bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social gradients in the receipt of medication for attention-deficit hyperactivity disorder in children and young people in Sheffield
Authors: Nunn Samuel P.T. , Kritsotakis Evangelos I. , Harpin Val , Parker Jack 
Published: February 2020

Background
Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterised by inattention and hyperactivity-impulsivity that can affect people throughout their life course. A social gradient exists in the prevalence of ADHD in the UK. Studies in other countries have shown that social gradients also exist in the receipt of medication for ADHD. Socioeconomic position is potentially an unrecognised and modifiable factor in children and young people's receipt of medication for ADHD in the UK.

Aim
The aim of the study was to investigate if socioeconomic position could explain in part whether or not children and young people in Sheffield are receiving medication for ADHD.

Method
We used multivariate logistic regression modelling to investigate whether socioeconomic position could explain variation in receipt of medication for ADHD in children and young people in a cross-sectional study. We collected data from 1354 children and young people with a diagnosis of ADHD across three Sheffield centres between January and December 2016. Independent variables were age, gender, religion, ethnicity, comorbidities, and Index of Multiple Deprivation decile (derived from home postcode).

Results
Our results showed a social gradient in the receipt of medication for ADHD (P<0.01); an increase in one decile of the Index of Multiple Deprivation was associated with 10% lower odds of receipt of medication for ADHD (adjusted odds ratio 0.90, 95% CI 0.84–0.97).

Conclusion
Children and young people from more deprived backgrounds are more likely to receive medication for ADHD. This is the first time that a social gradient in children and young people's receipt of medication for ADHD has been shown in a UK sample.
Telephone-based nurse-delivered interpersonal psychotherapy for postpartum depression: nationwide randomised controlled trial
Authors: Dennis Cindy-Lee , Grigoriadis Sophie , Zupancic John , Kiss Alex , Ravitz Paula 
Published: February 2020

BackgroundPostpartum depression and anxiety are under-addressed public health problems with numerous treatment access barriers, including insufficiently available mental health specialist providers.AimsTo examine the effectiveness of nurse-delivered telephone interpersonal psychotherapy (IPT) for postpartum depression. Trial registration ISRCTN88987377.MethodPostpartum women (n= 241) with major depression (on the Structured Clinical Interview for DSM-IV (SCID-I)) from 36 Canadian public health regions in rural and urban settings were randomly assigned to 12 weekly 60 min nurse-delivered telephone-IPT sessions or standard locally available care. The primary outcome was the proportion of women clinically depressed at 12 weeks post-randomisation, with masked intention-to-treat analysis. Secondary outcomes examined included comorbid anxiety, self-reported attachment and partner relationship quality.ResultsAt 12 weeks, 10.6% of women in the IPT group (11/104) and 35% in the control group (35/100) remained depressed (OR = 0.22, 95% CI 0.10–0.46), with the IPT group 4.5 times less likely to be clinically depressed (SCID); 21.2% in the IPT group and 51% in the control group had an Edinburgh Postnatal Depression Scale (EPDS) score >12 (OR = 0.26, 95% CI 0.14–0.48), and attachment avoidance decreased more in the IPT group than in the control group (P= 0.02). Significant differences favoured the IPT group for comorbid anxiety and partner relationship quality at all time points, with no differences in health service or antidepressant use. None of the IPT responders relapsed by 36 weeks. Between-group SCID differences were sustained at 24 weeks, but not at 36 weeks.ConclusionsNurse-delivered telephone IPT is an effective treatment for diverse urban and rural women with postpartum depression and anxiety that can improve treatment access disparities.
No Evidence of Increased Risk of Breast Cancer in Women With Lynch Syndrome Identified by Multigene Panel Testing
Authors: Stoll Jessica , Rosenthal Eric , Cummings Shelly , Willmott Jamie , Bernhisel Ryan , Kupfer Sonia S. 
Published: February 2020

