bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laminar Specificity of the Auditory Perceptual Awareness Negativity: A Biophysical Modeling Study
Authors: Pujol Carolina Fernandez , Blundon Elizabeth G. , Dykstra Andrew R. 
Published: March 2023

AbstractHow perception of sensory stimuli emerges from brain activity is a fundamental question of neuroscience. To date, two disparate lines of research have examined this question. On one hand, human neuroimaging studies have helped us understand the large-scale brain dynamics of perception. On the other hand, work in animal models (mice, typically) has led to fundamental insight into the micro-scale neural circuits underlying perception. However, translating such fundamental insight from animal models to humans has been challenging. Here, using biophysical modeling, we show that the auditory awareness negativity (AAN), an evoked response associated with perception of target sounds in noise, can be accounted for by synaptic input to the supragranular layers of auditory cortex (AC) that is present when target sounds are heard but absent when they are missed. This additional input likely arises from cortico-cortical feedback and/or non-lemniscal thalamic projections and targets the apical dendrites of layer-V pyramidal neurons (PNs). In turn, this leads to increased local field potential activity, increased spiking activity in layer-V PNs, and the AAN. The results are consistent with current cellular models of conscious processing and help bridge the gap between the macro and micro levels of perception-related brain activity.Author SummaryTo date, our understanding of the brain basis of conscious perception has mostly been restricted to large-scale, network-level activity that can be measured non-invasively in human subjects. However, we lack understanding of how such network-level activity is supported by individual neurons and neural circuits. This is at least partially because conscious perception is difficult to study in experimental animals, where such detailed characterization of neural activity is possible. To address this gap, we used biophysical modeling to gain circuit-level insight into an auditory brain response known as the auditory awareness negativity (AAN). This response can be recorded non-invasively in humans and is associated with perceptual awareness of sounds of interest. Our model shows that the AAN likely arises from specific cortical layers and cell types. These data help bridge the gap between circuit- and network-level theories of consciousness, and could lead to new, targeted treatments for perceptual dysfunction and disorders of consciousness.
Evaluating the theoretical performance of aircraft wastewater monitoring as a tool for SARS-CoV-2 surveillance
Authors: Shingleton Joseph W. , Lilley Chris J. , Wade Matthew J. 
Published: March 2023

AbstractBackgroundAir travel plays an import role in the cross-border spread of infectious diseases. During the SARS-CoV-2 pandemic many countries introduced strict border testing protocols to monitor the incursion of the virus. However, the high implementation cost and significant inconvenience to passengers has led public health authorities to consider alternative methods of disease surveillance at borders. Aircraft wastewater monitoring has been proposed as one such alternative. In this paper we assess the theoretical limits of aircraft wastewater monitoring and compare its performance to post-arrival border screening approaches.MethodsWe use an infectious disease model to simulate an unmitigated SARS-CoV-2 epidemic in a seed country. Seeding of the epidemic into the United Kingdom (UK) is simulated through daily flights between the two countries. We use a probabilistic approach to estimate the time of first detection of the disease in the UK in both aircraft wastewater and respiratory swab screening at the border.ResultsFor simulations across a broad range of model parameters, our analysis indicates that the median time between the first incursion of a pathogen and its detection in wastewater would be approximately 17 days (IQR: 7 - 28 days), resulting in a median of 25 cumulative cases (IQR: 6 - 84 cases) in the UK at the point of detection. Comparisons to respiratory swab screening suggest that aircraft wastewater monitoring is as effective as screening of 20% of passengers at the border, using a test with 95% sensitivity. For testing regimes with sensitivity of 85% or less, the required coverage to outperform wastewater monitoring increases to 30%. These results demonstrate the potential use cases of aircraft wastewater monitoring and its utility in a wider system of public health surveillance.
Sparse Activations for Interpretable Disease Grading
Authors: Donteu Djoumessi Kerol R. , Ilanchezian Indu , Kühlewein Laura , Faber Hanna , Baumgartner Christian F. , Bah Bubacarr , Berens Philipp , Koch Lisa M. 
Published: March 2023

