bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning to suppress likely distractor locations in visual search is driven by the local distractor frequency
Authors: Allenmark Fredrik , Zhang Bei , Shi Zhuanghua , Müller Hermann J. 
Published: May 2022

AbstractSalient but task-irrelevant distractors interfere less with visual search when they appear in a display region where distractors have appeared more frequently in the past (‘distractor-location probability cueing’). This effect could reflect the (re-)distribution of a global, limited attentional ‘inhibition resource’. Accordingly, changing the frequency of distractor appearance in one display region should also affect the magnitude of interference generated by distractors in a different region. Alternatively, distractor-location learning may reflect a local response (e.g., ‘habituation’) to distractors occurring at a particular location. In this case, the local distractor frequency in one display region should not affect distractor interference in a different region. To decide between these alternatives, we conducted three experiments in which participants searched for an orientation-defined target while ignoring a more salient orientation distractor that occurred more often in one vs. another display region. Experiment 1 varied the ratio of distractors appearing in the frequent vs. rare regions (60/40–90/10), with a fixed global distractor frequency. The results revealed the cueing effect to increase with increasing probability ratio. In Experiments 2 and 3, one (‘test’) region was assigned the same local distractor frequency as in one of the conditions of Experiment 1, but a different frequency in the other region – dissociating local from global distractor frequency. Together, the three experiments showed that distractor interference in the test region was not significantly influenced by the frequency in the other region, consistent with purely local learning. We discuss the implications for theories of statistical distractor-location learning.Public Significance StatementWe are frequently distracted by salient visual stimuli which are irrelevant to the task at hand. Previous studies have shown that ‘knowledge’ of the location(s) where a distractor is most likely to occur helps the observer to mitigate distraction. In this study we compared different theories of how the frequency and spatial distribution of distractor occurrence in different locations could influence the ability to avoid distraction. The results favored a local learning account: the ability to avoid distraction by distractors occuring in a particular spatial region is primarily influenced by how often distractors have occurred in that region.
Neural networks with optimized single-neuron adaptation uncover biologically plausible regularization
Authors: Geadah Victor , Horoi Stefan , Kerg Giancarlo , Wolf Guy , Lajoie Guillaume 
Published: May 2022

AbstractNeurons in the brain have rich and adaptive input-output properties. Features such as heterogeneous f-I curves and spike frequency adaptation are known to place single neurons in optimal coding regimes when facing changing stimuli. Yet, it is still unclear how brain circuits exploit single-neuron flexibility, and how network-level requirements may have shaped such cellular function. To answer this question, a multi-scaled approach is needed where the computations of single neurons and neural circuits must be considered as a complete system. In this work, we use artificial neural networks to systematically investigate single-neuron input-output adaptive mechanisms, optimized in an end-to-end fashion. Throughout the optimization process, each neuron has the liberty to modify its nonlinear activation function, parametrized to mimic f-I curves of biological neurons, and to learn adaptation strategies to modify activation functions in real-time during a task. We find that such networks show much-improved robustness to noise and changes in input statistics. Importantly, we find that this procedure recovers precise coding strategies found in biological neurons, such as gain scaling and fractional order differentiation/integration. Using tools from dynamical systems theory, we analyze the role of these emergent single-neuron properties and argue that neural diversity and adaptation play an active regularization role, enabling neural circuits to optimally propagate information across time.
Aggression and multimodal signaling in noise in a common urban songbird
Authors: Önsal Çağla , Yelimlieş Alper , Akçay Çağlar 
Published: May 2022

AbstractAnthropogenic noise may disrupt signals used to mediate aggressive interactions, leading to more physical aggression between opponents. One solution to this problem is to switch signaling effort to a less noisy modality (e.g., the visual modality). In the present study we investigate aggressive behaviors and signaling in urban and rural male European robins (Erithacus rubecula) in response to simulated intrusions with or without experimental noise. First, we predicted that urban birds, living in noisier habitats, would be generally more aggressive than rural birds. We also predicted that during simulated intrusions with experimental noise, robins would increase their physical aggression and show a multi-modal shift, i.e., respond with more visual threat displays and sing fewer songs. Finally, we expected the multi-modal shift in response to noise to be stronger in urban birds compared to rural birds. The results showed that urban birds were more aggressive than rural robins, but an increase in aggression with experimental noise was seen only in the rural birds. Urban but not rural birds decreased their song rate in response to noise. Contrary to the multi-modal shift hypothesis, however, there was no evidence of a concurrent increase in visual signals. These results point to a complex role of immediate plasticity and longer-term processes in affecting communication during aggressive interactions under anthropogenic noise.Significance StatementHuman activity has an enormous effect on wildlife, including on their social behavior. Animals living in urban areas often tend to be more aggressive than those living in rural areas, which may be due to urban acoustic noise making communication between individuals more difficult. In a study with a common songbird, the European robin, we investigated the role of urban acoustic noise in aggression and territorial communication. Urban robins were more aggressive than rural robins, and additional noise in the territory increased aggression in rural but not urban robins. While urban robins decreased their singing effort with additional noise, they did not increase visual signals concurrently. These results suggest that noise can indeed make animals behave more aggressively although the effect may depend on how noisy it is already. These results further our understanding of how human-made noise changes animal communication and social behavior.
Generic solving of physiologically-based kinetic models in support of next generation risk assessment due to chemicals
Authors: Charles Sandrine , Gestin Ophelia , Bruset Jérémie , Lamonica Dominique , Baudrot Virgile , Chaumot Arnaud , Geffard Olivier , Lacoue-Labarthe Thomas , Lopes Christelle 
Published: May 2022

