bluuebunny/crossref_metadata_2025 huggingface dataset:
Narrative Review of Cannabidiol as an Antipsychotic and Recommendations for Legal Regulations
Authors: Walkey Lisa Rachel Lena , Tanguay Robert L. , el-Guebaly Nady
Published: April 2019

Introduction:

This paper will review the effects of cannabidiol (CBD) in regards to psychosis and schizophrenia, and its purported treatment for psychosis.

Methods:

A PubMed search was completed using terms: "Cannabidiol and Psychosis," for which 63 studies were found; "Cannabidiol and Schizophrenia," for which 65 studies were found; and "Cannabidiol and Psychotomimetic," for which 37 studies were found. Inclusion criteria included English-language articles published from 2000 to present (July 2016) for human studies only, leading to 7 clinical trials for review. Following this search, 2 additional papers published in 2018 were added for completeness, totaling 9 clinical trials.

Results:

There have been recent studies showing psychosis is secondary to the tetrahydrocannabinol (THC) in marijuana; more striking is that studies were found showing CBD may be protective and actually have antipsychotic properties equal in efficacy to atypical antipsychotics. THC and CBD seem to have opposite physiologic effects on endogenous anandamide levels and cannabinol receptor binding, the mechanism likely leading to CBD's antipsychotic effect.

Conclusions:

Early evidence shows that CBD may be a novel and viable treatment for psychosis. This may have an effect on the regulation of CBD and THC percentages in regards to the prevention of early onset schizophrenia.

Introduction:

Cet article passera en revue les effets du cannabidiol (CBD) en ce qui concerne la psychose et la schizophrénie, et son prétendu traitement pour la psychose.

Méthodes:

Une recherche PubMed a été complétée en utilisant des termes: “Cannabidiol and Psychosis”, pour lesquels 63 études ont été repérées; “Cannabidiol and Schizophrenia”, pour lequel 65 études ont été repérées; et “Cannabidiol et Psychotomimetic,” pour lequel 37 études ont été repérées. Les critères d’inclusion comprenaient des articles de langue anglaise publiés de 2000 à aujourd’hui (juillet 2016) pour les études sur les humains seulement, menant à 7 essais cliniques d’évaluation. Suite à cette recherche, deux articles supplémentaires publiés en 2018 ont été ajoutés pour l’exhaustivité, totalisant 9 essais cliniques.

Résultats:

Des études récentes ont démontré que la psychose est secondaire au THC dans la marijuana; Il est plus marquant de constater que des études ont montré que le CBD peut être protecteur et avoir des propriétés antipsychotiques égales en efficacité aux antipsychotiques atypiques. Le THC et le CBD semblent avoir des effets physiologiques opposés sur les taux endogènes d’anandamide et de liaison au récepteur du cannabinol, mécanisme susceptible de conduire à l’effet antipsychotique du CBD.

Conclusions:

Les premières données montrent que le CBD peut être un traitement nouveau et viable contre la psychose. Cela pourrait avoir un effet sur la régulation des pourcentages de CBD et de THC en ce qui concerne la prévention de la schizophrénie précoce.
A Review of Infections in People Who Use Nonprescription Drugs
Authors: Lang Raynell , John Gill M.
Published: April 2019

La dépendance accroît le risque d’infection chez une personne par des facteurs directs et indirects. Le risque direct d’infection par injection ou inhalation de substances est bien reconnu. Cependant, les voies indirectes, telles que les effets immunosuppresseurs de certaines drogues et les conditions sociales de la dépendance, peuvent augmenter le risque d’infection. Environ 200 millions de personnes (5% de la population adulte mondiale) consomment des drogues illégales chaque année et au Canada, près de 5 millions de personnes en 2015.

Pour ceux qui gèrent une dépendance, une approche personnalisée visant à réduire les risques d’infection, suivie d’un dépistage, d’un diagnostic précoce et d’un lien avec les programmes de traitement est essentielle. Pour ceux qui traitent une infection chez des personnes présentant un trouble lié à l’utilisation de substances, une approche holistique peut être nécessaire pour atteindre les objectifs du traitement au-delà des protocoles de gestion standard. Le travail d’équipe est généralement essentiel. Il implique: le patient, les services spécialisés en toxicomanie, le travail social, la pharmaceutique et les spécialistes des maladies infectieuses que tous communiquent ensemble afin d’optimiser les résultats.

Dans cette analyse, nous visons à mettre en évidence les infections courantes et importantes sur le plan clinique reliées à la médecine de la toxicomanie, afin de contribuer à la prévention, à l’identification, au diagnostic et au traitement optimal de telles infections.

Addiction heightens an individual's risk for infection through both direct and indirect factors. The direct risk of infection from injecting or inhaling substances is well recognized. Indirect pathways, however, such as immunosuppressive effects of some drugs and the social circumstances of addiction may further increase the risk of infection. Approximately 200 million people (5% of the global adult population) use illegal drugs in any given year, and in Canada, this included nearly 5 million people in 2015.

For those managing addiction, a customized approach to reduce the risks for infection followed by screening, early diagnosis, and linkage to treatment programs is essential. For those treating infection in persons with substance use disorder, a holistic approach may be required to achieve treatment goals beyond standard management protocols. Teamwork is usually essential involving; the patient, addictions services, social work, pharmacy, and infectious disease specialists all communicating to optimize outcomes.

