bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of generalised DKI approach for brain glioma grading
Authors: Pogosbekian E.L. , Pronin I.N. , Zakharova N.E. , Batalov A.I. , Turkin A.M. , Konakova T.A. , Maximov I.I. 
Published: September 2020

AbstractPurposeAn accurate differentiation of brain glioma grade constitutes an important clinical issue. Powerful non-invasive approach based on diffusion MRI has already demonstrated its feasibility in glioma grade stratification. However, the conventional diffusion tensor (DTI) and kurtosis imaging (DKI) demonstrated moderate sensitivity and performance in glioma grading. In the present work, we apply generalised DKI (gDKI) approach in order to assess its diagnostic accuracy and potential application in glioma grading.MethodsDiffusion scalar metrics were obtained from 50 patients with different glioma grades confirmed by histological tests following biopsy or surgery. All patients were divided into two groups with low- and high-grade gliomas as II grade versus III and IV grades, respectively. For a comparison, trained radiologists segmented the brain tissue into three regions with solid tumour, oedema, and normal appearing white matter. For each region we estimated the conventional and gDKI metrics including DTI maps.ResultsWe found high correlations between DKI and gDKI metrics in high-grade glioma. Further, gDKI metrics enabled introduction of a complementary measure for glioma differentiation based on correlations between the conventional and generalised approaches. Both conventional and generalised DKI metrics showed quantitative maps of tumour heterogeneity and oedema behaviour. gDKI approach demonstrated largely similar sensitivity and specificity in low-high glioma differentiation as in the case of conventional DKI method.ConclusionThe generalised diffusion kurtosis imaging enables differentiation of low and high grade gliomas at the same level as the conventional DKI. Additionally, gDKI exhibited higher tissue contrast between tumour and healthy tissue and, thus, may contribute as a complementary source of information on tumour heterogeneity.
Mapping Isoform Abundance and Interactome of the Endogenous TMPRSS2-ERG Fusion Protein with Orthogonal Immunoprecipitation-Mass Spectrometry Assays
Authors: Fu Zhiqiang , Rais Yasmine , Chris Le X. , Drabovich Andrei P. 
Published: September 2020

SummaryTMPRSS2-ERG gene fusion, a molecular alteration driving nearly a half of prostate cancer cases, has been intensively characterized at the transcript level, while limited studies explored the molecular identity and function of the endogenous fusion at the protein level. Here, we developed and applied immunoprecipitation-mass spectrometry (IP-MS) assays for the measurement of a low-abundance T1E4 TMPRSS2-ERG fusion protein, its isoforms and its interactome in VCaP prostate cancer cells. IP-MS assays quantified total ERG (∼27,000 copies/cell) and its four unique isoforms, and revealed that the T1E4-ERG isoform accounts for 71% of the total ERG protein in VCaP cells. For the first time, the N-terminal peptide (methionine-truncated and N-acetylated TASSSSDYGQTSK) unique for the T1/E4 fusion was identified and quantified. IP-MS with the C-terminal antibodies identified 29 proteins in the ERG interactome, including SWI/SNF chromatin remodeling complex subunits and numerous transcriptional co-regulators. Our data also suggested that TMPRSS2-ERG protein-protein interactions were exerted through at least two different regions. Knowledge on the distinct TMPRSS2-ERG protein isoforms and interactomes may facilitate development of more accurate diagnostics and targeted therapeutics of prostate cancer.
Eye-head coordination and dynamic visual scanning as indicators of visuo-cognitive demands in driving simulator
Authors: Mikula Laura , Mejía-Romero Sergio , Chaumillon Romain , Patoine Amigale , Lugo Eduardo , Bernardin Delphine , Faubert Jocelyn 
Published: September 2020

