bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing for implicit emotion regulation in childhood
Authors: Uh Stepheni , Siugzdaite Roma , Anwyl-Irvine Alexander , Dalmaijer Edwin S. , Bignardi Giacomo , Smith Tess A. , Astle Duncan E. 
Published: December 2021

AbstractAlthough implicit emotion regulation is thought to be critical for psychosocial development and mental wellbeing, few studies have investigated the neural underpinnings of this form of emotion regulation in children. We used a modified emotional Go/NoGo block design fMRI task to explore the neural correlates of implicit emotion regulation and individual differences in a sample of 40 children (50% female, mean age = 8.65 ± 0.77). Conditions included happy, sad, neutral, and scrambled faces as implicit distractors within the actual Go/NoGo targets. We used a relatively standard preprocessing pipeline via fMRIprep, with T-contrasts for response inhibition and emotional effects, and a nonparametric multiple comparisons procedure, with SnPM, for our group-level analysis. There were multiple significant response inhibition effects, including larger NoGo vs Go activation in the IFG, insula, and MCC/ACC. Valence effects showed significantly greater right putamen activity for the Sad NoGo vs Go contrast and greater bilateral putamen and right pallidum activity for the Happy Go vs Sad Go contrast. These results provide preliminary findings of neural substrates, particularly the putamen, that may be associated with implicit emotion regulation in children.
Relatedness modulates reproductive competition among queens in ant societies with multiple queens
Authors: Helanterä Heikki , Ozan Martina , Sundström Liselotte 
Published: December 2021

AbstractReproductive sharing in animal groups with multiple breeders, insects and vertebrates alike, contains elements of both conflict and cooperation, and depends on both relatedness between co-breeders, as well as their internal and external conditions. We studied how queens of the ant Formica fusca adjust their reproductive efforts in response to experimental manipulations of the kin competition regime in their nest, as well as their own reproductive status. Queens respond to the presence of competitors by increasing their egg laying efforts, but only if the competitors are highly fecund and distantly related. Furthermore, queens only engage in cannibalism of eggs when the risk of erroneously destroying own offspring is absent. We demonstrate that queens of Formica fusca fine-tune their behaviours in response to kinship and fecundity of others as well as their own physiological state in an unusually precise manner.
Genome organization by SATB1 binding to base-unpairing regions (BURs) provides a scaffold for SATB1-regulated gene expression
Authors: Kohwi Yoshinori , Wong Xianrong , Grange Mari , Sexton Thomas , Richards Hunter W. , Kitagawa Yohko , Sakaguchi Shimon , Liang Ya-Chen , Chuong Cheng-Ming , Botchkarev Vladimir A. , Taniuchi Ichiro , Reddy Karen L. , Kohwi-Shigematsu Terumi 
Published: December 2021

AbstractMammalian genomes are organized by multi-level folding, yet how this organization contributes to cell type-specific transcription remain unclear. We uncovered that the nuclear protein SATB1 establishes two-tiered chromatin organization, one through indirect binding and another by direct binding of base-unpairing regions (BURs), which are genomic elements with high unwinding propensities. Published ChIP-seq datasets show SATB1 binding to highly accessible chromatin at enhancers and CTCF sites, but not to BURs. By employing urea ChIP-seq, which retains only directly bound protein:DNA complexes, we found that BURs, but not CTCF sites, are direct SATB1 binding targets. SATB1-bound BUR interactions with accessible chromatin can cross multiple topologically associated domains (TADs) and SATB1 is required for these megabase-scale interactions linked to cell type-specific gene expression. BURs are mainly found within lamina associated domains (LADs) sequestered at the nuclear lamina, but also in inter-LADs, and SATB1 binds a subset of BURs depending on cell type. Notably, despite the mutually exclusive SATB1-binding profiles uncovered by the two ChIP-seq methods, we found most peaks in both profiles are real and require SATB1. Together, we propose that SATB1 has functionally distinct modes of chromatin interaction by directly binding BURs to form a chromatin scaffold to which it indirectly tethers open chromatin. Such chromatin organization may provide a gene-regulatory network underlying cell type-specific gene expression.
Intracranial Electric Field Recording During Multichannel Transcranial Electrical Stimulation
Authors: Wang Minmin , Han Jiawei , Jiang Hongjie , Zhu Junming , Feng Wuwei , Chhatbar Pratik Y. , Zhang Jianmin , Zhang Shaomin 
Published: December 2021