In this review, we aim to highlight common and clinically important infections that interface with addiction medicine, in order to help prevent, identify, diagnose, and optimally treat such infections.
Tau pathology in cognitively normal older adults
Authors: Ziontz Jacob , Bilgel Murat , Shafer Andrea T. , Moghekar Abhay , Elkins Wendy , Helphey Jessica , Gomez Gabriela , June Danielle , McDonald Michael A. , Dannals Robert F. , Azad Babak Behnam , Ferrucci Luigi , Wong Dean F. , Resnick Susan M.
Published: April 2019

INTRODUCTION

Tau pathology, a hallmark of Alzheimer’s disease, is observed in the brains of virtually all individuals over 70.

METHODS

Using 18F-AV-1451 (18F-flortaucipir) PET, we evaluated tau pathology in 54 cognitively normal participants (mean age 77.5, SD 8.9) from the Baltimore Longitudinal Study of Aging. We assessed associations between PET signal and age, sex, race, and amyloid positivity. We investigated relationships between regional signal and retrospective rates of change in regional volumes and cognitive function adjusting for age, sex, and amyloid status.

RESULTS

Greater age, male sex, black race, and amyloid positivity were associated with higher 18F-AV-1451 retention in distinct brain regions. Retention in the entorhinal cortex was associated with lower entorhinal volume (β = −1.124, SE = 0.485, p = 0.025) and a steeper decline in memory performance (β = −0.086, SE = 0.039, p = 0.029).

DISCUSSION

Assessment of medial temporal tau pathology will provide insights into early structural brain changes associated with later cognitive impairment and Alzheimer’s disease.
On the Mathematics of Populations
Authors: Gomes M. Gabriela M.
Published: April 2019

Selection acting on unobserved heterogeneity is a fundamental issue in the mathematics of populations. As recognised in disciplines as diverse as demography [11, 23, 24], ecology [10, 9], evolution [21] and epidemiology [1, 4, 5], in any population, individuals differ in many characteristics and it is essential that researchers understand which of these are under selection and how selection processes operate. Here I describe conceptual and methodological developments in demography and ecology, and discuss the importance of adopting similar approaches in evolution and epidemiology.
No atypical white-matter structures in grapheme- or color-sensitive areas in synesthetes
Authors: Weiss Franziska , Greenlee Mark W. , Volberg Gregor
Published: April 2019

Grapheme-color synesthetes experience colors when presented with written language characters. In this study diffusion-weighted imaging was used to investigate white matter alterations in color-and grapheme-processing brain areas in synesthetes as a possible factor for the color sensations. Regions of interest were defined by means of neuroanatomical atlantes, functional localizer tasks and retinotopic mapping. None of the regions showed differences in white matter structure between synesthetes and a control population, as revealed by fractional anisotropy and mean diffusivity measures. Quite the contrary, the data broadly supported the null hypothesis of no group differences in white matter microstructure. This finding is in line with recent studies suggesting no atypical neuroanatomy in grapheme-color synesthetes.
Origin of a novel CYP20A1 transcript isoform through multiple Alu exaptations creates a potential miRNA sponge
Authors: Bhattacharya Aniket , Jha Vineet , Singhal Khushboo , Fatima Mahar , Singh Dayanidhi , Chaturvedi Gaura , Dholakia Dhwani , Kutum Rintu , Pandey Rajesh , Bakken Trygve E. , Seth Pankaj , Pillai Beena , Mukerji Mitali
Published: April 2019

Background

Primate-specific Alus contribute to transcriptional novelties in conserved gene regulatory networks. Alu RNAs are present at elevated levels in stress conditions and consequently leads to transcript isoform specific functional role modulating the physiological outcome. One of the possible mechanisms could be Alu nucleated mRNA-miRNA interplay.

Result

Using combination of bioinformatics and experiments, we report a transcript isoform of an orphan gene, CYP20A1 (CYP20A1_Alu-LT) through exaptation of 23 Alus in its 9kb 3’UTR. CYP20A1_Alu-LT, confirmed by 3’RACE, is an outlier in length and expressed in multiple cell lines. We demonstrate its presence in single nucleus RNA-seq of ∼16000 human cortical neurons (including rosehip neurons). Its expression is restricted to the higher primates. Most strikingly, miRanda predicts ∼4700 miRNA recognition elements (MREs; with threshold< −25kcal/mol) for ∼1000 miRNAs, which have majorly originated within the 3’UTR-Alus post exaptation. We hypothesized that differential expression of this transcript could modulate mRNA-miRNA networks and tested it in primary human neurons where CYP20A1_Alu-LT is downregulated during heat shock response and upregulated upon HIV1-Tat treatment. CYP20A1_Alu-LT could possibly function as a miRNA sponge as it exhibits features of a sponge RNA such as cytosolic localization and ≥10 MREs for 140 miRNAs. Small RNA-seq revealed expression of nine miRNAs that can potentially be sponged by CYP20A1_Alu-LT in neurons. Additionally, CYP20A1_Alu-LT expression was positively correlated (low in heat shock and high in Tat) with 380 differentially expressed genes that contain cognate MREs for these nine miRNAs. This set is enriched in genes involved in neuronal development and hemostasis pathways.

