bluuebunny/crossref_metadata_2025_split huggingface dataset:
The vertical position of visual information conditions spatial memory performance in healthy aging
Authors: Durteste M. , Van Poucke L. , Combariza S. , Benziane B. , Sahel J-A. , Ramanoël S. , Arleo A. 
Published: October 2022

AbstractMemory for objects and their location is a cornerstone of adequate cognitive functioning across the lifespan. Considering that human visual perception is dependent upon the position of stimuli within the visual field, we posit that the position of objects in the environment may be a determinant aspect of mnemonic performance. In this study, a population of young and older adults completed a source monitoring task with objects presented either in the upper or lower visual field. Using multinomial processing tree modeling, we revealed that while item memory remained intact in older age, spatial memory was impaired but only for objects that had been presented in the upper visual field. Spatial memory is therefore conditioned by the vertical position of information. These findings put into question the traditional view that age-related spatial mnemonic deficits are primarily attributable to high-order associative dysfunctions and suggest that they could also originate from altered encoding of object attributes.
The first complete mitochondrial genome ofDiadema antillarum(Diadematoida, Diadematidae)
Authors: Majeske Audrey J. , Mercado Capote Alejandro J. , Komissarov Aleksey , Bogdanova Anna , Schizas Nikolaos V. , Castro Márquez Stephanie O. , Hilkert Kenneth , Wolfsberger Walter , Oleksyk Tarás K. 
Published: October 2022

ABSTRACTThe mitochondrial genome of the long-spined black sea urchin,Diadema antillarum, was sequenced using Illumina next generation sequencing technology. The complete mitogenome is 15,708 bp in length, containing 2 rRNA, 22 tRNA and 13 protein-coding genes, plus a non-coding control region of 133 bp. The nucleotide composition includes 18.37% G, 23.79% C, 26.84% A and 30.99% T. The A + T bias is 57.84%. Phylogenetic analysis based on 12 complete mitochondrial genomes of sea urchins including four species of the family Diadematidae supported familial monophyly, however the twoDiademaspecies,D. antillarumandD. setosumwere not recovered as sister taxa.
Activin A promotes bone fracture repair and acts through a novel myofibroblastic cell population in callus
Authors: Yao Lutian , Zhong Leilei , Wei Yulong , Gui Tao , Wang Luqiang , Ahn Jaimo , Boerckel Joel , Rux Danielle , Mundy Christina , Qin Ling , Pacifici Maurizio 
Published: October 2022

AbstractInsufficient bone fracture repair represents a significant clinical burden, and identification of novel therapeutics enhancing repair would have substantial clinical and societal impact. Activin A is a TGF-β protein superfamily member known to stimulate ectopic bone formation, but its roles in fracture repair and its therapeutic potentials remain unclear. Using two mouse tibia fracture repair models, here we mapped activin A expression at the tissue and single cell levels, tested its requirement for normal repair and evaluated its ability to enhance repair when provided exogenously. Activin A was minimally expressed in periosteum of intact bones but was markedly upregulated in developing callus soon after fracture. Single cell RNA-sequencing revealed that the activin A-encoding gene Inhba marked a unique, highly proliferative progenitor cell (PPC) population with a myofibroblast character which emerged over repair time and lay at the center of a developmental trajectory bifurcation producing cartilage and bone cells within callus. Systemic administration of a neutralizing activin A antibody impaired fracture repair and its endochondral and intramembranous phases, whereas local delivery of recombinant activin A enhanced repair. Activin A delivery also induced SMAD2 phosphorylation in vivo and increased the fraction of αSMA+ myofibroblasts within fracture callus. Gain- and loss-of-function experiments in vitro showed that activin A directly stimulated myofibroblast differentiation, chondrogenesis and osteogenesis in periosteal progenitor cells. Together, these data identify a unique population of Inhba-expressing proliferative progenitor cells that give rise to chondrocytes and osteoblasts during fracture healing and establish activin A as a potential new therapeutic tool to enhance it.One Sentence SummaryDeficits in bone fracture repair remain a clinical challenge and the present study provides evidence for the therapeutic potentials of activin A
WWOX P47T loss-of-function mutation induces epilepsy, progressive neuroinflammation, and cerebellar degeneration in mice phenocopying human SCAR12
Authors: Hussain Tabish , Sanchez Kevin , Crayton Jennifer , Saha Dhurjhoti , Jeter Collene , Lu Yue , Abba Martin , Seo Ryan , Noebels Jeffrey L , Fonken Laura , Aldaz C Marcelo 
Published: October 2022

