bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and application of an evidence-based directed acyclic graph to evaluate the associations between metal mixtures and cardiometabolic outcomes
Authors: Riseberg Emily , Melamed Rachel D. , James Katherine A. , Alderete Tanya L. , Corlin Laura 
Published: March 2021

AbstractObjectivesSpecifying analytic models to assess relationships among metal mixtures and cardiometabolic outcomes requires evidence-based models of the causal structures; however, such models have not been previously published. The objective of this study was to develop and evaluate a directed acyclic graph diagraming metal mixture exposure and cardiometabolic outcomes.MethodsWe conducted a systematic literature search to develop the directed acyclic graph (DAG) of metal mixtures and cardiometabolic outcomes. To evaluate consistency of the DAG, we tested the suggested conditional independence statements using linear and logistic regression analyses with data from the San Luis Valley Diabetes Study (SLVDS; n=1795). We compared the proportion of statements supported by the data to the proportion of conditional independence statements supported by 100 DAGs with the same structure but randomly permuted nodes. Next, we used our DAG to identify minimally sufficient adjustment sets needed to estimate the association between metal mixtures and cardiometabolic outcomes in the SLVDS and applied them using Bayesian kernel machine regression models.ResultsFrom the 42 articles included in the review, we developed an evidence-based DAG with 163 testable conditional independence statements (64% supported by SLVDS data). Only 5% of DAGs with randomly permuted nodes indicated more agreement with the data than our evidence-based DAG. We did not observe evidence for an association between metal mixtures and cardiometabolic outcomes in the pilot analysis.ConclusionsWe developed, tested, and applied an evidence-based approach to analyze associations between metal mixtures and cardiometabolic health.
Investigating the first stage of the COVID-19 pandemic in Ukraine using epidemiological and genomic data
Authors: Gankin Yuriy , Nemira Alina , Koniukhovskii Vladimir , Chowell Gerardo , Weppelmann Thomas A. , Skums Pavel , Kirpich Alexander 
Published: March 2021

AbstractThe novel coronavirus SARS-CoV-2 was first detected in China in December 2019 and has rapidly spread around the globe. The World Health Organization declared COVID-19 a pandemic in March 2020 just three months after the introduction of the virus. Individual nations have implemented and enforced a variety of social distancing interventions to slow the virus spread, that had different degrees of success. Understanding the role of non-pharmaceutical interventions (NPIs) on COVID-19 transmission in different settings is highly important. While most such studies have focused on China, neighboring Asian counties, Western Europe, and North America, there is a scarcity of studies for Eastern Europe. The aim of this study is to contribute to filling this gap by analyzing the characteristics of thefirst months of the epidemicin Ukraine using agent-based modelling and phylodynamics. Specifically, first we studied the dynamics of COVID-19 incidence and mortality and explored the impact of epidemic NPIs. Our stochastic model suggests, that even a small delay of weeks could have increased the number of cases by up to 50%, with the potential to overwhelm hospital systems. Second, the genomic data analysis suggests that there have been multiple introductions of SARS-CoV-2 into Ukraine during the early stages of the epidemic. Our findings support the conclusion that the implemented travel restrictions may have had limited impact on the epidemic spread. Third, the basic reproduction number for the epidemic that has been estimated independently from case counts data and from genomic data suggest sustained intra-country transmissions.
A Patient-Specific Model of Transcatheter Valve Replacement in a Bicuspid Heart Valve
Authors: McGee Orla M. , McNamara Adrian , McNamara Laoise M. 
Published: March 2021

