bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental DNA metabarcoding provides enhanced detection of the European eelAnguilla anguillaand fish community structure in pumped river catchments
Authors: Griffiths Nathan P. , Bolland Jonathan D. , Wright Rosalind M. , Murphy Leona A. , Donnelly Robert K. , Watson Hayley V. , Hänfling Bernd 
Published: July 2020

AbstractThe European eelAnguilla anguilla(eel hereafter) is critically endangered and has a catadromous lifecycle, which means adult eels that live in pumped catchments must pass through pumps during their downstream spawning migration. We are currently lacking detailed site-by-site eel distribution information in order to estimate the overall impact of individual pumping stations on eel escapement, and as such lack the data to enable informed prioritisation of pumping station management and targeted mitigation. In this study, we investigated whether environmental DNA (eDNA) metabarcoding can provide increased detection sensitivity for eel and fish community structure in highly regulated pumped catchments, when compared directly to current standard practice fish survey protocols (seine netting/electric fishing). Eels were detected in 14/17 sites (82.4%) using eDNA metabarcoding in contrast to 3/17 (17.6%) using traditional catch methods. Additionally, when using eDNA monitoring species richness was higher in 16/17 sites (94.1%) and site occupancy ≥ traditional methods for 23/26 of the fish species detected (88.5%). While eDNA methods presented significantly higher average species richness and species site occupancy overall, eDNA and Catch methods were positively correlated in terms of species richness and site occupancy. We therefore found that eDNA metabarcoding was a high sensitivity method for detecting eels in pumped catchments, while also increasing the detection of overall fish community structure compared to traditional catch methods. In addition, we highlight how eDNA monitoring is especially suited to increased detection of particular species, with traditional methods sufficient for others. This high sensitivity, coupled with the ability to sample multiple sites in a short time frame suggests eDNA metabarcoding could be an invaluable tool when prioritising pumping station management.
Rapidin vitroassays for screening neutralizing antibodies and antivirals against SARS-CoV-2
Authors: Park Jun-Gyu , Oladduni Fatai S. , Chiem Kevin , Ye Chengjin , Pipenbrink Michael , Moran Thomas , Walter Mark R. , Kobie James , Martinez-Sobrido Luis 
Published: July 2020

AbstractTowards the end of 2019, a novel coronavirus (CoV) named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), genetically similar to severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1), emerged in Wuhan, Hubei province of China, and has been responsible of coronavirus disease 2019 (COVID-19) in humans. Since its first report, SARS-CoV-2 has resulted in a global pandemic, with over 10 million human infections and over 560,000 deaths reported worldwide at the end of June 2020. Currently, there are no United States (US) Food and Drug Administration (FDA)-approved vaccines and/or antivirals licensed against SARS-CoV-2, and the high economical and health impact of SARS-CoV-2 has placed global pressure on the scientific community to identify effective prophylactic and therapeutic treatments for the treatment of SARS-CoV-2 infection and associated COVID-19 disease. While some compounds have been already reported to reduce SARS-CoV-2 infection and a handful of monoclonal antibodies (mAbs) have been described that neutralize SARS-CoV-2, there is an urgent need for the development and standardization of assays which can be used in high through-put screening (HTS) settings to identify new antivirals and/or neutralizing mAbs against SARS-CoV-2. Here, we described a rapid, accurate and highly reproducible plaque reduction microneutralization (PRMNT) assay that can be quickly adapted for the identification and characterization of both neutralizing mAbs and antivirals against SARS-CoV-2. Importantly, our MNA is compatible with HTS settings to interrogate large and/or complex libraries of mAbs and/or antivirals to identify those with neutralizing and/or antiviral activity, respectively, against SARS-CoV-2.
Brain hierarchy score: Which deep neural networks are hierarchically brain-like?
Authors: Nonaka Soma , Majima Kei , Aoki Shuntaro C. , Kamitani Yukiyasu 
Published: July 2020