ABSTRACTWWOX gene loss-of-function (LoF) has been associated with neuropathologies resulting in developmental, epileptic, and ataxic phenotypes of varying severity based on the level of WWOX dysfunction. WWOX gene biallelic germline variant p.Pro47Thr (P47T) has been causally associated with a new form of autosomal recessive cerebellar ataxia with epilepsy and intellectual disability (SCAR12). This mutation affects the WW1 protein binding domain of WWOX, impairing its ability to interact with canonical proline-proline-X-tyrosine motifs in partner proteins. We generated a mutant knock-in mouse model of Wwox P47T that phenocopies SCAR12. WwoxP47T/P47T mice displayed epilepsy, profound social behavior and cognition deficits, and poor motor coordination, and unlike KO models that survive only for 1 month, live beyond 1 year of age. These deficits progressed with age, and mice became practically immobile, suggesting severe cerebellar dysfunction. WwoxP47T/P47T mice exhibited signs of progressive neuroinflammation with elevated astro-microgliosis that increased with age. The cerebellar cortex displayed significantly reduced molecular and granular layer thickness and a strikingly reduced number of Purkinje cells with degenerated dendrites. Transcriptome profiling from various brain regions from these Wwox LoF mice highlighted widespread changes in neuronal and glial pathways, enrichment of bioprocesses related to neuroinflammation and severe cerebellar dysfunction, activation of pathways compatible with compensatory neurogenesis along with major suppression of gene networks associated with excitability, neuronal cell differentiation and brain development. Our results show significant pathobiological effects and potential mechanisms through which WWOX LoF leads to epilepsy, cerebellar neurodegeneration, neuroinflammation, and ataxia. Additionally, the mouse model described here will be a useful tool for the study of WWOX in common neurodegenerative conditions in which it has been identified as a novel risk factor.
Resource-efficient Neural Network Architectures for Classifying Nerve Cuff Recordings on Implantable Devices
Authors: Hwang Y. E. , Genov R. , Zariffa J. 
Published: October 2022

AbstractBackgroundClosed-loop control of functional electrical stimulation involves using recorded nerve signals to make decisions regarding nerve stimulation in real-time. Surgically implanted devices that can implement this strategy have significant potential to restore natural movement after paralysis. Previous work demonstrated the use of convolutional neural networks (CNNs) to discriminate between activity from different neural pathways recorded by a high-density multi-contact nerve cuff electrode. Despite state-of-the-art performance, that approach required too much data storage, power and computation time for a practical implementation on surgically implanted hardware.ObjectiveTo reduce resource utilization for an implantable implementation, with a minimal performance loss for CNNs that can discriminate between neural pathways in multi-contact nerve cuff electrode recordings.MethodsNeural network (NN) architectures were evaluated on a dataset of rat sciatic nerve recordings previously collected using 56-channel (7 x 8) spiral nerve cuff electrodes to capture spatiotemporal neural activity patterns. The NNs were trained to classify individual, natural compound action potentials (nCAPs) elicited by sensory stimuli. Three architecture types were explored: the previously reported ESCAPE-NET, a fully convolutional network, and a recurrent neural network. Variations of each architecture yielded NNs with a range in the number of weights and required floating-point operations (FLOPs). Each NN was evaluated based on F1-score and resource requirements.ResultsNNs were identified that, when compared to ESCAPE-NET, required 1,132-1,787x fewer weights, 389-995x less memory, and 6-11,073x fewer FLOPs, while maintaining macro F1-scores of 0.70-0.71 compared to a baseline of 0.75. Memory requirements range from 22.69 KB to 58.11 KB, falling within the range of on-chip memory sizes from several published deep learning accelerators fabricated in 65nm ASIC technology.ConclusionReduced versions of ESCAPE-NET require significantly fewer resources without significant accuracy loss, thus can be more easily incorporated into a surgically implantable device that performs closed-loop real-time responsive neural stimulation.
Social investigation and social novelty in zebrafish: Roles of salience and novelty
Authors: do Nascimento Bianca Gomes , Maximino Caio 
Published: October 2022

