bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paediatric bipolar disorder and its controversy
Authors: Connors Michael H. 
Published: November 2022

AbstractObjectives:Paediatric bipolar disorder – bipolar disorder occurring in prepubertal children – is a diagnosis subject to considerable controversy. Whilst historically considered to be very rare, proponents since the 1990s have argued that mania can present differently in children and, as such, is much more common than previously thought. Such proposals raise questions about the validity of proposed phenotypes and potential risks of iatrogenic harm.Methods:I critically examine the construct of paediatric bipolar disorder using Robins and Guze’s (1970, American Journal of Psychiatry126, 983–987) influential criteria for the validity of a psychiatric diagnosis. I review, in turn, evidence relating to its clinical description, delimitation from other conditions, follow-up studies, family studies, laboratory studies, and treatment response.Results:Across domains, existing research highlights significant challenges establishing the diagnosis. This includes significant heterogeneity in operationalising criteria for children; variable or poor inter-rater reliability; difficulty distinguishing paediatric bipolar disorder from other conditions; large differences in rates of diagnosis between the United States of America and other countries; limited evidence of continuity with adult forms; and a lack of evidence for proposed paediatric phenotypes in children at genetic high-risk of the condition. Laboratory and treatment studies are limited, but also do not provide support for the construct.Conclusions:Evidence for the more widespread existence of paediatric bipolar disorder and its various proposed phenotypes remains weak. The ongoing popularity of the diagnosis, most evident in America, may reflect social pressures and broader limitations in psychiatric nosology. The uncertainty around the diagnosis highlights the need for careful longitudinal assessment of children potentially affected.
The policy agenda effects of problem indicators: a comparative study in seven countries
Authors: Kristensen Thomas Artmann , Mortensen Peter Bjerre , Green-Pedersen Christoffer , Seeberg Henrik Bech 
Published: November 2022

AbstractIndicators are important sources of information about problems across many policy areas. However, despite a growing number of indicators across most policy areas, such as health care, business promotion, or environmental protection, we still know little about if, how, and when such indicators affect the policy agenda. This article develops a theoretical answer to these questions and examines the implications using a new large-n dataset with 220,000 parliamentary questions asked by government and opposition MPs in Australia, Belgium, Denmark, Germany, France, Italy, and Spain. The data contain information on political attention to 17 problems, such as unemployment, C02 emission, and crime from 1960 to 2015. Across this wealth of data, the article demonstrates that politicians respond to the severity and development of problem indicators over time and in comparison to other countries. Results also show that politicians respond much more when problem indicators develop negatively than when they develop positively.
Middle childhood and adolescence sleep duration and behavior problems in adolescence
Authors: Zhu Mia Q. , Oliveros Henry , Marín Constanza , Mora-Plazas Mercedes , Villamor Eduardo 
Published: November 2022

AbstractWe examined the associations of middle childhood and adolescence nighttime sleep duration with adolescence internalizing and externalizing behavior problems per the Youth Self-Report (YSR) and the Child Behavior Checklist (CBCL) questionnaires, in a cohort of 889 Colombian schoolchildren. We estimated adjusted differences with 95% confidence intervals (CI) in mean behavior problem t-scores in standardized units between recommended sleep duration categories and as a continuous exposure using multiple linear regression and restricted cubic spline models, respectively. Compared with sleep duration within recommendations, middle childhood sleep above recommendations was related to 4.6 (95% CI: 1.6, 7.6; p = .004) and 5.4 (95% CI: 1.2, 9.7; p = .01) adjusted units higher YSR and CBCL externalizing problem scores, respectively. In continuous exposure analyses, this association seemed restricted to children aged ≥11 years. Longer sleep, both in categories and as a continuous exposure, was also associated with increased CBCL internalizing problems. Results did not differ by sex or weekend/weekday sleep. Sleeping under recommendations in middle childhood was not significantly related to behavior problems; nevertheless, shorter sleep in adolescence, in both categorical and continuous scales, was significantly related to behavior problems. In conclusion, behavior problems in adolescence are associated with longer sleep in middle childhood and shorter sleep in adolescence.
Automated external defibrillators and basic life support practices in secondary schools: a nationwide study
Authors: Abela Mark , Grech Victor , Sammut Mark A. 
Published: November 2022