AbstractIncreasing the confidence in using in vitro and in silico model-based data to aid the chemical risk assessment process is one, if not the most, important challenge currently facing regulatory authorities. A particularly crucial concern is to fully take advantage of scientifically valid Physiologically-Based Kinetic (PBK) models. Nevertheless, risk assessors remain still unwilling in employing PBK models within their daily work. Indeed, PBK models are not often included in current official guidance documents. In addition, most users have limited experience in using modelling in general. So, the complexity of PBK models, together with a lack to evaluation methods of their performances, certainly contributes to their under-use in practical risk assessment.This paper proposes an innovative and unified modelling framework, in both the writing of PBK equations as matrix ordinary differential equations (ODE), and in its exact solving simply expressed with matrix products. This generic PBK solution allows to consider as many as state-variables as needed to quantify chemical absorption, distribution, metabolism and excretion processes within living organisms when exposed to chemical substances. This generic PBK model makes possible any compartmentalisation to be considered, as well as all appropriate inter-connections between compartments and with the external medium.We first introduce our PBK modelling framework, with all intermediate steps from the matrix ODE to the exact solution. Then we apply this framework to bioaccumulation testing, before illustrating its concrete use through complementary case studies in terms of species, compounds and model complexity.Abstract Figure
Tensor Decomposition and Principal Component Analysis-Based Unsupervised Feature Extraction Outperforms State-of-the-Art Methods When Applied to Histone Modification Profiles
Authors: Roy Sanjiban Sekhar , Taguchi Y-h. 
Published: May 2022

AbstractIdentification of histone modification from datasets that contain high-throughput sequencing data is difficult. Although multiple methods have been developed to identify histone modification, most of these methods are not specific for histone modification but are general methods that aim to identify protein binding to the genome. In this study, tensor decomposition (TD) and principal component analysis (PCA)-based unsupervised feature extraction with optimized standard deviation were successfully applied to gene expression and DNA methylation. The proposed method was used to identify histone modification. Histone modification along the genome is binned within the region of lengthL. Considering principal components (PCs) or singular value vectors (SVVs) that TD or PCA attributes to samples, we can select PCs or SVVs attributed to regions. The selected PCs and SVVs further attributeP-values to regions, and adjusted P-values are used to select regions. The proposed method identified various histone modifications successfully and outperformed various state-of-the-art methods. This method is expected to serve as ade factostandard method to identify histone modification.
Alternative Factor Prescribing after Low-Dose Recombinant Factor VIIa Protocol in Cardiac Surgery
Authors: Momenzadeh Amanda , Meyer Jesse G. , De Leon Noelle , Tsourounis Candy 
Published: May 2022