AbstractBicuspid Aortic Valves (BAVs) are a common congenital heart disease where two cusps of the aortic heart valve become fused together, this leads to two unequally sized leaflets compared to the normal trileaflet valve. Transcatheter Aortic Valves are currently used in off-label treatmet of stenosed BAVs, however, due to the abnormal valve anatomy, debate surrounds the sizing of transcatheter valves. In this study, finite element models were developed to simulate the deployment of two different valves sizes (a 25 mm and a 27 mm) of the Lotus valve into the patient-specific aortic root geometry of a clinical stenosed BAV case. These models were used to investigate and compare the eccentricity, stress and mal-apposition of the two valve sizes. The results demonstrated that the 25 mm valve was the most suitable in terms of eccentricity and stress reduction. It was also shown that the smaller 25 mm valve size did not increase the likelihood of mal-apposition. As the 25 mm valve was deemed suitable based on current sizing algorithms, on the basis of these results traditional annulus measurement and device sizing may be suitable in the case of the Lotus valve.
Intra-epithelial non-canonical Activin A signalling safeguards prostate progenitor quiescence
Authors: Cambuli Francesco , Foletto Veronica , Alaimo Alessandro , De Felice Dario , Gandolfi Francesco , Palumbieri Maria Dilia , Zaffagni Michela , Genovesi Sacha , Lorenzoni Marco , Celotti Martina , Bertossio Emiliana , Mazzero Giosuè , Bertossi Arianna , Bisio Alessandra , Berardinelli Francesco , Antoccia Antonio , Gaspari Marco , Barbareschi Mattia , Fiorentino Michelangelo , Shen Michael M. , Loda Massimo , Romanel Alessandro , Lunardi Andrea 
Published: March 2021

AbstractThe healthy prostate is a relatively quiescent tissue. Yet, prostate epithelium overgrowth is a common condition during ageing, associated with urinary dysfunction and tumorigenesis. For over thirty years, TGF-β ligands have been known to induce cytostasis in a large variety of epithelia, but the intracellular pathway mediating this signal in the prostate, as well as its relevance for quiescence, have remained elusive.Here, using mouse prostate organoids to model epithelial progenitors, we found that intra-epithelial non-canonical Activin A signalling inhibited cell proliferation in a Smad-independent manner. Mechanistically, Activin A triggered Tak1 and p38 MAPK activity, leading to p16 and p21 nuclear import. Spontaneous evasion from this quiescent state occurred upon prolonged culture, due to reduced Activin A secretion, a condition associated with DNA replication stress and aneuploidy. Organoids capable to escape quiescencein vitrowere also able to implant with increased frequency into immunocompetent mice.Our study demonstrates that non-canonical Activin A signalling safeguards epithelial quiescence in the healthy prostate, with potential implications for the understanding of cancer initiation, and the development of therapies targeting quiescent tumour progenitors.
Reduction of genotyping marker density for genomic selection is not an affordable approach to long-term breeding in cross-pollinated crops
Authors: DoVale Júlio César , Carvalho Humberto Fanelli , Sabadin Felipe , Fritsche-Neto Roberto 
Published: March 2021

ABSTRACTThe selection of informative markers has been studied massively as an alternative to reduce genotyping costs for the genomic selection (GS) application. Low-density marker panels are attractive for GS because they decrease computational time-consuming and multicollinearity beyond more individuals can be genotyped with the same cost. Nevertheless, these inferences are usually made empirically using “static” training sets and populations, which are adequate only to predict a breeding program’s initial cycles but might not for long-term cycles. Moreover, to the best of our knowledge, none of these inferences considered the inclusion of dominance into the GS models, which is particularly important to predict cross-pollinated crops. Therefore, that reveals an important and unexplored topic for allogamous long-term breeding. To achieve this goal, we employed two approaches: the former used empirical maize datasets, and the latter simulations of long-term breeding cycles of phenotypic and genomic recurrent selection (intrapopulation and reciprocal). Then, we observed the reducing marker density effect on populations (mean, the best genotypes performance, accuracy, additive variance) over cycles and models (additive, additive-dominance, specific combining ability (SCA)). Our results indicate that the markers reduction based on different linkage disequili brium (LD) levels is viable only within a cycle and brings a significant decrease in predictive ability over generations. Furthermore, in the long-term, regardless of the selection scheme adopted, the more makers, the better because they buffer LD losses caused by recombination over breeding cycles. Finally, regarding the accuracy, the additive-dominant models tend to outperform the additive ones and perform similar to the SCA.
Neural responses to natural visual motion are spatially selective across the visual field, with selectivity differing across brain areas and task
Authors: Ki Jason J , Dmochowski Jacek P , Touryan Jonathan , Parra Lucas C 
Published: March 2021

