bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges of Deep Learning Methods for COVID-19 Detection Using Public Datasets
Authors: Hasan Md. Kamrul , Alam Md. Ashraful , Dahal Lavsen , Elahi Md. Toufick E , Roy Shidhartho , Wahid Sifat Redwan , Martí Robert , Khanal Bishesh 
Published: November 2020

ABSTRACTA large number of studies in the past months have proposed deep learning-based Artificial Intelligence (AI) tools for automated detection of COVID-19 using publicly available datasets of Chest X-rays (CXRs) or CT scans for training and evaluation. Most of these studies report high accuracy when classifying COVID-19 patients from normal or other commonly occurring pneumonia cases. However, these results are often obtained on cross-validation studies without an independent test set coming from a separate dataset and have biases such as the two classes to be predicted come from two completely different datasets. In this work, we investigate potential overfitting and biases in such studies by designing different experimental setups within the available public data constraints and highlight the challenges and limitations of developing deep learning models with such datasets. We propose a deep learning architecture for COVID-19 classification that combines two very popular classification networks, ResNet and Xception, and use it to carry out the experiments to investigate challenges and limitations. The results show that the deep learning models can overestimate their performance due to biases in the experimental design and overfitting to the training dataset. We compare the proposed architecture to state-of-the-art methods utilizing an independent test set for evaluation, where some of the identified bias and overfitting issues are reduced. Although our proposed deep learning architecture gives the best performance with our best possible setup, we highlight the challenges in comparing and interpreting various deep learning algorithms’ results. While the deep learning-based methods using chest imaging data show promise in being helpful for clinical management and triage of COVID-19 patients, our experiments suggest that a larger, more comprehensive database with less bias is necessary for developing tools applicable in real clinical settings.
A Deep Graph Neural Network Architecture for Modelling Spatio-temporal Dynamics in resting-state functional MRI Data
Authors: Azevedo Tiago , Campbell Alexander , Romero-Garcia Rafael , Passamonti Luca , Bethlehem Richard A.I. , Liò Pietro , Toschi Nicola 
Published: November 2020

AbstractResting-state functional magnetic resonance imaging (rs-fMRI) has been successfully employed to understand the organisation of the human brain. For rs-fMRI analysis, the brain is typically parcellated into regions of interest (ROIs) and modelled as a graph where each ROI is a node and pairwise correlation between ROI blood-oxygen-level-dependent (BOLD) time series are edges. Recently, graph neural networks (GNNs) have seen a surge in popularity due to their successes in modelling unstructured relational data. The latest developments with GNNs, however, have not yet been fully exploited for the analysis of rs-fMRI data, particularly with regards to its spatio-temporal dynamics. Herein we present a novel deep neural network architecture, combining both GNNs and temporal convolutional networks (TCNs), which is able to learn from the spatial and temporal components of rs-fMRI data in an end-to-end fashion. In particular, this corresponds to intra-feature learning (i.e., learning temporal dynamics with TCNs) as well as inter-feature learning (i.e., leveraging spatial interactions between ROIs with GNNs). We evaluate our model with an ablation study using 35,159 samples from the UK Biobank rs-fMRI database. We also demonstrate explainability features of our architecture which map to realistic neurobiological insights. We hope our model could lay the groundwork for future deep learning architectures focused on leveraging the inherently and inextricably spatio-temporal nature of rs-fMRI data.
Olfactory neuron turnover in adultDrosophila
Authors: Fernández-Hernández Ismael , Hu Eric , Bonaguidi Michael A. 
Published: November 2020

