bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haplotype Reconstruction in Connected Tetraploid F1 Populations
Authors: Zheng Chaozhi , Amadeu Rodrigo R. , Munoz Patricio R. , Endelman Jeffrey B. 
Published: December 2020

AbstractIn diploid species, many multi-parental populations have been developed to increase genetic diversity and quantitative trait loci (QTL) mapping resolution. In these populations, haplotype reconstruction has been used as a standard practice to increase QTL detection power in comparison with the marker-based association analysis. To realize similar benefits in tetraploid species (and eventually higher ploidy levels), a statistical framework for haplotype reconstruction has been developed and implemented in the software PolyOrigin for connected tetraploid F1 populations with shared parents. Haplotype reconstruction proceeds in two steps: first, parental genotypes are phased based on multi-locus linkage analysis; second, genotype probabilities for the parental alleles are inferred in the progeny. PolyOrigin can utilize genetic marker data from single nucleotide polymorphism (SNP) arrays or from sequence-based genotyping; in the latter case, bi-allelic read counts can be used (and are preferred) as input data to minimize the influence of genotype call errors at low depth. To account for errors in the input map, PolyOrigin includes functionality for filtering markers, inferring inter-marker distances, and refining local marker ordering. Simulation studies were used to investigate the effect of several variables on the accuracy of haplotype reconstruction, including the mating design, the number of parents, population size, and sequencing depth. PolyOrigin was further evaluated using an autotetraploid potato dataset with a 3×3 half-diallel mating design. In conclusion, PolyOrigin opens up exciting new possibilities for haplotype analysis in tetraploid breeding populations.
Interneuron origins in the embryonic porcine medial ganglionic eminence
Authors: Casalia Mariana L. , Li Tina , Ramsay Harrison , Ross Pablo J. , Paredes Mercedes F. , Baraban Scott C. 
Published: December 2020

Interneurons contribute to the complexity of neural circuits and maintenance of normal brain function. Rodent interneurons originate in embryonic ganglionic eminences, but developmental origins in other species are less understood. Here, we show that transcription factor expression patterns in porcine embryonic subpallium are similar to rodents, delineating a distinct medial ganglionic eminence (MGE) progenitor domain. On the basis of Nkx2.1, Lhx6 and Dlx2 expression,in vitrodifferentiation into neurons expressing GABA and robust migratory capacity in explant assays, we propose that cortical and hippocampal interneurons originate from a porcine MGE region. Following xenotransplantation into adult male and female rat hippocampus, we further demonstrate that porcine MGE progenitors, like those from rodents, migrate and differentiate into morphologically distinct interneurons expressing GABA. Our findings reveal that basic rules for interneuron development are conserved across species, and that porcine embryonic MGE progenitors could serve as a valuable source for interneuron-based xenotransplantation therapies.Significance StatementHere we demonstrate that porcine MGE, like rodents, exhibit a distinct transcriptional and pallial interneuron-specific antibody profile,in vitromigratory capacity and are amenable to xenotransplantation. This is the first comprehensive examination of embryonic pallial interneuron origins in the pig, and because a rich neurodevelopmental literature on embryonic mouse MGE exists (with some additional characterizations in other species like monkey and human) our work allows direct neurodevelopmental comparisons with this literature.
Optimizing ventilation cycles to control airborne transmission risk of SARS-CoV2 in school classrooms
Authors: Zivelonghi Alessandro , Lai Massimo 
Published: December 2020

AbstractOpen schools in winter in highly epidemic areas pose a controversial issue: ventilation of classrooms (an essential mitigation factor for airborne transmission) is expected to sensibly decrease due to outdoor temperatures getting colder and regulators going to allow less restrictive policies on windows closure. Fundamental questions to be addressed are therefore: to which extent can we contain airborne transmission risk in schools? what would be the optimal ventilation strategy during the cold season considering the fact that most schools are not provided with mechanical ventilation systems? To try answering these questions a risk model for airborne transmission of covid-19 in classrooms has been develped based on previous models for tubercolosis and influenza. The separate cases of infective student and infective teacher, as well as infective teacher with microphone are investigated. We explored 3500 different air ventilation cycles for different lesson+break times and carried out a numerical optimization of the risk function. Safety risk-zones for breaks and lessons durations were estimated combining the effect of surgical masks and optimal windows opening cycles.
SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe
Authors: Pedersen Eva SL , Goutaki Myrofora , Harris Amanda L , Dixon Lucy , Manion Michele , Rindlisbacher Bernhard ,   COVID-PCD patient advisory group, Lucas Jane S , Kuehni Claudia E 
Published: December 2020

