bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 vaccine-associated cerebral venous thrombosis in Germany
Authors: Schulz Jörg B. , Berlit Peter , Diener Hans-Christoph , Gerloff Christian , Greinacher Andreas , Klein Christine , Petzold Gabor C. , Piccininni Marco , Poli Sven , Röhrig Rainer , Steinmetz Helmuth , Thiele Thomas , Kurth Tobias ,   the DGN SARS-CoV-2 Vaccination Study Group
Published: May 2021

AbstractObjectiveReports of cerebral sinus and venous thrombosis (CVT) after ChAdOx1 vaccination against SARS-CoV-2 have raised safety concerns. We aimed to estimate the incidence of CVT within one month from first dose administration and the frequency of vaccine-induced immune thrombotic thrombocytopenia (VITT) as the underlying mechanism after vaccination with BNT162b2, ChAdOx1, and mRNA-1273, in Germany.MethodsA web-based questionnaire was e-mailed to all Departments of Neurology. We asked to report cases of CVT within one month of a COVID-19 vaccination. Other cerebral events could also be reported. Incidence rates of CVT were calculated by using official statistics of nine German States.ResultsA total of 45 CVT cases were reported. In addition, 9 primary ischemic strokes, 4 primary intracerebral hemorrhages, and 4 other neurological events were recorded. Of the CVT patients, 35 (77.8%) were female, and 36 (80.0%) were below the age of 60 years. Fifty-three events were observed after vaccination with ChAdOx1 (85.5%), 9 after BNT162b2 (14.5%), and none after mRNA-1273 vaccination. After 7,126,434 first vaccine doses, the incidence rate of CVT within one month from first dose administration was 6.5 (95% CI, 4.4-9.2) per 100,000 person-years for all vaccines and 17.9 (11.8-26.1) for ChAdOx1 (after 2,320,535 ChAdOx1 first doses). The adjusted incidence rate ratio was 9.68 (3.46-34.98) for ChAdOx1 compared to mRNA-based vaccines and 3.14 (1.22-10.65) for women compared to non-women. In 26/45 patients with CVT (57.8%), VITT was graded highly probable.ConclusionsGiven an incidence of 0.22–1.75 per 100,000 person-years for CVT in the general population, these findings point towards a higher risk for CVT after ChAdOx1 vaccination, especially for women.
Information and Communication Technology (ICT) in Medical Education: A Survey among Medical Students’ of Bangladesh
Authors: Ferdoush Jannatul , Jeenia Fatiha Tasmin , Khan IkramUllah , Chowdhury Tasfia Momtaj , Alam Zahangir , Morshed Md. Masud , Chowdhury Abhijit , Parveen Kohinoor , Ata Maliha , Biswas Rajat Sanker Roy 
Published: May 2021

AbstractBackgroundBangladesh is declared as Digital Bangladesh however medical students are least acquainted with the necessary ICT knowledge in the context of medical education. We have conducted a survey to know about Digital Equipment Ownership, therefore, carried out a self-reported assessment of knowledge and Utilization of ICT in relation to educational and clinical development.Materials and MethodsA cross-sectional, multi-centered questionnaire survey was conducted among the medical students during the period of October 2019.Result & DiscussionsIn total 467 medical students responded to the questionnaire in which 92% of the students owned a Google android smart phone and accessed the internet on their devices. 69% student has (1-5) medical related apps in their device and drug formulary apps most commonly used 43%. 59% of students have gained their present computer knowledge by via self-learning. For study work with fellow student, 90% student preferred Facebook group, Whats app and Viber. While there was a range of variation in the usage of non-academic search engines 72% Google and no usages were found for more dedicated academic services such as PubMed and Medscape. According to 74% of students, inadequate integration of ICT knowledge into their syllabus culminated in insufficient future professional skills. All students were keen for a Basic ICT learning program at the beginning of their medical courses.ConclusionThe study revealed that to prepare medical students for using ICT in their academic work adequately, introducing ICT training at the initial stage of the undergraduate program and designing the curriculum to develop a multiplicity of skills is essential in addition to an integrated teaching method.
Tree Diet: Reducing the Treewidth to Unlock FPT Algorithms in RNA Bioinformatics
Authors: Marchand Bertrand , Ponty Yann , Bulteau Laurent 
Published: May 2021