ABSTRACTSustained neurogenesis occurs in the olfactory epithelium of several species, including humans, to support olfactory function throughout life. We recently developed a modified lineage tracing method to identify adult neurogenesis inDrosophila. By applying this technique, here we report on the continuous generation of Olfactory Sensory Neurons (OSN) in the antennae of adultDrosophila. New neurons develop sensory dendrites and project axons targeting diverse glomeruli of the antennal lobes in the brain. Furthermore, we identified sustained apoptosis of OSN in the antennae of adult flies, revealing unexpected turnover in the adult olfactory system. Our results substantiateDrosophilaas a compelling platform to expedite research about mechanisms and compounds promoting neuronal regeneration, circuit remodeling and its contribution to behavior in the adult.
Molecular phylogenetics and character evolution inHaplanthodes(Acanthaceae), an endemic genus from peninsular India
Authors: Surveswaran Siddharthan , Tiwari Neha , Karanth Praveen K. , Deshmukh Pradip V. , Lekhak Manoj M. 
Published: November 2020

AbstractHaplanthodes(Acanthaceae) is an Indian endemic genus with four species. It is closely related toAndrographiswhich is also mainly distributed in India.Haplanthodesdiffers fromAndrographisby the presence of cladodes in the inflorescences, sub actinomorphic flowers, stamens included within the corolla tube, pouched stamens and oblate pollen grains. To understand the phylogenetic relationship ofHaplanthodeswithAndrographisandHaplanthus, another related genus, we used four plastid markers,matK, rbcL, psbA-trnHandtrnGRto construct a molecular phylogeny. Our results established the monophyly of this genus and revealed a sister relationship toAndrographisandHaplanthus. Further, to understand the historical biogeography of the genus, we inferred the divergence time and performed ancestral area reconstruction. Our analyses suggest thatHaplanthodeshas evolved during Late Miocene 5.85 Ma [95%HPD: 2.18-10.34 Ma] in peninsular India where it might have shared a common ancestor withAndrographis. To understand character evolution, the ancestral states of important morphological characters were inferred based on the equal rate model and discussed. The generic status ofHaplanthusis not resolved due to incomplete sampling.
SPDE: A Multi-functional Software for Sequence Processing and Data Extraction
Authors: Xu Dong , Lu Zhuchou , Jin Kangming , Qiu Wenmin , Qiao Guirong , Han Xiaojiao , Zhuo Renying 
Published: November 2020

AbstractEfficiently extracting information from biological big data can be a huge challenge for people (especially those who lack programming skills). We developedSequenceProcessing andDataExtraction (SPDE) as an integrated tool for sequence processing and data extraction for gene family and omics analyses. Currently, SPDE has seven modules comprising 100 basic functions that range from single gene processing (e.g., translation, reverse complement, and primer design) to genome information extraction. All SPDE functions can be used without the need for programming or command lines. The SPDE interface has enough prompt information to help users run SPDE without barriers. In addition to its own functions, SPDE also incorporates the publicly available analyses tools (such as, NCBI-blast, HMMER, Primer3 and SAMtools), thereby making SPDE a comprehensive bioinformatics platform for big biological data analysis.AvailabilitySPDE was built using Python and can be run on 32-bit, 64-bit Windows and macOS systems. It is an open-source software that can be downloaded fromhttps://github.com/simon19891216/SPDEv1.2.git.Contactxudongzhuanyong@163.com
Optimal Allocation of Limited Test Resources for the Quantification of COVID-19 Infections
Authors: Chatzimanolakis Michail , Weber Pascal , Arampatzis George , Wälchli Daniel , Kičić Ivica , Karnakov Petr , Papadimitriou Costas , Koumoutsakos Petros 
Published: November 2020