AbstractPeople with pre-existing chronic health conditions are reportedly at high risk of getting the coronavirus disease (COVID-19) and of having a severe disease course but little data exist on rare diseases such as Primary Ciliary Dyskinesia (PCD). We studied risk and severity of SARS-CoV-2 infections among people with PCD using data from the COVID-PCD, a participatory study that collects data in real-time directly from people with PCD. Data was collected using online questionnaires. A baseline questionnaire collected information on demographic data, information about the PCD diagnosis and severity. A short weekly questionnaire collected information about current symptoms and incident SARS-CoV-2 infections. 578 people participated in the COVID-PCD by December 7, 2020, with a median number of follow-up weeks of 9 (interquartile range: 4-19 weeks). 256 (45%) of the participants had been tested for SARS-CoV-2 and 12 tested positive prior to study entry or during study follow up (2.1% of the total included population, 95% confidence interval (CI) 1.1-3.6%). 4 people tested positive during the study follow-up, corresponding to an incidence rate of 2.5 per 100 person-years (95% CI: 0.9-6.5). Overall, reported severity was mild with two reporting no symptoms, eight reporting mild symptoms, one reporting severe symptom without hospitalisation, and one reporting hospitalisation for 9 days. The study suggests that with careful personal protection, people with PCD do not seem to have an increased risk of infection with SARS-COV-2, nor an especially severe disease course.Take home messageIn this longitudinal study of people with PCD followed weekly via online questionnaires, the incidence rate of COVID-19 and the proportion of participants infected were low, and the observed severity mostly mild.
Polaratio: A magnitude-contingent monotonic correlation metric and its improvements to scRNA-seq clustering
Authors: Wang Victor , Cicalese Pietro Antonio , Louis Sam Titus Anto Sam Crosslee , Mohan Chandra 
Published: December 2020

ABSTRACTMotivationSingle-cell RNA sequencing (scRNA-seq) technologies and analysis tools have allowed researchers to achieve remarkably detailed understandings of the roles and relationships between cells and genes. However, conventional distance metrics, such as Euclidean, Pearson, and Spearman distances, fail to simultaneously take into account the high dimensionality, monotonicity, and magnitude of gene expression data. To address several shortcomings in these commonly used metrics, we present a magnitude-contingent monotonic correlation metric called Polaratio which is designed to enhance the quality of scRNA-seq data analysis.ResultsWe integrate three interpretable clustering algorithms – Single-Cell Consensus Clustering (SC3), Hierarchical Clustering (HC), and K-Medoids (KM) – through a consensus cell clustering procedure, which we evaluate on various biological datasets to benchmark Polaratio against several well-known metrics. Our results demonstrate Polaratio’s ability to improve the accuracy of cell clustering on 5 out of 7 publicly available datasets.Availabilityhttps://github.com/dubai03nsr/PolaratioContactpcicalese@uh.edu
The CP110-CEP97-CEP290 module orchestrates a centriolar satellite dependent response to proteotoxic stress
Authors: Prosser Suzanna L. , Tkach Johnny , Gheiratmand Ladan , Morrison Ciaran G. , Pelletier Laurence 
Published: December 2020