AbstractBackgroundMultichannel transcranial electrical stimulation (tES) modeling and optimization have been widely studied in recent years. Its theoretical bases include quasi-static assumption and linear superposition. However, there is still a lack of direct in vivo evidence to validate the simulation model and theoretical assumptions.MethodsWe directly measured the multichannel tES-induced voltage changes with implanted stereotactic-electroencephalographic (sEEG) electrodes in 12 epilepsy subjects. By combining these measured data, we investigate the linear superposition and prediction accuracy of simulation models for multi-electrode stimulation and further compare the induced EF differences between transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS).ResultsOur in vivo measurements demonstrated that the multi-electrode tES-induced voltages were almost equal to the sum of the voltages generated independently by bipolar stimulation. Both measured voltages and electric fields obtained in vivo were highly correlated with the predicted values in our cohort (Voltages: r = 0.92, p < 0.001; electric fields: r = 0.74, p < 0.001). Under the same stimulation intensity, the tDCS-induced peak-zero voltages were highly correlated with the values of tACS (r = 0.99, p < 0.001; s = 0.99).ConclusionsThe in vivo measurements provides confirmatory results for linear superposition and quasi-static assumption within the human brain. Furthermore, we found that the individualized simulation model reliably predicted the multi-electrode tES-induced electric fields.
MOPower: an R-shiny application for the simulation and power calculation of multi-omics studies
Authors: Syed Hamzah , Otto Georg W , Kelberman Daniel , Bacchelli Chiara , Beales Philip L 
Published: December 2021

AbstractBackgroundMulti-omics studies are increasingly used to help understand the underlying mechanisms of clinical phenotypes, integrating information from the genome, transcriptome, epigenome, metabolome, proteome and microbiome. This integration of data is of particular use in rare disease studies where the sample sizes are often relatively small. Methods development for multi-omics studies is in its early stages due to the complexity of the different individual data types. There is a need for software to perform data simulation and power calculation for multi-omics studies to test these different methodologies and help calculate sample size before the initiation of a study. This software, in turn, will optimise the success of a study.ResultsThe interactive R shiny application MOPower described below simulates data based on three different omics using statistical distributions. It calculates the power to detect an association with the phenotype through analysis of n number of replicates using a variety of the latest multi-omics analysis models and packages. The simulation study confirms the efficiency of the software when handling thousands of simulations over ten different sample sizes. The average time elapsed for a power calculation run between integration models was approximately 500 seconds. Additionally, for the given study design model, power varied with the increase in the number of features affecting each method differently. For example, using MOFA had an increase in power to detect an association when the study sample size equally matched the number of features.ConclusionsMOPower addresses the need for flexible and user-friendly software that undertakes power calculations for multi-omics studies. MOPower offers users a wide variety of integration methods to test and full customisation of omics features to cover a range of study designs.
Electrical activity between skin cells regulates melanoma initiation
Authors: Tagore Mohita , Hergenreder Emiliano , Suresh Shruthy , Baron Maayan , Perlee Sarah C. , Melendez Stephanie , Hollmann Travis J. , Ideker Trey , Studer Lorenz , White Richard M. 
Published: December 2021

