bluuebunny/crossref_metadata_2025_split huggingface dataset:
TALAIA: A 3D visual dictionary for protein structures
Authors: Alemany-Chavarria Mercè , Rodríguez-Guerra Jaime , Maréchal Jean-Didier 
Published: November 2022

AbstractSummaryGraphical analysis of the molecular structure of proteins can be very complex. Full atom representations retain most of the geometric information but are generally crowded and key structural patterns can be difficult to catch. Non-full atom representations could be more instructive on physicochemical aspects but be insufficiently detailed regarding shapes (e.g., entity beans-like models in coarse grain approaches) or individualistic properties of amino acids (e.g., representation of superficial electrostatic properties). TALAIA aims at providing another layer of structural representations. It is a visual dictionary where each amino acid is represented by a unique object with differentiated shapes and colors. It makes it easier to spot important molecular information including patches of amino acids or key interactions between side chains. Most of the conventions used in TALAIA are common in chemistry and biochemistry so that experimentalists and modelers can rapidly grasp the meaning of any TALAIA depictions.MotivationThe aim of the work is to offer a visual grammar that combines simplistic representations of amino acids while retaining their general geometry and physicochemical properties.ResultsWe propose a tool that renders protein structures and encodes both structure and physicochemical aspects as a simple visual grammar. The approach is fast, highly informative, and simple, allowing the identification of possible interactions, hydrophobic patches, and other characteristic structural features at a simple glance.Availabilityhttps://github.com/insilichem/talaiaContactjeandidier.marechal@uab.cat
Experience Alters the Timing Rules Governing Synaptic Plasticity and Learning
Authors: Jayabal Sriram , Bhasin Brandon J. , Kounga Maxwell , DiSanto Jennifer , Suvrathan Aparna , Goldman Mark S. , Raymond Jennifer L. 
Published: November 2022

ABSTRACTThe brain learns about the statistical relationships between events in the world through associative synaptic plasticity, controlled by the timing between neural events. Here, we show that experience can dramatically alter the timing rules governing associative plasticity and learning. In normally reared mice, the timing requirements for short- and long-term associative plasticity at synapses in the oculomotor cerebellum are precisely matched to the 120 ms delay for visual feedback to the circuit about behavioral errors. This specialization of the plasticity rules for the constraints of a particular circuit and learning task is acquired through experience. In dark-reared mice that never experienced visual feedback about oculomotor errors, synapses defaulted to a coincidence-based plasticity rule, with a corresponding delay in the timing of learned eye movements. This temporal metaplasticity persists into adulthood; when mice reared normally from birth were moved to dark housing as adults, the task-specific timing requirements for plasticity and the temporal accuracy of learning were lost and then re-established when visual experience was restored. Computational modeling suggests two general classes of biologically plausible mechanisms, each with multiple possible implementations, that can tune plasticity to distinct features of the statistics of neural activity. Temporal metaplasticity provides a potentially general mechanism for experience-dependent improvement in the way a circuit solves the “temporal credit assignment problem” inherent in most learning tasks, thereby providing a candidate synaptic mechanism for meta-learning.
Methylmap: visualization of modified nucleotides for large cohort sizes
Authors: Coopman Elise , Van den Broeck Marleen , De Poorter Tim , Joris Geert , Dickson Dennis W , Strazisar Mojca , Rademakers Rosa , De Coster Wouter 
Published: November 2022

SummaryMethylmap is a tool developed for visualization of modified nucleotide frequencies per position, especially for large numbers of samples. Various input possibilities are supported, including the standardized BAM/CRAM files containing MM and ML tags.Availability and implementationMethylmap is written in Python3 and available through PyPI and bioconda. The source code is released under MIT license and can be found athttps://github.com/EliseCoopman/methylmap.
Brewpitopes: a pipeline to refine B-cell epitope predictions during public health emergencies
Authors: Farriol-Duran Roc , López-Aladid Ruben , Porta-Pardo Eduard , Torres Antoni , Fernández-Barat Laia 
Published: November 2022

