bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multiperspective on the broad dissemination of research findings to past research participants and the community-at-large
Authors: Mayo-Gamble Tilicia L , Cunningham-Erves Jennifer , Kas-Osoka Chioma , Johnson George W , Frazier Nicole , Joosten Yvonne 
Published: July 2021

AbstractDissemination of research findings to past research participants and the community-at-large is a critical element to improving health outcomes, yet it is often overlooked by researchers. Few studies have explored how to provide study findings to the community, and no studies have investigated how community members can be involved in this process. This study explored views on the broad dissemination of research findings to community members and the role of the community in the dissemination process. We conducted a comparative analysis from the perspective of researchers, community members, and program officers (POs) from national health research funding agencies. Semistructured interviews were conducted with community members (African American, N = 10; Latino, N = 10), academic researchers (N = 10), and POs (N = 5). Thematic analysis was utilized in which codes and themes were created. One cross-cutting theme was identified, Views on Disseminating Research Findings to Communities. There were three additional themes identified among community members, five among researchers, and four among POs. All groups perceived the value of dissemination to communities as meaningful and ethical. Groups differed in their perceptions of prioritization of dissemination audiences. This study highlighted consensus on the value of broad dissemination to the community-at-large and identified areas of insufficiency in the translational research continuum that could be expanded or improved to ensure targeted groups receive the intended benefits of positive research findings. The long-term benefit of disseminating findings to the community-at-large is increased acceptability of interventions and reduced mistrust in research and researchers.
Comparison of Two Genome-Wide Association Studies for Heart Rate Response to Exercise from the UK Biobank
Authors: Thakral Abhinav , Paterson Andrew D. 
Published: July 2021

AbstractThe short-term changes in heart rate (HR) during and after exercise are important physiologic traits mediated via the autonomic nervous system. Variations in these traits are associated with mortality from cardiovascular causes. We conducted a systematic review of genome-wide association studies for these traits (with >10,000 participants) with the aim of comparing Polygenic Risk Scores (PRS) from different studies. Additionally, we applied theSTrengthening ofReporting ofGeneticAssociation Studies (STREGA) statement for assessing the completeness of reporting of evidence. Our systematic search yielded two studies (Verweij et al. and Ramirez et al.) that met our inclusion criteria. Both were conducted on the UK Biobank. Both defined their exercise traits as the difference between resting HR and the maximum HR during exercise. Their recovery traits were defined differently. Verweij et al. defined 5 recovery traits as the differences between the peak HR during exercise and the HRs at 10-50 sec post exercise cessation. Ramirez et al. defined their recovery trait as the difference between peak HR during exercise and the minimum HR during the minute post exercise cessation. While Ramirez et al. divided their sample into discovery and replication subsets, Verweij et al. analyzed the whole sample together. In terms of results, there were several common SNPs identified between studies and traits. There was evidence for the phenomenon of winner’s curse operating for a SNP from the Ramirez study’s HR recovery analysis. Many of the SNPs were mutually exclusive between the studies. However, there was a good agreement of PRS from the studies. The differences in the results could be attributed to the different exclusion criteria, analytic approaches, and definitions of traits used. Both studies had an under-representation of individuals of non-European ancestry compared to those of European ancestry. Further studies with proportionate representation of individuals of all ancestries would help address this gap.Graphical Abstract
Assessing neuropathic pain in sickle cell disease: How useful is quantitative sensory testing?
Authors: Ramsay Zachary , Francis Damian , Bartlett Rachel , Ali Amza , Grant Justin , Gordon-Strachan Georgiana , Asnani Monika 
Published: July 2021