AbstractHard graph problems are ubiquitous in Bioinformatics, inspiring the design of specialized Fixed-Parameter Tractable algorithms, many of which rely on a combination of tree-decomposition and dynamic programming. The time/space complexities of such approaches hinge critically on low values for the treewidthtwof the input graph. In order to extend their scope of applicability, we introduce the Tree-Dietproblem,i.e. the removal of a minimal set of edges such that a given tree-decomposition can be slimmed down to a prescribed treewidthtw′. Our rationale is that the time gained thanks to a smaller treewidth in a parameterized algorithm compensates the extra post-processing needed to take deleted edges into account.Our core result is an FPT dynamic programming algorithm for Tree-Diet, using 2O(tw)ntime and space. We complement this result with parameterized complexity lower-bounds for stronger variants (e.g., NP-hardness whentw′ ortw−tw′ is constant). We propose a prototype implementation for our approach which we apply on difficult instances of selected RNA-based problems: RNA design, sequence-structure alignment, and search of pseudoknotted RNAs in genomes, revealing very encouraging results. This work paves the way for a wider adoption of tree-decomposition-based algorithms in Bioinformatics.
The immunological factors predisposing to severe COVID-19 are already present in healthy elderly and men
Authors: Kilic Gizem , Bulut Ozlem , Jaeger Martin , Horst Rob ter , Koeken Valerie A. C. M. , Moorlag Simone , Mourits Vera P. , de Bree Charlotte , Domínguez-Andrés Jorge , Joosten Leo A. B. , Netea Mihai G. 
Published: May 2021

AbstractBackgroundMale sex and old age are risk factors for COVID-19 severity, but the underlying causes are unknown. A possible explanation for this might be the differences in immunological profiles in males and the elderly before the infection. Given the seasonal profile of COVID-19, the seasonal response against SARS-CoV-2 could also be different in these groups.MethodsThe abundance of circulating proteins and immune populations associated with severe COVID-19 was analyzed in 2 healthy cohorts. PBMCs of female, male, young, and old subjects in different seasons of the year were stimulated with heat-inactivated SARS-CoV-2.ResultSeveral T cell subsets, which are known to be depleted in severe COVID-19 patients, were intrinsically less abundant in men and older individuals. Plasma proteins increasing with disease severity, including HGF, IL-8, and MCP-1, were more abundant in the elderly and males. The elderly produced significantly more IL-1RA and had a dysregulated IFNγ response with lower production in the summer compared with young individuals.ConclusionsThe immune characteristics of severe COVID-19, described by a differential abundance of immune cells and circulating inflammatory proteins, are intrinsically present in healthy men and the elderly. This might explain the susceptibility of men and the elderly to SARS-CoV-2 infection.SummaryImmunological profile of severe COVID-19, characterized by altered immune cell populations and inflammatory plasma proteins is intrinsically present in healthy men and the elderly. Different age and sex groups show distinct seasonal responses to SARS-CoV-2.
Infection Units: A novel approach to the modeling of COVID-19 spread
Authors: Merchuk Jose C. , García-Camacho Francisco , López-Rosales Lorenzo 
Published: May 2021

AbstractA novel mechanistic model describing the rate of COVID-19 spread is presented, that differs conceptually from previously published deterministic models. One of its main characteristics is that the pool of infected people is not assumed to be homogeneously mixed, but rather as a passage into which individuals enter upon contagion, move within it in a plug-flow manner and leave at recovery, within a fixed time period. So, the present model differs conceptually in the way it describes the dynamics of infection. An ‘infection unit’ is defined as the amount of COVID-19 virus that generates contagion, if it reaches a susceptible individual. This model separately considers various pools: symptomatic and asymptomatic infected patients; three different pools of recovered individuals; pools of assisted, hospitalized patients; the quarantined and, finally, those who died from COVID-19. The transmission of the disease from an infected person to others is described by aninfection rate function, while anencounter frequency functionmodulates the frequency of effective encounters between the infected and the susceptible. The influence of the model’s parameters on the predicted results is presented. The effect of social restrictions and of quarantine policy on pandemic spread is shown. For model calibration, a set of experimental data is used. The model enables the calculation of the actual behaviour of the studied pools during pandemic spread.
Actigraphy Informs Distinct Patient-Centered Outcomes in Pre-COPD
Authors: Chen Jianhong , Weldemichael Lemlem , Giang Brian , Geerts Jeroen , Zeng Siyang , Ching Wendy Czerina , Nishihama Melissa , Gold Warren M , Arjomandi Mehrdad 
Published: May 2021