Conclusion

We demonstrate a potential role for CYP20A1_Alu-LT as miRNA sponge through preferential presence of MREs within Alus in a transcript isoform specific manner. This highlights a novel component of Alu-miRNA mediated transcriptional modulation leading to physiological homeostasis.
Evidence for the rhythmic perceptual sampling of auditory scenes
Authors: Kayser Christoph
Published: April 2019

Converging results suggest that perception is controlled by rhythmic processes in the brain. In the auditory domain, neuroimaging studies show that the perception of brief sounds is shaped by rhythmic activity prior to the stimulus and electrophysiological recordings have linked delta band (1-2 Hz) activity to the functioning of individual neurons. These results have promoted theories of rhythmic modes of listening and generally suggest that the perceptually relevant encoding of acoustic information is structured by rhythmic processes along auditory pathways. A prediction from this perspective – which so far has not been tested – is that such rhythmic processes also shape how acoustic information is combined over time to judge extended soundscapes. The present study was designed to directly test this prediction. Human participants judged the overall change in perceived frequency content in temporally extended (1.2 to 1.8 s) soundscapes, while the perceptual use of the available sensory evidence was quantified using psychophysical reverse correlation. Model-based analysis of individual participant’s perceptual weights revealed a rich temporal structure, including linear trends, a U-shaped profile tied to the overall stimulus duration, and importantly, rhythmic components at the time scale of 1 to 2Hz. The collective evidence found here across four versions of the experiment supports the notion that rhythmic processes operating on the delta band time scale structure how perception samples temporally extended acoustic scenes.
Versatile polyketide biosynthesis platform for production of aromatic compounds in yeast
Authors: Jakočiūnas Tadas , Klitgaard Andreas K. , Romero-Suarez David , Petzold Christopher J. , Gin Jennifer W. , Tong Yaojun , Frandsen Rasmus J.N. , Weber Tilmann , Lee Sang Yup , Jensen Michael K. , Keasling Jay D.
Published: April 2019

To accelerate the shift to bio-based production and overcome complicated functional implementation of natural and artificial biosynthetic pathways to industry relevant organisms, development of new, versatile, bio-based production platforms is required. Here we present a novel yeast platform for biosynthesis of bacterial aromatic polyketides. The platform is based on a synthetic polyketide synthase system enabling a first demonstration of bacterial aromatic polyketide biosynthesis in a eukaryotic host.
First near complete haplotype phased genome assembly of River buffalo (Bubalus bubalis)
Authors: Ananthasayanam Sudhakar , Kothandaraman Harish , Nayee Nilesh , Saha Sujit , Baghel Dushyant Singh , Gopalakrishnan Kishore , Peddamma Sathish , Singh Ram Bahadur , Schatz Michael
Published: April 2019

This study reports the first haplotype phased reference quality genome assembly of ‘Murrah’ an Indian breed of river buffalo. A mother-father-progeny trio was used for sequencing so that the individual haplotypes could be assembled in the progeny. Parental DNA samples were sequenced on the Illumina platform to generate a total of 274 Gb paired-end data. The progeny DNA sample was sequenced using PacBio long reads and 10x Genomics linked reads at 166x coverage along with 802Gb of optical mapping data. Trio binning based FALCON assembly of each haplotype was scaffolded with 10x Genomics reads and super-scaffolded with BioNano Maps to build reference quality assembly of sire and dam haplotypes of 2.63Gb and 2.64Gb with just 59 and 64 scaffolds and N50 of 81.98Mb and 83.23Mb, respectively. BUSCO single copy core gene set coverage was > 91.25%, and gVolante-CEGMA completeness was >96.14% for both haplotypes. Finally, RaGOO was used to order and build the chromosomal level assembly with 25 scaffolds and N50 of 117.48 Mb (sire haplotype) and 118.51 Mb (dam haplotype). The improved haplotype phased genome assembly of river buffalo may provide valuable resources to discover molecular mechanisms related to milk production and reproduction traits.
EEG resting-state large-scale brain network dynamics are related to depressive symptoms
Authors: Damborská Alena , Tomescu Miralena I. , Honzírková Eliška , Barteček Richard , Hořínková Jana , Fedorová Sylvie , Ondruš Šimon , Michel Christoph M.
Published: April 2019

Background

The few previous studies on resting-state EEG microstates in depressive patients suggest altered temporal characteristics of microstates compared to those of healthy subjects. We tested whether resting-state microstate temporal characteristics could capture large-scale brain network dynamic activity relevant to depressive symptomatology.

Methods

To evaluate a possible relationship between the resting-state large-scale brain network dynamics and depressive symptoms, we performed EEG microstate analysis in patients with moderate to severe depression within bipolar affective disorder, depressive episode, and periodic depressive disorder, and in healthy controls.

Results

Microstate analysis revealed six classes of microstates (A-F) in global clustering across all subjects. There were no between-group differences in the temporal characteristics of microstates. In the patient group, higher symptomatology on the Montgomery-Åsberg Depression Rating Scale, a questionnaire validated as measuring severity of depressive episodes in patients with mood disorders, correlated with higher occurrence of microstate A (Spearman’s rank correlation, r = 0.70, p < 0.01).