ABSTRACTProtein degradation at the centrosome, the primary microtubule organizing centre of the cell, is critical to a myriad of cellular processes. Perturbation of the ubiquitin proteasome system causes the formation of an inclusion, or aggresome, at the centrosome. By systematic microscopy analysis, we have placed a subset of centrosomal proteins within the aggresome. Centriolar satellites, proteinaceous granules found in the vicinity of centrosomes, also became incorporated into this structure. Through high-resolution quantitative analysis, we have defined aggresome assembly at the centrosome, demonstrating a requirement for satellites in this process. Furthermore, a module consisting of CP110-CEP97-CEP290 was required to recruit aggresome components early in the pathway and senescent cells were defective in aggresome formation due to limiting amounts of CP110. Finally, satellites and the CP110-CEP97-CEP290 module were required for the aggregation of mutant huntingtin. The accumulation of protein aggregates is central to the pathology of a range of human disorders. These data thereby reveal new roles for CP110, its interactors, and centriolar satellites in controlling cellular proteostasis and the aggregation of disease relevant proteins.
Quantitative Control of Noise in Mammalian Gene Expression by Dynamic Histone Regulations
Authors: Tan Deng , Chen Rui , Mo Yuejian , Xu Wei , Lu Xibin , He Huiyu , Gu Shu , Jiang Fan , Fan Weimin , Wang Yilin , Chen Xi , Huang Wei 
Published: December 2020

AbstractFluctuation (‘noise’) in gene expression is critical for mammalian cellular processes. Numerous mechanisms contribute to its origins, yet large noises induced by single transcriptional activator species remain to be experimentally understood. Here, we combined the dynamic regulation of transcriptional activator binding, histone regulator inhibitors, and single-cell quantification of chromatin accessibility, mRNA, and protein to probe putative mechanisms. Using a light-induced expression system, we show that the transcriptional activator forms a positive feedback loop with histone acetyltransferases CBP/p300. It generates epigenetic bistability in H3K27ac, which contributes to large noise. Disable of the positive feedback loop by CBP/p300 and HDAC4/5 inhibitors also reduces heterogeneity in endogenous genes, suggesting a universal mechanism. We showed that the noise was reduced by pulse-wide modulation of transcriptional activator binding due to alternating the system between high and low monostable states. Our findings could provide a mechanism-based approach to modulate noise in synthetic and endogenous gene expressions.
Cross-covariance isolate detect: a new change-point method for estimating dynamic functional connectivity
Authors: Anastasiou Andreas , Cribben Ivor , Fryzlewicz Piotr 
Published: December 2020

AbstractEvidence of the non stationary behavior of functional connectivity (FC) networks has been observed in task based functional magnetic resonance imaging (fMRI) experiments and even prominently in resting state fMRI data. This has led to the development of several new statistical methods for estimating this time-varying connectivity, with the majority of the methods utilizing a sliding window approach. While computationally feasible, the sliding window approach has several limitations. In this paper, we circumvent the sliding window, by introducing a statistical method that finds change-points in FC networks where the number and location of change-points are unknown a priori. The new method, calledcross-covariance isolate detect(CCID), detects multiple change-points in the second-order (cross-covariance or network) structure of multivariate, possibly high-dimensional time series. CCID allows for change-point detection in the presence of frequent changes of possibly small magnitudes, can assign change-points to one or multiple brain regions, and is computationally fast. In addition, CCID is particularly suited to task based data, where the subject alternates between task and rest, as it firstly attempts isolation of each of the change-points within subintervals, and secondly their detection therein. Furthermore, we also propose a new information criterion for CCID to identify the change-points. We apply CCID to several simulated data sets and to task based and resting state fMRI data and compare it to recent change-point methods. CCID may also be applicable to electroencephalography (EEG), magentoencephalography (MEG) and electrocorticography (ECoG) data. Similar to other biological networks, understanding the complex network organization and functional dynamics of the brain can lead to profound clinical implications. Finally, the R packageccidimplementing the method from the paper is available from CRAN.
Alternate Grainy head isoforms regulateDrosophilamidgut intestinal stem cell differentiation
Authors: Dominado Nicole , Casagranda Franca , Heaney James , Siddall Nicole A. , Abud Helen E. , Hime Gary R. 
Published: December 2020