AbstractQuantitative sensory testing (QST) is a psychophysical test of sensory function which may assist in assessing neuropathic pain (NP). This study compares QST findings with a standardized NP questionnaire to assess their agreement among Jamaicans with sickle cell disease (SCD). A cross sectional study consecutively recruited SCD patients 14 years and older, not pregnant, and without history of clinical stroke or acute illness in Kingston, Jamaica. QST identified thresholds for cold detection, heat detection, heat pain and pressure pain at the dominant thenar eminence, opposite dorsolateral foot and the subject’s most frequent pain site. The Douleur Neuropathique 4 (DN4) was interviewer-administered to diagnose NP. Subjects were divided into low and high sensitization groups if below the 5th and above the 95th percentiles, respectively on QST measures. Kappa agreement coefficients, and receiver operator characteristic (ROC) curves were performed to compare QST with the DN4. Two-hundred and fifty-seven SCD subjects were recruited (mean age 31.7 ± 12.2 years, 55.7% female, 75% SS genotype). Kappa agreements were fair (0.2-0.4) to good (0.6-0.8) between DN4 individual items of itching, hypoesthesia to touch, hypoesthesia to pinprick and brush allodynia with various QST sensitization groups. However, kappa agreements between the NP overall diagnosis on the DN4 with sensitization groups were poor (<0.2). Only heat detection (0.75) and heat pain (0.75) at the leg as a pain site showed satisfactory area under the curve (>0.7). QST may assist in assessing individual components of NP but its use should be limited as a tool to augment clinical assessments.
Serum Oxidative Stress Markers in Women with Uterine Fibroids in Lagos, Nigeria
Authors: Soibi-Harry Adaiah Priscillia , Makwe Christian Chigozie , Oluwole Ayodeji Ayotunde , Garba Sunusi Rimi , Ajayi Abisoye Towuromola , Anyanwu Roosevelt , Anorlu Rose Ihuoma 
Published: July 2021

ABSTRACTBackgroundUterine fibroid is the most common benign gynaecological tumour in women of reproductive age group, with significant impact on the quality of life, economy, morbidity and sometimes mortality of affected women. Black women of reproductive age group are more likely to develop uterine fibroids. Although available evidence suggests racial and genetic predisposition to the aetiology of uterine fibroid, oxidative stress has been implicated in the onset and progression of uterine fibroids. Epidemiological and experimental studies have suggested that oxidative stress may play an important role in the pathogenesis of gynaecological diseases including uterine fibroids.Aim and ObjectivesThis study aims to assess the serum levels of antioxidants (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx)) and oxidants (protein carbonyl (PC), advanced oxidation protein products (AOPP)) in women with uterine fibroids and to identify any association between the size of uterine fibroids and serum levels of the analysed antioxidants and oxidants.MethodsForty-four women with ultrasound diagnosis of uterine fibroids and 44 women without uterine fibroids were recruited from a University Teaching Hospital. Blood samples were obtained and analysed for serum levels of selected antioxidants (CAT, SOD, GPx) and oxidants (PC, AOPP). Pelvic ultrasonography was performed on all study participants.ResultsThe median serum levels of antioxidants: CAT (2.20 vs 4.32 ng/ml; p < 0.001); SOD (285.54 vs 380.96 ng/ml; p < 0.001) and GPx (9.67 vs 11.26 µU/ml; p < 0.001) were significantly lower in women with uterine fibroids. The median serum levels of oxidants: PC (162.08 vs 142.36 ng/ml; p = 0.04); and AOPP (22.42 vs 13.94 ng/ml; p < 0.001) were significantly higher in women with uterine fibroids. There was a strong negative correlation between serum levels of AOPP and SOD (r = -0.95; p < 0.001) in women with uterine fibroids. The maximum diameter of fibroids showed a significant positive correlation with AOPP (r = 1.000; p < 0.001) and a negative correlation with SOD (r = -1.000; p < 0.001).ConclusionWomen with uterine fibroids had lower levels of antioxidants and higher levels of oxidants. In women with uterine fibroids, AOPP negatively correlated with SOD. There was a positive correlation between fibroid size and AOPP and a negative correlation between fibroid size and SOD. The findings of this study suggests that AOPP and SOD may play an important role in uterine fibroids.
Investigating Regional Specificity of Alzheimer’s Disease Pathology in the 5xFAD Mouse Model
Authors: Gyan Araba , Glass Emily D , Stevenson Tamara , Murphy Geoffrey G , Moore Shannon J 
Published: July 2021