AbstractSocial preference tests can be used to analyze variables that influence and modify social behaviors, and to investigate effects of substances such as medications, drugs, and hormones. They may become important tools for finding a valid model to study neuropsychiatric changes and to study human neurodevelopmental processes that have been impaired by social events. While a preference for conspecifics has been shown for different species, social novelty has been used as a model for anxiety-like behavior in rodents. The goal of this research was to understand the roles of stimulus salience (numerousness) and novelty in social investigation and social novelty tests in zebrafish (Danio rerioHamilton 1822). We used a sequential design, in which animals are exposed first to a social investigation test (with dichotomous presentation of novel conspecifics vs. empty tank) and then to a social novelty test (with dichotomous presentation of the already known conspecific and a novel conspecific). In experiment 1, animals were presented to either 1 or 3 (vs. an empty tank) conspecifics as stimuli. In experiment 2, animals were presented to 1 vs. 3 conspecifics as stimuli. In experiment 3, animals were observed in the social investigation and social novelty tests for 3 consecutive days. The results showed equivalence between 1 or 3 conspecifics in the social investigation and social novelty tests, although animals were able to discriminate between different shoal sizes. These preferences do not change with repeated test exposure, suggesting novelty to be a minor contributor to social investigation and social novelty in zebrafish.
Near Infrared Nanosensors Enable Optical Imaging of Oxytocin with Selectivity over Vasopressin in Acute Mouse Brain Slices
Authors: Navarro Nicole , Jeong Sanghwa , Ouassil Nicholas , Mun Jaewan , Leem Esther , Landry Markita P. 
Published: October 2022

AbstractOxytocin plays a critical role in regulating social behaviors, yet our understanding of its role in both neurological health and disease remains incomplete. Real-time oxytocin imaging probes with the spatiotemporal resolution relevant to its endogenous signaling are required to fully elucidate oxytocin function in the brain. Herein we describe a near-infrared oxytocin nanosensor (nIROx), a synthetic probe capable of imaging oxytocin in the brain without interference from its structural analogue, vasopressin. nIROx leverages the inherent tissue-transparent fluorescence of single-walled carbon nanotubes (SWCNT) and the molecular recognition capacity of an oxytocin receptor peptide fragment (OXTp) to selectively and reversibly image oxytocin. We employ these nanosensors to monitor electrically stimulated oxytocin release in brain tissue, revealing oxytocin release sites with a median size of 3 μm which putatively represents the spatial diffusion of oxytocin from its point of release. These data demonstrate that covalent SWCNT constructs such as nIROx are powerful optical tools that can be leveraged to measure neuropeptide release in brain tissue.
Eradication of tumors with pre-existing antigenic heterogeneity by vaccine-mediated co-engagement of CAR T and endogenous T-cells
Authors: Ma Leyuan , Morgan Duncan M. , Sulkaj Ina , Yousefpour Parisa , Whittaker Charles A. , Abraham Wuhbet , Li Na , Love J. Christopher , Irvine Darrell J. 
Published: October 2022

AbstractChimeric Antigen Receptor (CAR) T-cell therapy can be effective in treating human cancer but loss of the antigen recognized by the CAR poses a major obstacle. Here, we report an approach for vaccine boosting CAR T-cells, which triggers engagement of the endogenous immune system to circumvent antigen-negative tumor escape. Vaccine-boosted CAR T-cells promoted dendritic cell (DC) recruitment to tumors, increased tumor antigen uptake by DCs, and elicited priming of endogenous anti-tumor T-cells (antigen spreading). This process was accompanied by a shift in toward oxidative phosphorylation in CAR T-cells and was critically dependent on CAR-T-derived IFN-γ. Antigen spreading induced by vaccine-boosted CAR-T enabled a proportion of complete responses even when the initial tumor was 50% CAR-antigen-negative, and heterogenous tumor control was further enhanced by genetically amplifying CAR-T IFN-γ expression. Thus, CAR T-cell-derived IFN-γ plays a critical role in promoting antigen spreading, and vaccine boosting provides a clinically-translatable strategy to drive such responses against solid tumors.
Systemic inflammation impairs human myelopoiesis and interferon I responses
Authors: Keramati Farid , Leijte Guus P. , Bruse Niklas , Grondman Inge , Habibi Ehsan , Ruiz-Moreno Cristian , Megchelenbrink Wout , Peters van Ton Annemieke M. , Heesakkers Hidde , Bremmers Manita , van Grinsven Erinke , Tesselaar Kiki , van Staveren Selma , van der Velden Walter , Preijers Frank , Gerretsen Jelle , Netea Mihai G. , Stunnenberg Hendrik G. , Pickkers Peter , Kox Matthijs 
Published: October 2022