SummaryOncogenes can only initiate tumors in certain cellular contexts, which is referred to as oncogenic competence. In melanoma, whether cells in the microenvironment can endow such competence remains unclear. Using a combination of zebrafish transgenesis coupled with human tissues, we demonstrate that GABAergic signaling between keratinocytes and melanocytes promotes melanoma initiation by BRAFV600E. GABA is synthesized in melanoma cells, which then acts on GABA-A receptors on keratinocytes. Electron microscopy demonstrates synapse-like structures between keratinocytes and melanoma cells, and multi-electrode array analysis shows that GABA acts to inhibit electrical activity in melanoma/keratinocyte co-cultures. Genetic and pharmacologic perturbation of GABA synthesis abrogates melanoma initiation in vivo. These data suggest that electrical activity across the skin microenvironment determines the ability of oncogenes to initiate melanoma.
Time-resolved assessment of single-cell protein secretion by sequencing
Authors: Wu Tongjin , Womersley Howard John , Wang Jiehao , Scolnick Jonathan Adam , Cheow Lih Feng 
Published: December 2021

SUMMARYSecreted proteins play critical roles in cellular communication and functional orchestration. Methods enabling concurrent measurement of cellular protein secretion, phenotypes and transcriptomes are still unavailable. Here, we describe time-resolved assessment of protein secretion from single cells by sequencing (TRAPS-seq). Released proteins are trapped onto cell surface via affinity matrices, and the captured analytes together with phenotypic markers can be probed by oligonucleotide-barcoded antibodies and simultaneously sequenced with transcriptomes. We used TRAPS-seq to interrogate secretion dynamics of pleiotropic cytokines (IFN-γ, IL-2 and TNF-α) of early activated human T lymphocytes, unraveling limited correlation between cytokine secretion and its transcript abundance with regard to timing and strength. We found that early central memory T cells with CD45RA expression (TCMRA) are the most effective responders in multiple cytokine secretion, and polyfunctionality involves unique yet dynamic combinations of gene signatures over time. TRAPS-seq presents a useful tool for cellular indexing of secretions, phenotypes, and transcriptomes at single-cell resolution.
Self-confocal NIR-II fluorescence microscopy for in vivo imaging
Authors: Zhou Jing , Wu Tianxiang , Zhu Liang , Li Yifei , Chen Liying , Qian Jun 
Published: December 2021

AbstractBenefiting from low scatter of NIR-II light in biological tissues and high spatial resolution of confocal microscopy, NIR-II fluorescence confocal microscopy has been developed recently and achieve deep imaging in vivo. However, independence of excitation point and detection point makes this system difficult to be adjusted. New, improved, self-confocal NIR-II fluorescence confocal systems are created in this work. Based on a shared pinhole for excitation light and fluorescence, the system is easy and controlled to be adjusted. The fiber-pinhole confocal system is constructed for cerebrovascular and hepatocellular NIR-II fluorescence intensity imaging. The air-pinhole confocal system is constructed for cerebrovascular NIR-II fluorescence intensity imaging, hepatic NIR-II fluorescence lifetime imaging, and hepatic multiphoton imaging.
Towards mechanistic models of mutational effects: Deep Learning on Alzheimer’s Aβ peptide
Authors: Wang Bo , Gamazon Eric R. 
Published: December 2021

ABSTRACTAlzheimer’s Disease (AD) is a debilitating form of dementia with a high prevalence in the global population and a large burden on the community and health care systems. AD’s complex pathobiology consists of extracellular β-amyloid deposition and intracellular hyperphosphorylated tau. Comprehensive mutational analyses can generate a wealth of knowledge about protein properties and enable crucial insights into molecular mechanisms of disease. Deep Mutational Scanning (DMS) has enabled multiplexed measurement of mutational effects on protein properties, including kinematics and self-organization, with unprecedented resolution. However, potential bottlenecks of DMS characterization include experimental design, data quality, and the depth of mutational coverage. Here, we apply Deep Learning to comprehensively model the mutational effect of the AD-associated peptide Aβ42on aggregation-related biochemical traits from DMS measurements. Among tested neural network architectures, Convolutional Neural Networks (ConvNets) and Recurrent Neural Networks (RNN) are found to be the most cost-effective models with robust high performance even under insufficiently-sampled DMS studies. While sequence features are essential for satisfactory prediction from neural networks, geometric-structural features further enhance the prediction performance. Notably, we demonstrate how mechanistic insights into phenotype may be extracted from the neural networks themselves suitably designed. This methodological benefit is particularly relevant for biochemical systems displaying a strong coupling between structure and phenotype such as the conformation of Aβ42aggregate and nucleation, as shown here using a Graph Convolutional Neural Network (GCN) developed from the protein atomic structure input. In addition to accurate imputation of missing values (which here ranged up to 55% of all phenotype values at key residues), the mutationally-defined nucleation phenotype generated from a GCN shows improved resolution for identifying known disease-causing mutations relative to the original DMS phenotype. Our study suggests that neural network derived sequence-phenotype mapping can be exploited not only to provide direct support for protein engineering or genome editing but also to facilitate therapeutic design with the gained perspectives from biological modeling.
Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma
Authors: Yasumizu Yoshiaki , Ohkura Naganari , Murata Hisashi , Kinoshita Makoto , Funaki Soichiro , Nojima Satoshi , Kido Kansuke , Kohara Masaharu , Motooka Daisuke , Okuzaki Daisuke , Suganami Shuji , Takeuchi Eriko , Nakamura Yamami , Takeshima Yusuke , Arai Masaya , Tada Satoru , Okumura Meinoshin , Morii Eiichi , Shintani Yasushi , Sakaguchi Shimon , Okuno Tatsusada , Mochizuki Hideki 
Published: December 2021