ABSTRACTAlzheimer’s disease (AD) is a neurodegenerative disease that affects cognition and memory. Mouse models such as 5xFAD, incorporate mutations found in familial or early-onset (EOAD) AD; these mutations increase the production of the toxic AB species that contributes to plaque formation in the brain. However, not all brain regions in the 5xAD animals accumulate plaques to the same degree. For example, the cerebellum appears to be resistant to AB plaque formation, while other regions such as the cortex and subiculum develop copious plaques. The mechanism(s) underlying this regional specificity remains unclear. Thus, we used a fluorescent antibody to APP/AB to quantify the amount of these proteins in several brain regions of interest, including subiculum, cortex, and cerebellum. We found that the cerebellum had less APP/AB than the other regions quantified, which demonstrates a correlation between the levels of APP/AB and plaque formation. Taken together, this suggests that the regional specificity of AD pathology may be a result of different levels of protein expression.
Obtaining Spatially Resolved Tumor Purity Maps Using Deep Multiple Instance Learning In A Pan-cancer Study
Authors: Oner Mustafa Umit , Chen Jianbin , Revkov Egor , James Anne , Heng Seow Ye , Kaya Arife Neslihan , Alvarez Jacob Josiah Santiago , Takano Angela , Cheng Xin Min , Lim Tony Kiat Hon , Tan Daniel Shao Weng , Zhai Weiwei , Skanderup Anders Jacobsen , Sung Wing-Kin , Lee Hwee Kuan 
Published: July 2021

AbstractTumor purity is the proportion of cancer cells in the tumor tissue. An accurate tumor purity estimation is crucial for accurate pathologic evaluation and for sample selection to minimize normal cell contamination in high throughput genomic analysis. We developed a novel deep multiple instance learning model predicting tumor purity from H&E stained digital histopathology slides. Our model successfully predicted tumor purity from slides of fresh-frozen sections in eight different TCGA cohorts and formalin-fixed paraffin-embedded sections in a local Singapore cohort. The predictions were highly consistent with genomic tumor purity values, which were inferred from genomic data and accepted as the golden standard. Besides, we obtained spatially resolved tumor purity maps and showed that tumor purity varies spatially within a sample. Our analyses on tumor purity maps also suggested that pathologists might have chosen high tumor content regions inside the slides during tumor purity estimation in the TCGA cohorts, which resulted in higher values than genomic tumor purity values. In short, our model can be utilized for high throughput sample selection for genomic analysis, which will help reduce pathologists’ workload and decrease inter-observer variability. Moreover, spatial tumor purity maps can help better understand the tumor microenvironment as a key determinant in tumor formation and therapeutic response.
Behaviorally emergent hippocampal place maps remain stable during memory recall
Authors: Zemla Roland , Moore Jason J , Basu Jayeeta 
Published: July 2021

SummaryThe hippocampus is critical for the formation and recall of episodic memories1, 2which store past experience of events (‘what’) occurring at particular locations (‘where’) in time (‘when’). Hippocampal place cells, pyramidal neurons which show location-specific modulation of firing rates during navigation3, 4, together form a spatial representation of the environment. It has long been hypothesized that place cells serve as the neural substrate for long-term episodic memory of space5, 6. However, recent studies call to question this tenet of the field by demonstrating unexpected levels of representational drift in hippocampal place cells with respect to the duration of episodic memories in mice7, 8. In the present study, we examined behaviorally driven long-term organization of the place map, to resolve the relationship between memory and place cells. Leveraging the stability of two-photon calcium imaging, we tracked activity of the same set of CA1 pyramidal neurons during learning and memory recall in an operant, head-fixed, odorcued spatial navigation task. We found that place cells are rapidly recruited into task-dependent spatial maps, resulting in emergence of orthogonal as well as overlapping representations of space. Further, task-selective place cells used a diverse set of remapping strategies to represent changing task demands that accompany learning. We found behavioral performance dependent divergence of spatial maps between trial types occurs during learning. Finally, imaging during remote recall spanning up to 30 days revealed increased stabilization of learnt place cell maps following memory consolidation. Our findings suggest that a subset of place cells is recruited by rule based spatial learning, actively reconfigured to represent task-relevant spatial relationships, and stabilized following successful learning and consolidation.
Improved prediction of behavioral and neural similarity spaces using pruned DNNs
Authors: Tarigopula Homa Priya , Fairhall Scott Laurence , Hasson Uri 
Published: July 2021