ABSTRACTBackgroundActigraphy can clarify useful patient-centered outcomes for quantification of physical activity in the “real-world” setting.MethodsTo characterize the relationship of actigraphy outputs with “in-laboratory” measures of cardiopulmonary function and respiratory symptoms in pre-COPD, we obtained actigraphy data for 8 hours/day for 5 consecutive days a week before in-laboratory administration of respiratory questionnaires, PFT, and CPET to a subgroup of subjects participating in the larger study of the health effects of exposure to secondhand tobacco smoke who had air trapping but no spirometric obstruction (pre-COPD). Using machine learning approaches, we identified the most relevant actigraphy predictors and examined their associations with symptoms, lung function, and exercise outcomes.ResultsSixty-one subjects (age=66±7years; BMI=24±3kg/m2; FEV1/FVC=0.75±0.05; FEV1=103±17%predicted) completed the nested study. In the hierarchical cluster analysis, the activity, distance, and energy domains of actigraphy, including moderate to vigorous physical activity, were closely correlated with each other, but were only loosely associated with spirometric and peak exercise measures of oxygen consumption, ventilation, oxygen-pulse, and anaerobic threshold (VO2AT), and were divergent from symptom measures. Conversely, the sedentary domain clustered with respiratory symptoms, air trapping, airflow indices, and ventilatory efficiency. In Regression modeling, sedentary domain was inversely associated with baseline lung volumes and tidal breathing at peak exercise, while the activity domains were associated with VO2AT. Respiratory symptoms and PFT data were not associated with actigraphy outcomes.DiscussionOutpatient actigraphy can provide information for “real-world” patient-centered outcomes that are not captured by standardized respiratory questionnaires, lung function, or exercise testing. Actigraphy activity and sedentary domains inform of distinct outcomes.VISUAL ABSTRACT
COVID-19 wastewater surveillance in rural communities: Comparison of lagoon and pumping station samples
Authors: D’Aoust Patrick M. , Towhid Syeda Tasneem , Mercier Élisabeth , Hegazy Nada , Tian Xin , Bhatnagar Kamya , Zhang Zhihao , Naughton Colleen C. , MacKenzie Alex E. , Graber Tyson E. , Delatolla Robert 
Published: May 2021

AbstractWastewater-based epidemiology/wastewater surveillance has been a topic of significant interest over the last year due to its application in SARS-CoV-2 surveillance to track prevalence of COVID-19 in communities. Although SARS-CoV-2 surveillance has been applied in more than 50 countries to date, the application of this surveillance has been largely focused on relatively affluent urban and peri-urban communities. As such, there is a knowledge gap regarding the implementation of reliable wastewater surveillance in small and rural communities for the purpose of tracking rates of incidence of COVID-19 and other pathogens or biomarkers. This study examines the relationships existing between SARS-CoV-2 viral signal from wastewater samples harvested from an upstream pumping station and from an access port at a downstream wastewater treatment lagoon with the community’s COVID-19 rate of incidence (measured as percent test positivity) in a small, rural community in Canada. Real-time quantitative polymerase chain reaction (RT-qPCR) targeting the N1 and N2 genes of SARS-CoV-2 demonstrate that all 24-hr composite samples harvested from the pumping station over a period of 5.5 weeks had strong viral signal, while all samples 24-hr composite samples harvested from the lagoon over the same period were below the limit of quantification. RNA concentrations and integrity of samples harvested from the lagoon were both lower and more variable than from samples from the upstream pumping station collected on the same date, indicating a higher overall stability of SARS-CoV-2 RNA upstream of the lagoon. Additionally, measurements of PMMoV signal in wastewater allowed to normalize SARS-CoV-2 viral signal for fecal matter content, permitting the detection of actual changes in community prevalence with a high level of granularity. As a result, in sewered small and rural communities or low-income regions operating wastewater lagoons, samples for wastewater surveillance should be harvested from pumping stations or the sewershed as opposed to lagoons.
Mapping of pseudouridine residues on cellular and viral transcripts using a novel antibody-based technique
Authors: Campos Cecilia Martinez , Tsai Kevin , Courtney David G. , Bogerd Hal P. , Holley Christopher L. , Cullen Bryan R. 
Published: May 2021

