bluuebunny/crossref_metadata_2025_split huggingface dataset:
EMSNet: A neural network model with a self-attention mechanism for prehospital prediction of care needs
Authors: Jeong Joo , Kim Yu Jin , Kim Dae Kon , Kim Tackeun , Kim Joonghee 
Published: May 2020

AbstractBackgroundAn artificial intelligence (AI) system capable of predicting patient needs in the prehospital phase would be instrumental. We sought to develop a neural network (NN) model capable of predicting various care needs at initial contact by emergency medical service (EMS) using multimodal input data.MethodsWe used EMS records of a single emergency department (ED). We implemented two attention-based NN model (I and P) differing only by how they use contextual information. The models predict multiple events, including hospital admission, endotracheal intubation, mechanical ventilation, vasopressor infusion, cardiac catheterization, surgery, intensive care unit (ICU) admission, and cardiac arrest. The input features include both unstructured data (chief complaints, injury summary, past medical history, history of present illness) and structured data (age, sex, pupil status and initial vital signs, level of consciousness, and O2 saturation on pulse oximetry). We applied multi-task learning for training. We evaluated the relative performance of the models compared with a human expert, an emergency physician with 10-year experience as an EMS medical director.ResultsThe study population included 42,073 cases. The receiver operating characteristics (ROC) area under the curve (AUC) values of the models I and P ranged from 0.793 to 0.929 and 0.812 to 0.934, respectively. The precision-recall (PR) AUC values ranged from 0.149 to 0.673 and 0.156 to 0.683, respectively. With decision thresholds set to achieve equivalent recall levels, our AI models achieved precision levels not significantly different from those of a human expert except in prediction of mechanical ventilation and ICU admission, where the models achieved superior performance (p=0.030 [model I] and p=0.015 [model P], respectively).ConclusionsAI models using multimodal input data can predict medical resource requirements at initial contact by EMS with high accuracies.
Covid19db – An online database of trials of medicinal products to prevent or treat COVID-19, with a specific focus on drug repurposing
Authors: Pantziarka Pan , Vandeborne Liese , Meheus Lydie , Bouche Gauthier 
Published: May 2020

AbstractBackgroundThe global pandemic caused by SARS-CoV-2 virus has prompted an unprecedented international effort to seek medicines for prevention and treatment of infection. Drug repurposing has played a key part in this response. The rapid increase in trial activity has raised questions about efficiency and lack of coordination. Our objective was to develop a user-friendly, open access database to monitor and rapidly identify trials of medicinal products.MethodsUsing the US clinicaltrials.gov (NCT) registry, the EU Clinical Trials Register (EUCTR) and the WHO International Clinical Trials Registry Platform (WHO ICTRP), we identified all COVID-19 trials of medicinal products. Trials that were out of scope and duplicates were excluded. A manual encoding was performed to ascertain key information (e.g. trial aim, type of intervention etc). The database, Covid19db, is published online at:http://www.redo-project.org/covid19db/.ResultsDescriptive statistics of the database from April 4th 2020 through to August 18th show an increase from 186 to 1618 trials, or an average of 10.5 new trials registered per day. Over this period, the proportion of trials including a repurposing arm decreased slightly (from a maximum of 75% to 64% at the end of the covered period) as did the proportion of trials aiming to prevent infection (from a maximum of 16% to 13%). The most popular trial intervention is hydroxychloroquine (212 trials), followed by azithromycin (64 trials), tocilizumab, favipiravir and chloroquine (145 trials). Total planned enrolment is 1064556 participants as of 18thAugust 2020.Conclusionswe have developed an open access and regularly updated tool to monitor clinical trials of medicinal products to prevent or treat infection by SARS-CoV-2 globally. Our analysis shows a high number of ‘me-too’ trials, in particular for some repurposed drugs, such as hydroxychloroquine, azithromycin and tocilizumab, substantiating calls for better coordination and better use of trial resources.
Lopinavir-Ritonavir in treatment of COVID-19: A dynamic systematic benefit-risk assessment
Authors: Osborne Vicki , Davies Miranda , Lane Samantha , Evans Alison , Denyer Jacqueline , Dhanda Sandeep , Roy Debabrata , Shakir Saad 
Published: May 2020