AbstractMyasthenia gravis (MG) is a neurological disease caused by autoantibodies against neuromuscular-associated proteins. While MG is frequently developed in thymoma patients, the etiologic factors for MG are not well understood. Here, by constructing a comprehensive atlas of thymoma using bulk and single-cell RNA-seq, we identified ectopic expression of neuromuscular molecules in MG-associated thymoma (MG-thymoma). These molecules were originated from a distinct subpopulation of medullary thymic epithelial cells (mTECs), which we named neuromuscular mTECs (nmTECs). MG-thymoma also exhibited microenvironments dedicated to autoantibody production, including ectopic germinal center formation, T follicular helper cell accumulation, and type 2 conventional dendritic cell migration. Cell-cell interaction analysis also predicted the interaction between nmTECs and T/B cells viaCXCL12-CXCR4. The enrichment of nmTECs presenting neuromuscular molecules within MG-thymoma was further confirmed by immunohistochemically and by cellular composition estimation from MG-thymoma transcriptome. Altogether, this study suggests that nmTECs play a significant role in MG pathogenesis via ectopic expression of neuromuscular molecules.
PREVALENCE AND PREDICTORS OF STRESS AMONG COVID-19 HEALTH WORKERS IN KABWE DISTRICT- A CROSS SECTIONAL STUDY
Authors: Mukwasa L. L , Mutemwa R. , Zambwe M. , Nkhama E. , Chipimo P.J 
Published: December 2021

ABSTRACTOBJECTIVEThis study aimed at determining the magnitude of stress among COVID-19 health workers in Kabwe district.METHODSThe study was a cross-sectional study which recruited 138 health care workers managing COVID-19 cases in Kabwe. Data were collected through structured questionnaires and in-depth interviews. Quantitative data was analyzed using SPSS version 16 while qualitative data was analyzed using Nvivo8.RESULTSThe study obtained 100% responses from the respondents and the prevalence of stress among the respondents was 73%. The nurses were more perceived to experience stress compared to the pharmacy personnel (28% vs. 3%). Similarly, women displayed a higher likelihood of experiencing stress compared to men. Lack of support, increased workload and fear were among the factors leading to stress.CONCLUSIONThe study went out to determine stress among healthcare workers in Kabwe district. It was established that nurses were more vulnerable than groups. And women were found to be more stressed than men. It is therefore recommended that effective and meaningful interventions be put in place to mitigate the impact of long-term psychological distress and physical well-being in healthcare workers during the COVID-19 pandemic and future outbreaks.ARTICLE SUMMARYStrengths and limitations of the studyA cross-sectional study method was employed; it does not assist in determining the cause and effect, in addition, the timing of the snapshot may not guarantee representation of the situation overtime. Therefore, there may be need to evaluate the effects of the COVID-19 pandemic on health workers mental requirements using a longitudinal study design.There might have been bias from respondents as the outcomes were self-reported. However, irrespective of the aforementioned limitations, this is a novel study in Kabwe describing stress among health workers in the district during the COVID-19 pandemic.The study grants access to initial evidence on stress among health workers managing the COVID-19 pandemic in Kabwe district, with the expectation of drawing the attention to legislators, health facility supervisors and those involved in the response to COVID-19 or impending epidemics.
Comparing the Performance of HIV Rapid Diagnostic Tests used in Zambia - A Systematic Clinical Data Review
Authors: Mukuka L. , Theo A. , Zambwe M. , Chipimo P. J. 
Published: December 2021