AbstractDeep Neural Networks (DNNs) have become an important tool for modeling brain and behaviour. One key area of interest has been to apply these networks to model human similarity judgements. Several previous works have used the embeddings from the penultimate layer of vision DNNs and showed that a reweighting of these features improves the fit between human similarity judgments and DNNs. These studies underline the idea that these embeddings form a good basis set but lack the correct level of salience. Here we re-examined the grounds for this idea and on the contrary, we hypothesized that these embeddings, beyond forming a good basis set, also have the correct level of salience to account for similarity judgments. It is just that the huge dimensional embedding needs to be pruned to select those features relevant for the considered domain for which a similarity space is modeled. In Study 1 we supervised DNN pruning based on a subset of human similarity judgments. We found that pruning:i) improved out-of-sample prediction of human similarity judgments from DNN embeddings,ii) produced better alignment with WordNet hierarchy, andiii) retained much higher classification accuracy than reweighting. Study 2 showed that pruning by neurobiological data is highly effective in improving out-of-sample prediction of brain-derived representational dissimilarity matrices from DNN embeddings, at times fleshing out isomorphisms not otherwise observable. Pruning supervised by human brain/behavior therefore effectively identifies alignable dimensions of semantic knowledge between DNNs and humans and constitutes an effective method for understanding the organization of knowledge in neural networks.
Multi-morph eco-evolutionary dynamics in structured populations
Authors: Lion Sébastien , Boots Mike , Sasaki Akira 
Published: July 2021

AbstractOur understanding of the evolution of quantitative traits in nature is still limited by the challenge of including realistic trait distributions in the context of frequency-dependent selection and ecological feedbacks. We extend to class-structured populations a recently introduced “oligomorphic approximation” which bridges the gap between adaptive dynamics and quantitative genetics approaches and allows for the joint description of the dynamics of ecological variables and of the moments of multimodal trait distributions. Our theoretical framework allows us to analyse the dynamics of populations composed of several morphs and structured into distinct classes (e.g. age, size, habitats, infection status, species…). We also introduce a new approximation to simplify the eco-evolutionary dynamics using reproductive values. We illustrate the effectiveness of this approach by applying it to the important conceptual case of two-habitat migration-selection models. In particular, we show that our approach allows us to predict both the long-term evolutionary endpoints and the short-term transient dynamics of the eco-evolutionary process, including fast evolution regimes. We discuss the theoretical and practical implications of our results and sketch perspectives for future work.
Curcumin micronization by supercritical fluid:in vitroandin vivobiological relevance
Authors: Sachett Adrieli , Gallas-Lopes Matheus , Benvenutti Radharani , Marcon Matheus , Aguiar Gean Pablo S. , Herrmann Ana Paula , Oliveira J. Vladimir , Siebel Anna M. , Piato Angelo 
Published: July 2021

ABSTRACTCurcumin, a polyphenol extracted from the rhizome ofCurcuma longaL. (Zingiberaceae), is shown to have antioxidant, anti-inflammatory, neuroprotective, anxiolytic, and antidepressant properties in both preclinical and clinical studies. However, its low bioavailability is a limitation for its potential adoption as a therapeutic agent. The process of micronization can overcome this barrier by reducing the particle size and increasing the dissolution rate, potentially improving the bioavailability of the compounds of interest. In this study, we compared thein vitroantioxidant effects of curcumin (CUR) and micronized curcumin (MC) and studied their effects on behavioral and neurochemical parameters in zebrafish submitted to unpredictable chronic stress (UCS). MC (1 g/L) presented higher antioxidant activityin vitroas compared to CUR, as measured by iron-reducing antioxidant power (FRAP), 1,1-diphenyl-2-2-picyryl-hydrazyl radical removal (DPPH), and deoxyribose tests. UCS increased total distance traveled in the social interaction test (SI), while decreased crossings, time, and entries to the top area in the novel tank test (NTT). No effects of UCS were observed in the open tank test (OTT). The behavioral effects induced by UCS were not blocked by any curcumin preparation. UCS also decreased non-protein thiols (NPSH) levels, while increased glutathione reductase (GR) activity and thiobarbituric acid reactive substances (TBARS) levels on zebrafish brain. MC presented superior antioxidant properties than CURin vivo, blocking the stress-induced neurochemical effects. Although this study did not measure the concentration of curcumin on the zebrafish brain, our results suggest that micronization increases the bioavailability of curcumin, potentiating its antioxidant activity bothin vitroandin vivo. Our study also demonstrates that counteracting the oxidative imbalance induced by UCS is not sufficient to block its behavioral effects.
Phylotranscriptomics reveals discordance in the phylogeny of HawaiianDrosophilaandScaptomyza(Diptera: Drosophilidae)
Authors: Church Samuel H. , Extavour Cassandra G. 
Published: July 2021