AbstractBackgroundCOVID-19 is an ongoing, global public health crisis for which safe and effective treatments need to be identified. The benefit-risk balance for use of lopinavir-ritonavir in COVID-19 needs to be monitored on an ongoing basis, therefore a systematic benefit-risk assessment was designed and conducted. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation; although initially this evaluation is likely to contain limited information, it is required due to the urgent unmet public need. Importantly it allows additional data to be incorporated as it becomes available, and re-evaluation of the benefit-risk profile.MethodsA systematic benefit-risk assessment was conducted using the Benefit-Risk Action team (BRAT) framework. The exposure of interest was lopinavir-ritonavir treatment in COVID-19 compared to standard of care, placebo or other treatments. A literature search was conducted in PubMed and EmBase to identify peer-reviewed papers reporting clinical outcomes. Two clinicians constructed a value tree and ranked key benefits and risks in order of considered clinical importance.ResultsIn comparison to standard of care, data for several key benefits and risks were identified for lopinavir-ritonavir. Time to clinical improvement was not significantly different for lopinavir-ritonavir in comparison to standard of care (HR=1.31, 95% CI:0.95, 1.80). There appeared to be fewer serious adverse events with lopinavir-ritonavir (20%) vs standard of care (32%). In particular, there were fewer cases of acute respiratory distress syndrome with lopinavir-ritonavir compared to standard of care (13% vs 27%). Limited data were available for comparison of lopinavir-ritonavir to other treatments.ConclusionsBased on currently available data, there was no clear benefit for use of lopinavir-ritonavir compared to standard of care in severe COVID-19. Risk data suggested a possible decrease in serious adverse events, including acute respiratory distress syndrome. Overall, the benefit-risk profile for lopinavir-ritonavir in severe COVID-19 cannot be considered positive until further efficacy and effectiveness data become available.
The association between treatment with heparin and survival in patients with Covid-19
Authors: Ayerbe Luis , Risco Carlos , Ayis Salma 
Published: May 2020

AbstractObjectivesThis study investigates the association between the treatment with heparin and mortality in patients admitted with Covid-19.MethodsRoutinely recorded, clinical data, up to the 24th of April 2020, from the 2075 patients with Covid-19, admitted in 17 hospitals in Spain between the 1st of March and the 20th of April 2020 were used. The following variables were extracted for this study: age, gender, temperature, and saturation of oxygen on admission, treatment with heparin, hydroxychloroquine, azithromycin, steroids, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, together with data on mortality. Multivariable logistic regression models were used to investigate the associations.ResultsAt the time of collecting the data, 301 patients had died, 1447 had been discharged home from the hospitals, 201 were still admitted, and 126 had been transferred to hospitals not included in the study. Median follow up time was 8 (IQR:5-12) days. Heparin had been used in 1734 patients. Heparin was associated with lower mortality when the model was adjusted for age and gender, with OR (95%CI): 0.55 (0.37-0.82) p=0.003. This association remained significant when saturation of oxygen <90%, and temperature >37C were added to de model with OR: 0.54(0.36-0.82) p=0.003, and also when all the other drugs were included as covariates OR: 0.42 (0.26-0.66) p<0.001.ConclusionsThe association between heparin and lower mortality observed in this study can be acknowledged by clinicians in hospitals and in the community. Randomized controlled trials to assess the causal effects of heparin in different therapeutic regimes are required.-The administration of heparin was associated with lower mortality in patients admitted with Covid-19.-Our findings support that there is a thrombotic component in the development of respiratory distress for these patients.-The positive effect of heparin seems consistent and its use, when indicated, could be considered in clinical settings.-Randomized controlled trials are necessary to complement observational studies, and assess the causal associations between heparin, in different therapeutic regimes, and clinical outcomes.-Heparin is easy to administer, its use in ambulatory patients, to prevent admissions, or reduce their duration, could also be considered by clinicians and future researchers.
Factors affecting healthcare workers’ compliance with social and behavioural infection control measures during emerging infectious disease outbreaks: Rapid evidence review
Authors: Brooks Samantha K. , Greenberg Neil , Wessely Simon , Rubin G. James 
Published: May 2020

