bluuebunny/crossref_metadata_2025 huggingface dataset:
Treating social anxiety disorder remotely with cognitive therapy
Authors: Warnock-Parkes Emma , Wild Jennifer , Thew Graham R. , Kerr Alice , Grey Nick , Stott Richard , Ehlers Anke , Clark David M.
Published: July 2020

Remote delivery of evidence-based psychological therapies via video conference has become particularly relevant following the COVID-19 pandemic, and is likely to be an on-going method of treatment delivery post-COVID. Remotely delivered therapy could be of particular benefit for people with social anxiety disorder (SAD), who tend to avoid or delay seeking face-to-face therapy, often due to anxiety about travelling to appointments and meeting mental health professionals in person. Individual cognitive therapy for SAD (CT-SAD), based on the Clark and Wells (1995) model, is a highly effective treatment that is recommended as a first-line intervention in NICE guidance (NICE, 2013). All of the key features of face-to-face CT-SAD (including video feedback, attention training, behavioural experiments and memory-focused techniques) can be adapted for remote delivery. In this paper, we provide guidance for clinicians on how to deliver CT-SAD remotely, and suggest novel ways for therapists and patients to overcome the challenges of carrying out a range of behavioural experiments during remote treatment delivery.

Key learning aims

(1)

To learn how to deliver all of the core interventions of CT-SAD remotely.

(2)

To learn novel ways of carrying out behavioural experiments remotely when some in-person social situations might not be possible.
Suicide Prevention Gatekeeper Self-Efficacy Scale (GKSES)
Authors: Takahashi Asumi , Tachikawa Hirokazu , Morita Nobuaki , Aiba Miyuki , Shiratori Yuki , Nemoto Kiyotaka , Arai Tetsuaki
Published: July 2020

Abstract. Background: To date there is no standardized scale for the evaluation of self-efficacy of gatekeeper skills. Aim: The aim of this study was to develop the Gatekeeper Self-Efficacy Scale (GKSES), which consists of nine items assessing laypersons' confidence in their own gatekeeper skills, and to confirm its reliability and validity. Method: Altogether 875 participants joined in gatekeeper training between 2010 and 2017 and completed the GKSES both before and after training. After exploratory factor analysis, we analyzed Pearson's correlation between total GKSES scores and Attitude Toward Suicide Scale subscale scores and performed one-way analysis of variance for the score differences by demographics. Results: The GKSES is a univariate scale with good fit. Total GKSES score correlated with the appropriate attitudes for suicide prevention. Self-efficacy ratings after training improved irrespective of attribute. Participants who had had contact with suicidal individuals and those who had received previous suicide prevention training had high self-efficacy ratings, while a greater improvement was seen in the ratings of participants who had not had any previous contact or training. Limitations: It is necessary to assess the GKSES using more participants across other populations. Conclusion: The GKSES is a simple and useful measure with good internal consistency and validity for self-efficacy assessment of gatekeeper skills.
Magnetic Difference Between Deep and Surface Soil Within an Agricultural Area in Southern China: Implications for Magnetic Mineral Transformation During Pedogenic Process Under Subtropical Climate
Authors: Ouyang Tingping , Li Mingkun , Guo Yu , Peng Shasha , He Chenjian , Zhu Zhaoyu
Published: July 2020

Mineral magnetism is proved as a sensitive method of pedogenesis by numerous studies. However, formation pathways of magnetic minerals and subsequent magnetic response are quite different under different climate. In order to improve the understanding of magnetic assemblages in paddy soil layers in relation to soil formation conditions, a systematic magnetic investigation was performed for surface and its corresponding deep soil collected from 70 sampling sites within a paddy soil area under subtropical climate, south China. Rock magnetic results showed that superparamagnetic, single‐domain, and multiple domain maghematite and hematite were produced during ferrallitization pedogenic processes. Some fine superparamagnetic and single‐domain ferrimagnetic particles were dissolved during late gleyization of paddy soil formation with increased organic matter and reductive condition. As a result, magnetism of surface soil was weaker than that of deep soil despite basically consistent magnetic mineral composition.
Covariant Giant Gaussian Process Models With Improved Reproduction of Palaeosecular Variation
Authors: Bono Richard K. , Biggin Andrew J. , Holme Richard , Davies Christopher J. , Meduri Domenico G. , Bestard Jack
Published: July 2020

A commonly used family of statistical magnetic field models is based on a giant Gaussian process (GGP), which assumes each Gauss coefficient can be realized from an independent normal distribution. GGP models are capable of generating suites of plausible Gauss coefficients, allowing for palaeomagnetic data to be tested against the expected distribution arising from a time‐averaged geomagnetic field. However, existing GGP models do not simultaneously reproduce the distribution of field strength and palaeosecular variation estimates reported for the past 10 million years and tend to underpredict virtual geomagnetic pole (VGP) dispersion at high latitudes unless trade‐offs are made to the fit at lower latitudes. Here we introduce a new family of GGP models, BB18 and BB18.Z3 (the latter includes non‐zero‐mean zonal terms for spherical harmonic degrees 2 and 3). Our models are distinct from prior GGP models by simultaneously treating the axial dipole variance separately from higher degree terms, applying an odd‐even variance structure, and incorporating a covariance between certain Gauss coefficients. Covariance between Gauss coefficients, a property both expected from dynamo theory and observed in numerical dynamo simulations, has not previously been included in GGP models. Introducing covariance between certain Gauss coefficients inferred from an ensemble of “Earth‐like” dynamo simulations and predicted by theory yields a reduced misfit to VGP dispersion, allowing for GGP models which generate improved reproductions of the distribution of field strengths and palaeosecular variation observed for the last 10 million years.
Distribution of Earthquakes on a Branching Fault System Using Integer Programming and Greedy‐Sequential Methods
Authors: Geist Eric L. , Parsons Tom
Published: July 2020

