bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between SARS-CoV-2 Transmissibility, Viral Load, and Age in Households
Authors: Lyngse Frederik Plesner , Mølbak Kåre , Træholt Franck Kristina , Nielsen Claus , Skov Robert Leo , Voldstedlund Marianne , Cohen Arieh S. , Kirkeby Carsten Thure 
Published: March 2021

AbstractAimThe objective of this nationwide study was to investigate the association between SARS-CoV-2 transmissibility, viral load, and age of primary cases in Danish households.BackgroundSpread in households represents a major mode of transmission of SARS-CoV-2. In order to take proper action against the spread of the disease, it is important to have a better understanding of transmission in the household domain—including the role of viral load of primary cases.MethodsThe study was designed as an observational cohort study, using detailed administrative register data. We included the full population of Denmark and all SARS-CoV-2 tests (August 25, 2020 to February 10, 2021) to estimate transmissibility in house-holds comprising 2-6 people. RT-PCR Cycle threshold (Ct) values were used as a proxy for viral load.ResultsWe identified 63,657 primary cases and 139,882 household members of which 21% tested positive by RT-PCR within a 1-14 day period after the primary case. There was an approximately linear association between Ct value of the sample and transmissibility, implying that cases with samples having a higher viral load were more transmissible than cases with samples having a lower viral load. However, even for primary cases with relatively high sample Ct values, the transmissibility was not negligible, e.g., for primary cases with a sample Ct value of 38, we found that 13% of the primary cases had at least one secondary household case. Moreover, 34% of all secondary cases were found in households with primary cases having sample Ct values >30. An increasing transmissibility with age of the primary cases for adults (≥20 years) and a decreasing transmissibility with age for children (<20 years) were found.ConclusionsAlthough primary cases with sample high viral loads (low Ct values) were associated with higher SARS-CoV-2 transmissibility, we found no obvious cut-off for sample Ct values to eliminate transmissibility and a substantial amount of household transmission occurred in households where the primary cases had high sample Ct values (low viral load), The study further showed that transmissibility increases with age. These results have important public health implications, as they suggest that contact tracing should prioritize cases according to Ct values and age, and underline the importance of quick identification and isolation of cases. Furthermore, the study highlights that households can serve as a transmission bridge by creating connections between otherwise separate domains.
SARS-CoV-2 Load does not Predict Transmissibility in College Students
Authors: Tian Di , Lin Zhen , Kriner Ellie M. , Esneault Dalton J. , Tran Jonathan , DeVoto Julia C. , Okami Naima , Greenberg Rachel , Yanofsky Sarah , Ratnayaka Swarnamala , Tran Nicholas , Livaccari Maeghan , Lampp Marla , Wang Noel , Tim Scott , Norton Patrick , Scott John , Hu Tony Y. , Garry Robert , Delafontaine Patrice , Hamm Lee , Yin Xiao-Ming 
Published: March 2021

AbstractSARS-CoV2 is highly contagious and the global spread has caused significant medical, social and economic impacts. Other than vaccination, effective public health measures, including contact tracing, isolation and quarantine, is critical for deterring viral transmission, preventing infection progression and resuming normal activities. Viral transmission is affected by many factors but the viral load and vitality could be among the most important ones. Although in vitro culture studies have indicated that the amount of virus isolated from infected people determines the successful rate of virus isolation, whether the viral load carried at the individual level would affect the transmissibility was not known. We aimed to determine whether the Ct value, a measurement of viral load by RT-PCR assay, could differentiate the spreader from the non-spreader in a population of college students. Our results indicate that while at the population level the Ct value is lower, suggesting a higher viral load, in the symptomatic spreaders than the asymptomatic non-spreaders, there is a significant overlap in the Ct values between the two groups. Thus Ct values, or the viral load, at the individual level could not predict the transmissibility. Our studies also suggest that a sensitive method to detect the presence of virus is needed to identify asymptomatic persons who may carry a low viral load but can still be infectious.
An Explainable Artificial Intelligence based Prospective Framework for COVID-19 Risk Prediction
Authors: Sharma Vishal , Piyush  , Chhatwal Samarth , Singh Bipin 
Published: March 2021