PURPOSE Prior estimates of breast cancer risk in women with Lynch syndrome (LS) range from population risk to 18-fold increased risk with reported differences by gene. Here, breast cancer rates were determined in a large cohort of women with pathogenic variants (PVs) in a mismatch repair (MMR) gene detected through multigene panel testing and compared with rates in the US population and women undergoing panel testing. METHODS MMR gene PV carriers were identified among women tested for suspicion of LS or hereditary breast and ovarian cancer (HBOC) who met inclusion criteria. Standardized incidence ratios (SIRs) and 95% CIs of breast cancer were calculated compared with age-matched incidence in the general US female population and with women negative for PVs stratified by the test indication. RESULTS In total, 0.8% of women (30,362 of 441,966 women) carried MMR gene PVs. PVs in PMS2 (37.5%) and MSH6 (29.3%) were more common than in MLH1 (13.7%) and MSH2/EPCAM (19.4%). Women with PVs in PMS2 and MSH6 were tested more frequently for HBOC, whereas those with PVs in MLH1 and MSH2/EPCAM were tested more frequently for LS. Breast cancer rates in women with LS were lower than those in the general female population (SIR, 0.88; 95% CI, 0.81 to 0.96) and did not differ compared with women with negative panel testing for HBOC (SIR, 0.90; 95% CI, 0.82 to 0.99) or LS (SIR, 1.02; 95% CI, 0.78 to 1.30). CONCLUSION In this large cohort of women with LS identified through panel testing, there was no evidence for increased risk of breast cancer compared with the general US population or women undergoing panel testing. These findings support average-risk breast cancer screening in women with LS.
Tracing Squiggles: Laurence Sterne, E. T. A. Hoffmann, and Honoré de Balzac
Authors: Dickson Polly 
Published: February 2020

AbstractThis article examines the figure of an undulating line, or “squiggle,” printed initially in Laurence Sterne’s Tristram Shandy and copied by two nineteenth-century writers: first, by the German E. T. A. Hoffmann, in a little-known fragment, and, second, more famously, by the French Honoré de Balzac as the epigraph to his novel La peau de chagrin. These three squiggles form a triangulated relationship of imitation across two centuries, three countries, and three languages. Through attention to William Hogarth’s line of beauty and Johann Caspar Lavater’s physiognomic contour lines, the article considers the history of the undulating line as a figure for reading. It suggests that, for Sterne, Hoffmann, and Balzac, the inclusion of a pictured line within text may be seen as a “reverse ekphrastic” maneuver, one that aims to reflect the movement of narrative in visual form. In this way, the “squiggle” is foregrounded as a new and concrete motif for comparative criticism on Hoffmann and Balzac, identifying a shared interest in Sterne, as well as in the relationship and entanglement of text and image.
CLN3 regulates endosomal function by modulating Rab7A–effector interactions
Authors: Yasa Seda , Modica Graziana , Sauvageau Etienne , Kaleem Abuzar , Hermey Guido , Lefrancois Stephane 
Published: February 2020

ABSTRACT
Mutations in CLN3 are a cause of juvenile neuronal ceroid lipofuscinosis (JNCL), also known as Batten disease. Clinical manifestations include cognitive regression, progressive loss of vision and motor function, epileptic seizures and a significantly reduced lifespan. CLN3 localizes to endosomes and lysosomes, and has been implicated in intracellular trafficking and autophagy. However, the precise molecular function of CLN3 remains to be elucidated. Previous studies showed an interaction between CLN3 and Rab7A, a small GTPase that regulates several functions at late endosomes. We confirmed this interaction in live cells and found that CLN3 is required for the efficient endosome-to-TGN trafficking of the lysosomal sorting receptors because it regulates the Rab7A interaction with retromer. In cells lacking CLN3 or expressing CLN3 harbouring a disease-causing mutation, the lysosomal sorting receptors were degraded. We also demonstrated that CLN3 is required for the Rab7A–PLEKHM1 interaction, which is required for fusion of autophagosomes to lysosomes. Overall, our data provide a molecular explanation behind phenotypes observed in JNCL and give an indication of the pathogenic mechanism behind Batten disease.
This article has an associated First Person interview with the first author of the paper.
Genome editing approaches to augment livestock breeding programs
Authors: Bishop Thomas Frederick , Van Eenennaam Alison Louise 
Published: February 2020