AbstractBackgroundSafety concerns exist with the off-label use of recombinant factor VIIa (rFVIIa, Novoseven RT®) for refractory bleeding in cardiac surgery, including increased risk of thromboembolism. A rFVIIa protocol was implemented in December 2015 to standardize rFVIIa for cardiac surgery related hemorrhage.MethodsWe performed a retrospective, observational review of rFVIIa in adult cardiac surgery patients pre-protocol (January 2015 to November 2015) vs. post-protocol (December 2015 to March 2016). Study outcomes were rate of rFVIIa administration, rFVIIa dosing characteristics, length of stay, mortality, readmission rate, need for re-exploration, and rate of 4-factor Prothrombin Complex Concentrates (PCC; Kcentra®) administration.ResultsThere was a significant reduction in percentage of cardiac surgery cases receiving rFVIIa pre-vs. post-protocol (14.3 vs. 5.2%, p=0.015). Average total dose per patient decreased between groups (81.4 vs. 56.6 mcg/kg, p=0.059). In-hospital mortality, length of stay, need for re-exploration, readmission rates and 30-day mortality did not differ. Although 4-four-factor PCC significantly increased post-protocol (2.5% vs. 8%, p=0.02), overall use of factor products, rFVIIa or 4-factor PCC, did not change between study periods (16.8% vs. 13%, p=0.416). Mean cost of either rFVIIa or 4-factor PCC pre-protocol was significantly higher than that post-protocol ($8,778 vs. $4,421, p=0.0008).ConclusionsThe use of rFVIIa decreased after implementation of a rFVIIa protocol targeting 30 mcg/kg/dose without compromising morbidity or mortality outcomes. Four-factor PCC use significantly increased during the study, but the overall cost was reduced. Institutions wanting to implement a rFVIIa protocol should take careful measures to concurrently address off-label use of 4-factor PCC.
BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection
Authors: Cao Yunlong , Yisimayi Ayijiang , Jian Fanchong , Song Weiliang , Xiao Tianhe , Wang Lei , Du Shuo , Wang Jing , Li Qianqian , Chen Xiaosu , Yu Yuanling , Wang Peng , Zhang Zhiying , Liu Pulan , An Ran , Hao Xiaohua , Wang Yao , Wang Jing , Feng Rui , Sun Haiyan , Zhao Lijuan , Zhang Wen , Zhao Dong , Zheng Jiang , Yu Lingling , Li Can , Zhang Na , Wang Rui , Niu Xiao , Yang Sijie , Song Xuetao , Chai Yangyang , Hu Ye , Shi Yansong , Zheng Linlin , Li Zhiqiang , Gu Qingqing , Shao Fei , Huang Weijin , Jin Ronghua , Shen Zhongyang , Wang Youchun , Wang Xiangxi , Xiao Junyu , Xie Xiaoliang Sunney 
Published: May 2022

AbstractSARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.21. The new variants’ receptor binding and immune evasion capability require immediate investigation. Here, coupled with Spike structural comparisons, we show that BA.2.12.1 and BA.4/BA.5 exhibit comparable ACE2-binding affinities to BA.2. Importantly, BA.2.12.1 and BA.4/BA.5 display stronger neutralization evasion than BA.2 against the plasma from 3-dose vaccination and, most strikingly, from post-vaccination BA.1 infections. To delineate the underlying antibody evasion mechanism, we determined the escaping mutation profiles2, epitope distribution3 and Omicron neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory. The resulting elicited antibodies could neutralize both wildtype and BA.1 and are enriched on non-ACE2-competing epitopes. However, most of these cross-reactive NAbs are heavily escaped by L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1; nevertheless, these NAbs are largely escaped by BA.2/BA.4/BA.5 due to D405N and F486V, and react weakly to pre-Omicron variants, exhibiting poor neutralization breadths. As for therapeutic NAbs, Bebtelovimab4 and Cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
A mutation-level covariate model for mutational signatures
Authors: Kahane Itay , Leiserson Mark D.M. , Sharan Roded 
Published: May 2022

AbstractMutational processes and their exposures in particular genomes are key to our understanding of how these genomes are shaped. However, current analyses assume that these processes are uniformly active across the genome without accounting for potential covariates such as strand or genomic region that could impact such activities. Here we suggest the first mutation-covariate models that explicitly model the effect of different covariates on the exposures of mutational processes. We apply these models to test the impact of replication strand on these processes and compare them to strand-oblivious models across a range of data sets. Our models capture replication strand specificity, point to signatures affected by it, and score better on held-out data compared to standard models that do not account for mutation-level covariate information.
Raising the bar for patient experience during care transitions in Canada: A repeated cross-sectional survey evaluating a patient-oriented discharge summary at Ontario hospitals
Authors: Okrainec Karen , Chaput Audrey , Rac Valeria E. , Tomlinson George , Matelski John , Robson Mark , Troup Amy , Krahn Murray , Hahn-Goldberg Shoshana 
Published: May 2022

AbstractBackgroundPatient experience when transitioning home from hospital is an important quality metric linked to improved patient outcomes. We evaluated the impact of a hospital-based care transition intervention, patient-oriented discharge summary (PODS), on patient experience across Ontario acute care hospitals.MethodsWe used a repeated cross-sectional study design to compare yearly positive responses to four questions centered on discharge communication from the Canadian Patient Experience Survey (2016-2020) among three hospital cohorts with various levels of PODS implementation. Logistic regression using a binomial likelihood accounting for site level clustering was used to assess continuous linear time trends among cohorts and cohort differences during the post-implementation period. This research had oversight from a public advisory group of patient and caregiver partners from across the province.Results512,288 responses were included with mean age 69 ± 14 years (females) and 61 ± 20 years (males). Compared to non-implementation hospitals, hospitals with full implementation (>50% discharges) reported higher odds for having discussed the help needed when leaving hospital (OR=1.18, 95% CI=1.02-1.37) and having received information in writing about what symptoms to look out for (OR=1.44, 95%=1.17-1.78) post-implementation. The linear time trend was also significant when comparing hospitals with full versus no implementation for having received information in writing about what symptoms to look out for (OR=1.05, 95% CI=1.01-1.09).InterpretationPODS implementation was associated with higher odds of positive patient experience, particularly for discharge planning. Further efforts should center on discharge management, specifically: understanding of medications and what to do if worried once home.
Characterization of Extensive Diversity In Immunoglobulin Light Chain Variable Germline Genes Across Biomedically Important Mouse Strains
Authors: Kos Justin T. , Safonova Yana , Shields Kaitlyn M. , Silver Catherine A. , Lees William D. , Collins Andrew M. , Watson Corey T. 
Published: May 2022