AbstractThe application of B-cell epitope identification for the development of therapeutic antibodies is well established but consuming in terms of time and resources. For this reason, in the last few years, the immunoinformatic community has developed several computational predictive tools.While relatively successful, most of these tools only use a few properties of the candidate region to determine their likelihood of being a true B-cell epitope. However, this likelihood is influenced by a wide variety of protein features, including the presence of glycosylated residues in the neighbourhood of the candidate epitope, the subcellular location of the protein region or the three-dimensional information about their surface accessibility in the parental protein.In this study we created Brewpitopes, an integrative pipeline to curate computational predictions of B-cell epitopes by accounting for all the aforementioned features. To this end, we implemented a set of rational filters to mimic the conditions for thein vivoantibody recognition to enrich the B-cell epitope predictions in actionable candidates. To validate Brewpitopes, we analyzed the SARS-CoV-2 proteome. In the S protein, Brewpitopes enriched the initial predictions in 5-fold on epitopes with neutralizing potential (p-value < 2e-4). Other than S protein, 4 out of 16 proteins in the proteome contain curated B-cell epitopes and hence, have also potential interest for viral neutralization, since mutational escape mainly affects the S protein. Our results demonstrate that Brewpitopes is a powerful pipeline for the rapid prediction of refined B-cell epitopes during public health emergencies.Statement of significanceWe have created Brewpitopes, a new pipeline that integrates additional important features such as glycosylation or structural accessibility, to curate B-cell epitope more likely to be functional in vivo. We have also validated Brewpitopes against SARS-CoV-2 not only for S protein but also for the entire viral proteome demonstrating that is a rapid and reliable epitope predictive tool to be implemented in present or future public health emergencies. Brewpitopes has identified 7 SARS-CoV-2 epitopes in S and epitopes allocated in 4 other proteins. Overall, offering an accurate selection of epitopes that might be scaled up to the production of new antibodies.
The Detection of COVID-19 in Chest X-Rays Using Ensemble CNN Techniques
Authors: Kuzinkovas Domantas , Clement Sandhya 
Published: November 2022

AbstractAdvances in the field of image classification using convolutional neural networks (CNNs) have greatly improved the accuracy of medical image diagnosis by radiologists. Numerous research groups have applied CNN methods to diagnose respiratory illnesses from chest x-rays, and have extended this work to prove the feasibility of rapidly diagnosing COVID-19 to high degrees of accuracy. One issue in previous research has been the use of datasets containing only a few hundred images of chest x-rays containing COVID-19, causing CNNs to overfit the image data. This leads to a lower accuracy when the model attempts to classify new images, as would be clinically expected of it. In this work, we present a model trained on the COVID-QU-Ex dataset, overall containing 33,920 chest x-ray images, with an equal share of COVID-19, Non-COVID pneumonia, and Normal images. The model itself is an ensemble of pre-trained CNNs (ResNet50, VGG19, VGG16) and GLCM textural features. It achieved a 98.34% binary classification accuracy (COVID-19/no COVID-19) on a balanced test dataset of 6581 chest x-rays, and 94.68% for distinguishing between COVID-19, Non-COVID pneumonia and normal chest x-rays. Also, we herein discuss the effects of dataset size, demonstrating that a 98.82% 3-class accuracy can be achieved using the model if the training dataset only contains a few thousand images, but that generalisability of the model suffers with such small datasets.
Vaccine hesitancy, reactogenicity and immunogenicity of BNT162b2 and CoronaVac in pediatric patients with neuromuscular diseases
Authors: Yu Michael Kwan Leung , Chan Hoi Shan Sophelia , Cheng Samuel , Leung Daniel , Chan Sau Man , Suen Amy Ka Yan , Wong Wilfred Hing Sang , Peiris Malik , Lau Yu Lung , Rosa Duque Jaime S 
Published: November 2022

