bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterising within-hospital SARS-CoV-2 transmission events: a retrospective analysis integrating epidemiological and viral genomic data from a UK tertiary care setting across two pandemic waves
Authors: Lindsey Benjamin B. , Villabona-Arenas Ch. Julián , Campbell Finlay , Keeley Alexander J. , Parker Matthew D. , Shah Dhruv R , Parsons Helena , Zhang Peijun , Kakkar Nishchay , Gallis Marta , Foulkes Benjamin H. , Wolverson Paige , Louka Stavroula F , Christou Stella , State Amy , Johnson Katie , Raza Mohammad , Hsu Sharon , Jombart Thibaut , Cori Anne ,   Sheffield COVID-19 Genomics Group,   The COVID-19 Genomics UK (COG-UK) consortium,   CMMID COVID-19 working group, Evans Cariad M. , Partridge David G. , Atkins Katherine E. , Hué Stéphane , de Silva Thushan I. 
Published: July 2021

Structured abstractObjectivesTo characterise within-hospital SARS-CoV-2 transmission across two waves of the COVID-19 pandemic.DesignA retrospective Bayesian modelling study to reconstruct transmission chains amongst 2181 patients and healthcare workers using combined viral genomic and epidemiological data.SettingA large UK NHS Trust with over 1400 beds and employing approximately 17,000 staff.Participants780 patients and 522 staff testing SARS-CoV-2 positive between 1st March 2020 and 25th July 2020 (Wave 1); and 580 patients and 299 staff testing SARS-CoV-2 positive between 30th November 2020 and 24th January 2021 (Wave 2).Main outcome measuresTransmission pairs including who-infected-whom; location of transmission events in hospital; number of secondary cases from each individual, including differences in onward transmission from community and hospital onset patient cases.ResultsStaff-to-staff transmission was estimated to be the most frequent transmission type during Wave 1 (31.6% of observed hospital-acquired infections; 95% CI 26.9 to 35.8%), decreasing to 12.9% (95% CI 9.5 to 15.9%) in Wave 2. Patient-to-patient transmissions increased from 27.1% in Wave 1 (95% CI 23.3 to 31.4%) to 52.1% (95% CI 48.0 to 57.1%) in Wave 2, to become the predominant transmission type. Over 50% of hospital-acquired infections were concentrated in 8/120 locations in Wave 1 and 10/93 locations in Wave 2. Approximately 40% to 50% of hospital-onset patient cases resulted in onward transmission compared to less than 4% of definite community-acquired cases.ConclusionsPrevention and control measures that evolved during the COVID-19 pandemic may have had a significant impact on reducing infections between healthcare workers, but were insufficient during the second wave to prevent a high number of patient-to-patient transmissions. As hospital-acquired cases appeared to drive most onward transmissions, more frequent and rapid identification and isolation of these cases will be required to break hospital transmission chains in subsequent pandemic waves.
Viral Load of SARS-CoV-2 in Respiratory Aerosols Emitted by COVID-19 Patients while Breathing, Talking, and Singing
Authors: Coleman Kristen K. , Wen Tay Douglas Jie , Tan Kai Sen , Xiang Ong Sean Wei , Son Than The , Koh Ming Hui , Chin Yi Qing , Nasir Haziq , Mak Tze Minn , Hann Chu Justin Jang , Milton Donald K. , Chow Vincent T. K. , Tambyah Paul Anantharajah , Chen Mark , Wai Tham Kwok 
Published: July 2021