AbstractThe 2019-2020 outbreak of novel coronavirus has raised concerns about nosocomial transmission; that is, transmission within healthcare settings. Research from previous outbreaks of emerging infectious diseases suggests a major cause of nosocomial transmission is healthcare professionals’ poor compliance with recommended personal protective behaviours. This rapid evidence review explored existing literature on emerging infectious disease outbreaks to identify factors associated with compliance with social and behavioural infection control measures among healthcare staff. 56 papers were reviewed and several positive associations were found: Staff working in emergency or intensive care settings appeared more likely to comply with recommendations than those in other settings, and there was some evidence that contact with confirmed cases could improve compliance. There was some evidence that staff with higher levels of anxiety and higher concern about the risk of infection were more likely to comply with recommended behaviour, and that monitoring from superiors could improve compliance. Several negative associations were also found. Observed non-compliance of colleagues could hinder compliance. Staff identified many barriers to compliance related to personal protective equipment, including availability; perceived difficulty and effectiveness; inconvenience; discomfort; and a negative impact on patient care. There appeared to be many issues regarding the communication and ease of understanding of infection control guidance. Based on the results of this review we recommend provision of training and education tailored for different occupational roles within the healthcare setting; managerial staff ‘leading by example’; ensuring adequate resources for infection control; and timely provision of practical evidence-based infection control guidelines.
The Association Between Biomarkers and Clinical Outcomes in Novel Coronavirus (COVID-19) Pneumonia in a U.S. Cohort
Authors: Ayanian Shant , Reyes Juan , Lynn Lei , Teufel Karolyn 
Published: May 2020

AbstractBackgroundThe global pandemic caused by COVID-19 remains poorly understood by clinicians. Identifying biologic markers associated with prognosis can help clinicians recognize disease severity.ObjectiveTo describe the association between D-dimer, CRP, IL-6, ferritin, LDH, and clinical outcomes in a cohort of COVID-19 patients treated on the inpatient medical service at a university hospital in Washington, DC.DesignIn this retrospective study, we included all adults admitted to the inpatient medicine service at George Washington University Hospital between March 12, 2020 and May 9, 2020 with laboratory confirmed COVID-19. Clinical and laboratory data were extracted from electronic medical records and compared between survivors not requiring ICU transfer, survivors requiring ICU transfer, survivors requiring intubation, and non-survivors.Key Results299 patients were included in our study, of whom 69 required transfer to the ICU, 39 required intubation, and 71 died. Threshold values for IL-6 (≥50 pg/mL), D-dimer (≥3 mcg/mL), ferritin (≥450 ng/mL), CRP (≥100 mg/L), and LDH (1,200 u/L) were found to be statistically significant and independently associated with higher odd of clinical deterioration and death. Hypertension, CVA and heart disease independently had an increased risk of all three outcomes, while CKD had only an increased risk of death. Patient co-morbidities had no effect on the different biomarkers’ significant association with poor patient clinical outcomes, except cancer.ConclusionLaboratory markers of inflammation and coagulopathy can help clinicians identify patients who are at high risk for clinical deterioration, independent of clinically significant medical comorbidities.
Within-host genomics of SARS-CoV-2
Authors: Lythgoe Katrina A. , Hall Matthew , Ferretti Luca , de Cesare Mariateresa , MacIntyre-Cockett George , Trebes Amy , Andersson Monique , Otecko Newton , Wise Emma L. , Moore Nathan , Lynch Jessica , Kidd Stephen , Cortes Nicholas , Mori Matilde , Williams Rebecca , Vernet Gabrielle , Justice Anita , Green Angie , Nicholls Samuel M. , Ansari M. Azim , Abeler-Dörner Lucie , Moore Catrin E. , Peto Timothy E. A. , Eyre David W. , Shaw Robert , Simmonds Peter , Buck David , Todd John A. , Connor Thomas R. , da Silva Filipe Ana , Shepherd James , Thomson Emma C. ,   The COVID-19 Genomics UK (COG-UK) consortium, Bonsall David , Fraser Christophe , Golubchik Tanya 
Published: May 2020