AbstractIntroductionCOVID-19 causes global health and psychosocial devastation, particularly to high-risk patients such as those with neuromuscular diseases (NMDs). The mRNA-based BNT162b2 and inactivated whole-virus CoronaVac are two novel COVID-19 vaccines widely used across the world that confer immune protection to healthy individuals. However, hesitancy towards COVID-19 vaccination was common for patients with NMDs early in the pandemic due to the paucity of data on the safety and efficacy in this specific patient population. Therefore, we examined the underlying factors associated with vaccine hesitancy across time for these patients and included the assessment of the reactogenicity and immunogenicity of these two vaccines.MethodsPediatric patients were screened from our NMD registry. For the vaccine hesitancy arm, those aged 8-18 years with no cognitive delay were invited to complete surveys in January and April 2022. For the reactogenicity and immunogenicity arm, patients aged 2-21 years were enrolled for COVID-19 vaccination between June 2021 to April 2022. Participants recorded adverse reactions (ARs) for 7 days after vaccination. Peripheral blood was obtained before BNT162b2 or CoronaVac and within 49 days after vaccination to measure their serological antibody responses as compared to healthy children and adolescents.ResultsForty-one patients completed vaccine hesitancy surveys for both timepoints, and 22 joined our reactogenicity and immunogenicity arm of the study. Two or more family members vaccinated against COVID-19 was positively associated with intention of vaccination (odds ratio 11.7, 95% CI 1.81-75.1,p=0.010). Pain at the injection site, fatigue and myalgia were the commonest ARs. Most ARs were mild (75.5%, n=71/94). All 19 patients seroconverted against the wildtype SARS-CoV-2 after two doses of BNT162b2 or CoronaVac, although there was lower neutralization against the Omicron BA.1 variant.DiscussionThis study demonstrated vaccine hesitancy amongst patients with NMDs was influenced by family members and changed across time. BNT162b2 and CoronaVac were safe and immunogenic even for patients on low-dose corticosteroids. Future research is required to assess the durability of the COVID-19 vaccines, the effectiveness of booster doses and other routes of administration against emerging SARS-CoV-2 variants for these patients.
Factors affecting Transition Success and Satisfaction from Child to Adult Mental Health Services in the UK
Authors: Williams Paris , Willoughby Kate , Bennetts Alison , Brandt Valerie 
Published: November 2022

AbstractBackgroundQualitative research has identified factors affecting transition from child mental health services (CAMHS) to adult mental health services (AMHS) but it is unclear which of these factors may lead to disengagement from the young persons’ view.MethodsN= 272 participants (mean age = 20+/-2.31, 81% females) who had experience with the UK mental healthcare system (patients, carers, health workers) attempted the survey but only participants who had been treated in CAMHS were included in this study, resulting in a total N=144 (mean age = 19.8+/-2.3, 83% female). This study used a cross-sectional, quantitative survey assessing 12 pre-transition, 16 peri-transition, and 11 post-transition variables. The Client Attachment to Therapist Scale (CATS) was used to measure client attachment to CAMHS and AMHS therapists.ResultsSuccessful transition from CAMHS to AMHS was significantly predicted by using a helpful care plan, continuity of treatment between CAMHS and AMHS, and being engaged in a transition service. However, few clients were aware of transition services at the time of transition. Transition satisfaction was significantly predicted by the same variables. In addition, GP support during the transition, and a more secure attachment to AMHS therapists were associated with higher transition satisfaction.ConclusionsThe results suggest clients’ transition process might be significantly improved by focusing on useful individualised care plans, and ensuring continuity of treatment. Transition success and satisfaction could also be improved by making clients aware of and engaging them in transition services, involving GPs, and working on a secure attachment on the AMHS side.
Reliability of novel centre of pressure measures of quiet standing balance in people with chronic stroke
Authors: Jagroop David , Aryan Raabeae , Schinkel-Ivy Alison , Mansfield Avril 
Published: November 2022