AbstractSystemic inflammation (SI) plays a detrimental role in various conditions with high mortality rates1–4. SI manifests an acute hyperinflammation followed by long-lasting immunosuppression, increasing patients’ risks for secondary infections and impaired clinical outcomes5–7. Due to the extensive heterogeneity in SI etiology, the mechanisms governing these states are incompletely understood. Here, we characterized acute and late effects of lipopolysaccharide (LPS)-induced SI (LPS-SI8) on blood monocytes and bone marrow (BM) cells of healthy volunteers. Like clinical SI, LPS administration elicited a profound but transient acute response. Single-cell transcriptomic analysis of acute LPS-SI unveiled loss of BM monocytes and appearance of an inflammatory monocyte-like (i-Mono’s) population, expressing gene programs similar to early-stage sepsis patients9. In the ensuing late phase of LPS-SI, we observed reduced expression of interferon type I (IFN-I) responsive genes in monocytes and profound attenuation of in vivo response to a second LPS challenge. Furthermore, late LPS-SI led to impaired myelopoiesis with a loss of intermediate and non-classical monocytes. In accordance, we show compromised myelopoiesis also occurs in late-stage sepsis. Finally, IFNβ treatment reversed LPS-induced immunosuppression in monocytes. Our results reveal long-lasting effects of SI on myelopoiesis and substantiate the importance of IFN-I in the pathophysiology of SI-induced immunosuppression.
Antibody selection strategies and their impact in the analysis of malaria multi-sera data
Authors: Fonseca André , Spytek Mikolaj , Biecek Przemyslaw , Cordeiro Clara , Sepúlveda Nuno 
Published: October 2022

AbstractBackgroundNowadays, the chance of discovering the best antibody candidates for explaining naturally acquired protection to malaria and detecting exposure to malaria parasites has notably increased due to publicly available multi-sera data. The analysis of these data is typically divided into a feature selection phase followed by a predictive one where several models are constructed for the outcome of interest. A key question in the analysis is to determine which and how each feature should be included in the predictive stage.ResultsTo answer this question, we developed three approaches for classifying malaria protected and susceptible groups: (i) a basic and simple approach based on selecting antibodies via the nonparametric Mann-Whitney test; (ii) a dichotomization approach where each antibody was selected according to the optimal cut-off via maximization of the χ2statistic for two-way tables; (iii) a hybrid parametric/non-parametric approach that integrates Box-Cox transformation followed by a t-test, together with the use of finite mixture models and the Mann-Whitney test as a last resort. We illustrated the application of these three approaches with published serological data for predicting clinical malaria in 121 Kenyan children. The predictive analysis was based on a Super-Learner where predictions from multiple classifiers were pooled together. Our results led to almost similar areas under the Receiver Operating Characteristic curves of 0.72 (95% CI = [0.61, 0.82]), 0.80 (95% CI = [0.71, 0.90]), 0.79 (95% CI = [0.7, 0.88]) for the simple, dichotomization and hybrid approaches, respectively.ConclusionsThe three feature selection strategies provided a better predictive performance of the outcome when compared to the previous results solely relying on Random Forests alone (AUC=0.68). Given the similar predictive performance, we recommended the three strategies should be used in conjunction in the same data set and selected according to their complexity.
Predicting the combined effects of case isolation, safe funeral practices, and contact tracing during Ebola virus disease outbreaks
Authors: Bouba Aliou , Helle Kristina Barbara , Schneider Kristan Alexander 
Published: October 2022