AbstractBackgroundMultiple SARS-CoV-2 superspreading events suggest that aerosols play an important role in driving the COVID-19 pandemic. However, the detailed roles of coarse (>5μm) and fine (≤5μm) respiratory aerosols produced when breathing, talking, and singing are not well-understood.MethodsUsing a G-II exhaled breath collector, we measured viral RNA in coarse and fine respiratory aerosols emitted by COVID-19 patients during 30 minutes of breathing, 15 minutes of talking, and 15 minutes of singing.ResultsAmong the 22 study participants, 13 (59%) emitted detectable levels of SARS-CoV-2 RNA in respiratory aerosols, including 3 asymptomatic patients and 1 presymptomatic patient. Viral loads ranged from 63–5,821 N gene copies per expiratory activity per patient. Patients earlier in illness were more likely to emit detectable RNA, and loads differed significantly between breathing, talking, and singing. The largest proportion of SARS-CoV-2 RNA copies was emitted by singing (53%), followed by talking (41%) and breathing (6%). Overall, fine aerosols constituted 85% of the viral load detected in our study. Virus cultures were negative.ConclusionsFine aerosols produced by talking and singing contain more SARS-CoV-2 copies than coarse aerosols and may play a significant role in the transmission of SARS-CoV-2. Exposure to fine aerosols should be mitigated, especially in indoor environments where airborne transmission of SARS-CoV-2 is likely to occur. Isolating viable SARS-CoV-2 from respiratory aerosol samples remains challenging, and whether this can be more easily accomplished for emerging SARS-CoV-2 variants is an important enquiry for future studies.Key PointsWe sampled respiratory aerosols emitted by COVID-19 patients and discovered that fine aerosols (≤5μm) generated during talking and singing contain more SARS-CoV-2 copies than coarse aerosols (>5μm) and may play a significant role in the transmission of SARS-CoV-2.
COVID-19 Chest X-Ray Image Classification Using Deep Learning
Authors: Bacellar Gunther Correia , Chandrappa Mallikarjuna , Kulkarni Rajlakshman , Dey Soumava 
Published: July 2021

ABSTRACTThe rise of the coronavirus disease 2019 (COVID-19) pandemic has made it necessary to improve existing medical screening and clinical management of this disease. While COVID-19 patients are known to exhibit a variety of symptoms, the major symptoms include fever, cough, and fatigue. Since these symptoms also appear in pneumonia patients, this creates complications in COVID-19 detection especially during the flu season. Early studies identified abnormalities in chest X-ray images of COVID-19 infected patients that could be beneficial for disease diagnosis. Therefore, chest X-ray image-based disease classification has emerged as an alternative to aid medical diagnosis. However, manual detection of COVID-19 from a set of chest X-ray images comprising both COVID-19 and pneumonia cases is cumbersome and prone to human error. Thus, artificial intelligence techniques powered by deep learning algorithms, which learn from radiography images and predict presence of COVID-19 have potential to enhance current diagnosis process. Towards this purpose, here we implemented a set of deep learning pre-trained models such as ResNet, VGG, Inception and EfficientNet in conjunction with developing a computer vision AI system based on our own convolutional neural network (CNN) model: Deep Learning in Healthcare (DLH)-COVID. All these CNN models cater to image classification exercise. We used publicly available resources of 6,432 images and further strengthened our model by tuning hyperparameters to provide better generalization during the model validation phase. Our final DLH-COVID model yielded the highest accuracy of 96% in detection of COVID-19 from chest X-ray images when compared to images of both pneumonia-affected and healthy individuals. Given the practicality of acquiring chest X-ray images by patients, we also developed a web application (link: https://toad.li/xray) based on our model to directly enable users to upload chest X-ray images and detect the presence of COVID-19 within a few seconds. Taken together, here we introduce a state-of-the-art artificial intelligence-based system for efficient COVID-19 detection and a user-friendly application that has the capacity to become a rapid COVID-19 diagnosis method in the near future.
Neutralization of recombinant RBD-subunit vaccine ZF2001-elicited antisera to SARS-CoV-2 variants including Delta
Authors: Zhao Xin , Zheng Anqi , Li Dedong , Zhang Rong , Sun Huan , Wang Qihui , Gao George F. , Han Pengcheng , Dai Lianpan 
Published: July 2021