Conclusion

Our results suggest that the observed interindividual differences in resting-state EEG microstate parameters could reflect altered large-scale brain network dynamics relevant to depressive symptomatology during depressive episodes. These findings suggest the utility of the microstate analysis approach in an objective depression assessment.
Bifunctional Small Molecule Ligands of K-Ras Induce Its Association with Immunophilin Proteins
Authors: Zhang Ziyang , Shokat Kevan M.
Published: April 2019

Here we report the design, synthesis and characterization of bifunctional chemical ligands that induce the association of Ras with ubiquitously expressed immunophilin proteins such as FKBP12 and cyclophilin A. We show this approach is applicable to two distinct Ras ligand scaffolds, and that both the identity of the immunophilin ligand and the linker chemistry affect compound efficacy in biochemical and cellular contexts. These ligands bind to Ras in an immunophilin-dependent fashion and mediate the formation of tripartite complexes of Ras, immunophilin and the ligand. The recruitment of cyclophilin A to GTP-bound Ras blocks its interaction with B-Raf in biochemical assays. Our study demonstrates the feasibility of ligand-induced association of Ras with intracellular proteins and suggests it as a promising therapeutic strategy for Rasdriven cancers.
Epigenetic bookmarking of H2S exposure in Caenorhabditis elegans
Authors: Fawcett Emily M. , Johnson Jenna K. , Braden Chris , Garcia Esteli M. , Miller Dana L.
Published: April 2019

Physiological memories of environmental stress can serve to predict future environmental changes, allowing the organism to initiate protective mechanisms and survive. Although physiological memories, or bookmarks, of environmental stress have been described in a wide range of organisms, from bacteria to plants to humans, the mechanism by which these memories persist in the absence of stress is still largely unknown. We have discovered that C. elegans transiently exposed to low doses of hydrogen sulfide (H2S) survive subsequent exposure to otherwise lethal H2S concentrations and induce H2S-responsive transcripts more robustly than naïve controls. H2S bookmarking can occur at any developmental stage and persists through cell divisions and development but is erased by fasting. We show that maintenance of the H2S bookmark requires the SET-2 histone methyltransferase and the CoREST-like demethylase complex. We propose a model in which exposure to low doses of H2S generates a long-lasting, epigenetic memory by modulating H3K4me2 modifications at specific promoters. Understanding the fundamental aspects of H2S bookmarking in this tractable system can provide mechanistic insight into how environmental exposures are translated into the epigenetic landscape in animals.
Finding high-quality metal ion-centric regions across the worldwide Protein Data Bank
Authors: Yao Sen , Moseley Hunter N.B.
Published: April 2019

As the number of macromolecular structures in the worldwide Protein Data Bank (wwPDB) continues to grow rapidly, more attention is being paid to the quality of its data, especially for use in aggregated structural and dynamics analyses. In this study, we systematically analyzed 3.5 Å regions around all metal ions across all PDB entries with supporting electron density maps available from the PDB in Europe. All resulting metal ion-centric regions were evaluated with respect to four quality-control criteria involving electron density resolution, atom occupancy, symmetry atom exclusion, and regional electron density discrepancy. The resulting list of metal binding sites passing all four criteria possess high regional structural quality and should be beneficial to a wide variety of downstream analyses. This study demonstrates an approach for the pan-PDB evaluation of metal binding site structural quality with respect to underlying x-ray crystallographic experimental data represented in available electron density maps of proteins. For non-crystallographers in particular, we hope to change the focus and discussion of structural quality from a global evaluation to a regional evaluation, since all structural entries in the wwPDB appear to have both regions of high and low structural quality.
Effect of Septoria brown spot on soybean yield in Illinois
Authors: Lin Heng-An , Villamil María B. , Mideros Santiago X.
Published: April 2019

Brown spot caused by Septoria glycines is a prevalent foliar disease in all soybean production areas. Application of foliar fungicides after bloom reduces the disease severity, yet yield responses are not consistent among locations and years. Our research goal was to determine the effect of different levels of Septoria brown spot on yield. Different levels of disease severity were effectively obtained in the field by weekly application of chlorothalonil for three, six, and nine times after disease inoculation at V3/V4 stage. Fungicide treatments had a significant effect on vertical progress and chlorotic area with no statistically significant effect on yield. Soybean yield was negatively correlated with vertical progress of the disease (r = −0.36). The vertical progress was the best linear predictor of yield. Based on this model, when the vertical progress of brown spot at R6 increased by 10%, the yield decreased by 142.13 kg/ha (3.4%). A variance component analyses of our data showed that location was the most critical factor, illustrating the significant effect of local environmental conditions on the disease. Power analyses indicated that at least eight locations are needed to detect an effect of 269 kg/ha. Our results provide useful information to improve the experimental design for future experiments addressing the yield constrain by late season diseases of soybean.
Dropout from maternity continuum of care and associated factors among women in Debre Markos town, Northwest Ethiopia
Authors: Amare Nakachew Sewnet , Araya Bilen Mekonnen , Asaye Mengstu Melkamu
Published: April 2019

Introduction

Maternity continuum of care is the continuity of maternity health care services that a woman uses antenatal care, skill birth attendant, and postnatal care. This Continuum of care in maternal health has become one of the government concern and program for planning and evaluating strategies within currently existing maternal health system of Ethiopia. It is an important intervention in reducing maternal and neonatal morbidity and mortality. However, there is no clear information on the proportion of dropout from maternity continuum of care in Ethiopia.