AbstractIt is well established that neural responses to visual stimuli are enhanced at select locations in the visual field. While spatial selectivity and the effects of spatial attention are well-understood for discrete tasks (e.g., visual cueing paradigms), little is known about neural response during a naturalistic visual experience that involves complex dynamic visual stimuli, for instance, driving. In this study, we assess the strength of neural responses across the visual space during a kart race video game. Specifically, we measure the correlation strength of scalp evoked potentials with optical flow magnitude at individual locations on the screen. We find the strongest neural responses for task-relevant locations in visual space, selectively extending to areas beyond the focus of overt attention: while the driver’s gaze is directed upon the heading direction at the center of the screen, we observe robust neural evoked responses also to peripheral areas such as the road and surrounding buildings. Importantly, this spatial selectivity of neural responses differs across scalp locations. Moreover, during active gameplay, the strength of the spatially-selective neural responses are enhanced compared to passive viewing. Spatially selective neural gains have previously been interpreted as an attentional gain mechanism. In this view, the present data suggest that different brain areas focus attention on different task-relevant portions of the visual field, reaching beyond the focus of overt attention.
Pathogenic tau disrupts the cellular program that maintains neuronal identity
Authors: Beckmann Adrian , Ramirez Paulino , Gamez Maria , Ray William J. , Frost Bess 
Published: March 2021

AbstractNeurons in human Alzheimer’s disease acquire phenotypes that are also present in various cancers, including over-stabilization of the cytoskeleton, nuclear pleomorphism, decondensation of constitutive heterochromatin, and aberrant activation of the cell cycle. Unlike in cancer, in which cell cycle activation drives tumor formation, activation of the cell cycle in post-mitotic neurons is sufficient to induce neuronal death. Multiple lines of evidence suggest that abortive cell cycle activation is a consequence of pathogenic forms of tau, a protein that drives neurodegeneration in Alzheimer’s disease and related “tauopathies.” We have combined network analysis of human Alzheimer’s disease and mouse tauopathy with mechanistic studies inDrosophilato discover that pathogenic forms of tau drive abortive cell cycle activation by disrupting the cellular program that maintains neuronal identity. Mechanistically, we identify Moesin, a prognostic biomarker for cancer and mediator of the epithelial-mesenchymal transition (EMT), as a major effector of tau-induced neurotoxicity. We find that aberrant activation of Moesin in neurons acts through the actin cytoskeleton to dysregulate the cellular program that maintains neuronal identity. Our study identifies mechanistic parallels between tauopathy and cancer and sets the stage for novel therapeutic approaches.
Evaluate effects of multiple users in collaborative Brain-Computer Interfaces: A SSVEP study
Authors: Do Tien-Thong Nguyen , Huynh Thanh Tung 
Published: March 2021

AbstractThis study investigates the effects of collaboration on task performance in brain-computer interface (BCI) based on steady-state visually evoked potential (SSVEP). Navigation tasks were performed in a virtual environment under two conditions, e.g., individual performance and team performance. The results showed that average task completion time in the collaborative condition is decreased by 6 percent compared with that of individual performance, which is inline with other studies in collaborative BCI (cBCI) and joint decision-making. Our work is a step forward for the progress in BCI studies that include multi-user interactions.
Transcriptional-Regulatory Convergence Across Functional MDD Risk Variants Identified by Massively Parallel Reporter Assays
Authors: Mulvey Bernard , Dougherty Joseph D. 
Published: March 2021

ABSTRACTFamily and population studies indicate clear heritability of major depressive disorder (MDD), though its underlying biology remains unclear. The majority of single-nucleotide polymorphism (SNP) linkage blocks associated with MDD by genome-wide association studies (GWASes) are believed to alter transcriptional regulators (e.g., enhancers, promoters), based on enrichment of marks correlated with these functions. A key to understanding MDD pathophysiology will be elucidation of which SNPs are functional and how such functional variants biologically converge to elicit the disease. Furthermore, retinoids can elicit MDD in patients, and promote depressive behaviors in rodent models, acting via a regulatory system of retinoid receptor transcription factors (TFs). We therefore sought to simultaneously identify functional genetic variants and assess retinoid pathway regulation of MDD risk loci. Using Massively Parallel Reporter Assays (MPRAs), we functionally screened over 1 000 SNPs prioritized from 39 neuropsychiatric trait/disease GWAS loci, with SNPs selected based on overlap with predicted regulatory features—including expression quantitative trait loci (eQTL) and histone marks—from human brains and cell cultures. We identified >100 SNPs with allelic effects on expression in a retinoid-responsive model system. Further, functional SNPs were enriched for binding sequences of retinoic acid-receptive transcription factors (TFs); with additional allelic differences unmasked by treatment with all-transretinoic acid (ATRA). Finally, motifs overrepresented across functional SNPs corresponded to TFs highly specific to serotonergic neurons, suggesting anin vivosite of action. Our application of MPRAs to screen MDD-associated SNPs suggests a shared transcriptional regulatory program across loci, a subset of which are unmasked by retinoids.
Accounting for dispersal improves the understanding of species abundance patterns
Authors: Feng Xiao , Qiao Huijie 
Published: March 2021