AbstractThe systematic identification of infected individuals is critical for the containment of the COVID-19 pandemic. Presently, the spread of the disease is mostly quantified by the reported numbers of infections, hospitalizations, recoveries and deaths; these quantities inform epidemiology models that provide forecasts for the spread of the epidemic and guide policy making. The veracity of these forecasts depends on the discrepancy between the numbers of reported and unreported, yet infectious, individuals.We combine Bayesian experimental design with an epidemiology model and propose a methodology for the optimal allocation of limited testing resources in space and time, which maximizes the information gain for such unreported infections. The proposed approach is applicable at the onset and spreading of the epidemic and can forewarn for a possible recurrence of the disease after relaxation of interventions. We examine its application in Switzerland; the open source software is, however, readily adaptable to countries around the world.We find that following the proposed methodology can lead to vastly less uncertain predictions for the spread of the disease. Estimates of the effective reproduction number and of the future number of unreported infections are improved, which in turn can provide timely and systematic guidance for the effective identification of infectious individuals and for decision-making.
Phase 1 Assessment of the Safety and Immunogenicity of an mRNA- Lipid Nanoparticle Vaccine Candidate Against SARS-CoV-2 in Human Volunteers
Authors: Kremsner Peter , Mann Philipp , Bosch Jacobus , Fendel Rolf , Gabor Julian J. , Kreidenweiss Andrea , Kroidl Arne , Leroux-Roels Isabel , Leroux-Roels Geert , Schindler Christoph , Schunk Mirjam , Velavan Thirumalaisamy P. , Fotin-Mleczek Mariola , Müller Stefan , Quintini Gianluca , Schönborn-Kellenberger Oliver , Vahrenhorst Dominik , Verstraeten Thomas , Walz Lisa , Wolz Olaf-Oliver , Oostvogels Lidia 
Published: November 2020

ABSTRACTThere is an urgent need for vaccines to counter the COVID-19 pandemic due to infections with severe acute respiratory syndrome coronavirus (SARS-CoV-2). Evidence from convalescent sera and preclinical studies has identified the viral Spike (S) protein as a key antigenic target for protective immune responses. We have applied an mRNA-based technology platform, RNActive®, to develop CVnCoV which contains sequence optimized mRNA coding for a stabilized form of S protein encapsulated in lipid nanoparticles (LNP). Following demonstration of protective immune responses against SARS-CoV-2 in animal models we performed a dose-escalation phase 1 study in healthy 18-60 year-old volunteers.This interim analysis shows that two doses of CVnCoV ranging from 2 μg to 12 μg per dose, administered 28 days apart were safe. No vaccine-related serious adverse events were reported. There were dose-dependent increases in frequency and severity of solicited systemic adverse events, and to a lesser extent of local reactions, but the majority were mild or moderate and transient in duration. Immune responses when measured as IgG antibodies against S protein or its receptor-binding domain (RBD) by ELISA, and SARS-CoV-2-virus neutralizing antibodies measured by micro-neutralization, displayed dose-dependent increases. Median titers measured in these assays two weeks after the second 12 μg dose were comparable to the median titers observed in convalescent sera from COVID-19 patients. Seroconversion (defined as a 4-fold increase over baseline titer) of virus neutralizing antibodies two weeks after the second vaccination occurred in all participants who received 12 μg doses.Preliminary results in the subset of subjects who were enrolled with known SARS-CoV-2 seropositivity at baseline show that CVnCoV is also safe and well tolerated in this population, and is able to boost the pre-existing immune response even at low dose levels.Based on these results, the 12 μg dose is selected for further clinical investigation, including a phase 2b/3 study that will investigate the efficacy, safety, and immunogenicity of the candidate vaccine CVnCoV.
Identification of downstream effectors of retinoic acid specifying the zebrafish pancreas by integrative genomics
Authors: López-Pérez Ana R. , Balwierz Piotr J. , Lenhard Boris , Muller Ferenc , Wardle Fiona C. , Manfroid Isabelle , Voz Marianne L. , Peers Bernard 
Published: November 2020