AbstractInterpreting deep learning models typically relies on post-hoc saliency map techniques. However, these techniques often fail to serve as actionable feedback to clinicians, and they do not directly explain the decision mechanism. Here, we propose an inherently interpretable model that combines the feature extraction capabilities of deep neural networks with advantages of sparse linear models in interpretability. Our approach relies on straight-forward but effective changes to a deep bag-of-local-features model (BagNet). These modifications lead to fine-grained and sparse class evidence maps which, by design, correctly reflect the model’s decision mechanism. Our model is particularly suited for tasks which rely on characterising regions of interests that are very small and distributed over the image. In this paper, we focus on the detection of Diabetic Retinopathy, which is characterised by the progressive presence of small retinal lesions on fundus images. We observed good classification accuracy despite our added sparseness constraint. In addition, our model precisely highlighted retinal lesions relevant for the disease grading task and excluded irrelevant regions from the decision mechanism. The results suggest our sparse BagNet model can be a useful tool for clinicians as it allows efficient inspection of the model predictions and facilitates clinicians’ and patients’ trust.
Giving a voice to adults with COVID-19: An analysis of open-ended comments from smell longhaulers and non-longhaulers
Authors: Menger N. S. , Tognetti A. , Farruggia M. C. , Mucignat C. , Bhutani S. , Cooper K. W. , Rohlfs Dominguez P. , Heinbockel T. , Shields V. , D’Errico A. , Pereda-Loth V. , Pierron D. , Koyama S. , Croijmans I. 
Published: March 2023

AbstractSmell disorders are commonly reported with COVID-19 infection. Some patients show prolonged smell-related issues, even after the respiratory symptoms are resolved. To explore the concerns of patients, and to provide an overview for each specific smell disorder, we explored the longitudinal survey that was conducted by1, and contained self-reports on the changes of smell that participants experienced at two time points. People who still suffered from smell disorders at the second time point, hence named ‘longhaulers’, were compared to those who were not, hence named ‘non-longhaulers’. Specifically, three aims were pursued in this study. First, to classify smell disorders based on the participants’ self-reports. Second, to classify the sentiment of each self-report using a machine learning approach, and third, to find specific keywords that best describe the smell dysfunction in those self-reports. We found that the prevalence of parosmia and hyposmia was higher in longhaulers than in non-longhaulers. Furthermore, the results suggest that longhaulers stated self-reports with more negative sentiment than non-longhaulers. Finally, we found specific keywords that were more typical for either longhaulers compared to non-longhaulers. Taken together, our work shows consistent findings with previous studies, while at the same time, provides new insights for future studies investigating smell disorders.
A modelled analysis of the impact of COVID-19-related disruptions to HPV vaccination analysis
Authors: Velentzis Louiza S , Smith Megan A , Killen James , Brotherton Julia , Guy Rebecca , Canfell Karen 
Published: March 2023

AbstractCOVID-19 disrupted school attendance in many countries, delaying routine adolescent vaccination against human papillomavirus (HPV) in some settings. We used the ‘Policy1-Cervix’HPV model (natural history/vaccination/screening/HPV-related cancers), to estimate the impact on HPV-related cancers from disruptions to HPV vaccination in a high-income setting. Compared to no disruption (nonavalent vaccine uptake, age 12 [females:82.4%; males:75.5%] as in Australia), additional lifetime HPV-related cancer cases were calculated for three disruption scenarios affecting one birth cohort (2008): i) 1-year delay (no doses missed); ii) 1 to 7-year delay (slow catch-up); iii) no catch-up (herd effects only). A fourth scenario assumed no catch-up for two cohorts (2008,2009). We found a 1-year delay could result in ≤0.3% more HPV-related cancers (n=4) but the increase would be greater if catch-up was slower (5%; n=70), and especially if there was no catch-up (49%; n=750). Additional cancers for a single missed cohort were most commonly cervical (23%), oropharyngeal (males:20%) or anal (females:16%). In the worst-case scenario of two cohorts missing vaccination, ≤62% more HPV-related cancers would be diagnosed (n=1,892). In conclusion, providing catch-up of missed HPV vaccines is conducted, short-term delays in vaccinating adolescents are unlikely to have substantial long-term effects on cancer.
Identifying and overcoming the sampling challenges in relative binding free energy calculations of a model protein:protein complex
Authors: Zhang Ivy , Rufa Dominic A. , Pulido Iván , Henry Michael M. , Rosen Laura E. , Hauser Kevin , Singh Sukrit , Chodera John D. 
Published: March 2023