AbstractPseudouridine (Ψ) is the most common non-canonical ribonucleoside present on mammalian non-coding RNAs (ncRNAs), including rRNAs, tRNAs and snRNAs, where it contributes ∼7% of the total uridine level. However, Ψ constitutes only ∼0.1% of the uridines present on mRNAs and its effect on mRNA function remains unclear. Ψ residues have been shown to inhibit the detection of exogenous RNA transcripts by host innate immune factors, thus raising the possibility that viruses might have subverted the addition of Ψ residues to mRNAs by host pseudouridine synthase (PUS) enzymes as a way to inhibit antiviral responses in infected cells. Here, we describe and validate a novel antibody-based Ψ mapping technique called photo-crosslinking assisted Ψ sequencing (PA-Ψ-seq) and use it to map Ψ residues on not only multiple cellular RNAs but also on the mRNAs and genomic RNA encoded by HIV-1. We describe several 293T-derived cell lines in which human PUS enzymes previously reported to add Ψ residues to human mRNAs, specifically PUS1, PUS7 and TRUB1/PUS4, were inactivated by gene editing. Surprisingly, while this allowed us to assign several sites of Ψ addition on cellular mRNAs to each of these three PUS enzymes, the Ψ sites present on HIV-1 transcripts remained unaffected. Moreover, loss of PUS1, PUS7 or TRUB1 function did not significantly reduce the level of Ψ residues detected on total human mRNA below the ∼0.1% level seen in wild type cells, thus implying that the PUS enzyme(s) that adds the bulk of Ψ residues to human mRNAs remains to be defined.
SARS-CoV-2 Genome Sequencing Methods Differ In Their Ability To Detect Variants From Low Viral Load Samples
Authors: Lam C. , Gray K. , Gall M. , Sadsad R. , Arnott A. , Johnson-Mackinnon J. , Fong W. , Basile K. , Kok J. , Dwyer D. E. , Sintchenko V. , Rockett R.J. 
Published: May 2021

ABSTRACTSARS-CoV-2 genomic surveillance has been vital in understanding the spread of COVID-19, the emergence of viral escape mutants and variants of concern. However, low viral loads in clinical specimens affect variant calling for phylogenetic analyses and detection of low frequency variants, important in uncovering infection transmission chains. We systematically evaluated three widely adopted SARS-CoV-2 whole genome sequencing methods for their sensitivity, specificity, and ability to reliably detect low frequency variants. Our analyses highlight that the ARTIC v3 protocol consistently displays high sensitivity for generating complete genomes at low viral loads compared with the probe-based Illumina respiratory viral oligo panel, and a pooled long-amplicon method. We show substantial variability in the number and location of low-frequency variants detected using the three methods, highlighting the importance of selecting appropriate methods to obtain high quality sequence data from low viral load samples for public health and genomic surveillance purposes.
In silicoandin vitroDemonstration of Homoharrintonine’s Antagonism of RBD-ACE2 Binding and its Anti-inflammatory and anti-thrombogenic Properties in a 3D human vascular lung model
Authors: Saxena Shalini , Meher Kranti , Rotella Madhuri , Vangala Subhramanyam , Chandran Satish , Malhotra Nikhil , Palakodeti Ratnakar , Voleti Sreedhara R , Saxena Uday 
Published: May 2021