AbstractGiven the spread of COVID-19 to vast geographical regions and populations, it is not feasible to undergo or recommend the RT-PCR based tests to all individuals with flu-like symptoms. The reach of RT-PCR based testing is still limited due to the high cost of the test and huge population in few countries. Thus, alternative methods for COVID-19 infection risk prediction can be useful. We built an explainable artificial intelligence (AI) based integrated web-based prospective framework for COVID-19 risk prediction. We employed a two-step procedure for the non-clinical prediction of COVID19 infection risk. In the first step we assess the initial risk of COVID19 infection based on carefully selected parameters associated with COVID-19 positive symptoms from recent research. Generally, X-ray scans are cheaper and easily available in most government and private health centres. Therefore, based on the outcome of the computed initial risk in first step, we further provide an optional prediction using the chest X-ray scans in the second step of our proposed AI based prospective framework. Since there is a bottleneck to undergo an expensive RT-PCR based confirmatory test in economically backward nations, this is a crucial part of our explainable AI based prospective framework. The initial risk assessment outcome is analysed in combination with the advanced deep learning-based analysis of chest X-ray scans to provide an accurate prediction of COVID-19 infection risk. This prospective web-based AI framework can be employed in limited resource settings after clinical validation in future. The cost and time associated with the adoption of this prospective AI based prospective framework will be minimal and hence it will be beneficial to majority of the population living in low-income settings such as small towns and rural areas that have limited access to advanced healthcare facilities.
Evaluation of sample collection and transport strategies to enhance yield, accessibility, and biosafety of COVID-19 RT-PCR testing
Authors: Banada Padmapriya , Elson David , Daivaa Naranjargal , Park Claire , Desind Samuel , Montalvan Ibsen , Kwiatkowski Robert , Chakravorty Soumitesh , Alland David , Xie Yingda L. 
Published: March 2021

ABSTRACTSensitive, accessible, and biosafe sampling methods for COVID-19 reverse-transcriptase polymerase chain reaction (RT-PCR) assays are needed for frequent and widespread testing. We systematically evaluated diagnostic yield across different sample collection and transport workflows, including the incorporation of a viral inactivation buffer. We prospectively collected nasal swabs, oral swabs, and saliva, from 52 COVID-19 RT-PCR-confirmed patients, and nasopharyngeal (NP) swabs from 37 patients. Nasal and oral swabs were placed in both viral transport media (VTM) and eNAT™, a sterilizing transport buffer, prior to testing with the Xpert Xpress SARS-CoV-2 (Xpert) test. The sensitivity of each sampling strategy was compared using a composite positive standard. Overall, swab specimens collected in eNAT showed superior sensitivity compared to swabs in VTM (70% vs 57%, P=0.0022). Direct saliva 90.5%, (95% CI: 82%, 95%), followed by NP swabs in VTM and saliva in eNAT, was significantly more sensitive than nasal swabs in VTM (50%, P<0.001) or eNAT (67.8%, P=0.0012) and oral swabs in VTM (50%, P<0.0001) or eNAT (56%, P<0.0001). Saliva and use of eNAT buffer each increased detection of SARS-CoV-2 with the Xpert test; however, no single sample matrix identified all positive cases.
Network Theory Reveals Principles of Spliceosome Structure and Dynamics
Authors: Kaur Harpreet , van der Feltz Clarisse , Sun Yichen , Hoskins Aaron A. 
Published: March 2021