AbstractRegeneration of theDrosophilamidgut epithelium depends upon differential expression of transcription factors in intestinal stem cells and their progeny. Thegrainy headlocus produces multiple splice forms that result in production of two classes of transcription factor, designated Grh.O and Grh.N.grainy headexpression is associated with epithelial tissue and has roles in epidermal development and regeneration but had not been examined for a function in the midgut epithelium. Null mutant clones had a limited effect on intestinal stem cell (ISC) maintenance and proliferation, but specific loss of the Grh.O isoform results in loss of ISCs from the epithelium. This was confirmed by generation of a new Grh.O mutant to control for genetic background effects. Grh.O mutant ISCs were not lost due to cell death but were forced to differentiate. Ectopic expression of the Grh.N isoform also resulted in ISC differentiation suggesting that the two isoforms act in an opposing manner. Grh.O expression must be tightly regulated as high-level ectopic expression in enteroblasts, but not ISCs, resulted in cells with confused identity and promoted excess proliferation in the epithelium. Thus, midgut regeneration is not only dependent upon signalling pathways that regulate transcription factor expression, but also upon regulated mRNA splicing of these genes.
Spatiotemporal modelling and mapping of cervical cancer incidence among HIV positive women in South Africa: A nationwide study
Authors: Tafadzwa Dhokotera , Julien Riou , Lina Bartels , Eliane Rohner , Frederique Chammartin , Leigh Johnson , Elvira Singh , Victor Olago , Mazvita Muchengeti , Matthias Egger , Julia Bohlius , Garyfallos Konstantinoudis 
Published: December 2020

AbstractDisparities in invasive cervical cancer (ICC) incidence exist globally, particularly in HIV positive women who are at elevated risk compared to HIV negative women. We aimed to determine the spatial, temporal, and spatiotemporal incidence of ICC and the associated factors among HIV positive women in South Africa. We included ICC cases in women diagnosed with HIV from the South African HIV cancer match study during 2004-2014. We used the Thembisa model to estimate women diagnosed with HIV per municipality, age group and calendar year. We fitted Bayesian hierarchical models to estimate the spatiotemporal distribution of ICC incidence among women diagnosed with HIV. We also examined the association of deprivation, access to health (using the number of health facilities per municipality) and urbanicity with ICC incidence. We included 17,821 ICC cases and demonstrated a decreasing trend in ICC incidence, from 306 to 312 in 2004 and from 160 to 191 in 2014 per 100,000 person-years across all corrections. The spatial relative rate (RR) ranged from 0.27 to 4.43. In the model adjusting for covariates, the most affluent municipalities had a RR of 3.18 (95% Credible Interval 1.82, 5.57) compared to the least affluent ones, and municipalities with better access to health care had a RR of 1.52 (1.03, 2.27) compared to municipalities with worse access to health. More efforts should be made to ensure equitable access to health services, including mitigating physical barriers, such as transportation to health centres and strengthening of screening programmes.Novelty and ImpactThis is the first nationwide study in South Africa to evaluate spatial and spatiotemporal distribution of cervical cancer in women diagnosed with HIV. The results show an increased incidence of cervical cancer in affluent municipalities and in those with better access to health care. This is likely driven by better access to health care in more affluent areas. More efforts should be made to ensure equitable access to health services, including mitigating physical barriers.
Telehealth Applied to Deliver In-situ Behavioral Skills Training to Reduce Car Seat Misuse During the Covid-19 Pandemic
Authors: DeCarli James M. 
Published: December 2020

AbstractObjectiveThe use of telehealth has been a common approach to deliver health education before and during the COVID-19 pandemic. However, its ability to apply behavioral skills training (BST) for CRS education has been undocumented. This study assessed the efficacy of telehealth to deliver in-situ behavioral skills training (BST) to teach expectant parents how to install and use their child restraint system (CRS) to reduce misuse and improve retention during the COVID-19 pandemic.MethodA repeated measures group design was used to evaluate 171 individual participants, in a 37-step CRS task analysis for baseline, BST, and follow-up. Performance across all participants was aggregated for each task analysis. Participants were recruited from National Highway Traffic Safety Administration car seat fitting stations during the Covid-19 pandemic between March through July, 2020.ResultsBaseline results identified significant critical misuse across participants. With BST, delivered with telehealth, misuse decreased by 97% among 37 task objectives. A 2-week follow-up evaluation concluded that 100% of participants retained the skills they mastered during BST.ConclusionsThis study suggests the use of telehealth, as a method of BST delivery for CRS education, is an effective approach to reduce CRS misuse and the burden of child occupant motor vehicle injury. It was found to empower participants and improve their self-confidence, while ensuring the safety of their child occupant. While it was found to be an effective approach for expectant parents during the COVID-19 pandemic, it also has broader child passenger safety program and train-the-trainer implications beyond the COVID-19 pandemic.
Simultaneous in vitro simulation of multiple antimicrobial agents with different elimination half-lives in a pre-clinical infection model
Authors: Kesisoglou Iordanis , Eales Brianna M , Ledesma Kimberly R. , Merlau Paul R. , Tam Vincent H , Wang Weiqun , Nikolaou Michael 
Published: December 2020