AbstractDriving is an everyday task involving a complex interaction between visual and cognitive processes. As such, an increase in the cognitive and/or visual demands can lead to a mental overload which can be detrimental for driving safety. Compiling evidence suggest that eye and head movements are relevant indicators of visuo-cognitive demands and attention allocation. This study aims to investigate the effects of visual degradation on eye-head coordination as well as visual scanning behavior during a highly demanding task in a driving simulator. A total of 21 emmetropic participants (21 to 34 years old) performed dual-task driving in which they were asked to maintain a constant speed on a highway while completing a visual search and detection task on a navigation device. Participants did the experiment with optimal vision and with contact lenses that introduced a visual perturbation (myopic defocus). The results indicate modifications of eye-head coordination and the dynamics of visual scanning in response to the visual perturbation induced. More specifically, the head was more involved in horizontal gaze shifts when the visual needs were not met. Furthermore, the evaluation of visual scanning dynamics, based on time-based entropy which measures the complexity and randomness of scanpaths, revealed that eye and gaze movements became less explorative and more stereotyped when vision was not optimal. These results provide evidence for a reorganization of both eye and head movements in response to increasing visual-cognitive demands during a driving task. Altogether, these findings suggest that eye and head movements can provide relevant information about visuo-cognitive demands associated with complex tasks. Ultimately, eye-head coordination and visual scanning dynamics may be good candidates to estimate drivers’ workload and better characterize risky driving behavior.
Kinetics of self-assembly of inclusions due to lipid membrane thickness interactions
Authors: Liao Xinyu , Purohit Prashant K. 
Published: September 2020

AbstractSelf-assembly of proteins on lipid membranes underlies many important processes in cell biology, such as, exo- and endo-cytosis, assembly of viruses, etc. An attractive force that can cause self-assembly is mediated by membrane thickness interactions between proteins. The free energy profile associated with this attractive force is a result of the overlap of thickness deformation fields around the proteins. The thickness deformation field around proteins of various shapes can be calculated from the solution of a boundary value problem and is relatively well understood. Yet, the time scales over which self-assembly occurs has not been explored. In this paper we compute this time scale as a function of the initial distance between two inclusions by viewing their coalescence as a first passage time problem. The first passage time is computed using both Langevin dynamics and a partial differential equation, and both methods are found to be in excellent agreement. Inclusions of three different shapes are studied and it is found that for two inclusions separated by about hundred nanometers the time to coalescence is hundreds of milliseconds irrespective of shape. Our Langevin dynamics simulation of self-assembly required an efficient computation of the interaction energy of inclusions which was accomplished using a finite difference technique. The interaction energy profiles obtained using this numerical technique were in excellent agreement with those from a previously proposed semi-analytical method based on Fourier-Bessel series. The computational strategies described in this paper could potentially lead to efficient methods to explore the kinetics of self-assembly of proteins on lipid membranes.Author summarySelf-assembly of proteins on lipid membranes occurs during exo- and endo-cytosis and also when viruses exit an infected cell. The forces mediating self-assembly of inclusions on membranes have therefore been of long standing interest. However, the kinetics of self-assembly has received much less attention. As a first step in discerning the kinetics, we examine the time to coalescence of two inclusions on a membrane as a function of the distance separating them. We use both Langevin dynamics simulations and a partial differential equation to compute this time scale. We predict that the time to coalescence is on the scale of hundreds of milliseconds for two inclusions separated by about hundred nanometers. The deformation moduli of the lipid membrane and the membrane tension can affect this time scale.
Inferring microbial co-occurrence networks from amplicon data: a systematic evaluation
Authors: Kishore Dileep , Birzu Gabriel , Hu Zhenjun , DeLisi Charles , Korolev Kirill S. , Segrè Daniel 
Published: September 2020