ABSTRACT
The prospect of genome editing offers a number of promising opportunities for livestock breeders. Firstly, these tools can be used in functional genomics to elucidate gene function, and identify causal variants underlying monogenic traits. Secondly, they can be used to precisely introduce useful genetic variation into structured livestock breeding programs. Such variation may include repair of genetic defects, the inactivation of undesired genes, and the moving of useful alleles and haplotypes between breeds in the absence of linkage drag. Editing could also be used to accelerate the rate of genetic progress by enabling the replacement of the germ cell lineage of commercial breeding animals with cells derived from genetically elite lines. In the future, editing may also provide a useful complement to evolving approaches to decrease the length of the generation interval through in vitro generation of gametes. For editing to be adopted, it will need to seamlessly integrate with livestock breeding schemes. This will likely involve introducing edits into multiple elite animals to avoid genetic bottlenecks. It will also require editing of different breeds and lines to maintain genetic diversity, and enable structured cross-breeding. This requirement is at odds with the process-based trigger and event-based regulatory approach that has been proposed for the products of genome editing by several countries. In the absence of regulatory harmony, researchers in some countries will have the ability to use genome editing in food animals, while others will not, resulting in disparate access to these tools, and ultimately the potential for global trade disruptions.
Utilizing the blind cavefish Astyanax mexicanus to understand the genetic basis of behavioral evolution
Authors: Kowalko Johanna 
Published: February 2020

ABSTRACT
Colonization of novel habitats often results in the evolution of diverse behaviors. Comparisons between individuals from closely related populations that have evolved divergent behaviors in different environments can be used to investigate behavioral evolution. However, until recently, functionally connecting genotypes to behavioral phenotypes in these evolutionarily relevant organisms has been difficult. The development of gene editing tools will facilitate functional genetic analysis of genotype–phenotype connections in virtually any organism, and has the potential to significantly transform the field of behavioral genetics when applied to ecologically and evolutionarily relevant organisms. The blind cavefish Astyanax mexicanus provides a remarkable example of evolution associated with colonization of a novel habitat. These fish consist of a single species that includes sighted surface fish that inhabit the rivers of Mexico and southern Texas and at least 29 populations of blind cavefish from the Sierra Del Abra and Sierra de Guatemala regions of Northeast Mexico. Although eye loss and albinism have been studied extensively in A. mexicanus, derived behavioral traits including sleep loss, alterations in foraging and reduction in social behaviors are now also being investigated in this species to understand the genetic and neural basis of behavioral evolution. Astyanax mexicanus has emerged as a powerful model system for genotype–phenotype mapping because surface and cavefish are interfertile. Further, the molecular basis of repeated trait evolution can be examined in this species, as multiple cave populations have independently evolved the same traits. A sequenced genome and the implementation of gene editing in A. mexicanus provides a platform for gene discovery and identification of the contributions of naturally occurring variation to behaviors. This review describes the current knowledge of behavioral evolution in A. mexicanus with an emphasis on the molecular and genetic underpinnings of evolved behaviors. Multiple avenues of new research that can be pursued using gene editing tools are identified, and how these will enhance our understanding of behavioral evolution is discussed.
Diversity in reproductive seasonality in the three-spined stickleback,Gasterosteus aculeatus
Authors: Ishikawa Asano , Kitano Jun 
Published: February 2020