A new global optimization method is used to determine the distribution of earthquakes on a complex, connected fault system. The method, integer programming, has been advanced in the field of operations research but has not been widely applied to geophysical problems until recently. In this application, we determine the optimal distribution of earthquakes on mapped faults to minimize the global misfit in slip rates for multifault ruptures. Integer programming solves for a decision vector composed of every possible location that a sample of earthquakes can occur on every fault, subject to slip rate uncertainty constraints. Step over connections are straightforward to include, whereas branching fault connections are not. To include branching ruptures, we distinguish between individual multifault rupture paths, as opposed to formulating the integer programming problem based on individual faults as in previous studies. The new method is applied to the complex fault system in the San Francisco Bay Area as a case study. Results from the integer programming method are compared to those from a local optimization method, termed the greedy‐sequential method. Several experiments using these two methods indicate that shape of the on‐fault magnitude distributions and which branching faults are involved in multifault ruptures depend on how much emphasis is placed on fitting the target slip rate. In cases where the underlying data are not strong enough to warrant chasing the target slip rate, it is better to focus on the distribution of feasible results that better represents the uncertainty in the solutions imposed by the data.
Longitudinal Responses of the Equatorial/Low‐Latitude Ionosphere Over the Oceanic Regions to Geomagnetic Storms of May and September 2017
Authors: Akala A. O. , Oyeyemi E. O. , Amaechi P. O. , Radicella S. M. , Nava B. , Amory‐Mazaudier C.
Published: July 2020

This study presents the longitudinal dependence of responses of the equatorial/low‐latitude ionosphere over the oceanic regions to geomagnetic storms of 28 May and 8 September 2017. We investigated the interplanetary origins of the storms. Total electron content (TEC) data were obtained from Global Navigation Satellite System stations, located around the oceanic areas in the equatorial/low‐latitude regions. The Rate of change of TEC Index (ROTI) was used as a proxy for ionospheric irregularities over the study locations. Further, variations of the horizontal component of the Earth's magnetic fields, obtained from ground‐based magnetometers were studied. We used ionospheric disturbance currents, polar cap and auroral electrojet indices to monitor the storm time electric fields. The May 2017 storm was driven by sheath and magnetic cloud fields, while the September 2017 storm was driven by sheath fields. We observed a comparative dominance of TEC intensities over the Oceans than over the landlocked areas. Empirically, our results validated a theoretical suggestion of the existence of a dynamic ocean‐ionosphere coupling made by Godin et al. (2015, http://10.0.4.162/s40623-015-0212-4). Prompt Penetration Electric Fields (PPEF) was observed to be a key factor that controls TEC responses to storms. PPEFs caused TEC enhancements, mainly over the Pacific Ocean longitudes during the May 2017 storm and enhanced TEC over the Atlantic Ocean and the Pacific Oceans longitudes during the September 2017 storm. These PPEFs triggered irregularities over the Pacific Ocean longitudes, particularly during the main phase of May 2017 storm. Irregularities were generally inhibited by the September 2017 storm.
Nanoparticle meta-grid for enhanced light extraction from light-emitting devices
Authors: Sikdar Debabrata , Pendry John B. , Kornyshev Alexei A.
Published: July 2020

Based on a developed theory, we show that introducing a meta-grid of sub-wavelength-sized plasmonic nanoparticles (NPs) into existing semiconductor light-emitting-devices (LEDs) can lead to enhanced transmission of light across the LED-chip/encapsulant interface. This results from destructive interference between light reflected from the chip/encapsulant interface and light reflected by the NP meta-grid, which conspicuously increase the efficiency of light extraction from LEDs. The “meta-grid”, should be inserted on top of a conventional LED chip within its usual encapsulating packaging. As described by the theory, the nanoparticle composition, size, interparticle spacing, and distance from the LED-chip surface can be tailored to facilitate maximal transmission of light emitted from the chip into its encapsulating layer by reducing the Fresnel loss. The analysis shows that transmission across a typical LED-chip/encapsulant interface at the peak emission wavelength can be boosted up to ~99%, which is otherwise mere ~84% at normal incidence. The scheme could provide improved transmission within the photon escape cone over the entire emission spectrum of an LED. This would benefit energy saving, in addition to increasing the lifetime of LEDs by reducing heating. Potentially, the scheme will be easy to implement and adopt into existing semiconductor-device technologies, and it can be used separately or in conjunction with other methods for mitigating the critical angle loss in LEDs.
Long-term treatment with a glucagon-like peptide-1 receptor agonist reduces ethanol intake in male and female rats
Authors: Vallöf Daniel , Kalafateli Aimilia Lydia , Jerlhag Elisabet
Published: July 2020

