNNB1 influences the risk of SCZ in the Han Chinese population and modifies the binding of miR‐485 to CTNNB1.
Vitamin D insufficiency predicts mortality among older men, but not women: A nationwide retrospective cohort from Thailand
Authors: Srinonprasert Varalak , Chalermsri Chalobol , Chailurkit La‐or , Ongphiphadhanakul Boonsong , Aekplakorn Wichai
Published: October 2018

Aim

Previous studies on the association between low vitamin D level and increased mortality mainly came from high‐income countries. The primary objective of the present study was to examine the effect of sex on the association between 25‐hydroxyvitamin D2 and D3 and mortality among community‐dwelling older people in Thailand.

Methods

A cohort of individuals aged ≥60 years from the Thai 4th National Health Examination Survey carried out in 2008 were followed and linked to a vital registry in 2015. Data regarding comorbid diseases, physical activity and serum vitamin D were obtained at the baseline assessment. Factors associated with all‐cause mortality were determined using Cox proportional hazards models.

Results

A total of 1268 participants with a median age of 74.0 years (interquartile range 67.0–81.0) were included. The prevalence of vitamin D insufficiency was 24.5% and 43.9% in men and women, respectively. Vitamin D insufficiency was significantly associated with all‐cause mortality only among men (adjusted HR 1.77, 95% CI 1.25–2.51), but not women. Analysis of 25‐hydroxyvitamin D3 divided into tertiles also showed an association with an adjusted HR of 1.83 (95% CI 1.23–2.72) for the lowest tertile in men. Diabetes was an effect modifier for low serum vitamin D and male sex, with HR 3.34 (95% CI 1.76–6.33, P < 0.001) in diabetic men with vitamin D insufficiency.

Conclusions

Low serum vitamin D is an independent risk factor for increased mortality in community‐dwelling Thai older men. Further randomized controlled study to investigate the benefit of vitamin D3 supplementation in older persons, particularly men, is warranted. Geriatr Gerontol Int 2018; 18: 1585–1590.
CITY EQUILIBRIUM WITH BORROWING CONSTRAINTS: STRUCTURAL ESTIMATION AND GENERAL EQUILIBRIUM EFFECTS
Authors: Ouazad Amine , Rancière Romain
Published: October 2018

This article develops a general equilibrium model of location choice where mortgage approval rates determine household‐specific choice sets. Estimation of the model using San Francisco Bay area data reveals that the price sensitivity of borrowing constraints explains about two‐thirds of the price elasticity of neighborhood demand. General equilibrium analysis of the 2000–2006 relaxation of lending standards predicts the following impacts on prices and neighborhood demographics: (i) an increase in house prices accompanied by a compression of the price distribution and (ii) a reduction in the isolation of Whites reflecting gentrification. Both predictions are supported by empirical observation.
NETWORK SEARCH: CLIMBING THE JOB LADDER FASTER
Authors: Arbex Marcelo , O'Dea Dennis , Wiczer David
Published: October 2018

We introduce an irregular network structure into a model of frictional, on‐the‐job search in which workers find jobs through their network connections or directly from firms. We show network‐found jobs have higher wages, and thus better‐connected workers climb the job ladder faster. The mean field approach allows us to formulate heterogeneous workers' recursive problem tractably. Our calibration is consistent with several empirical findings because of a composition—not information—effect. We also introduce new model‐consistent evidence: Job‐to‐job switches at higher ladder rungs are more likely to use networks.
Awareness of oral medicine among medical practitioners, evidence of the unbridged interdisciplinary gap
Authors: Alrashdan Mohammad S. , Darwazeh Azmi M.G. , Hassona Yazan , Bader Dima H. , Khader Yousef S.
Published: October 2018

Rationale, aims, and objectives

Inadequate awareness of oral health and related disciplines appears to be common among medical practitioners. This study was designed to evaluate the awareness of oral medicine (OM) specialty and its scope of practice among Jordanian medical practitioners and to outline potential strategies for improvement where appropriate.

Method

A specially designed questionnaire was electronically distributed to Jordanian medical practitioners and thereafter via personal interviews to improve the response rate. The questionnaire comprised nine questions and covered demographical details and characteristics of participants, in addition to their awareness of OM and agreement to refer a group of common oral and dental conditions to OM specialists. Pearson Chi‐square tests were used to examine the significance of association between the variables of respondents and awareness of OM. Significance level was set at P values < 0.05.

Results

A total of 1492 respondents completed the questionnaire, of which 779 (52.2%) were aware of OM as an independent specialty. Age group, higher degrees in medicine, country of graduation, and the specialty type were significant determinants of OM awareness level. Oral ulceration and other mucosal pathology, including fungal infections, were the most likely conditions to be referred to OM specialists while participants had apparent problems separating the scope of practice of OM from other dental disciplines.

Conclusion

This study provides evidence on the profound interdisciplinary gap between medicine and dentistry and highlights the importance of more focused education and training in oral health‐related disciplines to be provided to clinicians and medical trainees as described.