AbstractThe light chain immunoglobulin genes of biomedically relevant mouse strains are poorly documented in current germline gene databases. We previously showed that IGH loci of wild-derived mouse strains representing the major mouse subspecies contained 247 germline IGHV sequences not curated in the international ImMunoGeneTics (IMGT) information system, which is the most commonly used database that curates the germline repertoires used for sequence alignment in AIRR-seq analysis. Despite containing levels of polymorphism similar to the IGH locus, the germline gene content and diversity of the light chain loci have not been comprehensively cataloged. To explore the extent of germline light chain repertoire diversity across mouse strains commonly used in the biomedical sciences, we performed AIRR-seq analysis and germline gene inference for 18 inbred mouse strains, including the four wild-derived strains with diverse sub-species origins. We inferred 1582 IGKV and 63 IGLV sequences, representing 459 and 22 unique IGKV and IGLV sequences. Of the unique inferred germline IGKV and IGLV sequences, 67.8% and 59%, respectively, were undocumented in IMGT. Across strains we observed germline IGKV sequences shared by three distinct IGK haplotypes and a more conserved IGLV germline repertoire. In addition, J gene inference indicated a novel IGK2 allele shared between PWD/PhJ and MSM/MsJ and a novel IGLJ1 allele for LEWES/EiJ and IGLJ2 allele for MSM/MsJ. Finally, a combined IGHV, IGKV, and IGLV phylogenetic analysis of wild-derived germline repertoires displayed reduced germline diversity for the light chain repertoire compared to the heavy chain repertoire, suggesting potential evolutionary differences between the two chains.
Leveraging spatio-temporal genomic breeding value estimates of dry matter yield and herbage quality in ryegrass via random regression models
Authors: Bornhofen Elesandro , Fè Dario , Lenk Ingo , Greve Morten , Didion Thomas , Jensen Christian Sig , Asp Torben , Janss Luc 
Published: May 2022

AbstractJoint modeling of correlated multi-environment and multi-harvest data of perennial crop species may offer advantages in prediction schemes and a better understanding of the underlying dynamics in space and time. The goal of the present study was to investigate the relevance of incorporating the longitudinal dimension of within-season multiple harvests of biomass yield and nutritive quality traits of forage perennial ryegrass (Lolium perenneL.) in a reaction norm model setup that additionally accounts for genotype-environment interactions. Genetic parameters and accuracy of genomic breeding value predictions were investigated by fitting three random regression (random coefficients) linear mixed models (gRRM) using Legendre polynomial functions to the data. All models accounted for heterogeneous residual variance and moving average-based spatial adjustments within environments. The plant material consisted of 381 bi-parental family pools and four check varieties of diploid perennial ryegrass evaluated in eight environments for biomass yield and nutritive quality traits. The longitudinal dimension of the data arose from multiple harvests performed four times annually. The specified design generated a total of 16,384 phenotypic data points for each trait. Genomic DNA sequencing was performed using DNA nanoball-based technology (DNBseq) and yielded 56,645 single nucleotide polymorphisms (SNPs) which were used to calculate the allele frequency-based genomic relationship matrix used in all genomic random regression models. Biomass yield’s estimated additive genetic variance and heritability values were higher in later harvests. The additive genetic correlations were moderate to low in early measurements and peaked at intermediates, with fairly stable values across the environmental gradient, except for the initial harvest data collection. This led to the conclusion that complex genotype-by-environment interaction (G×E) arises from spatial and temporal dimensions in the early season, with lower re-ranking trends thereafter. In general, modeling the temporal dimension with a second-order orthogonal polynomial in the reaction norm mixed model framework improved the accuracy of genomic estimated breeding value prediction for nutritive quality traits, but no gain in prediction accuracy was detected for dry matter yield. This study leverages the flexibility and usefulness of gRRM models for perennial ryegrass research and breeding and can be readily extended to other multi-harvest crops.