ABSTRACTThe annual timing of reproduction is a key life history trait with a large effect on fitness. Populations often vary in the timing and duration of reproduction to adapt to different seasonality of ecological and environmental variables between habitats. However, little is known about the molecular genetic mechanisms underlying interpopulation variation in reproductive seasonality. Here, we demonstrate that the three-spined stickleback (Gasterosteus aculeatus) is a good model for molecular genetic analysis of variations in reproductive seasonality. We first compiled data on reproductive seasons of diverse ecotypes, covering marine-anadromous, lake and stream ecotypes, of three-spined stickleback inhabiting a wide range of latitudes. Our analysis showed that both ecotype and latitude significantly contribute to variation in reproductive seasons. Stream ecotypes tend to start breeding earlier and end later than other ecotypes. Populations from lower latitudes tend to start breeding earlier than those from higher latitudes in all three ecotypes. Additionally, stream ecotypes tend to have extended breeding seasons at lower latitudes than at higher latitudes, leading to nearly year-round reproduction in the most southern stream populations. A review of recent progress in our understanding of the physiological mechanisms underlying seasonal reproduction in the three-spined stickleback indicates that photoperiod is an important external cue that stimulates and/or suppresses reproduction in this species. Taking advantage of genomic tools available for this species, the three-spined stickleback will be a good model to investigate what kinds of genes and mutations underlie variations in the physiological signalling pathways that regulate reproduction in response to photoperiod.
How to study enhancers in non-traditional insect models
Authors: Tomoyasu Yoshinori , Halfon Marc S. 
Published: February 2020

ABSTRACTTranscriptional enhancers are central to the function and evolution of genes and gene regulation. At the organismal level, enhancers play a crucial role in coordinating tissue- and context-dependent gene expression. At the population level, changes in enhancers are thought to be a major driving force that facilitates evolution of diverse traits. An amazing array of diverse traits seen in insect morphology, physiology and behavior has been the subject of research for centuries. Although enhancer studies in insects outside of Drosophila have been limited, recent advances in functional genomic approaches have begun to make such studies possible in an increasing selection of insect species. Here, instead of comprehensively reviewing currently available technologies for enhancer studies in established model organisms such as Drosophila, we focus on a subset of computational and experimental approaches that are likely applicable to non-Drosophila insects, and discuss the pros and cons of each approach. We discuss the importance of validating enhancer function and evaluate several possible validation methods, such as reporter assays and genome editing. Key points and potential pitfalls when establishing a reporter assay system in non-traditional insect models are also discussed. We close with a discussion of how to advance enhancer studies in insects, both by improving computational approaches and by expanding the genetic toolbox in various insects. Through these discussions, this Review provides a conceptual framework for studying the function and evolution of enhancers in non-traditional insect models.
Impact of accumulated alterations in driver and passenger genes on response to radiation therapy
Authors: Seo Yuji , Tamari Keisuke , Takahashi Yutaka , Minami Kazumasa , Isohashi Fumiaki , Suzuki Osamu , Sumida Iori , Ogawa Kazuhiko 
Published: February 2020

Objective:
Although various single genetic factors have been shown to affect radiosensitivity, high-throughput DNA sequencing analyses have revealed complex genomic landscapes in many cancer types. The aim of this study is to elucidate the association between accumulated alterations in driver and passenger genes and radiation therapy response.

Methods:
We used 59 human solid cancer cell lines derived from 11 organ sites. Radiation-induced cell death was measured using a standard colony-forming assay delivered as a single dose ranging from 0 to 12 Gy. Comprehensive genomic data for the cell lines were acquired from the Catalogue Of Somatic Mutations In Cancer v. 80. Random forest classifiers were constructed to predict radioresistant phenotypes using genomic features. The Cancer Genome Atlas data sets were used to evaluate the clinical impact of the genomic feature following radiotherapy.

Results:
The 59 cancer cell lines harbored either nucleotide variations or copy number variations in a median of 157 genes per cell. Radiosensitivity of the cancer cells was correlated with neither the number of driver gene mutations nor the number of passenger gene mutations. However, the proportion of driver gene alterations to total gene alterations in gene sets selected from the Kyoto Encyclopedia Genes and Genomes predicted radioresistant cells with sensitivity of 85% and specificity of 73%. High probability of radioresistance predicted by the model was associated with worse overall survival following definitive radiotherapy in patients of The Cancer Genome Atlas data sets.

Conclusion:
Cellular radiosensitivity was associated with the proportion of driver to total gene alterations in the selected oncogenic pathways, which may be a biomarker candidate for response to radiation therapy.