AbstractMicrobes tend to organize into communities consisting of hundreds of species involved in complex interactions with each other. 16S ribosomal RNA (16S rRNA) amplicon profiling provides snapshots that reveal the phylogenies and abundance profiles of these microbial communities. These snapshots, when collected from multiple samples, have the potential to reveal which microbes co-occur, providing a glimpse into the network of associations in these communities. The inference of networks from 16S data is prone to statistical artifacts. There are many tools for performing each step of the 16S analysis workflow, but the extent to which these steps affect the final network is still unclear. In this study, we perform a meticulous analysis of each step of a pipeline that can convert 16S sequencing data into a network of microbial associations. Through this process, we map how different choices of algorithms and parameters affect the co-occurrence network and estimate steps that contribute most significantly to the variance. We further determine the tools and parameters that generate the most accurate and robust co-occurrence networks based on comparison with mock and synthetic datasets. Ultimately, we develop a standardized pipeline (available athttps://github.com/segrelab/MiCoNE) that follows these default tools and parameters, but that can also help explore the outcome of any other combination of choices. We envisage that this pipeline could be used for integrating multiple data-sets, and for generating comparative analyses and consensus networks that can help understand and control microbial community assembly in different biomes.ImportanceTo understand and control the mechanisms that determine the structure and function of microbial communities, it is important to map the interrelationships between its constituent microbial species. The surge in the high-throughput sequencing of microbial communities has led to the creation of thousands of datasets containing information about microbial abundances. These abundances can be transformed into networks of co-occurrences across multiple samples, providing a glimpse into the structure of microbiomes. However, processing these datasets to obtain co-occurrence information relies on several complex steps, each of which involves multiple choices of tools and corresponding parameters. These multiple options pose questions about the accuracy and uniqueness of the inferred networks. In this study, we address this workflow and provide a systematic analysis of how these choices of tools and parameters affect the final network, and on how to select those that are most appropriate for a particular dataset.
Respiratory disease in cats associated with human-to-cat transmission of SARS-CoV-2 in the UK
Authors: Hosie Margaret J , Epifano Ilaria , Herder Vanessa , Orton Richard J , Stevenson Andrew , Johnson Natasha , MacDonald Emma , Dunbar Dawn , McDonald Michael , Howie Fiona , Tennant Bryn , Herrity Darcy , Da Silva Filipe Ana , Streicker Daniel G , Willett Brian J , Murcia Pablo R , Jarrett Ruth F , Robertson David L , Weir William ,   the COVID-19 Genomics UK (COG-UK) consortium
Published: September 2020

AbstractTwo cats from different COVID-19-infected households in the UK were found to be infected with SARS-CoV-2 from humans, demonstrated by immunofluorescence,in situhybridisation, reverse transcriptase quantitative PCR and viral genome sequencing. Lung tissue collected post-mortem from cat 1 displayed pathological and histological findings consistent with viral pneumonia and tested positive for SARS-CoV-2 antigens and RNA. SARS-CoV-2 RNA was detected in an oropharyngeal swab collected from cat 2 that presented with rhinitis and conjunctivitis. High throughput sequencing of the virus from cat 2 revealed that the feline viral genome contained five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS-CoV-2 sequence. An analysis of cat 2’s viral genome together with nine other feline-derived SARS-CoV-2 sequences from around the world revealed no shared catspecific mutations. These findings indicate that human-to-cat transmission of SARS-CoV-2 occurred during the COVID-19 pandemic in the UK, with the infected cats developing mild or severe respiratory disease. Given the versatility of the new coronavirus, it will be important to monitor for human-to-cat, cat-to-cat and cat-to-human transmission.
Sex-specific effects ofin vitrofertilization on adult metabolic phenotypes and hepatic transcriptomic and proteomic pathways in mouse
Authors: Narapareddy Laren , Rhon-Calderon Eric A. , Vrooman Lisa A. , Baeza Josue , Nguyen Duy K. , Lan Yemin , Garcia Benjamin A. , Schultz Richard M. , Bartolomei Marisa S. 
Published: September 2020