AbstractCryo-EM has revolutionized structural biology of the spliceosome and dozens of distinct spliceosome structures representing much of the splicing cycle have now been determined. However, comparison of these structures is challenging due to extreme compositional and conformational dynamics of the splicing machinery and the thousands of intermolecular interactions created or dismantled as splicing progresses. We have used network theory to quantitatively analyze the dynamic interactions of splicing factors throughout the splicing cycle by constructing structure-based networks from every protein-protein, protein-RNA, and RNA-RNA interaction found in eight different spliceosome structures. Our networks reveal that structural modules comprising the spliceosome are highly dynamic with factors oscillating between modules during each stage along with large changes in the algebraic connectivities of the networks. Overall, the spliceosome’s connectivity is focused on the active site in part due to contributions from non-globular proteins and components of the NTC. Many key components of the spliceosome including Prp8 and the U2 snRNA exhibit large shifts in both eigenvector and betweenness centralities during splicing. Other factors show transiently high betweenness centralities only at certain stages thereby suggesting mechanisms for regulating splicing by briefly bridging otherwise poorly connected network nodes. These observations provide insights into the organizing principles of spliceosome architecture and provide a framework for comparative network analysis of similarly complex and dynamic macromolecular machines.
Kinetic structure of recycling vesicle pool at the Calyx of Held synapse under in vivo-like activities
Authors: Liu Zili , Zhu Ying , Hu Yubing , Sun Jianyuan 
Published: March 2021

AbstractSynaptic transmission at mammalian central synapses has ongoing background activity at physiological temperature. The recycling vesicle pool, with proper kinetics, ensures sustained synaptic transmission. However, the kinetic structure of recycling vesicle pool has never been quantitatively analyzed before, and most studies were performed at room temperature and under resting conditions. With the combination of presynaptic capacitance measurement and postsynaptic EPSC recording on calyx of Held synapses at physiological temperature, we studied vesicle recycling under sustained presynaptic stimulation. The kinetics of vesicle reuse was revealed by impeding transmitter refilling with folimycin. We kinetically dissected the recycling vesicle pool as sequentially connected sub-pools and depicted the complete kinetic structure. The sizes and transition rates among these sub-pools were dynamically regulated by neuronal activity, in order to ensure efficient synaptic transmission. Our work highlights the impact of the vesicle recycling machinery on stable and reliable synaptic transmission under variable levels of neuronal activity.Impact statementThe recycling pool of vesicles are kinetically dissected as four populated pools ensuring stable and reliable synaptic transmission
Disinfection of SARS-CoV-2 contaminated surfaces of personal items with UVC-LED disinfection boxes
Authors: Bormann M. , Alt M. , Schipper L. , van de Sand L. , Otte M. , Meister T. L. , Dittmer U. , Witzke O. , Steinmann E. , Krawczyk A. 
Published: March 2021

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted from person-to-person by close contact, small aerosol respiratory droplets and potentially via contact with contaminated surfaces. Here, we investigated the effectiveness of commercial UVC-LED disinfection boxes in inactivating SARS-CoV-2 contaminated surfaces of personal items. We contaminated glass, metal and plastic samples representing the surfaces of personal items such as smartphones, coins or credit cards with SARS-CoV-2 formulated in an organic matrix mimicking human respiratory secretions. For disinfection, the samples were placed at different distances from UVC emitting LEDs inside commercial UVC-LED disinfection boxes and irradiated for different time periods (up to 10 minutes). High viral loads of SARS-CoV-2 were effectively inactivated on all surfaces after 3 minutes of irradiation. Even 10 seconds of UVC-exposure strongly reduced viral loads. Thus, UVC-LED boxes proved to be an effective method for disinfecting SARS-CoV-2 contaminated surfaces that are typically found on personal items.
Evaluating the role of reference-genome phylogenetic distance on evolutionary inference
Authors: Prasad Aparna , Lorenzen Eline D , Westbury Michael V 
Published: March 2021