Objective

The aim of this study was to assess proportion and associated factors of dropout from maternity continuum of care among mothers who gave birth in the last 12 months in Debre Markos town, Northwest Ethiopia, 2018.

Methods

A community-based cross-sectional study with cluster sampling technique was conducted among 605 mothers who gave birth in the last 12 months in Debre Markos town. The data were collected from August 1-30/ 2018 by face to face interview through pretested and semi-structured questionnaire. Binary logistic regressions (Bivariable and Multivariable) logistic regression model were done. In multivariable analysis variables with P-value < 0.05 in 95% confidence interval for Adjusted odds ratio (AOR) was used to determine factors associated with dropout from maternity continuum of care.

Results

The proportion of drop out from maternity continuum of care was found to be 32.2 %(95%CI: 28.4-36.2). Have not exposure to media (AOR= 2.62, CI: 1.465-4.675), women who heard about PNC (AOR= 0.07, 95%CI: 0.035-0.154), unplanned pregnancy (AOR= 3.40, CI: 1.114-10.389), and having<4 ANC follow up (AOR = 3.03, CI: 1.963-4.685) were statistically significant variable with the dropout from maternity continuum of care.

Conclusion and recommendations

In this study, the proportion of dropout from maternity continuum of care is found to be high. The greatest gap and predictors for dropout was observed at postnatal care level, to reduce this drop out interventions on specified associated factors need to be implemented.
Learning supervised embeddings for large scale sequence comparisons
Authors: Kimothi Dhananjay , Biyani Pravesh , Hogan James M , Soni Akshay , Kelly Wayne
Published: April 2019

Similarity-based search of sequence collections is a core task in bioinformatics, one dominated for most of the genomic era by exact and heuristic alignment-based algorithms. However, even efficient heuristics such as BLAST may not scale to the data sets now emerging, motivating a range of alignment-free alternatives exploiting the underlying lexical structure of each sequence.

In this paper, we introduce SuperVec, a novel supervised approach to learning sequence embeddings. Our method extends earlier Representation Learning (RL) based methods to include jointly contextual and class-related information for each sequence during training. This ensures that related sequence fragments have proximal representations in the target space, better reflecting the structure of the domain.

Such representations may be used for downstream machine learning tasks or employed directly. Here, we apply SuperVec embeddings to a sequence retrieval task, where the goal is to retrieve sequences with the same family label as a given query. The SuperVec approach is extended further through H-SuperVec, a tree-based hierarchical method which learns embeddings across a range of feature spaces based on the class labels and their exclusive and exhaustive subsets.

Experiments show that supervised learning of embeddings based on sequence labels using SuperVec and H-SuperVec provides a substantial improvement in retrieval performance over existing (unsupervised) RL-based approaches. Further, the new methods are an order of magnitude faster than BLAST for the database retrieval task, supporting hybrid approaches in which SuperVec rapidly filters the collection so that only potentially relevant records remain, allowing slower, more accurate methods to be executed quickly over a far smaller dataset. Thus, we may achieve faster query processing and higher precision than before.

Finally, for some problems, direct use of embeddings is already sufficient to yield high levels of precision and recall. Extending this work to encompass weaker homology is the subject of ongoing research.
Mapping of multiple complementary sex determination loci in a parasitoid wasp
Authors: Matthey-Doret Cyril , van der Kooi Casper J. , Jeffries Daniel L. , Bast Jens , Dennis Alice B. , Vorburger Christoph , Schwander Tanja
Published: April 2019

Sex determination has evolved in a variety of ways and can depend on environmental and genetic signals. A widespread form of genetic sex determination is haplodiploidy, where unfertilized, haploid eggs develop into males and fertilized diploid eggs into females. One of the molecular mechanisms underlying haplodiploidy in Hymenoptera, a large insect order comprising ants, bees and wasps, is known as complementary sex determination (CSD). In species with CSD, heterozygosity at one or several loci induces female development. Here, we identify the genomic regions putatively underlying multi-locus CSD in the parasitoid wasp Lysiphlebus fabarum using restriction-site associated DNA sequencing. By analysing segregation patterns at polymorphic sites among 331 diploid males and females, we identify four CSD candidate regions, all on different chromosomes. None of the candidate regions feature evidence for homology with the csd gene from the honeybee, the only species in which CSD has been characterized, suggesting that CSD in L. fabarum is regulated via a novel molecular mechanism. Moreover, no homology is shared between the candidate loci, in contrast to the idea that multi-locus CSD should emerge from duplications of an ancestral single-locus system. Taken together, our results suggest that the molecular mechanisms underlying CSD in Hymenoptera are not conserved between species, raising the question as to whether CSD may have evolved multiple times independently in the group.