AbstractAlthoughin vitrofertilization (IVF) is associated with adverse perinatal outcomes, an increasing concern is the long-term health implications. We augmented our IVF mouse model to longitudinally investigate cardiometabolic outcomes in offspring from optimal neonatal litter sizes. We found that IVF-conceived females had higher body weight and cholesterol levels compared to naturally-conceived females, whereas IVF-conceived males had higher levels of triglycerides and insulin, and increased body fat composition. Through transcriptomics and proteomics of adult liver, we identified sexually-dimorphic dysregulation of the sterol regulatory element binding protein (SREBP) pathways that are associated with the sex-specfic phenotypes. We also found that global loss of DNA methylation in placenta was linked to higher cholesterol levels in IVF-conceived females. Our findings indicate that IVF procedures have long-lasting sex-specific effects on metabolic health of offspring and lay the foundation to utilize the placenta as a predictor of long-term outcomes.
Increased mGlu5 mRNA expression in BLA glutamate neurons facilitates resilience to the long-term effects of a single predator scent stress exposure
Authors: Shallcross John , Wu Lizhen , Knackstedt Lori A. , Schwendt Marek 
Published: September 2020

AbstractPost-traumatic stress disorder (PTSD) develops in a subset of individuals exposed to a trauma with core features being increased anxiety, and impaired fear extinction. To model the heterogeneity of PSTD behavioral responses, we exposed Sprague-Dawley rats to predator scent stress (TMT) once for 10 minutes and then tested for anxiety-like behavior 7 days later using the elevated plus-maze and acoustic startle response. Rats displaying anxiety-like behavior in both tasks were classified as stress-Susceptible, and rats exhibiting behavior no different from unstressed Controls were classified as stress-Resilient. Our previous findings revealed increased mRNA expression of mGlu5 in the amygdala and PFC and CB1R mRNA in the amygdala of Resilient rats. Here, we performed fluorescent in situ hybridization (FISH) to determine the subregion and cell-type-specific expression of these genes in Resilient rats. We found higher mRNA expression of mGlu5 in the BLA, IL, and PL, and CB1R in the BLA of Resilient rats relative to Controls. Using dual-labeled FISH we determined that mGlu5 and CB1R mRNA increases were limited to vGlut+ cells. To test the necessity of mGlu5 receptor activity for attenuating contextual fear, intra-BLA infusions of the mGlu5 negative allosteric modulator MTEP were administered prior to context re-exposure. MTEP increased contextual fear on the day of administration, which extinguished over the course of two additional un-drugged sessions. These results suggest that an enhanced mGlu5 expression within BLA glutamate neurons contributes to the behavioral flexibility observed in stress-Resilient animals by facilitating a capacity for extinguishing contextual fear associations.
Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis
Authors: Burke Thomas P. , Engström Patrik , Tran Cuong J. , Glasner Dustin R. , Espinosa Diego A. , Harris Eva , Welch Matthew D. 
Published: September 2020

AbstractRickettsiaare arthropod-borne pathogens that cause severe human disease worldwide. The spotted fever group (SFG) pathogenRickettsia parkerielicits skin lesion (eschar) formation in humans after tick bite. However, intradermal inoculation of inbred mice with millions of bacteria fails to elicit eschar formation or disseminated disease, hindering investigations into understanding eschar-associated rickettsiosis. Here, we report that intradermal infection of mice deficient for both interferon receptors (Ifnar-/-Ifngr-/-) withR. parkericauses eschar formation, recapitulating the hallmark clinical feature of human disease. Intradermal infection with doses that recapitulate tick infestation caused eschar formation and lethality, including with as few as 10 bacteria. Using this model, we found that the actin-based motility protein Sca2 is required forR. parkeridissemination from the skin to internal organs and for causing lethal disease, and that the abundantR. parkeriouter membrane protein OmpB contributes to eschar formation. We also found that immunizing mice withsca2andompBmutantR. parkeriprotects against subsequent rechallenge with wild-type bacteria, revealing live-attenuated vaccine candidates. Thus, interferon receptor-deficient mice are a tractable model to investigate rickettsiosis, bacterial virulence factors, and immunity. Our results suggest that differences in interferon signaling in the skin between mice and humans may explain the discrepancy in susceptibility to SFGRickettsia.
Hybrid dedicated and distributed coding in PMd/M1 provides separation and interaction of bilateral arm signals
Authors: Dixon Tanner C. , Merrick Christina M. , Wallis Joni D. , Ivry Richard B. , Carmena Jose M. 
Published: September 2020