AbstractAim:Cardiac arrest prevention in schools has recently gained momentum. The survival benefit in schools who have access to defibrillators is clear, with far better survival outcomes in children or adults who sustain a cardiac arrest on school grounds. The main objectives of this study were to assess sudden cardiac arrest prevention in Maltese schools, specifically the availability of defibrillators and staff competence in delivering resuscitation.Methodology and results:An online-based questionnaire was distributed to all secondary schools across the Maltese archipelago. Data were collected, tabulated, and analysed using SPSS V.23. Most schools (n = 40, 74.1%) completed the questionnaire. Two schools documented a cardiac arrest in the past 10 years. 87.5% agreed that cardiac arrest prevention is an important health topic. Most have a defibrillator on the premises (n = 37, 92.5%). Only one defibrillator is usually available (n = 27, 75.0%). Despite the majority claiming its ease of accessibility (n = 35, 97.2%), most were not available on every floor (n = 37, 97.2%). Only one-third were close to a sporting facility (n = 11, 30.6%). Schools do not organise regular resuscitation courses (n = 21, 58.3%), with eight schools having five or more certified staff members (23.5%). The number of defibrillators did not influence the frequency of resuscitation courses at school (p = 0.607), and there was no association with the number of certified individuals (p = 0.860).Conclusion:Defibrillators are not readily available at secondary schools and are often installed in low-risk areas. Most schools have only one staff member certified in resuscitation. These factors should be addressed with urgency.
Malaysian Disaster Medicine Research: A Bibliographic Study of Publication Trends
Authors: Adnan Mohd Syafwan Bin , Hart Alexander , Hertelendy Attila J. , Tin Derrick , Abelanes Sally-Mae , Issa Fadi , Ciottone Gregory R. 
Published: November 2022

AbstractIntroduction:Despite the increasing risks and complexity of disasters, education for Malaysian health care providers in this domain is limited. This study aims to assess scholarly publications by Malaysian scholars on Disaster Medicine (DM)-related topics.Methodology:An electronic search of five selected journals from 1991 through 2021 utilizing multiple keywords relevant to DM was conducted for review and analysis.Results:A total of 154 articles were included for analysis. The mean number of publications per year from 1991 through 2021 was 5.1 publications. Short reports were the most common research type (53.2%), followed by original research (32.4%) and case reports (12.3%). Mean citations among the included articles were 12.4 citations. Most author collaborations were within the same agency or institution, and there was no correlation between the type of collaboration and the number of citations (P = .942). While a few clusters of scholars could build a strong network across institutions, most research currently conducted in DM was within small, isolated clusters.Conclusion:Disaster Medicine in Malaysia is a growing medical subspecialty with a significant recent surge in research activity, likely due to the SARS-CoV-2/coronavirus disease 2019 (COVID-19) global pandemic. Since most publications in DM have been on infectious diseases, the need to expand DM-related research on other topics is essential.
Does the Threshold of Sediment Motion Constrain the Width of an Incising Laboratory River?
Authors: Ashley T. C. , Strom K. 
Published: November 2022

AbstractA physically rational model for river width is critical to predict macroscopic landscape evolution driven by fluvial sediment transport. Growing evidence suggests that rivers widen until the stress exerted by the fluid on the bed surface is close to the critical entrainment stress of the bank material. In this study, we test the limits of this model as a closure assumption in dynamically evolving river systems. We consider a simple laboratory channel with a fixed water discharge, monodisperse bed material, no sediment supply, and an initial relief that was sufficiently large to guarantee a finite transport capacity. Over time, the transport capacity approaches zero through changes in channel morphology. Concurrent measurements of width and sediment load illustrate how theory developed for equilibrium rivers fails to predict transient channel processes. Similarity to first order trends in natural rivers suggest that many rivers could be far from equilibrium.
Density Staircases Generated by Symmetric Instability in a Cross‐Equatorial Deep Western Boundary Current
Authors: Goldsworth F. W. , Johnson H. L. , Marshall D. P. 
Published: November 2022