Author summary

The genetic or environmental signals that govern whether an organism develops into a male or female differ across species, and understanding their evolution is a key aspect of biology. In this paper, we focus on complementary sex determination (CSD), a genetic sex determination system found in many species of bees, ants and wasps where heterozygosity at one or multiple genetic regions determines the sex of the individual. We identify multiple genetic regions in the parasitoid wasp species Lysiphlebus fabarum that are likely underlying CSD. We show that these candidate CSD regions share no similarity with each other and that they differ from the CSD region known in the honey bee, the only species with a well-characterized CSD system. Our results suggest a different molecular mechanism underlying CSD in the wasp and that multiple CSD regions do not necessarily arise from duplications as generally thought.
Robust Genome Editing of Single-Base PAM Targets with Engineered ScCas9 Variants
Authors: Chatterjee Pranam , Jakimo Noah , Jacobson Joseph M.
Published: April 2019

Programmable CRISPR enzymes are powerful and versatile tools for genome editing. They, however, require a specific protospacer adjacent motif (PAM) flanking the target site, which constrains the accessible sequence space for position-specific genome editing applications, such as base editing and homology-directed repair. For example, the standard Cas9 from Streptococcus pyogenes requires a PAM sequence of 5’-NGG-3’ downstream of its RNA-programmed target. Recently, three separate Cas9 enzymes (xCas9-3.7, SpCas9-NG, and ScCas9) have been independently engineered or discovered to reduce the PAM specificity to a single guanine (G) nucleotide, thus greatly expanding the number of targetable sequences. In this study, we have employed motifs from closely-related orthologs to engineer and optimize ScCas9 to exhibit enhanced genome editing and higher fidelity. Our engineered variants demonstrate superior activity within gene repression and nucleolytic contexts and possess effective base editing capabilities.
Evaluation of a crystallographic surrogate for kallikrein 5 in the discovery of novel inhibitors for Netherton syndrome
Authors: Thorpe James H. , Edgar Emma V. , Smith Kathrine J. , Lewell Xiao Q. , Rella Monika , White Gemma V. , Polyakova Oxana , Nassau Pamela , Walker Ann L. , Holmes Duncan S. , Pearce Andrew C. , Wang Yichen , Liddle John , Hovnanian Alain
Published: April 2019

The inhibition of kallikrein 5 (KLK5) has been identified as a potential strategy for treatment of the genetic skin disorder Netherton syndrome, in which loss-of-function mutations in the SPINK5 gene lead to down-regulation of the endogenous inhibitor LEKTI-1 and profound skin-barrier defects with severe allergic manifestations. To aid in the development of a medicine for this target, an X-ray crystallographic system was developed to facilitate fragment-guided chemistry and knowledge-based drug-discovery approaches. Here, the development of a surrogate crystallographic system in place of KLK5, which proved to be challenging to crystallize, is described. The biochemical robustness of the crystallographic surrogate and the suitability of the system for the study of small nonpeptidic fragments and lead-like molecules are demonstrated.
Phasing with calcium at home
Authors: Guo Shuaiqi , Campbell Robert , Davies Peter L. , Allingham John S.
Published: April 2019

With better tools for data processing and with synchrotron beamlines that are capable of collecting data at longer wavelengths, sulfur-based native single-wavelength anomalous dispersion (SAD) phasing has become the `first-choice' method for de novo protein structure determination. However, for many proteins native SAD phasing can be simplified by taking advantage of their interactions with natural metal cofactors that are stronger anomalous scatterers than sulfur. This is demonstrated here for four unique domains of a 1.5 MDa calcium-dependent adhesion protein using the anomalous diffraction of the chelated calcium ions. In all cases, low anomalous multiplicity X-ray data were collected on a home-source diffractometer equipped with a chromium rotating anode (λ = 2.2909 Å). In all but one case, calcium SAD phasing alone was sufficient to allow automated model building and refinement of the protein model after the calcium substructure had been determined. Given that Ca atoms will be present in a significant percentage of proteins that remain uncharacterized, many aspects of the data-collection and processing methods described here could be broadly applied for routine de novo structure elucidation.
Accounting for modern slavery: an analysis of Australian listed company disclosures
Authors: Christ Katherine Leanne , Rao Kathyayini Kathy , Burritt Roger Leonard
Published: April 2019

Purpose

Given the impending introduction of legislation requiring large Australian listed companies to make supply chain disclosures about modern slavery, the paper aims to reveal current voluntary practice. The purpose of this paper is to provide a benchmark for assessing the current engagement of large companies with modern slavery in Australia.

Design/methodology/approach

Institutional theory provides the foundation for assessing current voluntary practice in relation to modern slavery disclosures by large Australian listed companies. Content analysis is used to identify quantity and quality of modern slavery disclosures of the top 100 companies listed on the Australian Stock Exchange. The contents of annual and standalone reports available on websites, as well as other online disclosures, are examined using terms associated with modern slavery identified from the literature.

Findings

Evidence gathered about modern slavery disclosures by ASX 100 companies shows information in annual and standalone reports reveal far less than other disclosures on company websites. Overall, the volume and quality of disclosures are low and, where made, narrative. A wide range of themes on modern slavery are disclosed with bribery and corruption and human rights issues dominant. Although currently in line with institutional theory, as there appear to be mimetic processes encouraging disclosure, results support the idea that legislation is needed to encourage further engagement.