AbstractA long-standing question in ecology is how are species’ population distributed across space. The highest abundance has been hypothesized to be in the spatial or niche center, though mixed patterns from empirical studies has triggered a recent debate. Here we propose a conceptual framework based on environmental suitability and dispersal to interpret the mixed evidence. We demonstrate that the highest abundance could occur in the spatial center, in the niche center, or somewhere in-between the two centers, depending on the environmental setup and dispersal ability. We found that spatial and niche centers rarely overlap, suggesting the counteracting effect between the two factors, rather than reinforcement, is the norm in determining abundance patterns. The varied locations of highest abundance mirror the mixed evidence in literature, suggesting the “abundant-centre” and “abundant-niche centre” hypotheses are not mutually exclusive. This highlights the importance in understanding the biogeographic patterns through the lens of underlying mechanisms.
A STUDY OF ETIOLOGICAL AND CLINICAL PROFILE OF PATIENTS WITH LMN CRANIAL NERVE PALSY IN A TERTIARY CARE CENTER AT THANJAVUR MEDICAL COLLEGE AND HOSPITAL
Authors: Priyanka B. Nandini , Gunasekaran A. , Thangaraj M. 
Published: March 2021

BackgroundNeurological presentation with isolated/multiple cranial nerve palsy is normal and its different causes incorporate infection, autoimmune, neoplastic, and inflammatory pathologies. The etiological range may rely on geological areas. We attempted this study to investigate the clinical range and etiological profile of numerous cranial nerve palsy.Materials and methodsThis planned observational study was led from January 2020 to January 2021. All the patients with cranial nerve palsy coming to the neurology OPD were taken for examinations. Essential targets were to characterize anatomical disorder/cranial nerve combinations and to set up etiology. The primary goals were to examine related components. Patients with neuromuscular junction disorder, anterior horn cell disease, myopathies, first and second cranial nerve dysfunction were excluded from the study. All patients went through an organized convention of clinical assessment, examinations, and few particular examinations as per clinical protocol for analysis.ResultsCavernous sinus was the commonest anatomical condition of different cranial nerve paralyses and tuberculous disease was the commonest cause in this investigation.7thcranial nerve was the common isolated nerve involved with idiopathic ethology, diabetes was the most common cause overall found with third nerve involvement.
Multiplexed Ion Beam Imaging Readout of Single-Cell Immunoblotting
Authors: Lomeli Gabriela , Bosse Marc , Bendall Sean C. , Angelo Michael , Herr Amy E. 
Published: March 2021