Given the limited efficacy of available pharmacotherapies for treatment of alcohol use disorder (AUD), the need for new medications is substantial. Preclinical studies have shown that acute administration of glucagon-like peptide-1 receptor (GLP-1R) agonists inhibits various ethanol-related behaviours, indicating this system as a potential target for AUD. However, the effects of long-term systemic treatment of GLP-1R agonists on ethanol intake in male and female rodents are to date unknown. Therefore, we investigated the effects of 9 or 5 weeks of once weekly administration of dulaglutide, a long-acting GLP-1R agonist, on ethanol intake in male and female rats. The ethanol intake during treatment discontinuation was also monitored. In an initial attempt to identify preliminary underlying mechanisms, the effects of 9 weeks of once weekly dulaglutide treatment on monoaminergic signalling in reward-related areas were explored in both sexes. We found that 9 or 5 weeks of once weekly dulaglutide treatment reduced ethanol intake and preference in male and female rats. Following discontinuation of dulaglutide treatment, the decrease in ethanol consumption was prolonged in males, but not females. We demonstrated that 9 weeks of dulaglutide treatment differentially influenced monoaminergic signalling in reward-related areas of male and female rats. Collectively, these data imply that the GLP-1R attracts interest as a potential molecular target in the medical treatment of AUD in humans: more specifically, dulaglutide should be evaluated as a potential medication for treatment thereof.
Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium
Authors: Sánchez-Maldonado J. M. , Campa D. , Springer J. , Badiola J. , Niazi Y. , Moñiz-Díez A. , Hernández-Mohedo F. , González-Sierra P. , Ter Horst R. , Macauda A. , Brezina S. , Cunha C. , Lackner M. , López-Nevot M. A. , Fianchi L. , Pagano L. , López-Fernández E. , Potenza L. , Luppi M. , Moratalla L. , Rodríguez-Sevilla J. J. , Fonseca J. E. , Tormo M. , Solano C. , Clavero E. , Romero A. , Li Y. , Lass-Flörl C. , Einsele H. , Vazquez L. , Loeffler J. , Hemminki K. , Carvalho A. , Netea M. G. , Gsur A. , Dumontet C. , Canzian F. , Försti A. , Jurado M. , Sainz J.
Published: July 2020

The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.
The integrated stress response induces R-loops and hinders replication fork progression
Authors: Choo Josephine Ann Mun Yee , Schlösser Denise , Manzini Valentina , Magerhans Anna , Dobbelstein Matthias
Published: July 2020

The integrated stress response (ISR) allows cells to rapidly shutdown most of their protein synthesis in response to protein misfolding, amino acid deficiency, or virus infection. These stresses trigger the phosphorylation of the translation initiation factor eIF2alpha, which prevents the initiation of translation. Here we show that triggering the ISR drastically reduces the progression of DNA replication forks within 1 h, thus flanking the shutdown of protein synthesis with immediate inhibition of DNA synthesis. DNA replication is restored by compounds that inhibit eIF2alpha kinases or re-activate eIF2alpha. Mechanistically, the translational shutdown blocks histone synthesis, promoting the formation of DNA:RNA hybrids (R-loops), which interfere with DNA replication. R-loops accumulate upon histone depletion. Conversely, histone overexpression or R-loop removal by RNaseH1 each restores DNA replication in the context of ISR and histone depletion. In conclusion, the ISR rapidly stalls DNA synthesis through histone deficiency and R-loop formation. We propose that this shutdown mechanism prevents potentially detrimental DNA replication in the face of cellular stresses.
Association of self-reported sleep duration and quality with BaPWV levels in hypertensive patients
Authors: Hu Huan , Li Huan , Huang Xiao , Bao Huihui , Song Yun , Wang Binyan , Liu Chengzhang , Xu Richard , Liu Lishun , Wang Xiaobin , Huo Yong , Xu Xiping , Cheng Xiaoshu , Qin Xianhui , Li Ping
Published: July 2020