SummaryAchievement of human-level image recognition by deep neural networks (DNNs) has spurred interest in whether and how DNNs are brain-like. Both DNNs and the visual cortex perform hierarchical processing, and correspondence has been shown between hierarchical visual areas and DNN layers in representing visual features. Here, we propose the brain hierarchy (BH) score as a metric to quantify the degree of hierarchical correspondence based on the decoding of individual DNN unit activations from human brain activity. We find that BH scores for 29 pretrained DNNs with varying architectures are negatively correlated with image recognition performance, indicating that recently developed high-performance DNNs are not necessarily brain-like. Experimental manipulations of DNN models suggest that relatively simple feedforward architecture with broad spatial integration is critical to brain-like hierarchy. Our method provides new ways for designing DNNs and understanding the brain in consideration of their representational homology.
Incoherent feedforward regulation via Sox9 and Erk underpins mouse tracheal cartilage development
Authors: Yoshida Takuya , Matsuda Michiyuki , Hirashima Tsuyoshi 
Published: July 2020

AbstractTracheal cartilage provides architectural integrity to the respiratory airway, and defects in this structure during embryonic development cause severe congenital anomalies. Previous genetic studies have revealed genes that are critical for the development of tracheal cartilage. However, it is still unclear how crosstalk between these proteins regulates tracheal cartilage formation. Here we show a core regulatory network underlying murine tracheal chondrogenesis from embryonic day (E) 12.5 to E15.5, by combining volumetric imaging of fluorescence reporters, inhibitor assays, and mathematical modeling. We focused on SRY-box transcription factor 9 (Sox9) and extracellular signal-regulated kinase (Erk) in the tracheal mesenchyme, and observed a synchronous, inverted U-shaped temporal change in both Sox9 expression and Erk activity with a peak at E14.5, whereas the expression level of downstream cartilage matrix genes, such as collagen II alpha 1 (Col2a1) and aggrecan (Agc1), monotonically increased. Inhibitor assays revealed that the Erk signaling pathway functions as an inhibitory regulator of tracheal cartilage differentiation during this period. These results suggest that expression of the cartilage matrix genes is controlled by an incoherent feedforward loop via Sox9 and Erk, which is supported by a mathematical model. Furthermore, the modeling analysis suggests that a Sox9-Erk incoherent feedforward regulation augment the robustness against the variation of upstream factors. The present study provides a better understanding of the regulatory network underlying the tracheal development and will be helpful for efficient induction of tracheal organoids.
Detection of clustered anomalies in single-voxel morphometry as a rapid automated method for identifying intracranial aneurysms
Authors: Allenby Mark C , Liang Ee Shern , Harvey James , Woodruff Maria A , Prior Marita , Winter Craig D , Alonso-Caneiro David 
Published: July 2020

AbstractUnruptured intracranial aneurysms (UIAs) are prevalent neurovascular anomalies which, in rare circumstances, rupture to create a catastrophic subarachnoid haemorrhage. Although surgical management can reduce rupture risk, the majority of IAs exist undiscovered until rupture. Current computer-aided UIA diagnoses sensitively detect and measure UIAs within cranial angiograms, but remain limited to low specificities whose output requires considerable neuroradiologist interpretation not amenable to broad screening efforts. To address these limitations, we propose an analysis which interprets single-voxel morphometry of segmented neurovasculature to identify UIAs. Once neurovascular anatomy of a specified resolution is segmented, interrelationships between voxel-specific morphometries are estimated and spatially-clustered outliers are identified as UIA candidates. Our automated solution detects UIAs within magnetic resonance angiograms (MRA) at unmatched 86% specificity and 81% sensitivity using 3 minutes on a conventional laptop. Our approach does not rely on interpatient comparisons or training datasets which could be difficult to amass and process for rare incidentally discovered UIAs within large MRA files, and in doing so, is versatile to user-defined segmentation quality, to detection sensitivity, and across a range of imaging resolutions and modalities. We propose this method as a unique tool to aid UIA screening, characterisation of abnormal vasculature in at-risk patients, morphometry-based rupture risk prediction, and identification of other vascular abnormalities.Graphical AbstractHighlightsRapid and automated detection of unruptured intracranial aneurysms (UIAs) in MRAsHighly specific, sensitive UIA detection to reduce radiologist input for screeningDetection is versatile to image resolution, modality and has tuneable mm sensitivity
COVID-19 Intensive Care Admissions Have Twice the Corrected Mortality of non-COVID-19 Viral Pneumonia
Authors: Nicolau Dan V. , Hasson Alexander 
Published: July 2020