AbstractRetinoic acid (RA) is a key signal for the specification of the pancreas. Still, the gene regulatory cascade triggered by RA in the endoderm remains poorly characterized. In this study, we investigated this regulatory network in zebrafish by combining RNA-seq, RAR ChIP-seq and ATAC-seq assays. By analysing the effect of RA and of the RA receptor (RAR) antagonist BMS439 on the transcriptome and on the chromatin accessibility of endodermal cells, we identified a large set of genes and regulatory regions regulated by RA signalling. RAR ChIP-seq further defined the direct RAR target genes including the knownhoxgenes as well as several pancreatic regulators likemnx1, insm1b, hnf1baandgata6. Comparison of our zebrafish data with available murine RAR ChIP-seq data highlighted conserved direct target genes and revealed that some RAR sites are under strong evolutionary constraints. Among them, a novel highly conserved RAR-induced enhancer was identified downstream of theHoxBlocus and driving expression in the nervous system and in the gut in a RA-dependant manner. Finally, ATAC-seq data unveiled the role of the RAR-direct targets Hnf1ba and Gata6 in opening chromatin at many regulatory loci upon RA treatment.Summary statementCombination of RNA-seq, ChIP-seq and ATAC-seq assays identifies genes directly and indirectly regulated by RA signalling in zebrafish endoderm. Comparison with murine data highlights RAR binding sites conserved among vertebrates.
The self-peptide repertoire plays a critical role in transplant tolerance induction
Authors: Son Eric T. , Faridi Pouya , Paul-Heng Moumita , Leong Mario , English Kieran , Ramarathinam Sri H. , Braun Asolina , Dudek Nadine L. , Alexander Ian E. , Lisowski Leszek , Bertolino Patrick , Bowen David G. , Purcell Anthony W. , Mifsud Nicole A. , Sharland Alexandra F. 
Published: November 2020

AbstractWhile direct allorecognition underpins both solid organ allograft rejection and tolerance induction, the specific molecular targets of most directly-alloreactive CD8+T cells have not been defined. In this study, we used a combination of genetically-engineered MHC class I (MHC I) constructs, mice with a hepatocyte-specific mutation in the class I antigen-presentation pathway and immunopeptidomic analysis to provide definitive evidence for the contribution of the peptide cargo of allogeneic MHC I molecules to transplant tolerance induction. We established a systematic approach for the discovery of directly-recognised pMHC epitopes, and identified 17 strongly immunogenic H-2Kb-associated peptides recognised by CD8+T cells from B10.BR (H-2k) mice, 13 of which were also recognised by BALB/c (H-2d) mice. As few as five different tetramers used together were able to identify a high proportion of alloreactive T cells within a polyclonal population, suggesting that there are immunodominant allogeneic MHC-peptide complexes that can account for a large component of the alloresponse.
Chromosome-levelde novoassembly ofCoprinopsis cinerea A43mut B43mut pab1-1#326 and genetic variant identification of mutants using Nanopore MinION sequencing
Authors: Xie Yichun , Zhong Yiyi , Chang Jinhui , Kwan Hoi Shan 
Published: November 2020

AbstractThe homokaryoticCoprinopsis cinereastrainA43mut B43mut pab1-1#326 is a widely used experimental model for developmental studies in mushroom-forming fungi. It can grow on defined artificial media and complete the whole lifecycle within two weeks. The mutations in mating type factorsAandBresult in the special feature of clamp formation and fruiting without mating. This feature allows investigations and manipulations with a homokaryotic genetic background. Current genome assembly of strain #326 was based on short-read sequencing data and was highly fragmented, leading to the bias in gene annotation and downstream analyses. Here, we report a chromosome-level genome assembly of strain #326. Oxford Nanopore Technology (ONT) MinION sequencing was used to get long reads. Illumina short reads was used to polish the sequences. A combined assembly yield 13 chromosomes and a mitochondrial genome as individual scaffolds. The assembly has 15,250 annotated genes with a high synteny with theC. cinereastrain Okayama-7 #130. This assembly has great improvement on contiguity and annotations. It is a suitable reference for further genomic studies, especially for the genetic, genomic and transcriptomic analyses in ONT long reads. Single nucleotide variants and structural variants in six mutagenized and cisplatin-screened mutants could be identified and validated. A 66 bp deletion in Ras GTPase-activating protein(RasGAP)was found in all mutants. To make a better use of ONT sequencing platform, we modified a high-molecular-weight genomic DNA isolation protocol based on magnetic beads for filamentous fungi. This study showed the use of MinION to construct a fungal reference genome and to perform downstream studies in an individual laboratory. An experimental workflow was proposed, from DNA isolation and whole genome sequencing, to genome assembly and variant calling. Our results provided solutions and parameters for fungal genomic analysis on MinION sequencing platform.HighlightA chromosome-level genome assembly ofC. cinerea #326A fast and efficient high-molecular-weight fungal genomic DNA isolation protocolStructural variant and single nucleotide variant calling using Nanopore readsA series of solutions and reference parameters for fungal genomic analysis on MinION
Characterisation of bacteriophage JD419, a Staphylococcal phage with an unusual morphology and broad host range
Authors: Feng Tingting , Leptihn Sebastian , Dong Ke , Loh Belinda , Zhang Yan , Li Mingyue , Guo Xiaokui , Cui Zelin 
Published: November 2020