The association between sleep conditions and arterial stiffness remains inconclusive. We aimed to investigate the relationship of sleep duration and quality with brachial-ankle pulse-wave velocity (baPWV) in hypertensive patients. A total of 14,485 hypertensive adults were included in this cross-sectional analysis. Information about sleep duration and quality was obtained via questionnaire. A baPWV level ≥1800 cm/s was defined as indicative of arterial stiffness. Compared with participants with a sleep duration <8 h per day, participants with a sleep duration ≥8 h per day had a significantly higher baPWV level (β = 13.7 cm/s; 95% CI: 3.9, 23.5) and a nonsignificantly higher prevalence of arterial stiffness (39.7% vs. 33.0%; OR, 1.08; 95% CI: 0.99–1.19). Similarly, compared with participants with good or medium sleep quality, participants with poor sleep quality had a significantly higher baPWV level (β = 16.3 cm/s; 95% CI: 0.1, 32.6) and a nonsignificantly greater prevalence of arterial stiffness (36.6% vs. 35.3%; OR, 1.13; 95% CI: 0.97–1.32). When sleep duration and quality were examined jointly, participants with a sleep duration ≥8 h and/or poor sleep quality had a significantly higher baPWV level (β = 14.4 cm/s; 95% CI: 5.3, 23.4) and a greater prevalence of arterial stiffness (38.8% vs. 32.7%; OR, 1.10; 95% CI: 1.01–1.20) than those with a sleep duration <8 h and good/medium sleep quality. In summary, among hypertensive patients, a longer sleep duration (≥8 h per day) and poor sleep quality were associated with higher baPWV levels and a higher prevalence of arterial stiffness.
Using operando techniques to understand and design high performance and stable alkaline membrane fuel cells
Authors: Peng Xiong , Kulkarni Devashish , Huang Ying , Omasta Travis J. , Ng Benjamin , Zheng Yiwei , Wang Lianqin , LaManna Jacob M. , Hussey Daniel S. , Varcoe John R. , Zenyuk Iryna V. , Mustain William E.
Published: July 2020

There is a need to understand the water dynamics of alkaline membrane fuel cells under various operating conditions to create electrodes that enable high performance and stable, long-term operation. Here we show, via operando neutron imaging and operando micro X-ray computed tomography, visualizations of the spatial and temporal distribution of liquid water in operating cells. We provide direct evidence for liquid water accumulation at the anode, which causes severe ionomer swelling and performance loss, as well as cell dryout from undesirably low water content in the cathode. We observe that the operating conditions leading to the highest power density during polarization are not generally the conditions that allow for long-term stable operation. This observation leads to new catalyst layer designs and gas diffusion layers. This study reports alkaline membrane fuel cells that can be operated continuously for over 1000 h at 600 mA cm−2 with voltage decay rate of only 32-μV h−1 – the best-reported durability to date.
Automatic precursor recognition and real-time forecasting of sudden explosive volcanic eruptions at Whakaari, New Zealand
Authors: Dempsey D. E. , Cronin S. J. , Mei S. , Kempa-Liehr A. W.
Published: July 2020

Sudden steam-driven eruptions strike without warning and are a leading cause of fatalities at touristic volcanoes. Recent deaths following the 2019 Whakaari eruption in New Zealand expose a need for accurate, short-term forecasting. However, current volcano alert systems are heuristic and too slowly updated with human input. Here, we show that a structured machine learning approach can detect eruption precursors in real-time seismic data streamed from Whakaari. We identify four-hour energy bursts that occur hours to days before most eruptions and suggest these indicate charging of the vent hydrothermal system by hot magmatic fluids. We developed a model to issue short-term alerts of elevated eruption likelihood and show that, under cross-validation testing, it could provide advanced warning of an unseen eruption in four out of five instances, including at least four hours warning for the 2019 eruption. This makes a strong case to adopt real-time forecasting models at active volcanoes.
Multi-layered proteomic analyses decode compositional and functional effects of cancer mutations on kinase complexes
Authors: Mehnert Martin , Ciuffa Rodolfo , Frommelt Fabian , Uliana Federico , van Drogen Audrey , Ruminski Kilian , Gstaiger Matthias , Aebersold Ruedi
Published: July 2020

Rapidly increasing availability of genomic data and ensuing identification of disease associated mutations allows for an unbiased insight into genetic drivers of disease development. However, determination of molecular mechanisms by which individual genomic changes affect biochemical processes remains a major challenge. Here, we develop a multilayered proteomic workflow to explore how genetic lesions modulate the proteome and are translated into molecular phenotypes. Using this workflow we determine how expression of a panel of disease-associated mutations in the Dyrk2 protein kinase alter the composition, topology and activity of this kinase complex as well as the phosphoproteomic state of the cell. The data show that altered protein-protein interactions caused by the mutations are associated with topological changes and affected phosphorylation of known cancer driver proteins, thus linking Dyrk2 mutations with cancer-related biochemical processes. Overall, we discover multiple mutation-specific functionally relevant changes, thus highlighting the extensive plasticity of molecular responses to genetic lesions.
Five-year change in body mass index category of childhood and the establishment of an obesity prediction model
Authors: Sun Yuelin , Xing Yufang , Liu Junfeng , Zhang Xiaoxia , Liu Jingyu , Wang Zhaoxia , Bi Jingyang , Ping Xianghe , Shen Qiqiang , Zhao Zhouqiao , Xu Jinjie
Published: July 2020