AbstractRelative alchemical binding free energy calculations are routinely used in drug discovery projects to optimize the affinity of small molecules for their drug targets. Alchemical methods can also be used to estimate the impact of amino acid mutations on protein:protein binding affinities, but these calculations can involve sampling challenges due to the complex networks of protein and water interactions frequently present in protein:protein interfaces. We investigate these challenges by extending a GPU-accelerated open-source relative free energy calculation package (Perses) to predict the impact of amino acid mutations on protein:protein binding. Using the well-characterized model system barnase:barstar, we describe analyses for identifying and characterizing sampling problems in protein:protein relative free energy calculations. We find that mutations with sampling problems often involve charge-changes, and inadequate sampling can be attributed to slow degrees of freedom that are mutation-specific. We also explore the accuracy and efficiency of current state-of-the-art approaches—alchemical replica exchange and alchemical replica exchange with solute tempering—for overcoming relevant sampling problems. By employing sufficiently long simulations, we achieve accurate predictions (RMSE 1.61, 95% CI: [1.12, 2.11] kcal/mol), with 86% of estimates within 1 kcal/mol of the experimentally-determined relative binding free energies and 100% of predictions correctly classifying the sign of the changes in binding free energies. Ultimately, we provide a model workflow for applying protein mutation free energy calculations to protein:protein complexes, and importantly, catalog the sampling challenges associated with these types of alchemical transformations. Our free open-source package (Perses) is based on OpenMM and available athttps://github.com/choderalab/perses.
Empowering Beginners in Bioinformatics with ChatGPT
Authors: Shue Evelyn , Liu Li , Li Bingxin , Feng Zifeng , Li Xin , Hu Gangqing 
Published: March 2023

AbstractThe impressive conversational and programming abilities of ChatGPT make it an attractive tool for facilitating the education of bioinformatics data analysis for beginners. In this study, we proposed an iterative model to fine-tune instructions for guiding a ChatGPT in generating code for bioinformatics data analysis tasks. We demonstrated the feasibility of the model by applying it to various bioinformatics topics. Additionally, we discussed practical considerations and limitations regarding the use of the model in chatbot-aided bioinformatics education.
A sample preparation procedure enables acquisition of 2-channel super-resolution 3D STED image of an entire oocyte
Authors: Frolikova Michaela , Blazikova Michaela , Capek Martin , Chmelova Helena , Valecka Jan , Kolackova Veronika , Valaskova Eliska , Gregor Martin , Komrskova Katerina , Horvath Ondrej , Novotny Ivan 
Published: March 2023

ABSTRACTSuper-resolution (SR) microscopy is a cutting-edge method that can provide detailed structural information with high resolution. However, the thickness of the specimen has been a major limitation for SR methods, and larger structures have posed a challenge. To overcome this, the key step is to optimize sample preparation to ensure optical homogeneity and clarity, which can enhance the capabilities of SR methods for the acquisition of thicker structures.Oocytes are the largest cells in the mammalian body and are crucial objects in reproductive biology. They are especially useful for studying membrane proteins. However, oocytes are extremely fragile and sensitive to mechanical manipulation and osmotic shocks, making sample preparation a critical and challenging step.We present an innovative, simple, and sensitive approach to oocyte sample preparation for 3D STED acquisition. This involves alcohol dehydration and mounting into a high refractive index medium. This extended preparation procedure allowed us to successfully obtain a unique 2-channel 3D STED super-resolution image of an entire mouse oocyte.By optimizing sample preparation, we can overcome the limitations of SR methods and obtain high-resolution images of larger structures, such as oocytes, Knowledge of which are important for understanding fundamental biological processes.RESEARCH HIGHLIGHTSThis study aimed to develop a successful sample preparation protocol for imaging mouse oocytes using 3D STED super-resolution microscopy.The results showed that the oocyte sample was optically homogenous, enhancing the capability of the 3D STED method to capture high-resolution images throughout the full depth of the sample, resulting in highly similar SR images.The 3D STED point spread function (PSF) pattern of the depletion laser was successfully secured throughout the entire volume of the sample, including the top and bottom.This study presents the first-ever full volume 3D image of the mouse oocyte, which was acquired using a 2-channel 3D STED method.GRAPHICAL ABSTRACTIntroducing an extended sample preparation procedure resulted in an outstanding optical quality sample environment pronounced by high refractive index, high transparency, and minimal spherical aberration. This procedure allowed 3D STED within the entire oocyte.
Bacillus thuringiensisbioinsecticide influencesDrosophilaoviposition decision
Authors: Babin Aurélie , Gatti Jean-Luc , Poirié Marylène 
Published: March 2023