AbstractDensity staircases are observed in an idealized model of a deep western boundary current upon crossing the equator. We propose that the staircases are generated by the excitement of symmetric instability as the current crosses the equator. The latitude at which symmetric instability is excited can be predicted using simple scaling arguments. Symmetric instability generates overturning cells which, in turn, cause the inhomogenous mixing of waters with different densities. The mixing barriers and well mixed regions in density profiles coincide, respectively, with the boundaries and centers of the overturning cells generated by the symmetric instability. This new mechanism for producing density staircases may require us to re‐evaluate the origins of some of the density staircases observed in the Tropical Atlantic.
Amplitude Scintillation Severity and Fading Profiles Under Alignment Between GPS Propagation Paths and Equatorial Plasma Bubbles
Authors: Sousasantos J. , Affonso B. J. , Moraes A. , Rodrigues F. S. , Abdu M. A. , Salles L. A. , Vani B. C. 
Published: November 2022

AbstractIonospheric scintillation and fading events over low‐latitude regions are often caused by severely depleted geomagnetic field‐aligned structures known as Equatorial Plasma Bubbles. These events are subject of interest to scientific investigations and concern to technological applications. Over the past several years, most of scintillation studies have focused on the dependence of these events on density gradients, location, local time, geomagnetic conditions, and so forth. This work presents a discussion about the role of the alignment between the signal propagation path and the depleted structures or, equivalently, the geomagnetic field lines, on the observed scintillation and deep fading characteristics. Data from three stations (dip latitudes: 16.13°S, 19.87°S, and 22.05°S) located around the Equatorial Ionization Anomaly (EIA) region were used to assess the amplitude scintillation severity and the deep fading events features under aligned and nonaligned conditions. The results show that the alignment condition plays a crucial role in the occurrence of strong scintillation. The study also revealed that, as stations far from the crests of the EIA are considered, the alignment influence seems to increase, and that a combination of strong plasma density fluctuation and increased aligned path is, presumably, the configuration under which the most severe scintillation and drastic deep fading events are observed. The results indicate that this conjunction is typically met in regions somewhat distinct from that with largest plasma density background over the Brazilian region, therefore, strongest scintillation and largest deep fading rates were observed by a station slightly off‐the EIA peak.
Polygenic risk scores for schizophrenia and major depression are associated with socio-economic indicators of adversity in two British community samples
Authors: Machlitt-Northen Sandra , Keers Robert , Munroe Patricia B. , Howard David M. , Pluess Michael 
Published: November 2022

AbstractSchizophrenia (SCZ) and major depressive disorder (MDD) are complex psychiatric disorders which contribute substantially to the global burden of disease. Both psychopathologies are heritable with some genetic overlap between them. Importantly, SCZ and MDD have also been found to be associated with environmental risk factors. However, rather than being independent of genetic influences, exposure to environmental risk factors may be under genetic control, known as gene-environment correlation (rGE). In this study we investigated rGE in relation to polygenic risk scores for SCZ and MDD in adults, derived from large genome-wide association studies, across two different British community samples: Understanding Society (USoc) and the National Child Development Study (NCDS). We tested whether established environmental risk factors for SCZ and/or MDD are correlated with polygenic scores in adults and whether these associations differ between the two disorders and cohorts. Findings partially overlapped between disorders and cohorts. In NCDS, we identified a significant correlation between the genetic risk for MDD and an indicator of low socio-economic status, but no significant findings emerged for SCZ. In USoc, we replicated associations between indicators of low socio-economic status and the genetic propensity for MDD. In addition, we identified associations between the genetic susceptibility for SCZ and being single or divorced. Results across both studies provide further evidence that the genetic risk for SCZ and MDD were associated with common environmental risk factors, specifically MDD’s association with lower socio-economic status.
MiMIC analysis reveals an isoform specific role for Drosophila Musashi in follicle stem cell maintenance and escort cell function
Authors: Siddall Nicole A. , Casagranda Franca , Johanson Timothy M. , Dominado Nicole , Heaney James , Sutherland Jessie M. , McLaughlin Eileen A. , Hime Gary R. 
Published: November 2022