The prevalence of childhood obesity in China has recently become increasingly severe, and intervention measures are needed to stop its growth. Currently, there is a lack of assessment and prediction methods for childhood obesity. We develop a predictive model that uses currently measured predictors [gender, age, urban/rural, height and body mass index (BMI)] to quantify children’s probabilities of belonging to one of four BMI category 5 years later and identify the high-risk group for possible intervention. A total of 88,980 students underwent a routine standard physical examination and were reexamined 5 years later to complete the study. The full model shows that boys, urban residence and height have positive effects and that age has a negative effect on transition to the overweight or obese category along with significant BMI effects. Our model correctly predicts BMI categories 5 years later for 70% of the students. From 2018 to 2023, the prevalence of obesity in rural boys and girls is expected to increase by 4% and 2%, respectively, while that in urban boys and girls is expected to remain unchanged. Predictive models help us assess the severity of childhood obesity and take targeted interventions and treatments to prevent it.
HIV X4 Variants Increase Arachidonate 5-Lipoxygenase in the Pulmonary Microenvironment and are associated with Pulmonary Arterial Hypertension
Authors: Almodovar Sharilyn , Wade Brandy E. , Porter Kristi M. , Smith Justin M. , Lopez-Astacio Robert A. , Bijli Kaiser , Kang Bum-Yong , Cribbs Sushma K. , Guidot David M. , Molehin Deborah , McNair Bryan K. , Pumarejo-Gomez Laura , Perez Hernandez Jaritza , Salazar Ethan A. , Martinez Edgar G. , Huang Laurence , Kessing Cari F. , Suarez-Martinez Edu B. , Pruitt Kevin , Hsue Priscilla Y. , Tyor William R. , Flores Sonia C. , Sutliff Roy L.
Published: July 2020

Pulmonary Arterial Hypertension (PAH) is overrepresented in People Living with Human Immunodeficiency Virus (PLWH). HIV protein gp120 plays a key role in the pathogenesis of HIV-PAH. Genetic changes in HIV gp120 determine viral interactions with chemokine receptors; specifically, HIV-X4 viruses interact with CXCR4 while HIV-R5 interact with CCR5 co-receptors. Herein, we leveraged banked samples from patients enrolled in the NIH Lung HIV studies and used bioinformatic analyses to investigate whether signature sequences in HIV-gp120 that predict tropism also predict PAH. Further biological assays were conducted in pulmonary endothelial cells in vitro and in HIV-transgenic rats. We found that significantly more persons living with HIV-PAH harbor HIV-X4 variants. Multiple HIV models showed that recombinant gp120-X4 as well as infectious HIV-X4 remarkably increase arachidonate 5-lipoxygenase (ALOX5) expression. ALOX5 is essential for the production of leukotrienes; we confirmed that leukotriene levels are increased in bronchoalveolar lavage fluid of HIV-infected patients. This is the first report associating HIV-gp120 genotype to a pulmonary disease phenotype, as we uncovered X4 viruses as potential agents in the pathophysiology of HIV-PAH. Altogether, our results allude to the supplementation of antiretroviral therapy with ALOX5 antagonists to rescue patients with HIV-X4 variants from fatal PAH.
Quantitative immunohistochemical analysis of myeloid cell marker expression in human cortex captures microglia heterogeneity with anatomical context
Authors: Swanson Molly E. V. , Murray Helen C. , Ryan Brigid , Faull Richard L. M. , Dragunow Mike , Curtis Maurice A.
Published: July 2020

Current immunohistochemical methods of studying microglia in the post-mortem human brain do not capture the heterogeneity of microglial function in response to damage and disease. We therefore investigated the expression of eight myeloid cell proteins associated with changes in function alongside Iba1. To study the myeloid cells we used immunohistochemistry on post-mortem human middle temporal gyrus sections from neurologically normal individuals. First we investigated co-labelling between the classical ‘activation’ marker, HLA-DR and each of the other markers of interest. Significant co-labelling between HLA-DR with CD206, CD32, CD163, or L-Ferritin was observed, although complete overlap of expression of HLA-DR with aforementioned markers was not observed. A qualitative assessment also demonstrated that perivascular macrophages expressed higher levels of the markers of interest we investigated than microglia, suggesting perivascular macrophages show a more phagocytic and antigen presentation state in the human brain. To determine whether the markers of interest were expressed in different functional states, the immunoreactivity for each marker was qualitatively assessed on microglial morphologies. Degenerating marker, L-Ferritin, was specific for dystrophic microglia. We demonstrate that microglial heterogeneity can be investigated in immunohistochemically stain post-mortem human tissue by integrating the single-cell abundance of proteins and cell morphology to infer function.
RPmirDIP: Reciprocal Perspective improves miRNA targeting prediction
Authors: Kyrollos Daniel G. , Reid Bradley , Dick Kevin , Green James R.
Published: July 2020

MicroRNAs (miRNAs) are short, non-coding RNAs that interact with messenger RNA (mRNA) to accomplish critical cellular activities such as the regulation of gene expression. Several machine learning methods have been developed to improve classification accuracy and reduce validation costs by predicting which miRNA will target which gene. Application of these predictors to large numbers of unique miRNA–gene pairs has resulted in datasets comprising tens of millions of scored interactions; the largest among these is mirDIP. We here demonstrate that miRNA target prediction can be significantly improved ($$p < 0.001$$p<0.001) through the application of the Reciprocal Perspective (RP) method, a cascaded, semi-supervised machine learning method originally developed for protein-protein interaction prediction. The RP method, aptly named RPmirDIP, augments the original mirDIP prediction scores by leveraging local thresholds from the two complimentary views available to each miRNA–gene pair, rather than apply a traditional global decision threshold. Application of this novel RPmirDIP predictor promises to help identify new, unexpected miRNA–gene interactions. A dataset of RPmirDIP-scored interactions are made available to the scientific community at cu-bic.ca/RPmirDIP and https://doi.org/10.5683/SP2/LD8JKJ.
Robust genome-wide ancestry inference for heterogeneous datasets: illustrated using the 1,000 genome project with 3D facial images
Authors: Li Jiarui , Zarzar Tomás González , White Julie D. , Indencleef Karlijne , Hoskens Hanne , Matthews Harry , Nauwelaers Nele , Zaidi Arslan , Eller Ryan J. , Herrick Noah , Günther Torsten , Svensson Emma M. , Jakobsson Mattias , Walsh Susan , Van Steen Kristel , Shriver Mark D. , Claes Peter
Published: July 2020