AbstractSARS-CoV-2 variants brought new waves of infection worldwide. In particular, Delta variant (B.1.617.2 lineage) has become predominant in many countries. These variants raised the concern for their potential immune escape to the currently approved vaccines. ZF2001 is a subunit vaccine received emergency use authorization (EUA) in both China and Uzbekistan, with more than 100-million doses administrated with a three-dose regimen. The tandem-repeat dimer of SARS-CoV-2 spike protein receptor binding domain (RBD) was used as the antigen. In this work, we evaluated the neutralization of ZF2001-elicited antisera to SARS-CoV-2 variants including all four variants of concern (Alpha, Beta, Gamma and Delta) and other three variants of interest (Epsilon, Eta and Kappa) by pseudovirus-based assay. We found antisera preserved majority of the neutralizing activity against these variants. E484K/Q substitution is the key mutation to reduce the RBD-elicited sera neutralization. Moreover, ZF2001-elicited sera with a prolonged intervals between the second and third dose enhanced the neutralizing titers and resilience to SARS-CoV-2 variants.
Understanding Mechanisms of Chamber-Specific Differentiation Through Combination of Lineage Tracing and Single Cell Transcriptomics
Authors: Gonzalez David M. , Schrode Nadine , Ebrahim Tasneem , Beaumont Kristin G. , Sebra Robert , Dubois Nicole C. 
Published: July 2021

AbstractThe specification and differentiation of atrial and ventricular myocardial cell types during development is incompletely understood. We have previously shown that Foxa2 expression during gastrulation identifies a population of ventricular fated progenitors, allowing for labeling of these cells prior to the morphogenetic events that lead to chamber formation and acquisition of bona fide atrial or ventricular identity. In this study, we performed single cell RNA sequencing of Foxa2Cre;mTmG embryos at the cardiac crescent (E8.25), primitive heart tube (E8.75) and heart tube (E9.25) stage in order to understand the transcriptional mechanisms underlying formation of atrial and ventricular cell types at the earliest stages of cardiac development. We find that progression towards differentiated myocardial cell types occurs primarily based on heart field progenitor identity, and that different progenitor populations contribute to ventricular or atrial identity through separate differentiation mechanisms. We identified a number of candidate markers that define such differentiation processes, as well as differential regulation of metabolic processes that distinguish atrial and ventricular fated cells at the earliest stages of development. We further show that exogenous injection with retinoic acid during formation of the cardiac primordia causes defects in ventricular chamber size and is associated with dysregulation in FGF signaling in anterior second heart field cells and a shunt in differentiation towards orthogonal lineages. Retinoic acid also causes defects in cell-cycle exit in myocardial committed progenitors that result in formation of hypomorphic ventricles with decreased expression of important metabolic processes and sarcomere assembly. Collectively, our data identify, at a single cell level, distinct lineage trajectories during cardiac progenitor cell specification and differentiation, and the precise effects of manipulating cardiac progenitor field patterning via exogenous retinoic acid signaling.
Network-based pathogenicity prediction for variants of uncertain significance
Authors: Kamada Mayumi , Takagi Atsuko , Kojima Ryosuke , Tanaka Yoshihisa , Nakatsui Masahiko , Tanabe Noriko , Hirata Makoto , Yoshida Teruhiko , Okuno Yasushi 
Published: July 2021

SummaryWhile the number of genome sequences continues to increase, the functions of many detected gene variants remain to be identified. These variants of uncertain significance constitute a major barrier to precision medicine 1–3. Although many computational methods have been developed to predict the function of these variants, they all rely on individual gene features and do not consider complex molecular relationships. Here we develop PathoGN, a molecular network-based approach for predicting variant pathogenicity. PathoGN significantly outperforms existing methods using benchmark datasets. Moreover, PathoGN successfully predicts the pathogenicity of 3,994 variants of uncertain significance in the real-world database ClinVar and designates potential pathogenicity. This is the first computational method for the clinical interpretation of variants using biomolecular networks, and we anticipate our method to be broadly useful for the clinical interpretation of variants and for assigning biological function to unknown variants at the genomic scale.
A rapid F0 CRISPR screen in zebrafish to identify regulators of neuronal development in the enteric nervous system
Authors: Davidson Ann E , Straquadine Nora RW , Cook Sara A , Liu Christina G , Ganz Julia 
Published: July 2021