AbstractStudying the ICNARC Case Mix Programme Database has yielded results showing intensive care admissions by those infected with COVID-19 have twice the corrected mortality of patients presenting with non-COVID-19 viral pneumonia. A basis of an APACHE-II-like score denoted as “BASCA” is also outlined in this study.
Epigenetic Element-Based Transcriptome-Wide Association Study Identifies Novel Genes for Bipolar Disorder
Authors: Yao Shi , Ding Jing-Miao , Wu Hao , Hao Ruo-Han , Rong Yu , Ke Xin , Guo Jing , Dong Shan-Shan , Guo Yan 
Published: July 2020

AbstractBipolar disorder (BD) is a highly heritable neuropsychiatric disorder characterized by recurrent episodes of depression and mania. Since the signals identified by genome-wide association study (GWAS) often reside in the non-coding regions, understanding the biological relevance of these genetic loci has proven to be complicated. Transcriptome-wide association studies (TWAS) providing a powerful approach to identify novel disease risk genes and uncover possible causal genes at loci identified previously by GWAS. However, these methods did not consider the importance of epigenetic regulation in gene expression. Here, we developed a novel epigenetic element-based transcriptome-wide association study (ETWAS) that tests the effects of genetic variants on gene expression levels with the epigenetic features as prior and further mediates the association between predicted expression and BD. We conducted an ETWAS consisting of 20,352 cases and 31,358 controls and identified 44 transcriptome-wide significant hits. We found 14 conditionally independent genes, and 11 did not previously implicate with BD, which regarded as novel candidate genes, such asASB16in the cerebellar hemisphere (P= 9.29×10−8). We demonstrated that several genome-wide significant signals from the BD GWAS driven by genetically regulated expression, and conditioning ofNEK4explaining 90.1% of the GWAS signal. Additionally, ETWAS identified genes could explain heritability beyond that explained by GWAS-associated SNPs (P= 0.019). In conclusion, ETWAS is a powerful method, and we identified several novel candidate genes associated with BD.
High variation expected in the pace and burden of SARS-CoV-2 outbreaks across sub-Saharan Africa
Authors: Rice Benjamin L. , Annapragada Akshaya , Baker Rachel E. , Bruijning Marjolein , Dotse-Gborgbortsi Winfred , Mensah Keitly , Miller Ian F. , Motaze Nkengafac Villyen , Raherinandrasana Antso , Rajeev Malavika , Rakotonirina Julio , Ramiadantsoa Tanjona , Rasambainarivo Fidisoa , Yu Weiyu , Grenfell Bryan T. , Tatem Andrew J. , Metcalf C. Jessica E. 
Published: July 2020

AbstractA surprising feature of the SARS-CoV-2 pandemic to date is the low burdens reported in sub-Saharan Africa (SSA) countries relative to other global regions. Potential explanations (e.g., warmer environments1, younger populations2–4) have yet to be framed within a comprehensive analysis accounting for factors that may offset the effects of climate and demography. Here, we synthesize factors hypothesized to shape the pace of this pandemic and its burden as it moves across SSA, encompassing demographic, comorbidity, climatic, healthcare and intervention capacity, and human mobility dimensions of risk. We find large scale diversity in probable drivers, such that outcomes are likely to be highly variable among SSA countries. While simulation shows that extensive climatic variation among SSA population centers has little effect on early outbreak trajectories, heterogeneity in connectivity is likely to play a large role in shaping the pace of viral spread. The prolonged, asynchronous outbreaks expected in weakly connected settings may result in extended stress to health systems. In addition, the observed variability in comorbidities and access to care will likely modulate the severity of infection: We show that even small shifts in the infection fatality ratio towards younger ages, which are likely in high risk settings, can eliminate the protective effect of younger populations. We highlight countries with elevated risk of ‘slow pace’, high burden outbreaks. Empirical data on the spatial extent of outbreaks within SSA countries, their patterns in severity over age, and the relationship between epidemic pace and health system disruptions are urgently needed to guide efforts to mitigate the high burden scenarios explored here.
SARS-CoV-2 receptor Angiotensin I-Converting Enzyme type 2 (ACE2) is expressed in human pancreatic β-cells and in the human pancreas microvasculature
Authors: Fignani Daniela , Licata Giada , Brusco Noemi , Nigi Laura , Grieco Giuseppina E. , Marselli Lorella , Overbergh Lut , Gysemans Conny , Colli Maikel L. , Marchetti Piero , Mathieu Chantal , Eizirik Decio L. , Sebastiani Guido , Dotta Francesco 
Published: July 2020