Estimates of individual-level genomic ancestry are routinely used in human genetics, and related fields. The analysis of population structure and genomic ancestry can yield insights in terms of modern and ancient populations, allowing us to address questions regarding admixture, and the numbers and identities of the parental source populations. Unrecognized population structure is also an important confounder to correct for in genome-wide association studies. However, it remains challenging to work with heterogeneous datasets from multiple studies collected by different laboratories with diverse genotyping and imputation protocols. This work presents a new approach and an accompanying open-source toolbox that facilitates a robust integrative analysis for population structure and genomic ancestry estimates for heterogeneous datasets. We show robustness against individual outliers and different protocols for the projection of new samples into a reference ancestry space, and the ability to reveal and adjust for population structure in a simulated case–control admixed population. Given that visually evident and easily recognizable patterns of human facial characteristics co-vary with genomic ancestry, and based on the integration of three different sources of genome data, we generate average 3D faces to illustrate genomic ancestry variations within the 1,000 Genome project and for eight ancient-DNA profiles, respectively.
Fluorescent recognition of Fe3+ in acidic environment by enhanced-quantum yield N-doped carbon dots: optimization of variables using central composite design
Authors: Issa Mohammed Abdullah , Abidin Zurina Z. , Sobri Shafreeza , Rashid Suraya Abdul , Mahdi Mohd Adzir , Ibrahim Nor Azowa
Published: July 2020

A versatile synthetic approach for development of highly fluorescent nitrogen-doped carbon dots (N-CDs) from carboxymethylcellulose in the presence of linear polyethyleneimine (LPEI) has been developed. According to single factor method, central composite design incorporated with response surface methodology matrix was applied to find and model optimal conditions for the temperature (220–260 °C), duration (1–3 h) and LPEI weight (0.5–1.5%). The statistical results show that duration was the most significant parameter for efficient carbonization conversion rate in comparison with temperature and LPEI weight. The reduced cubic model (R2 = 0.9993) shows a good correlation between the experimental data and predicted values. The optimal variables were temperature of 260 °C, duration of 2 h and LPEI weight of 1%. Under these conditions, quantum yield of up to 44% was obtained. The numerically optimized N-CDs have an average size of 3.4 nm with graphitic nature owing to the abundant amino species incorporated into the carbon core framework. The blue-green N-CDs possess emission dependent upon the solvent polarity, wide pH stability with enhanced emission in an acidic environment. Impressively, the N-CDs show long-shelf-life for up to 1 year with no noticeable precipitation. The N-CDs were able to recognize a high concentration of Fe3+ ions with a detection limit of 0.14 μM in acidic solution owing to the special coordination for Fe3+ to be captured by electron-donating oxygen/ amino groups around N-CDs. Moreover, the N-CDs can also be used as a new kind of fluorescent ink for imaging applications.
The Andaman day gecko paradox: an ancient endemic without pronounced phylogeographic structure
Authors: Mohan Ashwini V. , Orozco-terWengel Pablo , Shanker Kartik , Vences Miguel
Published: July 2020

The Andaman day gecko (Phelsuma andamanensis) is endemic to the Andaman Archipelago, located ~ 6000 km away from Madagascar where the genusPhelsumalikely evolved. We complemented existing phylogenetic data with additional markers to show that this species consistently branches off early in the evolution of the genusPhelsuma,and this early origin led us to hypothesize that island populations within the Andaman Archipelago could have further diversified. We sampled the Andaman day gecko from all major islands in the Andamans, developed new microsatellite markers and amplified mitochondrial markers to study population diversification. We detected high allelic diversity in microsatellites, but surprisingly poor geographical structuring. This study demonstrates that the Andaman day gecko has a panmictic population (K = 1), but with weak signals for two clusters that we name ‘North’ (North Andaman, Middle Andaman, Interview, Baratang, Neil, and Long Islands) and ‘South’ (Havelock, South Andaman, Little Andaman Islands). The mitochondrial COI gene uncovered wide haplotype sharing across islands with the presence of several private haplotypes (except for the Little Andaman Island, which only had an exclusive private haplotype) signalling ongoing admixture. This species differs from two other Andaman endemic geckos for which we provide comparative mitochondrial data, where haplotypes show a distinct phylogeographic structure. Testing population history scenarios for the Andaman day gecko using Approximate Bayesian Computation (ABC) supports two possible scenarios but fails to tease apart whether admixture or divergence produced the two weak clusters. Both scenarios agree that admixture and/or divergence prior to the onset of the last glacial maximum shaped the genetic diversity and structure detected in this study. ABC supports population expansion, possibly explained by anthropogenic food subsidies via plantations of cash crops, potentially coupled with human mediated dispersal resulting in the observed panmictic population. The Andaman day gecko may thus be a rare example of an island endemic reptile benefiting from habitat modification and increased movement in its native range.
Probiotics have beneficial metabolic effects in patients with type 2 diabetes mellitus: a meta-analysis of randomized clinical trials
Authors: Kocsis Tícia , Molnár Bálint , Németh Dávid , Hegyi Péter , Szakács Zsolt , Bálint Alexandra , Garami András , Soós Alexandra , Márta Katalin , Solymár Margit
Published: July 2020