AbstractBehavioural avoidance has obvious benefits for animals facing environmental stressors such as pathogen-contaminated foods. Most current bioinsecticides are based on the environmental and opportunistic bacteriumBacillus thuringiensis(Bt) that kills targeted insect pests upon ingestion. While food and oviposition avoidance ofBtbioinsecticide by targeted insect species was reported, this remained to be addressed in non-target organisms, especially those affected by chronic exposure toBtbioinsecticide such asDrosophilaspecies. Here, using a two-choice oviposition test, we showed that female flies of threeDrosophilaspecies (four strains ofD. melanogaster,D. busckiiandD. suzukii) avoided laying eggs in the presence ofBtvar.kurstakibioinsecticide, with potential benefits for the offspring and female’s fitness. Avoidance occurred rapidly, regardless of the fraction of the bioinsecticide suspension (spores and toxin crystals versus soluble toxins/components) and independently of the female motivation for egg laying. Our results suggest that, in addition to recent findings of developmental and physiological alterations upon chronic exposure of non-targetDrosophila, this bioinsecticide may have greater ecological implications in the field for theDrosophilacommunity and their associated natural enemies than previously thought.
TAD Evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function
Authors: Okhovat Mariam , VanCampen Jake , Lima Ana C. , Nevonen Kimberly A. , Layman Cora E. , Ward Samantha , Herrera Jarod , Stendahl Alexandra M. , Yang Ran , Harshman Lana , Li Weiyu , Sheng Rory R. , Mao Yafei , Fedorov Lev , Ndjamen Blaise , Vigh-Conrad Katinka A. , Matthews Ian R. , Easow Sarah A. , Chan Dylan K. , Jan Taha A. , Eichler Evan E. , Rugonyi Sandra , Conrad Donald F. , Ahituv Nadav , Carbone Lucia 
Published: March 2023

ABSTRACTTopological associating domains (TADs) are self-interacting genomic units crucial for shaping gene regulation patterns. Despite their importance, the extent of their evolutionary conservation and its functional implications remain largely unknown. In this study, we generate Hi-C and ChIP-seq data and compare TAD organization across four primate and four rodent species, and characterize the genetic and epigenetic properties of TAD boundaries in correspondence to their evolutionary conservation. We find that only 14% of all human TAD boundaries are shared among all eight species (ultraconserved), while 15% are human-specific. Ultraconserved TAD boundaries have stronger insulation strength, CTCF binding, and enrichment of older retrotransposons, compared to species-specific boundaries. CRISPR-Cas9 knockouts of two ultraconserved boundaries in mouse models leads to tissue-specific gene expression changes and morphological phenotypes. Deletion of a human-specific boundary near the autism-relatedAUTS2gene results in upregulation of this gene in neurons. Overall, our study provides pertinent TAD boundary evolutionary conservation annotations, and showcase the functional importance of TAD evolution.
Mapping of corticotropin-releasing factor, receptors and binding protein mRNA in the chicken telencephalon throughout development
Authors: Metwalli Alek H. , Pross Alessandra , Desfilis Ester , Abellán Antonio , Medina Loreta 
Published: March 2023