Advances in knowledge:
These findings suggest that accumulated alterations in not only driver genes but also passenger genes affect radiosensitivity.
Nuclear shape coexistence in 194Hg
Authors: Fotiades N. , Harissopulos S. , Kalfas C. A. , Kossionides S. , Papadopoulos C. T. , Vlastou R. , Serris M. , Sharpey-Schafer J. F. , Joyce M. J. , Beausang C. W. , Dagnall P. J. , Forsyth P. D. , Gale S. J. , Jones P. M. , Paul E. S. , Twin P. J. , Simpson J. , Cullen D. M. , Fallon P. , Riley M. A. , Clark R. M. , Hauschild K. , Wadsworth R. 
Published: February 2020

High spin states in the isotope 194Hg were populated using the 150Nd (48Ca,4n) reaction at a beam energy of 213 MeV. A sequence of dip ole transitions has been observed above 8 MeV excitation energy. Cross-over transitions have also been identified. An interpretation connecting this sequence to a nuclear shape change is attempted. A comparison with similar structures in the neighbouring Hg isotopes is also attempted.
National culture as a correlate of research output and impact
Authors: Abraham Juneman 
Published: February 2020

National culture has been overlooked in discussions related to research output and impact owing to individual, socio-political structure, and economic factors. This study shows the relationships between the dimensions of cultural value orientation of the nation and research output & impact. More than 60 countries were included, and Spearman correlation analysis was employed. The variables were taken from Geert Hofstede and Scimago Journal & Country Rank worksheets. This study found that (1) Power distance - the positive inclination of the culture toward power disparities among people - is negatively correlated with research impact; (2) Individualism - the level of independence a society keeps up among its individuals - are positively correlated with research output and research impact; (3) Indulgence - the degree to which society members do not attempt to control their urges - is positively correlated with research impact; and (4) after controlling the Log GDP per capita, uncertainty avoidance - the manner in which that a society seeks to manage the actuality that the future can never be controlled - is negatively correlated with research impact.
Acute and sub-acute toxicity study of the root extracts of Fagaropsis hildebrandtii in mice and evaluation of their antimicrobial effects
Authors: Muia Beatrice Mwende , Mbaria James Mucunu , Kanja Laetitia Wakonyu , Gitahi Nduhiu , Okumu Paul Onyango , Okumu Mitchel Otieno 
Published: February 2020

Background: Among the Kamba community of Kenya, roots ofFagaropsis hildebrandtii(FH) are boiled and used in managing cough, fertility problems, and microbial infections. The safety of this plant in oral administration and the validity of the ethnomedical claims are unverified. This study evaluated the toxicity of the aqueous and hexane root extracts of FH in mice and antimicrobial effects againstStaphylococcus aureus,Salmonella typhimuriumandCandida albicans.Methods: Doses (300 and 2000 mg/kg) of the extracts were administered orally to mice for 14 days. The weight, feed, and water consumption, organ weight of mice and gross macroscopy of the liver were used in evaluating acute toxicity. Mice were additionally treated with 250, 500, and 1000 mg/kg body-weight doses of the extracts for 28 days and haematological, biochemical, and histological parameters noted. The minimum inhibitory and minimum bactericidal/fungicidal concentrations (MIC; MBC/MFC) of the extracts against the aforementioned pathogens were determined by broth dilution.Results: Acute oral toxicity of the extracts was >2000 mg/kg, there were dose dependent changes in haematological and biochemical parameters, all female mice died when treated with doses of 1000mg/kg and doses ≥500 mg/kg caused tubular degeneration and haemorrhage of the kidney, cloudy swelling of hepatocytes, and multifocal necrosis and pyknosis in the liver. The MBC/MIC ratio of each of the extracts againstStaph. aureusandS. typhimuriumwas 2, whileC. albicanswas not sensitive to any of the extracts.Conclusions: Long term use of FH root extracts was associated with dose-dependent changes in the mice kidney, liver and in biochemical and haematological parameters. Root extracts of FH are bactericidal againstStaph. aureusandS. typhimuriumbut have no effect onC. albicans. Future work should aim at identifying the metabolites responsible for the observed toxic and bactericidal effects of the FH root extracts.