AbstractThe enteric nervous system (ENS) provides the intrinsic innervation of the gastrointestinal (GI) tract with millions of neurons and diverse neuronal subtypes and glial cells. The ENS regulates essential gut functions such as motility, nutrient uptake, and immune response, but basic information about the genes that control ENS neuronal specification and differentiation remains largely unknown. Deficits in ENS neuron numbers and composition cause gut dysfunction with debilitating GI symptoms, and are associated with e.g. Hirschsprung disease, inflammatory gut diseases, autism spectrum disorder, and neurodegenerative diseases such as Parkinson’s disease. The genetic basis of most of these ENS disorders remains unknown. Recent transcriptomic analyses have identified many candidate genes for regulating ENS neurogenesis. However, functional evaluation of these candidate genes significantly lags because experimental testing of their role in ENS neurogenesis is time-consuming and expensive. Here, we have developed a rapid, scalable F0 CRISPR genome editing screen in zebrafish to functionally determine which candidate genes control neuronal development in the ENS. Proof-of-concept experiments targeting the known ENS regulators sox10 and ret phenocopy stable mutants with high efficiency and precision showing that our approach is reliable to identify regulators ENS neurogenesis using F0 guide RNA-injected larvae (F0 crispants). We then evaluate the role of 10 transcription factor genes for regulating ENS neurogenesis and function. Pools of guide RNAs targeting 2-3 candidate genes are co-injected with Cas9 protein into one-cell stage phox2bb:GFP transgenic zebrafish embryos to directly assess qualitative change in ENS neuron numbers compared to controls in 6-day old F0 crispants. Target genes from crispant pools exhibiting reduced ENS neuronal numbers were then tested individually to identify the responsible gene(s). We identify five transcription factors that show a reduction in ENS neurons indicating an influence on enteric progenitor cell differentiation into ENS neurons. Adding a simple and efficient test to further assess crispant gut motility, we find that loss-of-function of two of the transcription factor genes reduced intestinal transit of fluorescently labeled food through the gut. In summary, our novel, multistep, yet straight-forward CRISPR screening approach in zebrafish enables testing the genetic basis of ENS developmental and disease gene functions that will facilitate high-throughput evaluation of the manifold candidate genes emerging from transcriptomic, genome-wide association or other ENS-omics studies. Such in vivo ENS crispant screens will contribute to a better understanding of ENS neuronal development regulation in vertebrates and what goes awry in ENS disorders.
Structural Characterization of the PawL-Derived Peptide Family, an Ancient Subfamily of Orbitides
Authors: Payne Colton D. , Fisher Mark F. , Mylne Joshua S. , Rosengren K. Johan 
Published: July 2021

ABSTRACTPlants are an excellent source of bioactive peptides, often with disulfide bonds and/or a cyclic backbone. While focus has predominantly been directed at disulfide-rich peptides, a large family of small, cyclic but non-disulfide bonded plant peptides, known as orbitides, has been relatively ignored. A recently discovered subfamily of orbitides is the PawL-Derived Peptides (PLPs), produced during the maturation of precursors for seed storage albumins. Although their evolutionary origins have been dated, in-depth exploration of the family’s structural characteristics and potential bioactivities remains to be conducted. Here we present an extensive and systematic characterization of the PLP family. Nine PLPs were chosen and prepared by solid phase peptide synthesis. Their structural features were studied using solution NMR spectroscopy and seven were found to possess regions of backbone order. Ordered regions consist of β-turns, with some PLPs adopting two well-defined β-turns within sequences as short as seven residues, which are largely the result of side chain interactions. Our data highlight that the sequence diversity within this family results in equally diverse molecular scaffolds. None of these nine PLPs showed antibacterial or antifungal activity.
High-accuracy measurement of mass attenuation coefficients and the imaginary component of the atomic form factor of zinc from 8.51 keV to 11.59 keV, and X-ray absorption fine structure with investigation of zinc theory and nanostructure
Authors: Ekanayake Ruwini S. K. , Chantler Christopher T. , Sier Daniel , Schalken Martin J. , Illig Alexis J. , de Jonge Martin D. , Johannessen Bernt , Kappen Peter , Tran Chanh Q. 
Published: July 2021