AbstractExtensive global sampling and whole genome sequencing of the pandemic virus SARS-CoV-2 have enabled researchers to characterise its spread, and to identify mutations that may increase transmission or enable the virus to escape therapies or vaccines. Two important components of viral spread are how frequently variants arise within individuals, and how likely they are to be transmitted. Here, we characterise the within-host diversity of SARS-CoV-2, and the extent to which genetic diversity is transmitted, by quantifying variant frequencies in 1390 clinical samples from the UK, many from individuals in known epidemiological clusters. We show that SARS-CoV-2 infections are characterised by low levels of within-host diversity across the entire viral genome, with evidence of strong evolutionary constraint in Spike, a key target of vaccines and antibody-based therapies. Although within-host variants can be observed in multiple individuals in the same phylogenetic or epidemiological cluster, highly infectious individuals with high viral load carry only a limited repertoire of viral diversity. Most viral variants are either lost, or occasionally fixed, at the point of transmission, consistent with a narrow transmission bottleneck. These results suggest potential vaccine-escape mutations are likely to be rare in infectious individuals. Nonetheless, we identified Spike variants present in multiple individuals that may affect receptor binding or neutralisation by antibodies. Since the fitness advantage of escape mutations in highly-vaccinated populations is likely to be substantial, resulting in rapid spread if and when they do emerge, these findings underline the need for continued vigilance and monitoring.
Evaluation of commercial qPCR kits for detection of SARS-CoV-2 in pooled samples
Authors: Petrovan Vlad , Vrajmasu Virgil , Dimon Paula , Zaulet Mihaela 
Published: May 2020

AbstractDue to the current pandemic, global shortage of reagents has drawn interest in developing alternatives to increase the number coronavirus tests. One such alternative is sample pooling. Here we compared commercial kits that are used in COVID-19 diagnostics, in terms of sensitivity and feasibility for use in pooling. We showed that pooling of up to 60 samples did not affect the efficiency of the kits. Also, the RNA dependent RNA polymerase (RdRp) is a more suitable target in pooled samples than the Envelope (E) protein. This approach could provide an easy method of screening large number of samples and help adjust different government regulations.
Proteomic identification ofCoxiella burnetiieffector proteins targeted to the host cell mitochondria during infection
Authors: Fielden Laura F. , Scott Nichollas E. , Palmer Catherine S. , Khoo Chen Ai , Newton Hayley J , Stojanovski Diana 
Published: May 2020

AbstractModulation of the host cell is integral to the survival and replication of microbial pathogens. Several intracellular bacterial pathogens deliver a cohort of bacterial proteins, termed ‘effector proteins’ into the host cell during infection by sophisticated protein translocation systems which manipulate cellular processes and functions. Despite the importance of these proteins during infection the functional contribution of individual effectors is poorly characterised, particularly in intracellular bacterial pathogens with large effector protein repertoires. Technical caveats have limited the capacity to study these proteins during a native infection, with many effector proteins having only been demonstrated to be translocated during over-expression of tagged versions. Here we present development of a novel strategy to examine effector proteins in the context of infection. We coupled a broad, unbiased proteomics-based screen with organelle purification to study the host-pathogen interactions occurring between the host cell mitochondrion and the Gram-negative, Q fever pathogenCoxiella burnetii.We identify 4 novel mitochondrially-targetedC. burnetiieffector proteins, renamed MitochondrialCoxiellaeffector protein (Mce) B to E. Examination of the subcellular localisation of ectopically expressed proteins in epithelial cells confirmed the mitochondrial localisation, demonstrating the robustness of our approach. Subsequent biochemical analysis and affinity enrichment proteomics of one of these effector proteins, MceC, revealed the protein is imported into mitochondria and can interact with components of the mitochondrial quality control machinery. Our study adapts high-sensitivity proteomics to the study of intracellular host-pathogen interactions occurring during infection, providing a robust strategy to examine the sub-cellular localisation of effector proteins during native infection. This approach could be applied to a range of pathogens and host cell compartments to provide a rich map of effector dynamics throughout infection.
The Incubot: A 3D Printer-Based Microscope for Long-Term Live Cell Imaging within a Tissue Culture Incubator
Authors: Merces George O. T. , Kennedy Conor , Lenoci Blanca , Reynaud Emmanuel G. , Burke Niamh , Pickering Mark 
Published: May 2020