ABSTRACTBackgroundPeople with stroke often have asymmetric motor impairment. Investigating asymmetries in, and dynamic properties of, centre of pressure movement during quiet standing can inform how well balance is controlled.Research questionWhat are the test-retest reliabilities of novel measures of quiet standing balance control in people with chronic stroke?MethodsTwenty people with chronic stroke (>6 months post-stroke), who were able to stand for at least 30 seconds without support, were recruited. Participants completed two 30-second quiet standing trials in a standardized position. Novel measures of quiet standing balance control included: symmetry of variability in centre of pressure displacement and velocity, between-limb synchronization, and sample entropy. Root mean square of centre of pressure displacement and velocity in the antero-posterior and medio-lateral directions were also calculated. Intraclass correlation coefficients (ICCs) were used to determine test-retest reliability, and Bland-Altman plots were created to examine proportional biases.ResultsICC3,2were between 0.79 and 0.95 for all variables, indicating ‘good’ to ‘excellent’ reliability (>0.75). However, ICC3,1for symmetry indices and between-limb synchronization were <0.75. Bland-Altman plots revealed possible proportional biases for root mean square of medio-lateral centre of pressure displacement and velocity and between-limb synchronization, with larger between-trial differences for participants with worse values.SignificanceThese findings suggest that centre of pressure measures extracted from a single 30-second quiet standing trial may have sufficient reliability for some research studies in chronic stroke. However, for clinical applications, the average of at least two trials may be required.
Establishing And Maintaining The Blood-Brain Barrier: Epigenetic And Signaling Determinants
Authors: Sadanandan Jayanarayanan , Thomas Sithara , Mathew Iny Elizabeth , Huang Zhen , Blackburn Spiros L , Tandon Nitin , Lokhande Hrishikesh , McCrea Pierre D , Bresnick Emery H. , Dash Pramod K , McBride Devin W , Harmanci Arif , Ahirwar Lalit K , Jose Dania , Dienel Ari C , Zeineddine Hussein A , Hong Sungha , Peeyush Kumar T 
Published: November 2022

AbstractThe blood-brain barrier (BBB) controls the movement of molecules into and out of the central nervous system (CNS). Since a functional BBB forms by mouse embryonic day E15.5, we reasoned that gene cohorts expressed in CNS endothelial cells (EC) at E13.5 contribute to BBB formation. In contrast, adult gene signatures reflect BBB maintenance mechanisms. Supporting this hypothesis, transcriptomic analysis revealed distinct cohorts of EC genes involved in BBB formation and maintenance. Here, we demonstrate that epigenetic regulator’s histone deacetylase 2 (HDAC2) and polycomb repressive complex 2 (PRC2) control EC gene expression for BBB development and prevent Wnt/β-catenin (Wnt) target genes from being expressed in adult CNS ECs. Low Wnt activity during development modifies BBB genes epigenetically for the formation of functional BBB. As a Class-I HDAC inhibitor induces adult CNS ECs to regain Wnt activity and BBB genetic signatures that support BBB formation, our results inform strategies to promote BBB repair.
Repurposing Vanoxerine as a new antimycobacterial drug and its impact on the mycobacterial membrane
Authors: Kingdon Alexander D. H. , Meosa John Asti-Rochelle , Batt Sarah M. , Besra Gurdyal S. 
Published: November 2022

AbstractMycobacterium tuberculosisis a deadly pathogen, currently the leading cause of death worldwide from a single infectious agent through tuberculosis infections. If the End TB 2030 strategy is to be achieved, additional drugs need to be identified and made available to supplement the current treatment regimen. In addition, drug resistance is a growing issue, leading to significantly lower treatment success rates, necessitating further drug development. Vanoxerine (GBR12909), a dopamine re-uptake inhibitor, was recently identified as having anti-mycobacterial activity. Repurposing vanoxerine or its analogues to treat tuberculosis infections may allow a faster route to clinical use than novel drug discovery. However, its effects on Mycobacteria were not well characterised. Herein, we report vanoxerine as a disruptor of the membrane potential, inhibiting mycobacterial efflux and survival, with an undetectable level of resistance. This study suggests a mechanism of action for vanoxerine, which will allow for its continued development and optimisation for pre-clinical testing.
How many ecological niches are defined by the superabundant marine microbeProchlorococcus?
Authors: Miyagi Miriam , Morrison Maike , Kirkpatrick Mark 
Published: November 2022

ABSTRACTDetermining the identities, frequencies, and memberships of ecotypes inProchlorococcusand other superabundant microbes (SAMs) is essential to studies of their evolution and ecology. This is challenging, however, because the extremely large population sizes of SAMs likely cause violations of foundational assumptions made by standard methods used in molecular evolution and phylogenetics. Here we present a tree-free likelihood method to identify ecotypes, which we define as populations with genome sequences whose high similarity is maintained by purifying selection. We applied the method to 96 genomes of the superabundant marine cyanobacteriumProchlorococcusand find that this sample is comprised of about 24 ecotypes, substantially more than the five major ecotypes that are generally recognized. The method presented here may prove useful with other superabundant microbes.
A general method for the development of multicolor biosensors with large dynamic ranges
Authors: Hellweg Lars , Edenhofer Anna , Barck Lucas , Huppertz Magnus-Carsten , Frei Michelle. S. , Tarnawski Miroslaw , Bergner Andrea , Koch Birgit , Johnsson Kai , Hiblot Julien 
Published: November 2022