AbstractIsland radiations present natural laboratories for studying the evolutionary process. The Hawaiian Drosophil-idae are one such radiation, with nearly 600 described species and substantial morphological and ecological diversification. These species are largely divided into a few major clades, but the relationship between these clades remains uncertain. Here we present 12 new assembled transcriptomes from across these clades, and use these transcriptomes to resolve the base of the evolutionary radiation. We recover a new hypothesis for the relationship between clades, and demonstrate its support over previously published hypotheses. We then use the evolutionary radiation to explore dynamics of concordance in phylogenetic support, by analyzing the gene and site concordance factors for every possible topological combination of major groups. We show that high bootstrap values mask low evolutionary concordance, and we demonstrate that the most likely topology is distinct from the topology with the highest support across gene trees and from the topology with highest support across sites. We then combine all previously published genetic data for the group to estimate a time-calibrated tree for over 300 species of drosophilids. Finally, we digitize dozens of published Hawaiian Drosophilidae descriptions, and use this to pinpoint probable evolutionary shifts in reproductive ecology as well as body, wing, and egg size. We show that by examining the entire landscape of tree and trait space, we can gain a more complete understanding of how evolutionary dynamics play out across an island radiation.
Flexible utilization of spatial- and motor-based codes for the storage of visuo-spatial information
Authors: Henderson Margaret , Rademaker Rosanne L. , Serences John T. 
Published: July 2021

AbstractWorking memory provides flexible storage of information in service of upcoming behavioral goals. Some models propose specific fixed loci and mechanisms for the storage of visual information in working memory, such as sustained spiking in parietal and prefrontal cortex during working memory maintenance. An alternative view is that information can be remembered in a flexible format that best suits current behavioral goals. For example, remembered visual information might be stored in sensory areas for easier comparison to future sensory inputs, or might be re-coded into a more abstract action-oriented format and stored in motor areas. Here, we tested this hypothesis using a visuo-spatial working memory task where the required behavioral response was either known or unknown during the memory delay period. Using fMRI and multivariate decoding, we found that there was less information about remembered spatial position in early visual and parietal regions when the required response was known versus unknown. Further, a representation of the planned motor action emerged in primary somatosensory, primary motor, and premotor cortex during the same task condition where spatial information was reduced in early visual cortex. These results suggest that the neural networks supporting working memory can be strategically reconfigured depending on specific behavioral requirements during a canonical visual working memory paradigm.
Dimensionality reduction and data integration for scRNA-seq data based on integrative hierarchical Poisson factorisation
Authors: Wong Thomas , Barahona Mauricio 
Published: July 2021

AbstractSingle-cell RNA sequencing (scRNA-seq) data sets consist of high-dimensional, sparse and noisy feature vectors, and pose a challenge for classic methods for dimensionality reduction. Such problems are compounded when dealing with composite data sets formed by different batches. We introduce Integrative Hierarchical Poisson Factorisation (IHPF), an extension of HPF that makes use of a noise ratio hyper-parameter to tune the variability attributed to batches vs. biological sources (cell phenotypes). We exemplify the application of IHPF under different data integration scenarios with varying alignments of batches and cell diversity, and show that IHPF produces latent factors that can be advantageously applied for cell clustering and visualisation. In addition, the extracted factors have a dual block structure in both cell and gene spaces with enhanced biological interpretability.