ABSTRACTObjectiveTo investigate the performance of the HIV RDTs used in Zambia.Method2,564 participants aged between 15 and 95 years from two sites in Lusaka province years were tested on OraQuick ADVANCE, Abbot Determine™, and then confirmed on Uni-Gold™ Recombigen®. The data from the participants were analyzed using SPSS version 25.0.ResultsThe 3 RDTs when compared to the 4th generation Abbot Architect results had the following results: OraQuick ADVANCE®, Alere Determine and Uni-Gold Ultra, at 95% CI had Sensitivities of: 91.8%, 93.3% and 92.5% respectively. The specificities of OraQuick ADVANCE® and Uni-Gold were the same (100.0%; 95% CI: 98.8 -100.0) but slightly different from Alere Determine (99.8%). Positive predictive values at 95% CI were 100% for OraQuick ADVANCE® and Uni-Gold and 98.4% for Alere Determine. Negative predictive values (at 95% CIs) were 99.1, 99.2 and 99.1 for OraQuick ADVANCE®, Alere Determine, and Uni-Gold Ultra respectively. The results showed that these RDTs could only detect 12 out of every 13 HIV positive results.ConclusionThird generation RDTs are not effective in detecting acute positive cases. Fourth generation Rapid Tests are required to capture the positive cases being missed out.
VaxiMap: optimal delivery of vaccinations for housebound patients
Authors: Kirk Thomas F. , Barker Adam J. , Bodossian Armen , Staruch Robert 
Published: December 2021

AbstractBackgroundThroughout the UK’s Covid-19 vaccination campaign, responsibility for vaccinating housebound patients has rested with individual GP surgeries, posing them a difficult logistical challenge (the travelling salesman problem). In response to demand from GPs, and a lack of existing solutions tailored specifically to vaccination, VaxiMap was created. This tool provides optimal routes for vaccine delivery and has been free to all users since its inception in January 2021.MethodsVaxiMap generates optimal routes subject to the constraint that the number of patients per route should be fixed. This ensures that a known quantity of vaccine can be set aside for each route and minimises wastage. The user need only upload an Excel spreadsheet of patient postcodes to be visited. A divide-and-conquer approach of iterative k-means clustering followed by within-cluster route optimisation is used to generate the routes.FindingsWe find substantial savings in the time taken to plan vaccinations, as well as savings in the time taken to visit housebound patients. We estimate total savings to date of 4,700 hours of practitioner time, equivalent to 2.5 work-years, or approximately £91k at typical practitioner salaries.InterpretationThe adoption of VaxiMap yielded both time and cost savings for GP surgeries and accelerated the UK’s Covid-19 vaccination campaign at a critical moment.FundingFinancial support for VaxiMap was provided by Magdalen College, Oxford, Oxford University Innovation, and JHubMed, part of UK Strategic Command. These parties were not involved in the preparation of this manuscript.
Analysis of cutoff point estimation for determining seropositivity in the context of SARS-CoV-2 infections
Authors: Domingues Tiago Dias , Mouriño Helena , Sepúlveda Nuno 
Published: December 2021

AbstractIn this work will apply mixture models based on distributions from the SMSN family to antibody data against four SARS-CoV-2 virus antigens. Furthermore, since the true infection status of individuals is knowna priori, performance measures will be calculated for the methods proposed for cutoff point estimation such as sensitivity, specificity and accuracy. The results of a simulation study will also be presented.