Research limitations/implications

The paper provides a baseline of understanding about the volume and quality of modern slavery disclosures as a foundation for future research into the practices of Australian companies prior to the signalled introduction of legislation mandating reporting. It also identifies potential lines of research. The sample only examines large Australian listed companies which restricts generalisation from the results.

Originality/value

This is the first academic research paper to examine quantity and quality of modern slavery disclosures of large Australian companies. Results add support for the introduction of legislation by government.
Incivility, satisfaction and turnover intention of tourist hotel chefs
Authors: Chen Hsi-Tien , Wang Chih-Hung
Published: April 2019

Purpose

This study examines the relationships among workplace incivility, job satisfaction and turnover intention for tourist hotel chefs. Furthermore, emotional intelligence is taken as the moderating variable on the relationships between workplace incivility and job satisfaction and workplace incivility and turnover intention.

Design/methodology/approach

Tourist hotel chefs were invited to participate in this study using purposive sampling, and a structured questionnaire was administered to carry out the investigation on tourist hotel chefs.

Findings

The results show that workplace incivility has negative effects on job satisfaction and casts positive effects on turnover intention through job satisfaction. Emotional intelligence has a significant moderating effect on the relationship between workplace incivility and job satisfaction.

Originality/value

This study firstly demonstrated the relationships among workplace incivility, job satisfaction and turnover intention for tourist hotel chefs. Furthermore, the moderating effect of emotional intelligence on the relationship between workplace incivility and job satisfaction was also validated.
Indonesian clinical psychologists’ perceptions of complementary and alternative medicine research and knowledge: a content analysis study
Authors: Liem Andrian
Published: April 2019

Purpose

As part of a nationwide research about knowledge, attitude, experiences and educational needs towards complementary and alternative medicine (CAM) among Indonesian clinical psychologists (CPs), the purpose of this paper is to explore CPs’ perceptions of CAM research and their interest in learning CAM.

Design/methodology/approach

A link to an online survey was e-mailed to all 1,045 CPs across Indonesia. At the end of the survey, two open-ended questions were asked: “What do you think about CAM research in Indonesia?” and “Why are you interested in learning about CAM?”, which were responded to by 127 participants (87 per cent of females;Mage=36.67, SD=9.02). Participants’ responses were analysed using inductive qualitative content analysis.

Findings

It was found that two global themes for CPs’ perceptions of CAM were to improve participants’ professionalism and as part of continuing education and development for mental health professionals. The favourable responses in this study may reflect participants’ willingness to be involved in collaborative CAM research and education. Moreover, CAM was perceived as part of Indonesian culture and participants viewed CAM research and knowledge as a chance to promote Indonesian local wisdom to complement conventional psychotherapy.

Research limitations/implications

These findings might call for stakeholders to integrate CAM knowledge into psychology education, facilitate CAM research in psychology settings and encourage collaborative CAM research. However, self-selection bias may limit the findings of this study.

Originality/value

This study explored perceptions of CAM research and interest in learning CAM that have rarely been investigated among mental health professionals and particularly, until now, have not been investigated in Indonesia.
The impact of national culture on financial crime
Authors: Yamen Ahmed , Al Qudah Anas , Badawi Ahmed , Bani-Mustafa Ahmed
Published: April 2019

Purpose

Despite the existence of laws, regulations and sanctions, financial crime remains widespread. The Panama leaks have proven that people from all over the world are participating in money laundering and other financial crimes. This study aims to investigate the influence of national culture on financial crimes across 78 countries.

Design/methodology/approach

This study uses Hofstede’s cultural framework as a basis for its hypotheses on financial crime. It also uses the Basel anti-money laundering index as a proxy for measuring the incidence of financial crime across the countries under review.

Findings

The findings show that countries whose cultural profiles are characterized by low uncertainty avoidance, low individualism, high masculinity and low long-term orientation have high rates of financial crime. The finding also shows that countries whose cultural profiles are characterized by individualism or positive collectivism, uncertainty avoidance and long-term orientation have low rates of financial crime.

Originality/value

Laws, regulations and sanctions are not the only factors that can help deter the crime; governments should also take a holistic approach that includes the cultural factors that encourage deterrence.
The SOMOAR operationalization: a holistic concept to travel decision modelling
Authors: Laesser Christian , Luo Jieqing , Beritelli Pietro
Published: April 2019

Purpose

Most state-of-the-art approaches for the analysis of the process of travel decision-making follow Woodworth’s neo-behaviouristic S–R (stimulus–response) or S–O–R (stimulus–organism–response) model. However, within this model, scholars primarily focus on the S–R relationship, investigating specific decisions by describing or explaining an outcome as the result of an input of several stimuli. There is a lack of investigation into the “O” dimension of the S–O–R model. This paper aims to contribute towards closing of this gap by conceptually and holistically expanding existing models with new perspectives and components.

Design/methodology/approach

The authors base the conceptual process on a subjective/interpretative research paradigm, by combining outcomes from different theories and concepts into a new, more holistic approach; and challenging this approach by seeking counterarguments as well as supportive arguments at three conferences and workshops.

Findings

The paper expands the body of literature by positing a generic conceptual operationalization model focusing on the organism (“O”) domain of decision-making. To achieve this, and further to operationalize the S–O–R model, the paper proposes to integrate an M–O–A (motivation–opportunity–ability) approach.