AbstractAs an antimicrobial therapy, therapeutic phages, also known as “Phage therapy” are able to inactivate multi-drug resistant bacteria such as methicillin and vancomycin resistantS. aureusand thus present a possible treatment for infections that are otherwise incurable. In this paper, we present a novel phage called JD419, which has a remarkably wide host-range. The virulent phage JD419 exhibits an elongated capsid and was able to infect and lyse 83 of all 129 tested clinical strains (64.3%) of multi-drug resistantS. aureusincluding MRSA. To evaluate the potential as a therapeutic phage, we tested the ability of phage JD419 to remain infectious after treatment exceeding physiological pH or temperature. The lytic activity of the phage was retained at pH values of 6.0-8.0 and at temperatures below 50°C. As phages sometimes contain virulence genes, we sequenced the complete genome of JD419. The 45509 bp genome contains a predicted 65 ORFs, none of which show homology to any known virulence or antibiotic resistance genes. Our study illustrates thatStaphylococcusphage JD419 has the potential to be used for diagnostic, prophylaxic and therapeutic purposes.
Nafamostat Mesylate in lipid carrier for nasal SARS-CoV2 titer reduction in a hamster model
Authors: Cornelissen Lisette , Hoefsmit Esmee , Rao Disha , Lijnsvelt Judith , van Keulen Lucien , van Es Marieke , Grimm Volker , Medema René H. , Blank Christian U. 
Published: November 2020

AbstractSevere acute respiratory syndrome corona virus 2 (SARS-CoV-2) has been responsible for the largest pandemic in recent decades. After seemingly being in control due to consequent lock-downs and social distancing, the majority of countries faces currently a second wave of exponentially increasing infections, hospital referrals and deaths due to SARS-CoV-2-mediated disease (COVID-19). To date, no effective vaccination has been found, and wearing masks and social distancing are the only effective approaches to reduce further spreading.However, unwillingness in the societies to distance again and consequently wear masks might be reasons for the second SARS-CoV-2 infection wave. User-friendly chemicals interfering at the host site with viral entry might be an approach to contain the pandemic. In addition, such an approach would work synergistic with vaccinations that miss new virus mutants.Nafamostat (NM) has been shownin vitroto interfere with cellular virus entry by inhibition of the host transmembrane protease serine 2 (TMPRSS2), an enzyme required for SARS-CoV-2 spike protein cleavage, a prerequisite for cell entry.We hypothesized that nasal application of NM in a liposomal layer (as additional mechanical barrier) could lower the nasal viral load and subsequently reduce the severity of COVID-19. We found, indeed, that nasal viral load one day post single NM application, was lowered in a hamster SARS-CoV-2 infection model. However, severity of subsequent local tissue destruction and weight loss due to pneumonitis was not favorably altered.In conclusion, a single NM application reduced nasal viral load, but did not favorably improve the outcome of COVID-19, likely due to the short half-time of NM. Improvement of NM stability or repetitive application (which was not permitted in this animal model according to Dutch law) might circumvent these challenges.