High-accuracy X-ray mass attenuation coefficients were measured from the first X-ray Extended Range Technique (XERT)-like experiment at the Australian Synchrotron. Experimentally measured mass attenuation coefficients deviate by ∼50% from the theoretical values near the zinc absorption edge, suggesting that improvements in theoretical tabulations of mass attenuation coefficients are required to bring them into better agreement with experiment. Using these values the imaginary component of the atomic form factor of zinc was determined for all the measured photon energies. The zinc K-edge jump ratio and jump factor are determined and results raise significant questions regarding the definitions of quantities used and best practice for background subtraction prior to X-ray absorption fine-structure (XAFS) analysis. The XAFS analysis shows excellent agreement between the measured and tabulated values and yields bond lengths and nanostructure of zinc with uncertainties of from 0.1% to 0.3% or 0.003 Å to 0.008 Å. Significant variation from the reported crystal structure was observed, suggesting local dynamic motion of the standard crystal lattice. XAFS is sensitive to dynamic correlated motion and in principle is capable of observing local dynamic motion beyond the reach of conventional crystallography. These results for the zinc absorption coefficient, XAFS and structure are the most accurate structural refinements of zinc at room temperature.
Mixed embeddedness of Brazilian entrepreneurs in Toronto
Authors: Falcão Roberto Pessoa de Queiroz , Machado Michel Mott , Cruz Eduardo Picanço , Hossein Caroline Shenaz 
Published: July 2021

PurposeThe purpose of this article is to investigate how social integration, immigrant networks and barriers to ventureing affect the entrepreneurial activities of Brazilians in Canada, indicating how mixed embeddedness takes place in that context.Design/methodology/approachData were collected in Toronto, through the application of a survey with 74 Brazilian entrepreneur respondents and 42 semi-structured interviews with selected subjects, thus representing a multi-method approach. The analysis included descriptive statistics from the survey data and a qualitative analysis of the trajectories and life stories of Brazilian immigrants.FindingsOur sample comprises respondents with a high level of education and proficiency in English, coming predominantly from the southeast of Brazil, white, aged from 30 to 49. The majority of businesses are small and related to the service sector. The article contributes to the literature by discussing the elements related to mixed embeddedness, including the need for cultural adaptation and for the creation of networks as a crucial element for business venturing.Research limitations/implicationsThe study focuses on entrepreneurs regardless of their businesses sector or formality/informality status. It could be used as an instrument to support Canadian public policies for welcoming Brazilians and for the Brazilian government to prevent the evasion of potential entrepreneurs.Originality/valueThe article contributes to the body of knowledge of immigrant entrepreneurship in Canada and of Brazilian entrepreneurship overseas. The results suggest factors that may be relevant to the expansion of their business, such as social networking, cultural embeddedness and adaptation of the products/services to a wider range of target customers.
The tourism intermediaries' profitability in Portugal and Spain–differences and similarities
Authors: Gomes Conceição , Oliveira Fernanda 
Published: July 2021

PurposeThis study aims to compare the financial performance of the tourism distribution sector between Portugal and Spain, regarding the years 2007 and 2017. It is also intended to determine which variables influence the performance of tourism intermediaries' enterprises.Design/methodology/approachThis is a quantitative study based on financial information available on SABI database, with official data of Spanish and Portuguese enterprises. The final sample gathers 6095 intermediaries (1585 Portuguese and 4510 Spanish) which were analyzed regarding their profitability through DuPont model and an additional variable – size.FindingsThe return on equity (ROE) calculation in 2007 and 2017 identifies an increase of 12.8% for Portugal and 19.6% for Spain. Through Spearman's Rho, return on sales (ROS), asset turnover and return on asset (ROA) have a positive association with ROE, but the results about asset on equity and enterprise size did not reveal such precise evidence.Research limitations/implicationsThis study intends to reinforce the literature in terms of performance evaluation techniques to be used in this type of enterprises, applying DuPont model. At a practical level, besides aiming the maximization of the enterprise's profit, managers are faced with other financial challenges. Thus, this study provides important indications about aspects that should be considered to improve the enterprise's financial performance, supporting managers' decision making.Originality/valueFinancial studies focusing on the tourism distribution sector are limited. Even less frequent are studies with financial and official data from large samples, representative of the universe under study. The value of this study is based on these two aspects, allowing to strengthen the knowledge about tourism intermediaries and their financial performance, in a comparative approach between two countries.