AbstractCommercial live cell imaging systems represent a large financial burden to research groups, while current open source incubator microscopy systems lack adaptability and are sometimes inadequate for complex imaging experimentation. We present here a low-cost microscope designed for inclusion within a conventional tissue culture incubator. The build is constructed using an entry level 3D printer as the basis for the motion control system, with Raspberry Pi imaging and software integration, allowing for reflected, oblique, and fluorescence imaging of live cell monolayers. The open source nature of the design is aimed to facilitate adaptation by both the community at large and by individual researchers/groups. The development of an adaptable and easy-to-use graphic user interface (GUI) allows for the scientist to be at the core of experimental design. Simple modifications of the base GUI code, or generation of an entirely purpose-built script, will allow microscopists to place their experimental design as the priority, as opposed to designing experiments to fit their current equipment. The build can be constructed for a cost of roughly C1000 and thus serves as a low-cost and adaptable addition to the open source microscopy community.Abstract Figure
Phylogenetic clustering of the Indian SARS-CoV-2 genomes reveals the presence of distinct clades of viral haplotypes among states
Authors: Bhattacharjee Bornali , Pandit Bhaswati 
Published: May 2020

AbstractThe first Indian cases of COVID-19 caused by SARS-Cov-2 were reported in February 29, 2020 with a history of travel from Wuhan, China and so far above 4500 deaths have been attributed to this pandemic. The objectives of this study were to characterize Indian SARS-CoV-2 genome-wide nucleotide variations, trace ancestries using phylogenetic networks and correlate state-wise distribution of viral haplotypes with differences in mortality rates. A total of 305 whole genome sequences from 19 Indian states were downloaded from GISAID. Sequences were aligned using the ancestral Wuhan-Hu genome sequence (NC_045512.2). A total of 633 variants resulting in 388 amino acid substitutions were identified. Allele frequency spectrum, and nucleotide diversity (π) values revealed the presence of higher proportions of low frequency variants and negative Tajima’s D values across ORFs indicated the presence of population expansion. Network analysis highlighted the presence of two major clusters of viral haplotypes, namely, clade G with the S:D614G, RdRp: P323L variants and a variant of clade L [Lv] having the RdRp:A97V variant. Clade G genomes were found to be evolving more rapidly into multiple sub-clusters including clade GH and GR and were also found in higher proportions in three states with highest mortality rates namely, Gujarat, Madhya Pradesh and West Bengal.
Reciprocal repulsions instruct the precise assembly of parallel hippocampal networks
Authors: Pederick Daniel T. , Lui Jan H. , Gingrich Ellen C. , Xu Chuanyun , Wagner Mark J. , Liu Yuanyuan , He Zhigang , Quake Stephen R. , Luo Liqun 
Published: May 2020

AbstractParallel information processing is a salient feature of complex nervous systems. For example, the medial and lateral hippocampal networks (MHN and LHN) preferentially process spatial- and object-related information, respectively. However, the mechanisms underlying parallel network assembly during development remain largely unknown. Here, we show that complementary expression of cell-surface molecules Teneurin-3 (Ten3) and Latrophilin-2 (Lphn2) in the MHN and LHN, respectively, guides the precise assembly of both the MHN and LHN. Viral-genetic perturbationsin vivodemonstrate that Ten3+ axons are repelled by target-derived Lphn2, revealing that Lphn2/Ten3-mediated repulsion and Ten3/Ten3-mediated attraction cooperate to control precise target selection of MHN axons. In the LHN, Lphn2+ axons are confined to Lphn2+ targets via repulsion from Ten3+ targets. Our findings demonstrate that assembly of parallel hippocampal networks follows a ‘Ten3→Ten3, Lphn2→Lphn2’ rule instructed by reciprocal repulsions.