Originality/value

The analysis of the body literature reveals that there is still a lack of analytical and especially workable models/approaches for the analysis of the process of tourist decision-making. The paper contributes to that discussion by offering an alternative and generic operationalization of the tourist decision-making process by inducing a theoretical framework from the deductions gleaned from a number of existing theories.
Psychometric evaluation of the Medicare Advantage and prescription drug plan disenrollment reasons survey
Authors: Martino Steven C. , Elliott Marc N. , Zaslavsky Alan M. , Orr Nate , Bogart Andy , Ye Feifei , Damberg Cheryl L.
Published: April 2019

Objectives

To develop and assess the reliability and validity of composite measures of reasons for disenrollment from Medicare Advantage (MA) and prescription drug plans (PDPs).

Data Source

Medicare beneficiaries who responded to the Medicare Advantage and Prescription Drug Plan Disenrollment Reasons Survey.

Study Design

Separate multilevel factor analyses of MA and PDP data suggested groupings of survey items to form composite measures, for which internal consistency and interunit reliability were estimated. The association of each composite with an overall plan rating was examined to evaluate criterion validity.

Principal Findings

Five composites were identified: financial reasons for disenrollment; problems with prescription drug benefits and coverage; problems getting information and help from the plan; problems getting needed care, coverage, and cost information; and problems with coverage of doctors and hospitals. Beneficiary‐level internal consistency reliability exceeded 0.70 for all but one composite (financial reasons); plan‐level internal consistency reliability exceeded 0.80 for all composites; average interunit reliability for plans with ≥ 30 survey completes exceeded 0.75 for 3 of 5 composites. As expected, greater endorsement of reasons for disenrollment was associated with lower overall plan ratings.

Conclusions

The Disenrollment Reasons Survey provides a reliable and valid assessment of beneficiaries' reasons for leaving their plans. Multiple reasons for disenrollment may indicate especially poor experiences.
Effective elimination of Staphylococcal contamination from hospital surfaces by a bacteriophage–probiotic sanitation strategy: a monocentric study
Authors: D'Accolti Maria , Soffritti Irene , Lanzoni Luca , Bisi Matteo , Volta Antonella , Mazzacane Sante , Caselli Elisabetta
Published: April 2019

Persistent contamination of hospital surfaces and antimicrobial resistance (AMR) is recognized as major causes of healthcare‐associated infections (HAI). We recently showed that probiotic‐based sanitation (PCHS) can stably decrease surface pathogens and reduce AMR and HAIs. However, PCHS action is slow and non‐specific. By contrast, bacteriophages have been proposed as a decontamination method as they can rapidly attack specific targets, but their routine application has never been tested. Here, we analysed the feasibility and effectiveness of phage addition to PCHS sanitation, aiming to obtain a rapid and stable abatement of specific pathogens in the hospital environment. Staphylococcal contamination in the bathrooms of General Medicine wards was analysed, being those areas the most contaminated and Staphylococci the most prevalent bacteria in such settings. Results showed that a daily phage application by nebulization induced a rapid and significant decrease in Staphylococcus spp. load on treated surfaces, up to 97% more than PCHS alone (P < 0.001), suggesting that such a system might be considered as a part of prevention and control strategies, to counteract outbreaks of specific pathogens and prevent associated infections.
The Danish Rural Eye Study: prevalence of strabismus among 3785 Danish adults – a population‐based cross‐sectional study
Authors: Hultman Oscar , Beth Høeg Tracy , Munch Inger Christine , Ellervik Christina , la Cour Morten , Andersson Grönlund Marita , Buch Hesgaard Helena
Published: April 2019

Purpose

To determine the prevalence of strabismus among Danish adults and to find the frequency of history of strabismus and strabismus surgery. Furthermore, to evaluate the prevalence of strabismus‐associated amblyopia among participants with strabismus and to relate the results to the current national vision screening programme.

Methods

In total, 3785 adults in the Danish Rural Eye Study underwent an interview regarding eye health, visual acuity measurement, Hirschberg test and retinal photography. Participants were categorized into groups based on their birth date in relation to the introduction of the national vision screening programme.

Results

In total, the prevalence of strabismus was 1.1% (41/3785; 95% CI: 0.8–1.5); no differences were found in relation to gender or screening status. The prevalence of exotropia (XT) was 0.3% (12/3785; 95% CI: 0.2–0.6) and of esotropia (ET) 0.8% (29/3785; 95% CI: 0.5–1.1), resulting in an XT:ET ratio of 1:2.7. A history of strabismus was present in 4.6% (174/3785; 95% CI: 4.0–5.3), and a history of strabismus surgery was present in 0.8% (32/3785; 95% CI: 0.6–1.2) of the participants. Among participants with manifest strabismus, 24% had strabismus‐associated amblyopia.

Conclusion

In this first European population‐based study of strabismus prevalence in adults, the prevalence was similar to three out of five previous studies using cover test. The use of Hirschberg test may have led to an underestimation of the true prevalence. The prevalence was neither related to screening status nor gender. Our results are the first to display a predominance of ET among Caucasian Scandinavian adults.