Probiotics have been reported to have a positive impact on the metabolic control of patients with type 2 diabetes. We aimed to systematically evaluate the effects of probiotics on cardiometabolic parameters in type 2 diabetes based on randomized controlled studies. MEDLINE, Embase, and CENTRAL databases were reviewed to search for randomized controlled trials that examined the effects of probiotic supplementation on cardiometabolic parameters in patients with type 2 diabetes. 32 trials provided results suitable to be included in the analysis. The effects of probiotics were calculated for the following parameters: BMI, total cholesterol levels, LDL, triglycerides, HDL, CRP, HbA1c levels, fasting plasma glucose, fasting insulin levels, systolic and diastolic blood pressure values. Data analysis showed a significant effect of probiotics on reducing total cholesterol, triglyceride levels, CRP, HbA1c, fasting plasma glucose, fasting insulin levels, and both systolic and diastolic blood pressure values. Supplementation with probiotics increased HDL levels however did not have a significant effect on BMI or LDL levels. Our data clearly suggest that probiotics could be a supplementary therapeutic approach in type 2 diabetes mellitus patients to improve dyslipidemia and to promote better metabolic control. According to our analysis, probiotic supplementation is beneficial in type 2 diabetes mellitus.
Segregation dynamics with reinforcement learning and agent based modeling
Authors: Sert Egemen , Bar-Yam Yaneer , Morales Alfredo J.
Published: July 2020

Societies are complex. Properties of social systems can be explained by the interplay and weaving of individual actions. Rewards are key to understand people’s choices and decisions. For instance, individual preferences of where to live may lead to the emergence of social segregation. In this paper, we combine Reinforcement Learning (RL) with Agent Based Modeling (ABM) in order to address the self-organizing dynamics of social segregation and explore the space of possibilities that emerge from considering different types of rewards. Our model promotes the creation of interdependencies and interactions among multiple agents of two different kinds that segregate from each other. For this purpose, agents use Deep Q-Networks to make decisions inspired on the rules of the Schelling Segregation model and rewards for interactions. Despite the segregation reward, our experiments show that spatial integration can be achieved by establishing interdependencies among agents of different kinds. They also reveal that segregated areas are more probable to host older people than diverse areas, which attract younger ones. Through this work, we show that the combination of RL and ABM can create an artificial environment for policy makers to observe potential and existing behaviors associated to rules of interactions and rewards.
Global distribution of epidemic-related Shiga toxin 2 encoding phages among enteroaggregative Escherichia coli
Authors: Kimata Keiko , Lee Kenichi , Watahiki Masanori , Isobe Junko , Ohnishi Makoto , Iyoda Sunao
Published: July 2020

Since the Shiga toxin-producing enteroaggregative Escherichia coli (Stx-EAEC) O104:H4 strain caused a massive outbreak across Europe in 2011, the importance of Stx-EAEC has attracted attention from a public health perspective. Two Stx-EAEC O86 isolates were obtained from patients with severe symptoms in Japan in 1999 and 2015. To characterize the phylogeny and pathogenic potential of these Stx-EAEC O86 isolates, whole-genome sequence analyses were performed by short-and long-read sequencing. Among genetically diverse E. coli O86, the Stx-EAEC O86 isolates were clustered with the EAEC O86:H27 ST3570 subgroup. Strikingly, there were only two loci with single nucleotide polymorphisms (SNPs) between the Stx2a phage of a Japanese O86:H27 isolate and that of the European epidemic-related Stx-EAEC O104:H4 isolate. These results provide evidence of global distribution of epidemic-related Stx2a phages among various lineages of E. coli with few mutations.
FMR1 mRNA from full mutation alleles is associated with ABC-CFX scores in males with fragile X syndrome
Authors: Baker Emma K. , Arpone Marta , Kraan Claudine , Bui Minh , Rogers Carolyn , Field Michael , Bretherton Lesley , Ling Ling , Ure Alexandra , Cohen Jonathan , Hunter Matthew F. , Santa María Lorena , Faundes Victor , Curotto Bianca , Morales Paulina , Trigo Cesar , Salas Isabel , Alliende Angelica , Amor David J. , Godler David E.
Published: July 2020