AbstractBackgroundThe recent outbreaks of Ebola virus disease (EVD) in Uganda and the Marburg virus disease in Ghana reflect a persisting threat of Filoviridae to the global health community. Characteristic of Filoviridae are not just their high case fatality rates, but also that corpses are highly contagious and prone to cause infections in the absence of appropriate precautions. Vaccines against the most virulent Ebolavirus species, the Zaire ebolavirus (ZEBOV) are approved. However, there exists no approved vaccine or treatment against the Sudan ebolavirus (SUDV) which causes the current outbreak of EVD. Hence, the control of the outbreak relies on case isolation, safe funeral practices, and contact tracing. So far, the effectiveness of these control measures was studied only separately by epidemiological models, while the impact of their interaction is unclear.Methods and findingsTo sustain decision making in public health-emergency management, we introduce a predictive model to study the interaction of case isolation, safe funeral practices, and contact tracing. The model is a complex extension of an SEIR-type model, and serves as an epidemic preparedness tool. The model considers different phases of the EVD infections, the possibility of infections being treated in isolation (if appropriately diagnosed), in hospital (if not properly diagnosed), or at home (if the infected do not present to hospital for whatever reason). It is assumed that the corpses of those who died in isolation are buried with proper safety measures, while those who die outside isolation might be buried unsafely, such that transmission can occur during the funeral. Furthermore, the contacts of individuals in isolation will be traced. Based on parameter estimates from the scientific literature, the model suggests that proper diagnosis and hence isolation of cases has the highest impact in reducing the size of the outbreak. However, the combination of case isolation and safe funeral practices alone are insufficient to fully contain the epidemic under plausible parameters. This changes if these measures are combined with contact tracing. In addition, shortening the time to successfully trace back contacts contribute substantially to contain the outbreak.ConclusionsIn the absence of an approved vaccine and treatment, EVD management by proper and fast diagnostics in combination with epidemic awareness are fundamental. Awareness will particularly facilitate contact tracing and safe funeral practices. Moreover, proper and fast diagnostics are a major determinant of case isolation. The model introduced here is not just applicable to EVD, but also to other hemorrhagic diseases such as the MVD or the Lassa fever.
Comparative Efficacy and Safety of Tenecteplase and Alteplase in Acute Ischemic Stroke: A Pairwise and Network Meta-analysis of Randomized Controlled Trials
Authors: Rehman Aqeeb Ur , Mohsin Aleenah , Cheema Huzaifa Ahmad , Zahid Afra , Rehman Muhammad Ebaad Ur , Ameer Muhammad Zain , Ayyan Muhammad , Ehsan Muhammad , Shahid Abia , Ur Rehman Muhammad Aemaz , Shah Jaffer , Khawaja Ayaz 
Published: October 2022

AbstractBackgroundStudies on tenecteplase have been yielding mixed results on several important variables at different doses, thus hampering objective guideline recommendations in acute ischemic stroke management. This meta-analysis stratifies doses in order to refine our interpretation of outcomes and quantify the benefits and harms of tenecteplase at different doses.MethodsPubMed/MEDLINE, the Cochrane Library, and reference lists of the included articles were systematically searched. Several efficacy and safety outcomes were pooled and reported as risk ratios (RRs) with 95% confidence intervals (CIs). Network meta-analysis was used to find the optimal dose of tenecteplase. Meta-regression was run to investigate the impact of baseline NIHSS scores on functional outcomes and mortality.ResultsTen randomized controlled trials with a total of 4140 patients were included. 2166 (52.32%) patients were enrolled in the tenecteplase group and 1974 (47.68%) in the alteplase group. Tenecteplase at 0.25 mg/kg dose demonstrated significant improvement in excellent functional outcome at 3 months (RR 1.14, 95% CI 1.04-1.26), and early neurological improvement (RR 1.53, 95% CI 1.03-2.26). There was no statistically significant difference between tenecteplase and alteplase in terms of good functional outcome, intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality at any dose. Meta-regression demonstrated superior tenecteplase efficacy with increasing stroke severity, however, the results were statistically nonsignificant.ConclusionsTenecteplase at 0.25 mg/kg dose is more efficacious and at least as safe as alteplase for stroke thrombolysis. Newer analyses need to focus on direct comparison of tenecteplase doses and whether tenecteplase is efficacious at longer needle times.