AbstractWhen a high-quality genome assembly of a target species is unavailable, an option to avoid the costlyde novoassembly process is a mapping-based assembly. However, mapping shotgun data to a distant relative may lead to biased or erroneous evolutionary inference. Here, we used short-read data from a mammal and a bird species (beluga and rowi kiwi) to evaluate whether reference genome phylogenetic distance can impact downstream demographic (PSMC) and genetic diversity (heterozygosity, runs of homozygosity) analyses. We mapped to assemblies of species of varying phylogenetic distance (conspecific to genome-wide divergence of >7%), andde novoassemblies created using cross-species scaffolding. We show that while reference genome phylogenetic distance has an impact on demographic analyses, it is not pronounced until using a reference genome with >3% divergence from the target species. When mapping to cross-species scaffolded assemblies, we are unable to replicate the original beluga demographic analyses, but can with the rowi kiwi, presumably reflecting the more fragmented nature of the beluga assemblies. As for genetic diversity estimates, we find that increased phylogenetic distance has a pronounced impact; heterozygosity estimates deviate incrementally as phylogenetic distance increases. Moreover, runs of homozygosity are removed when mapping to any non-conspecific assembly. However, these biases can be reduced when mapping to a cross-species scaffolded assembly. Taken together, our results show that caution should be exercised when selecting the reference genome for mapping assemblies. Cross-species scaffolding may offer a way to avoid a costly, traditionalde novoassembly, while still producing robust, evolutionary inference.
The quasi-universality of nestedness in the structure of quantitative plant-parasite interactions
Authors: Benoît Moury , Jean-Marc Audergon , Sylvie Baudracco-Arnas , Safa Ben Krima , François Bertrand , Nathalie Boissot , Mireille Buisson , Valérie Caffier , Mélissa Cantet , Sylvia Chanéac , Carole Constant , François Delmotte , Catherine Dogimont , Juliette Doumayrou , Frédéric Fabre , Sylvain Fournet , Valérie Grimault , Thierry Jaunet , Isabelle Justafré , Véronique Lefebvre , Denis Losdat , Marcel Thierry C. , Josselin Montarry , Morris Cindy E. , Mariem Omrani , Manon Paineau , Sophie Perrot , Marie-Laure Pilet-Nayel , Youna Ruellan 
Published: March 2021

AbstractUnderstanding the relationships between host range and pathogenicity for parasites, and between the efficiency and scope of immunity for hosts are essential to implement efficient disease control strategies. In the case of plant parasites, most studies have focused on describing qualitative interactions and a variety of genetic and evolutionary models has been proposed in this context. Although plant quantitative resistance benefits from advantages in terms of durability, we presently lack models that account for quantitative interactions between plants and their parasites and the evolution of these interactions. Nestedness and modularity are important features to unravel the overall structure of host-parasite interaction matrices. Here, we analysed these two features on 32 matrices of quantitative pathogenicity trait data gathered from 15 plant-parasite pathosystems consisting of either annual or perennial plants along with fungi or oomycetes, bacteria, nematodes, insects and viruses. The performance of several nestedness and modularity algorithms was evaluated through a simulation approach, which helped interpretation of the results. We observed significant modularity in only six of the 32 matrices, with two or three modules detected. For three of these matrices, modules could be related to resistance quantitative trait loci present in the host. In contrast, we found high and significant nestedness in 30 of the 32 matrices. Nestedness was linked to other properties of plant-parasite interactions. First, pathogenicity trait values were explained in majority by a parasite strain effect and a plant accession effect, with no or minor parasite-plant interaction term. Second, correlations between the efficiency and scope of the resistance of plant genotypes, and between the host range breadth and pathogenicity level of parasite strains were overall positive. This latter result questions the efficiency of strategies based on the deployment of several genetically-differentiated cultivars of a given crop species in the case of quantitative plant immunity.
CHRM1 is a Druggable Melanoma Target Whose Endogenous Activity is Determined by Inherited Genetic Variation in DOPA Production
Authors: Doepner Miriam , Natale Christopher A. , Lee In Young , Venkat Swati , Kim Sung Hoon , Katzenellenbogen John A. , Katzenellenbogen Benita S. , Feigin Michael E. , Ridky Todd W. 
Published: March 2021