Fragile X syndrome (FXS) is caused by a hypermethylated full mutation (FM) expansion with ≥ 200 CGG repeats, and a decrease in FMR1 mRNA and its protein. However, incomplete silencing from FM alleles has been associated with more severe autism features in FXS males. This study compared scores on the Aberrant Behavior Checklist-Community-FXS version (ABC-CFX) in 62 males affected with FXS (3 to 32 years) stratified based on presence or absence of mosaicism and/or FMR1 mRNA silencing. Associations between ABC-CFX subscales and FMR1 mRNA levels, assessed using real-time PCR relative standard curve method, were also examined. The FXS group mosaic for premutation (PM: 55–199 CGGs) and FM alleles had lower irritability (p = 0.014) and inappropriate speech (p < 0.001) scores compared to males with only FM alleles and complete loss of FMR1 mRNA. The PM/FM mosaic group also showed lower inappropriate speech scores compared to the incomplete silencing (p = 0.002) group. Increased FMR1 mRNA levels were associated with greater irritability (p < 0.001), and lower health-related quality of life scores (p = 0.004), but only in the incomplete silencing FM-only group. The findings suggest that stratification based on CGG sizing and FMR1 mRNA levels may be warranted in future research and clinical trials utilising ABC-CFX subscales as outcome measures.
Assessing mandibular body changes in growing subjects: a comparison of CBCT and reconstructed lateral cephalogram measurements
Authors: Maspero Cinzia , Farronato Marco , Bellincioni Francesca , Cavagnetto Davide , Abate Andrea
Published: July 2020

The aim of this study is to compare cone-beam computed tomography (CBCT) and bi-dimensional reconstructed lateral cephalograms (RLCs) in assessing mandibular body length and growth and to evaluate how mandibular reshaping influences the error in measuring mandibular body growth in bi-dimensional radiographs. Twenty-five patients with two CBCT scans taken at a mean distance of 2.21 ± 0.5 years were selected. The following measurements were performed: right and left mandibular body length at each point in time, mandibular growth, inter-gonial distance and mandibular symphyseal angle. From each CBCT, an RLC was obtained, and mandibular body length and growth were measured. Data analysis revealed a statistically and clinically significant difference in CBCT and RLC regarding the mandibular length of each patient at each point in time. However, mandibular growth was almost identical. A linear regression was performed to predict growth distortion between RLCs and CBCT depending on the ratio between transverse and sagittal mandibular growth. The expected maximum and minimum distortion, however, appeared not to be significant. In fact, a second linear regression model and a Bland–Altman test revealed a strong correlation between measurements of average mandibular body growth by CBCT and RLCs. As the same distortion occurs in the first and second RLCs, bi-dimensional radiographs remain the method of choice in evaluating mandibular body growth.
Fibrinogen protects neutrophils from the cytotoxic effects of histones and delays neutrophil extracellular trap formation induced by ionomycin
Authors: Locke Matthew , Francis Robert J. , Tsaousi Evgenia , Longstaff Colin
Published: July 2020

Neutrophils are pivotal players in immune defence which includes a process of release of histones and DNA as neutrophil extracellular traps (NETs). Histones, while toxic to invading pathogens, also kill host cells, including neutrophils. Bacteria have evolved mechanisms to escape neutrophils, including the secretion of leucocidins (e.g. ionomycin). Live cell video microscopy showed how fibrinogen and fibrin influence NETosis and neutrophil responses to extracellular histones. Histones were rapidly lethal to neutrophils after binding to cells, but formation of fibrinogen/fibrin-histone aggregates prevented cell death. Histone cytotoxicity was also reduced by citrullination by peptidyl arginine deiminase 4, or digestion by serine proteases. Ionomycin and phorbol 12-myristate 13 acetate (PMA) are used to trigger NETosis. Fibrinogen was responsible for a second distinct mechanism of neutrophil protection after treatment with ionomycin. Fibrinogen clustered on the surface of ionomycin-stimulated neutrophils to delay NETosis; and blocking the β integrin receptor, αMβ2, abolished fibrinogen protection. Fibrinogen did not bind to or protect neutrophils stimulated with PMA. Fibrinogen is an acute phase protein that will protect exposed cells from damaging circulating histones or leucocidins; but fibrinogen depletion/consumption, as in trauma or sepsis will reduce protection. It is necessary to consider the role of fibrinogen in NETosis.
Structure and dynamics of the Pacific North Equatorial Subsurface Current
Authors: Li Xiang , Yang Ya , Li Rui , Zhang Linlin , Yuan Dongliang
Published: July 2020

The North Equatorial Subsurface Current (NESC) has recently been found to flow westward below the North Equatorial Countercurrent in the subsurface layer across the Pacific Ocean. The structure, water mass properties, and the dynamics of the NESC are studied using Argo profiles and geostrophic currents, combined with moored current meter observations. The mean westward geostrophic currents of the NESC has been validated with moored current meter measurements at 4.7° N, 142° E in the far western tropical Pacific Ocean. Sizable seasonal-to-interannual variability of the NESC is indicated by the observations, with strong transports in boreal summer and during La Niña events, whereas weak transports in boreal winter and during El Niño events. The water masses of the NESC appear to be the mixture of the North and South Pacific intermediate waters, with the waters immediately below the thermocline closer to the North than to the South Pacific waters. A simulation using a linear continuously stratified model of ocean circulation suggests that the mean NESC is forced by wind curl through low baroclinic mode responses of the ocean.