AbstractFluorescent biosensors enable to study cell physiology with spatiotemporal resolution, yet most biosensors suffer from relatively low dynamic ranges. Here, we introduce a family of designed Förster Resonance Energy Transfer (FRET) pairs with near quantitative FRET efficiencies based on the reversible interaction of fluorescent proteins with a fluorescently labeled HaloTag. These FRET pairs enabled the straightforward design of biosensors for calcium, ATP and NAD+with unprecedented dynamic ranges. The color of each of these biosensors can be readily tuned by either changing the fluorescent protein or the synthetic fluorophore, which enabled to monitor simultaneously free NAD+in different subcellular compartments upon genotoxic stress. Minimal modifications furthermore allow the readout of these biosensors to be switched to fluorescence intensity, lifetime or bioluminescence. These FRET pairs thus establish a new concept for the development of highly sensitive and tunable biosensors.Graphical abstract
Biochemical-free enrichment or depletion of RNA classes in real-time during direct RNA sequencing with RISER
Authors: Sneddon Alexandra , Ravindran Agin , Shanmuganandam Somasundhari , Kanchi Madhu , Hein Nadine , Jiang Simon , Shirokikh Nikolay , Eyras Eduardo 
Published: November 2022

AbstractThe heterogeneous composition of cellular transcriptomes poses a major challenge for detecting weakly expressed RNA classes, as they can be obscured by abundant RNAs. Although biochemical protocols can enrich or deplete specified RNAs, they are time-consuming, expensive and can compromise RNA integrity. Here we introduce RISER, a biochemical-free technology for the real-time enrichment or depletion of RNA classes. RISER performs selective rejection of molecules during direct RNA sequencing by identifying RNA classes directly from nanopore signals with deep learning and communicating with the sequencing hardware in real time. By targeting the dominant messenger and mitochondrial RNA classes for depletion, RISER reduced their respective read counts by more than 85%, resulting in an increase in sequencing depth of up to 93% for long non-coding RNAs. We also applied RISER for the depletion of globin mRNA in whole blood, achieving a decrease in globin reads by more than 90% as well as a significant increase in non-globin reads. Furthermore, using a GPU or a CPU, RISER is faster than GPU-accelerated basecalling and mapping. RISER’s modular and retrainable software and intuitive command-line interface allow easy adaptation to other RNA classes. RISER is available athttps://github.com/comprna/riser.
The worldwide allometric relationship in anatomical structures for plant roots
Authors: Zhang Yue , Cao Jing-Jing , Yang Qing-Pei , Wu Ming-Zuo , Zhao Yong , Kong De-Liang 
Published: November 2022

AbstractThe anatomical structures, i.e., the cortex and stele, are fundamental for the absorptive function of plant roots. Unraveling how the allometric structures are assembled in absorptive roots is essential for our understanding the plant ecology, physiology and responses to global environmental changes. In this review study, we first compile a globally largest dataset on key root structural traits, i.e., root diameter, cortex thickness and stele radius across 512 species. Using this largest dataset, we confirm an allometric relationship of absorptive root structures in a previous study using a much smaller species pool, i.e., the cortex thickness increased much faster than the stele radius with increasing root diameter. The allometric relationship is further validated within and across different plant growth forms (woody, grass, and liana species), mycorrhiza types (arbuscular mycorrhiza, ectomycorrhiza, and orchid mycorrhizas), phylogenetic gradients (from ferns to Orchidaceae of primitive angiosperms), and environmental change scenarios (e.g., the elevation of atmospheric CO2concentration and nitrogen fertilization), supporting the universal allometric relationship in plant roots. We then summarized recent proceedings as well as possible issues on mechanisms underlying the root allometric relationship. The ecological and evolutionary implications for this allometric relationship in roots are also discussed. Finally, we propose several directions that should be stressed in future studies regarding the allometric relationship in plant roots.