AbstractMelanoma risk is 30 times higher in people with lightly pigmented skin compared to those with darkly pigmented skin. Here we show that this difference results from more than melanin pigment and its ultraviolet radiation (UVR) shielding effect. Using primary human melanocytes representing the full human skin pigment continuum and several preclinical melanoma models, we show that cell-intrinsic differences between dark and light melanocytes regulate melanocyte proliferative capacity, overall cellular differentiation state, and susceptibility to malignant transformation,independently of melanin and UV exposure.We determined that these differences result from dihydroxyphenylalanine (DOPA), a melanin precursor synthesized at higher levels in melanocytes from dark skin. Although DOPA was not previously known to have specific signaling activity, we used both high throughput pharmacologic and geneticin vivoCRISPR screens to determine that DOPA limits melanocyte and melanoma cell proliferation by directly inhibiting the muscarinic acetylcholine receptor M1 (CHRM1), a G Protein-Coupled Receptor (GPCR) not previously known to bind DOPA, nor to affect melanoma pathobiology. Pharmacologic CHRM1 antagonism in melanoma leads to depletion of c-Myc and FOXM1, both of which are proliferation drivers associated with aggressive melanoma. In preclinical mouse melanoma models using both immune deficient and syngeneic immune competent mice, pharmacologic inhibition of CHRM1 or FOXM1 inhibited tumor growth. CHRM1 and FOXM1 may be new therapeutic targets for melanoma.
SPOT: a web-tool enabling Swift Profiling Of Transcriptomes
Authors: Farr Elias , Sattler Julia M. , Frischknecht Friedrich 
Published: March 2021

AbstractThe increasing number of single cell and bulk RNAseq data sets describing complex gene expression profiles in different organisms, organs or cell types calls for an intuitive tool allowing rapid comparative analysis. Here we present Swift Profiling Of Transcriptomes (SPOT) as a web tool that allows not only differential expression analysis but also fast ranking of genes fitting transcription profiles of interest. Based on a heuristic approach the spot algorithm ranks the genes according to their proximity to the user-defined gene expression profile of interest. The best hits are visualized as a table, bar chart or dot plot and can be exported as an Excel file. While the tool is generally applicable, we tested it on RNAseq data from malaria parasites that undergo multiple stage transformations during their complex life cycle as well as on data from multiple human organs during development and cell lines infected by the SARS-CoV-2 virus. SPOT should enable non-bioinformaticians to easily analyse their own and any available dataset.
Closer appendage spacing augments metachronal swimming speed by promoting tip vortex interactions
Authors: Ford Mitchell P. , Santhanakrishnan Arvind 
Published: March 2021

AbstractNumerous species of aquatic invertebrates, including crustaceans, swim by oscillating multiple closely spaced appendages. The coordinated, out-of-phase motion of these appendages, known as “metachronal paddling”, has been well-established to improve swimming performance relative to synchronous paddling. Invertebrates employing this propulsion strategy cover a wide range of body sizes and shapes, but the ratio of appendage spacing (G) to the appendage length (L) has been reported to lie in a comparatively narrow range of 0.2 <G/L≤ 0.65. The functional role ofG/Lon metachronal swimming performance is unknown. We hypothesized that for a given Reynolds number and stroke amplitude, hydrodynamic interactions promoted by metachronal stroke kinematics with smallG/Lcan increase forward swimming speed. We used a dynamically scaled self-propelling robot to comparatively examine swimming performance and wake development of metachronal and synchronous paddling under varyingG/L, phase lag, and stroke amplitude.G/Lwas varied from 0.4 to 1.5, with the expectation that whenG/Lis large, there should be no performance difference between metachronal and synchronous paddling due to a lack of interaction between vortices that form on the appendages. Metachronal stroking at non-zero phase lag withG/Lin the biological range produced faster swimming speeds than synchronous stroking. AsG/Lincreased and as stroke amplitude decreased, the influence of phase lag on the swimming speed of the robot was reduced. For smallerG/L, vortex interactions between adjacent appendages generated a horizontally-oriented wake and increased momentum fluxes relative to largerG/L, which contributed to increasing swimming speed. We find that while metachronal motion augments swimming performance for closely spaced appendages (G/L< 1), moderately spaced appendages (1.0 ≤G/L≤ 1.5) can benefit from metachronal motion only when the stroke amplitude is large.