AbstractIncreasing evidence demonstrated that the expression of Angiotensin I-Converting Enzyme type 2 (ACE2), is a necessary step for SARS-CoV-2 infection permissiveness. In the light of the recent data highlighting an association between COVID-19 and diabetes, a detailed analysis aimed at evaluating ACE2 expression pattern distribution in human pancreas is still lacking. Here, we took advantage of INNODIA network EUnPOD biobank collection to thoroughly analyse ACE2, both at mRNA and protein level, in multiple human pancreatic tissues and using several methodologies.Using multiple reagents and antibodies, we showed that ACE2 is expressed in human pancreatic islets, where it is preferentially expressed in subsets of insulin producing β-cells. ACE2 is also is highly expressed in pancreas microvasculature pericytes and moderately expressed in rare scattered ductal cells. By using different ACE2 antibodies we showed that a recently described short-ACE2 isoform is also prevalently expressed in human β-cells.Finally, using RT-qPCR, RNA-seq and High-Content imaging screening analysis, we demonstrated that pro-inflammatory cytokines, but not palmitate, increases ACE2 expression in the β-cell line EndoC-βH1 and in primary human pancreatic islets.Taken together, our data indicate a potential link between SARS-CoV-2 and diabetes through putative infection of pancreatic microvasculature and/or ductal cells and/or through direct β-cell virus tropism.
Single-dose intranasal vaccination elicits systemic and mucosal immunity against SARS-CoV-2
Authors: An Xingyue , Martinez-Paniagua Melisa , Rezvan Ali , Fathi Mohsen , Singh Shailbala , Biswas Sujit , Pourpak Melissa , Yee Cassian , Liu Xinli , Varadarajan Navin 
Published: July 2020

AbstractA safe and durable vaccine is urgently needed to tackle the COVID19 pandemic that has infected >15 million people and caused >620,000 deaths worldwide. As with other respiratory pathogens, the nasal compartment is the first barrier that needs to be breached by the SARS-CoV-2 virus before dissemination to the lung. Despite progress at remarkable speed, current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. We report the development of an intranasal subunit vaccine that contains the trimeric or monomeric spike protein and liposomal STING agonist as adjuvant. This vaccine induces systemic neutralizing antibodies, mucosal IgA responses in the lung and nasal compartments, and T-cell responses in the lung of mice. Single-cell RNA-sequencing confirmed the concomitant activation of T and B cell responses in a germinal center-like manner within the nasal-associated lymphoid tissues (NALT), confirming its role as an inductive site that can lead to long-lasting immunity. The ability to elicit immunity in the respiratory tract has can prevent the initial establishment of infection in individuals and prevent disease transmission across humans.
Cell-ID: gene signature extraction and cell identity recognition at individual cell level
Authors: Akira Cortal , Loredana Martignetti , Emmanuelle Six , Antonio Rausell 
Published: July 2020

AbstractThe exhaustive exploration of human cell heterogeneity requires the unbiased identification of molecular signatures that can serve as unique cell identity cards for every cell in the body. However, the stochasticity associated with high-throughput single-cell sequencing has made it necessary to use clustering-based computational approaches in which the characterization of cell-type heterogeneity is performed at cell-subpopulation level rather than at full single-cell resolution. We present here Cell-ID, a clustering-free multivariate statistical method for the robust extraction of per-cell gene signatures from single-cell sequencing data. Cell-ID signatures allow unbiased cell identity recognition across different donors, tissues-of-origin, model organisms and single-cell omics technologies. Cell-ID is distributed as an open-source R software package:https://github.com/RausellLab/CelliD.
Bacterial dormancy: a subpopulation of viable but non-culturable cells demonstrates better fitness for revival
Authors: Wagley Sariqa , Morcrette Helen , Kovacs-Simon Andrea , Yang Zheng R. , Power Ann , Tennant Richard K. , Love John , Murray Neil , Titball Richard W. , Butler Clive S. 
Published: July 2020