AbstractThe Drosophila ovary is regenerated from germline and somatic stem cell populations that have provided fundamental conceptual understanding on how adult stem cells are regulated within their niches. Recent ovarian transcriptomic studies have failed to identify mRNAs that are specific to follicle stem cells (FSCs), suggesting that their fate may be regulated post-transcriptionally. We have identified that the RNA-binding protein, Musashi (Msi) is required for maintaining the stem cell state of FSCs. Loss of msi function results in stem cell loss, due to a change in differentiation state, indicated by upregulation of Lamin C in the stem cell population. In msi mutant ovaries, Lamin C upregulation was also observed in posterior escort cells that interact with newly formed germ cell cysts. Mutant somatic cells within this region were dysfunctional, as evidenced by the presence of germline cyst collisions, fused egg chambers and an increase in germ cell cyst apoptosis. The msi locus produces two classes of mRNAs (long and short). We show that FSC maintenance and escort cell function specifically requires the long transcripts, thus providing the first evidence of isoform-specific regulation in a population of Drosophila epithelial cells. We further demonstrate that although male germline stem cells have previously been shown to require Msi function to prevent differentiation this is not the case for female germline stem cells, indicating that these similar stem cell types have different requirements for Msi, in addition to the differential use of Msi isoforms between soma and germline. In summary, we show that different isoforms of the Msi RNA-binding protein are expressed in specific cell populations of the ovarian stem cell niche where Msi regulates stem cell differentiation, niche cell function and subsequent germ cell survival and differentiation.
Causal deep learning reveals the comparative effectiveness of antihyperglycemic treatments in poorly controlled diabetes
Authors: Belthangady Chinmay , Giampanis Stefanos , Jankovic Ivana , Stedden Will , Alves Paula , Chong Stephanie , Knott Charlotte , Norgeot Beau 
Published: November 2022

AbstractType-2 diabetes is associated with severe health outcomes, the effects of which are responsible for approximately 1/4th of the total healthcare spending in the United States (US). Current treatment guidelines endorse a massive number of potential anti-hyperglycemic treatment options in various combinations. Strategies for optimizing treatment selection are lacking. Real-world data from a nationwide population of over one million high-risk diabetic patients (HbA1c ≥ 9%) in the US is analyzed to evaluate the comparative effectiveness for HbA1c reduction in this population of more than 80 different treatment strategies ranging from monotherapy up to combinations of five concomitant classes of drugs across each of 10 clinical cohorts defined by age, insulin dependence, and a number of other chronic conditions. A causal deep learning approach developed on such data allows for more personalized evaluation of treatment selection. An average confounder-adjusted reduction in HbA1c of 0.69% [−0.75, −0.65] is observed between patients receiving high vs low ranked treatments across cohorts for which the difference was significant. This method can be extended to explore treatment optimization for other chronic conditions.
Energy requirements and carbon emissions for a low-carbon energy transition
Authors: Slameršak Aljoša , Kallis Giorgos , O’Neill Daniel W. 
Published: November 2022

AbstractAchieving the Paris Agreement will require massive deployment of low-carbon energy. However, constructing, operating, and maintaining a low-carbon energy system will itself require energy, with much of it derived from fossil fuels. This raises the concern that the transition may consume much of the energy available to society, and be a source of considerable emissions. Here we calculate the energy requirements and emissions associated with the global energy system in fourteen mitigation pathways compatible with 1.5 °C of warming. We find that the initial push for a transition is likely to cause a 10–34% decline in net energy available to society. Moreover, we find that the carbon emissions associated with the transition to a low-carbon energy system are substantial, ranging from 70 to 395 GtCO2 (with a cross-scenario average of 195 GtCO2). The share of carbon emissions for the energy system will increase from 10% today to 27% in 2050, and in some cases may take up all remaining emissions available to society under 1.5 °C pathways.
Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells
Authors: Haythorne Elizabeth , Lloyd Matthew , Walsby-Tickle John , Tarasov Andrei I. , Sandbrink Jonas , Portillo Idoia , Exposito Raul Terron , Sachse Gregor , Cyranka Malgorzata , Rohm Maria , Rorsman Patrik , McCullagh James , Ashcroft Frances M. 
Published: November 2022