ABSTRACTPronounced activity is observed in both hemispheres of the motor cortex during preparation and execution of unimanual movements. The organizational principles of bi-hemispheric signals and the functions they serve throughout motor planning remain unclear. Using an instructed-delay reaching task in monkeys, we identified two components in population responses spanning PMd and M1. A “dedicated” component, which segregated activity at the level of individual units, emerged in PMd during preparation. It was most prominent following movement when M1 became strongly engaged, and principally involved the contralateral hemisphere. In contrast to recent reports, these dedicated signals solely accounted for divergence of arm-specific neural subspaces. The other “distributed” component mixed signals for each arm within units, and the subspace containing it did not discriminate between arms at any stage. The statistics of the population response suggest two functional layers of the cortical network: one that spans both hemispheres for supporting preparatory and ongoing processes, and another that is predominantly housed in the contralateral hemisphere and specifies unilateral output.
Early alterations of large-scale brain networks temporal dynamics in young children with autism
Authors: Bochet Aurélie , Sperdin Holger Franz , Rihs Tonia Anahi , Kojovic Nada , Franchini Martina , Jan Reem Kais , Michel Christoph Martin , Schaer Marie 
Published: September 2020

ABSTRACTDisruption of large-scale brain networks is associated with autism spectrum disorders (ASD). Recently, we found that directed functional connectivity alterations of social brain networks are a core component of atypical brain development at early developmental stages in ASD (Sperdin et al., 2018). Here, we investigated the spatio-temporal dynamics of whole-brain neuronal networks at a subsecond scale in 90 toddlers and preschoolers (47 with ASD) using an EEG microstate approach. Results revealed the presence of five microstate classes that best described the entire dataset (labeled as microstate classes A-E). Microstate class C related to the Default Mode Network (DMN) occurred less in children with ASD. Analysis of brain-behavioural relationships within the ASD group suggested that a compensatory mechanism from microstate C was associated with less severe symptoms and better adaptive skills. These results demonstrate that the temporal properties of some specific EEG microstates are altered in ASD at early developmental stages.
Developing scaled tools for residential and nursing home inspection: feasibility study
Authors: Taylor Brian J. , Osterhus Insa , Stewart Rachel , Cunningham Suzanne , MacLeod Olive , McColgan Mary 
Published: September 2020

PurposeThis study explored the feasibility of developing scaled inspection tools for use during external inspection of health and social care facilities to give improved accuracy in identifying facilities “at risk”, a tool for risk-adjusted frequency of inspection, and greater consistency of judgements.Design/methodology/approachThis paper summarises the development through working groups and workshops involving 20 experienced inspectors (nurses and social workers) of the Regulation and Quality Improvement Authority who inspect the 206 nursing and 182 residential care homes in Northern Ireland. A brief evaluation survey, including response to a case vignette, gathered inspectors' views after using the tools for six months.FindingsEight two-dimensional Scaled Inspection Tools were created, each embodying a scale of performance (seriousness of risk issue) and a scale of the ability of the facility to manage that issue, each axis comprising four points. The Scaled Inspection Tools were used for on-site inspections during 2017–18. Evaluative comments were generally positive. The case vignette seemed to highlight greater risk aversion amongst newer inspectors.Research limitations/implicationsThe creation of scaled inspection tools adds credibility to the potential for developing risk-based governance in service regulation. Further testing of domains and their scope is required.Practical implicationsPrompts for each domain were found essential to guide inspectors. Despite the challenge of change, inspectors became enthusiastic about use for evaluating risks, and managers about improvements in consistency of inspection.Social implicationsKnowledge derived from statistical approaches needs to be incorporated into inspection and regulation, just as in other aspects of professional practice.Originality/valueScaled inspection tools, with two orthogonal axes corresponding to seriousness of risk and ability to manage the risk (inverse of likelihood of harm), proved acceptable and intuitive in use. The study gives credibility to the possibility of developing screening and surveillance approaches to risk-based governance in service regulation.