AbstractUnderstanding the neural mechanisms that regulate the stress response is critical to know how animals adapt to a changing world and is one of the key factors to be considered for improving animal welfare. Corticotropin releasing factor (CRF) is crucial for regulating physiological and endocrine responses, triggering the activation of the sympathetic nervous system and the hypothalamo – pituitary – adrenal axis (HPA) during stress. In mammals, several telencephalic areas, such as the amygdala and the hippocampus, regulate the autonomic system and the HPA responses. These centers include subpopulations of CRF containing neurons that, by way of CRF receptors, play modulatory roles in the emotional and cognitive aspects of stress. CRF binding protein also plays a role, buffering extracellular CRF and regulating its availability. CRF role in activation of the HPA is evolutionary conserved in vertebrates, highlighting the relevance of this system to help animals cope with adversity. However, knowledge on CRF systems in the avian telencephalon is very limited, and no information exists on detailed expression of CRF receptors and binding protein. Knowing that the stress response changes with age, with important variations during the first week posthatching, the aim of this study was to analyze mRNA expression of CRF, CRF receptors 1 and 2, and CRF binding protein in chicken telencephalon throughout embryonic and early posthatching development, using in situ hybridization. Our results demonstrate an early expression of CRF and its receptors in pallial areas regulating sensory processing, sensorimotor integration and cognition, and a late expression in subpallial areas regulating the stress response. However, CRF buffering system develops earlier in the subpallium than in the pallium. These results help to understand the mechanisms underlying the negative effects of noise and light during prehatching stages in chicken, and suggest that stress regulation becomes more sophisticated with age.
Mapping the Complex Genetic Landscape of Human Neurons
Authors: Sun Chen , Kathuria Kunal , Emery Sarah B , Kim ByungJun , Burbulis Ian E. , Shin Joo Heon ,   Brain Somatic Mosaicism Network, Weinberger Daniel R. , Moran John V. , Kidd Jeffrey M. , Mills Ryan E. , McConnell Michael J. 
Published: March 2023

AbstractWhen somatic cells acquire complex karyotypes, they are removed by the immune system. Mutant somatic cells that evade immune surveillance can lead to cancer. Neurons with complex karyotypes arise during neurotypical brain development, but neurons are almost never the origin of brain cancers. Instead, somatic mutations in neurons can bring about neurodevelopmental disorders, and contribute to the polygenic landscape of neuropsychiatric and neurodegenerative disease. A subset of human neurons harbors idiosyncratic copy number variants (CNVs, “CNV neurons”), but previous analyses of CNV neurons have been limited by relatively small sample sizes. Here, we developed an allele-based validation approach, SCOVAL, to corroborate or reject read-depth based CNV calls in single human neurons. We applied this approach to 2,125 frontal cortical neurons from a neurotypical human brain. This approach identified 226 CNV neurons, as well as a class of CNV neurons with complex karyotypes containing whole or substantial losses on multiple chromosomes. Moreover, we found that CNV location appears to be nonrandom. Recurrent regions of neuronal genome rearrangement contained fewer, but longer, genes.
Electronic wallet technology and the enabling environment of smallholder farmers in Nigeria
Authors: Uduji Joseph Ikechukwu , Okolo-Obasi Elda Nduka , Asongu Simplice Anutecia 
Published: March 2023

PurposeThe purpose of this paper is to critically examine the impact of a growth enhancement support scheme (GESS) on the enabling environment of smallholder farmers in sub-Saharan Africa. The main aim is to investigate the impact of the GESS on access to rural farm credit and the transport cost of smallholder farmers in the agricultural transformation agenda (ATA) in Nigeria.Design/methodology/approachThis paper adopts a survey research technique, aimed at gathering information from a representative sample of the population, as it is essentially cross-sectional, describing and interpreting the current situation. A total of 1,200 were sampled across the six geopolitical zones of Nigeria.FindingsThe results from the use of a double-hurdle model indicate that the GESS has a significant impact on farmers’ access to credit, but does not significantly impact on rural farm transport cost, which subsequently influences the price of food in the country.Practical implicationsThis implies that if the Federal Government of Nigeria is to work toward an ideal agricultural transformation agenda, transport networks should be closely aligned with the GESS priorities to provide connectivity to rural areas that provide most of the country’s agricultural output.Originality/valueThis research adds to the literature on the agricultural and rural development debate in developing countries. It concludes that embracing a rural finance and transportation infrastructure should form the foundation of the ATA in Nigeria, which, in turn, would provide a conducive environment for a more widespread rural economy in sub-Saharan Africa.