AbstractChronic hyperglycaemia causes a dramatic decrease in mitochondrial metabolism and insulin content in pancreatic β-cells. This underlies the progressive decline in β-cell function in diabetes. However, the molecular mechanisms by which hyperglycaemia produces these effects remain unresolved. Using isolated islets and INS-1 cells, we show here that one or more glycolytic metabolites downstream of phosphofructokinase and upstream of GAPDH mediates the effects of chronic hyperglycemia. This metabolite stimulates marked upregulation of mTORC1 and concomitant downregulation of AMPK. Increased mTORC1 activity causes inhibition of pyruvate dehydrogenase which reduces pyruvate entry into the tricarboxylic acid cycle and partially accounts for the hyperglycaemia-induced reduction in oxidative phosphorylation and insulin secretion. In addition, hyperglycaemia (or diabetes) dramatically inhibits GAPDH activity, thereby impairing glucose metabolism. Our data also reveal that restricting glucose metabolism during hyperglycaemia prevents these changes and thus may be of therapeutic benefit. In summary, we have identified a pathway by which chronic hyperglycaemia reduces β-cell function.
Cytoskeletal components can turn wall-less spherical bacteria into kinking helices
Authors: Lartigue Carole , Lambert Bastien , Rideau Fabien , Dahan Yorick , Decossas Marion , Hillion Mélanie , Douliez Jean-Paul , Hardouin Julie , Lambert Olivier , Blanchard Alain , Béven Laure 
Published: November 2022

AbstractBacterial cell shape is generally determined through an interplay between the peptidoglycan cell wall and cytoplasmic filaments made of polymerized MreB. Indeed, some bacteria (e.g., Mycoplasma) that lack both a cell wall and mreB genes consist of non-motile cells that are spherical or pleomorphic. However, other members of the same class Mollicutes (e.g., Spiroplasma, also lacking a cell wall) display a helical cell shape and kink-based motility, which is thought to rely on the presence of five MreB isoforms and a specific fibril protein. Here, we show that heterologous expression of Spiroplasma fibril and MreB proteins confers helical shape and kinking ability to Mycoplasma capricolum cells. Isoform MreB5 is sufficient to confer helicity and kink propagation to mycoplasma cells. Cryoelectron microscopy confirms the association of cytoplasmic MreB filaments with the plasma membrane, suggesting a direct effect on membrane curvature. However, in our experiments, the heterologous expression of MreBs and fibril did not result in efficient motility in culture broth, indicating that additional, unknown Spiroplasma components are required for swimming.
Adenine base editing efficiently restores the function of Fanconi anemia hematopoietic stem and progenitor cells
Authors: Siegner Sebastian M. , Ugalde Laura , Clemens Alexandra , Garcia-Garcia Laura , Bueren Juan A. , Rio Paula , Karasu Mehmet E. , Corn Jacob E. 
Published: November 2022

AbstractFanconi Anemia (FA) is a debilitating genetic disorder with a wide range of severe symptoms including bone marrow failure and predisposition to cancer. CRISPR-Cas genome editing manipulates genotypes by harnessing DNA repair and has been proposed as a potential cure for FA. But FA is caused by deficiencies in DNA repair itself, preventing the use of editing strategies such as homology directed repair. Recently developed base editing (BE) systems do not rely on double stranded DNA breaks and might be used to target mutations in FA genes, but this remains to be tested. Here we develop a proof of concept therapeutic base editing strategy to address two of the most prevalent FANCA mutations in patient hematopoietic stem and progenitor cells. We find that optimizing adenine base editor construct, vector type, guide RNA format, and delivery conditions leads to very effective genetic modification in multiple FA patient backgrounds. Optimized base editing restored FANCA expression, molecular function of the FA pathway, and phenotypic resistance to crosslinking agents. ABE8e mediated editing in primary hematopoietic stem and progenitor cells from FA patients was both genotypically effective and restored FA pathway function, indicating the potential of base editing strategies for future clinical application in FA.