ABSTRACTImprovements in single-cell protein analysis are required to study the cell-to-cell variation inherent to diseases, including cancer. Single-cell immunoblotting (scIB) offers proteoform detection specificity, but often relies on fluorescence-based readout and is therefore limited in multiplexing capability. Among rising multiplexed imaging methods is multiplexed ion beam imaging by time of flight (MIBI-TOF), a mass spectrometry imaging technology. MIBI-TOF employs metal-tagged antibodies that do not suffer from spectra overlap to the same degree as fluorophore-tagged antibodies. We report for the first-time MIBI-TOF of single-cell immunoblotting (scIB-MIBI-TOF). The scIB assay subjects single-cell lysate to protein immunoblotting on a microscale device consisting of a 50- to 75-μm thick hydrated polyacrylamide (PA) gel matrix for protein immobilization prior to in-gel immunoprobing. We confirm antibody-protein binding in the PA gel with indirect fluorescence readout of metal-tagged antibodies. Since MIBI-TOF is a layer-by-layer imaging technique, and our protein target is immobilized within a 3D PA gel layer, we characterize the protein distribution throughout the PA gel depth by fluorescence confocal microscopy and find that the highest signal-to-noise ratio is achieved by imaging the entirety of the PA gel depth. Accordingly, we report the required MIBI-TOF ion dose strength needed to image varying PA gel depths. Lastly, by imaging ~42% of PA gel depth with MIBI-TOF, we detect two isoelectrically separated TurboGFP (tGFP) proteoforms from individual glioblastoma cells, demonstrating that highly multiplexed mass spectrometry-based readout is compatible with scIB.
Context dependency of time-based event-related expectations for different modalities
Authors: Ball Felix , Andreca Julia , Noesselt Toemme 
Published: March 2021

AbstractExpectations about the temporal occurrence of events (when) are often tied with the expectations about certain event-related properties (what and where) happening at these time points. For instance, slowly waking up in the morning we expect our alarm clock to go off; however, the longer we do not hear it the more likely we already missed it. However, most current evidence for complex time-based event-related expectations (TBEEs) is based on the visual modality. Here we tested whether TBEEs can also act cross-modally. To this end, visual and auditory stimulus streams were presented which contained early and late targets embedded among distractors (to maximise temporal target uncertainty). Foreperiod-modality-contingencies were manipulated run-wise so that visual targets either occurred early in 80% of trials and auditory targets occurred late in 80 % of trials or vice versa. Participants showed increased sensitivity for expected auditory early/visual late targets which increased over time while the opposite pattern was observed for visual early/auditory late targets. A benefit in reaction times was only found for auditory early trials. Together, this pattern of results suggests that context-dependent TBEEs for auditory targets after short foreperiods (be they correct or not) dominated and determined which modality became more expected at the late position irrespective of the veridical statistical regularity. Hence, TBEEs in cross-modal and uncertain environments are context-dependent, shaped by the dominant modality in temporal tasks (i.e. auditory) and only boost performance cross-modally when expectations about the event after the short foreperiod match with the run-wise context (i.e. auditory early/visual late).
Aberrant Temporal-spatial Patterns to Sad expressions in Major Depressive Disorders via Hidden Markov Model
Authors: Dai Zhongpeng , Zhang Siqi , Zhou Hongliang , Wang Xinyi , Wang Huan , Yao Zhjjian , Lu Qing 
Published: March 2021

AbstractBackgroundThe pathological mechanisms of Major depressive disorders (MDD) is associated with over-expressing of negative emotions, and the overall temporal-spatial patterns underlying over-representation in depression still remained to be revealed to date. We hypothesized that the aberrant spatio-temporal attributes of the process of sad expressions relate to MDD and help to detect depression severity.MethodsWe enrolled a total of 96 subjects including 47 MDDs and 49 healthy controls (HCs), and recorded their Magnetoencephalography data under a sad expressions recognition task. A hidden Markov model (HMM) was applied to separate the whole neural activity into several brain states, then to characterize the dynamics. To find the disrupted spatial-temporal features, power estimations and fractional occupancy of each state were contrasted between MDDs and HCs.ResultsThree states were found over the period of emotional stimuli processing procedure. The visual state was mainly distributed in early stage (0 - 270ms) and the limbic state in middle and later stage (270ms - 600ms) of the task, while the fronto-parietal state remained a steady proportion across the whole period. MDDs activated statistically more in limbic system during limbic state (p= 0.0045) and less in frontoparietal control network during fronto-parietal state (p =5.38*10−5) relative to HCs. Hamilton-Depression-Rating Scale scores was significantly correlated with the predicted severity value using the state descriptors (p= 0.0062,r= 0.3933).DiscussionAs human brain exhibited varied activation patterns under the negative stimuli, MDDs expressed disrupted temporal-spatial activated patterns across varied stages involving the primary visual perception and emotional contents processing compared to HCs, indicting disordered regulation of brain functions. Furthermore, descriptors built by HMM could be potential biomarkers for identifying the severity of depression disorders.