AbstractThe viable but non culturable (VBNC) state is a condition in which bacterial cells are viable and metabolically active, but resistant to cultivation using a routine growth medium. We investigated the ability ofV. parahaemolyticusto form VBNC cells, and to subsequently become resuscitated. The ability to control VBNC cell formation in the laboratory allowed us to selectively isolate VBNC cells using fluorescence activated cell sorting, and to differentiate subpopulations based on their metabolic activity, cell shape and the ability to cause disease inGalleria mellonella. Our results showed that two key subpopulations (P1 and P2) ofV. parahaemolyticusVBNC cells exist and can remain dormant in the VBNC state for long periods. The two subpopulations displayed different abilities for revival under favourable conditions. Proteomic analysis of these subpopulations (at two different time points: 12 days (T12) and 50 days (T50) post VBNC) has also revealed that the proteome of P2 was more similar to that of the starting microcosm culture (T0) than the proteome of P1. The proteins that were significantly up and down regulated between the different VBNC populations were determined and significantly regulated proteins were assigned into 23 functional groups, the majority being included in metabolism functional categories. A lactate dehydrogenase (lldD) protein was significantly upregulated in all subpopulations of VBNC cells and is responsible for converting lactate to pyruvate. Deletion of the lactate dehydrogenase (RIMD2210633:ΔlldD) gene causes the cells to enter the VBNC state significantly faster than the wild-type, and exogenously adding lactate to VBNC cells aided resuscitation and extended the resuscitation window. Addition of pyruvate to the RIMD2210633:ΔlldDstrain restored the wild-type VBNC formation profile. This study suggests that lactate dehydrogenase plays a putative key role in regulating the VBNC state.
The first AI-based mobile application for antibiotic resistance testing
Authors: Pascucci Marco , Royer Guilhem , Adamek Jakub , Aristizabal David , Blanche Laetitia , Bezzarga Amine , Boniface-Chang Guillaume , Brunner Alex , Curel Christian , Dulac-Arnold Gabriel , Malou Nada , Nordon Clara , Runge Vincent , Samson Franck , Sebastian Ellen , Soukieh Dena , Vert Jean-Philippe , Ambroise Christophe , Madoui Mohammed-Amin 
Published: July 2020

ABSTRACTAntimicrobial resistance is a major global health threat and its development is promoted by antibiotic misuse. While disk diffusion antibiotic susceptibility testing (AST, also called antibiogram) is broadly used to test for antibiotic resistance in bacterial infections, it faces strong criticism because of inter-operator variability and the complexity of interpretative reading. Automatic reading systems address these issues, but are not always adapted or available to resource-limited settings. We present the first artificial intelligence (AI)-based, offline smartphone application for antibiogram analysis. The application captures images with the phone’s camera, and the user is guided throughout the analysis on the same device by a user-friendly graphical interface. An embedded expert system validates the coherence of the antibiogram data and provides interpreted results. The fully automatic measurement procedure of our application’s reading system achieves an overall agreement of 90% on susceptibility categorization against a hospital-standard automatic system and 98% against manual measurement (gold standard), with reduced inter-operator variability. The application’s performance showed that the automatic reading of antibiotic resistance testing is entirely feasible on a smartphone. Moreover our application is suited for resource-limited settings, and therefore has the potential to significantly increase patients’ access to AST worldwide.
Bimolecule detection for Extracellular Vesicle Screening
Authors: Kaneda Hisako , Ida Yui , Kuwahara Ryusuke , Sato Izumi , Nakano Takanari , Tokuda Haruhiko , Sato Tsuyoshi , Murakoshi Takayuki , Honke Koichi , Kotani Norihiro 
Published: July 2020

AbstractExtracellular vesicle (EV) has been investigated for use in clinical testing in recent years. Specific EV surface proteins provide distinguishing characteristics, but are insufficient for more detailed classification of EVs. Here, we suggest a novel “Bimolecular surface antigen expressed in EV” (BiEV) as a potential indicator for more efficient EV screening. A BiEV can be identified using a previously developed method, enzyme-mediated activation of radical sources, to label the components proximal (within 20 nm) to a given molecule. We examined the screening of cancer cell-secreted EV (cEV) included in serum EVs from a model mouse for lung cancer. The cEV-specific BiEVs were first identified by through a comparison of serum EVs from wild-type and lung cancer mice, showing that the CHL1-SLC4A1 bimolecule was a significant candidate for cEV-specific BiEV. Enzyme-linked immunosorbent assay quantification of CHL1-SLC4A1 BiEV appeared to suggest a potential for cancer screening of these mice. Using the same protocols, we found that CHL1-caspase 14 BiEV was significantly elevated in lung cancer patients compared with healthy persons. A BiEV strategy may be able to make a contribution to more effective EV screening, resulting in novel biological and clinical applications.