AbstractSince 2019 the world has seen severe onslaught of SARS-CoV-2 viral pandemic. There is an urgent need for drugs that can be used to either prevent or treat the potentially fatal disease COVD-19. To this end, we screened FDA approved antiviral drugs which could be repurposed for COVID-19 through molecular docking approach in the various active sites of receptor binding domain (RBD). The RBD domain of SARS-CoV-2 spike protein is a promising drug target due to its pivotal role in viral-host attachment. Specifically, we focussed on identifying antiviral drugs which could a) block the entry of virus into host cells, b) demonstrate anti-inflammatory and/or anti-thrombogenic properties. Drugs which poses both properties could be useful for prevention and treatment of the disease. While we prioritized a few antiviral drugs based on molecular docking, corroboration within vitrostudies including a new 3D human vascular lung model strongly supported the potential ofHomoharringtonine, a drug approved for chronic myeloid leukaemia to be repurposed for COVID-19. This natural product drug not only antagonized the biding of SARS-CoV-2 spike protein RBD binding to human angiotensin receptor 2 (ACE-2) protein but also demonstrated for the first time anti-thrombogenic and anti-leukocyte adhesive properties in a human cell model system. Overall, this work provides an important lead for development of rapid treatment of COVID-19 and also establishes a screening paradigm using molecular modelling and 3D human vascular lung model of disease to identify drugs with multiple desirable properties for prevention and treatment of COVID-19.
Human organoid systems reveal in vitro correlates of fitness for SARS-CoV-2 B.1.1.7
Authors: Lamers Mart M. , Breugem Tim I. , Mykytyn Anna Z. , Wang Yiquan , Groen Nathalie , Knoops Kèvin , Schipper Debby , van der Vaart Jelte , Koopman Charlotte D. , Zhang Jingshu , Wu Douglas C. , van den Doel Petra B. , Bestebroer Theo , GeurtsvanKessel Corine H. , Peters Peter J. , Muraro Mauro J. , Clevers Hans , Wu Nicholas C. , Haagmans Bart L. 
Published: May 2021

AbstractA new phase of the COVID-19 pandemic has started as several SARS-CoV-2 variants are rapidly emerging globally, raising concerns for increased transmissibility. As animal models and traditional in vitro systems may fail to model key aspects of the SARS-CoV-2 replication cycle, representative in vitro systems to assess variants phenotypically are urgently needed. We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Our findings unveil human organoids as powerful tools to phenotype viral variants and suggest extended shedding as a correlate of fitness for SARS-CoV-2.One-Sentence SummaryBritish SARS-CoV-2 variant (clade B.1.1.7) infects organoids for extended time and has a higher fitness in vitro.
Context Free and Context-Dependent Conceptual Representation in the Brain
Authors: Gao Zhiyao , Zheng Li , Gouws André , Krieger-Redwood Katya , Wang Xiuyi , Varga Dominika , Smallwood Jonathan , Jefferies Elizabeth 
Published: May 2021

AbstractHow concepts are coded in the brain is a core issue in cognitive neuroscience. Studies have focused on how individual concepts are processed, but the way in which conceptual representation changes to suit the context is unclear. We parametrically manipulated the association strength between words, presented in pairs one word at a time using a slow event-related fMRI design. We combined representational similarity analysis and computational linguistics to probe the neurocomputational content of these trials. Individual word meaning was maintained in supramarginal gyrus (associated with verbal short-term memory) when items were judged to be unrelated, but not when a linking context was retrieved. Context-dependent meaning was instead represented in left lateral prefrontal gyrus (associated with controlled retrieval), angular gyrus and ventral temporal lobe (regions associated with integrative aspects of memory). Analyses of informational connectivity, examining the similarity of activation patterns across trials between sites, showed that control network regions had more similar multivariate responses across trials when association strength was weak, reflecting a common controlled retrieval state when the task required more unusual associations. These findings indicate that semantic control and representational sites amplify contextually-relevant meanings in trials judged to be related.
MLL4 is a critical mediator of differentiation and ferroptosis in the epidermis
Authors: Egolf Shaun , Zou Jonathan , Anderson Amy , Aubert Yann , Ge Kai , Seykora John T. , Capell Brian C. 
Published: May 2021

ABSTRACTThe epigenetic regulator,MLL4(KMT2D), has been described as an essential gene in both humans and mice1,2. In addition, it is one of the most commonly mutated genes in all of cancer biology3–7. Here, we identify a critical role for Mll4 in the promotion of epidermal differentiation and ferroptosis, a key mechanism of tumor suppression8,9. Mice lacking epidermalMll4, but not the related enzymeMll3(Kmt2c), display features of impaired differentiation and human pre-cancerous neoplasms, including epidermal hyperplasia, atypical keratinocytes, and a loss of polarization, all of which progress with age. Mll4 deficiency profoundly alters epidermal gene expression, and uniquely rewires the expression of key genes and markers of ferroptosis (Alox12,Alox12b,Aloxe3)10. Beyond identifying a novel role forMll4-mediated tumor suppression in the skin, our data reveal a potentially much more broad and general role for ferroptosis in the process of epidermal differentiation and skin homeostasis.