AbstractCombination therapy for treatment of multi-drug resistant bacterial infections is becoming increasingly common. In vitro testing of drug combinations under realistic pharmacokinetic conditions is needed before a corresponding combination is eventually put into clinical use. The current standard for in vitro simulation of the pharmacokinetics of two drugs with distinct elimination half-lives cannot be extended for combinations of three or more agents, posing a growing need. To address that need we develop a general method to design an in vitro model for simultaneous simulation of the kinetics of an arbitrary number ofNdrugs with different half-lives. The method developed entails two possible configurations: (a) An in-series configuration, which generalizes the standard two-drug design forNdrugs and offers additional flexibility even for two drugs, and (b) an in-parallel configuration, which is new, and offers yet additional flexibility over the in-series configuration. Corresponding design equations for sizing and operation of each configuration are rigorously developed for immediate use by experimenters. These equations were used for experimental verification using a combination of three antibiotics with distinctly different half-lives (meropenem, ceftazidime, and levofloxacin). While experimental verification involved antibiotics, the method is applicable to any anti-infective or anti-cancer drugs with distinct elimination pharmacokinetics. With increasing importance of in vitro simulation of the kinetics of an arbitrary number of drugs in combination, the methods developed here are an important new tool for the design of such in vitro models.
Multicohort Analysis of Publicly-available Monocyte Expression Data Identifies Gene Signatures to Accurately Monitor Subset-specific Changes in Human Diseases
Authors: Vallania Francesco , Zisman Liron , Macaubas Claudia , Hung Shu-Chen , Rajasekaran Narendiran , Mason Sonia , Graf Jonathan , Nakamura Mary , Mellins Elizabeth D , Khatri Purvesh 
Published: December 2020

Monocytes and monocyte-derived cells play important roles in the regulation of inflammation, both as precursors as well as effector cells. Monocytes are heterogeneous and characterized by three distinct subsets in humans. Classical and non-classical monocytes represent the most abundant subsets, each carrying out distinct biological functions. Consequently, altered frequencies of different subsets have been associated with inflammatory conditions, such as infections and autoimmune disorders including lupus, rheumatoid arthritis, inflammatory bowel disease, and, more recently, COVID-19. Dissecting the contribution of different monocyte subsets to disease is currently limited by samples and cohorts, often resulting in underpowered studies and, consequently, poor reproducibility. Public transcriptomes provide an alternative source of data characterized by high statistical power and real world heterogeneity. However, most transcriptome datasets profile bulk blood or tissue samples, requiring the use ofin silicoapproaches to quantify changes in the levels of specific cell types.Here, we integrated 853 publicly available microarray expression profiles of sorted human monocyte subsets from 45 independent studies to identify robust and parsimonious gene expression signatures, consisting of 10 genes specific to each subset. These signatures, although derived using only datasets profiling healthy individuals, maintain their accuracy independent of the disease state in an independent cohort profiled by RNA-sequencing (AUC = 1.0). Furthermore, we demonstrate that our signatures are specific to monocyte subsets compared to other immune cells such as B, T, dendritic cells (DCs) and natural killer (NK) cells (AUC = 0.87~0.88, p<2.2e-16). This increased specificity results in estimated monocyte subset levels that are strongly correlated with cytometry-based quantification of cellular subsets (r = 0.69, p = 6.7e-4). Consequently, we show that these monocyte subset-specific signatures can be used to quantify changes in monocyte subsets levels in expression profiles from patients in clinical trials. Finally, we show that proteins encoded by our signature genes can be used in cytometry-based assays to specifically sort monocyte subsets. Our results demonstrate the robustness, versatility, and utility of our computational approach and provide a framework for the discovery of new cellular markers.