bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predominance of the SARS-CoV-2 lineage P.1 and its sublineage P.1.2 in patients from the metropolitan region of Porto Alegre, Southern Brazil in March 2021: a phylogenomic analysis
Authors: Franceschi Vinícius Bonetti , Caldana Gabriel Dickin , Perin Christiano , Horn Alexandre , Peter Camila , Cybis Gabriela Bettella , Ferrareze Patrícia Aline Gröhs , Rotta Liane Nanci , Cadegiani Flávio Adsuara , Zimerman Ricardo Ariel , Thompson Claudia Elizabeth 
Published: May 2021

AbstractAlmost a year after the COVID-19 pandemic had begun, The United Kingdom, South Africa, and Brazil became the epicenter of new lineages, the Variant of Concern (VOCs), B.1.1.7, B.1.351, and P.1, respectively. These VOCs are increasingly associated with enhanced transmissibility, immunity evasion, and mortality. The previous most prevalent lineages in the state of Rio Grande do South (Brazil), B.1.1.28 and B.1.1.33 were rapidly replaced by P.1 and P.2, two B.1.1.28-derived lineages harboring the E484K mutation. To perform a genomic characterization of SARS-CoV-2 samples from COVID-19 patients from the metropolitan region of Porto Alegre (Rio Grande do Sul, Southern Brazil), in this second pandemic wave, we sequenced viral samples from patients of this region to: (i) identify the prevalence of SARS-CoV-2 lineages in the region, the state and bordering countries/states, (ii) characterize the mutation spectra, and (iii) hypothesize possible viral dispersal routes by using phylogenetic and phylogeographic approaches. As results, we not only confirmed that 96.4% of the samples belonged to the P.1 lineage but also that approximately 20% of which could be assigned as the newer P.1.2 (a P.1 derived new sublineage harboring new signature substitutions recently described and present in other Brazilian states and foreign countries). Moreover, P.1 sequences from this study were allocated in several distinct branches (four clades and five clusters) of the P.1 phylogeny, suggesting multiple introductions of P.1 in Rio Grande do Sul still in 2020 and placing this state as a potential core of diffusion and emergence of P.1-derived clades. It is still uncertain if the emergence of P.1.2 and other P.1 clades are related to further virological, clinical, or epidemiological consequences. However, the clear signs of viral molecular diversification from recently introduced P.1 warrant further genomic surveillance.
Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation
Authors: Tripodo Claudio , Bassani Barbara , Jachetti Elena , Cancila Valeria , Chiodoni Claudia , Portararo Paola , Botti Laura , Valenti Cesare , Perrone Milena , Ponzoni Maurilio , Comoli Patrizia , Curti Antonio , Colombo Mario Paolo , Sangaletti Sabina 
Published: May 2021

AbstractNeutrophil extracellular traps (NET) are web-like chromatin structures composed by dsDNA and histones, decorated with anti-microbial proteins. Their interaction with dendritic cells (DC) allows DC activation and maturation toward presentation of NET-associated antigens. Differently from other types of cell death that imply protein denaturation, NETosis preserves the proteins localized onto the DNA threads for proper enzymatic activity and conformational status, including immunogenic epitopes. Besides neutrophils, leukemic cells can release extracellular traps displaying leukemia-associated antigens, prototypically mutant nucleophosmin (NPMc+) that upon mutation translocates from nucleolus to the cytoplasm localizing onto NET threads. We tested NPMc+ immunogenicity through a NET/DC vaccine to treat NPMc-driven myeloproliferation in transgenic and transplantable models. Vaccination with DC loaded with NPMc+ NET (NPMc+ NET/DC) reduced myeloproliferation in transgenic mice, favoring the development of antibodies to mutant NPMc and and the induction of a CD8+ T cell response. The efficacy of this vaccine was also tested in mixed NPMc/WT bone marrow chimeras in a competitive bone marrow transplantation setting, where the NPMc+ NET/DC vaccination impaired the expansion of NPMc+ in favor of WT myeloid compartment. NPMc+ NET/DC vaccination also achieved control of an aggressive leukemia transduced with mutant NPMc, effectively inducing an anti-leukemia CD8 T cell memory response.eTOC SummaryNPMc is an AML-triggering mutation inducing translocation of NPM into the cytoplasm, allowing its association to NET threads. On NET, NPMc becomes immunogenic acting as an alarmin and exposing immunogenic peptides. We demonstrate that NET can be exploited as anti-tumor weapons in DC-based vaccination strategies.
Application of transposon-insertion sequencing to determine gene essentiality in the acetogen Clostridium autoethanogenum
Authors: Woods Craig , Humphreys Christopher M. , Tomi-Andrino Claudio , Henstra Anne M. , Köpke Michael , Simpson Sean D. , Winzer Klaus , Minton Nigel P. 
Published: May 2021

ABSTRACTThe majority of the genes present in bacterial genomes remain poorly characterised with up to one third of those that are protein encoding having no definitive function. Transposon insertion sequencing represents a high-throughput technique that can help rectify this deficiency. The technology, however, can only be realistically applied to easily transformable species leaving those with low DNA-transfer rates out of reach. Here we have developed a number of approaches that overcome this barrier in the autotrophic species Clostridium autoethanogenum using a mariner-based transposon system. The inherent instability of such systems in the Escherichia coli conjugation donor due to transposition events was counteracted through the incorporation of a conditionally lethal codA marker on the plasmid backbone. Relatively low frequencies of transformation of the plasmid into C. autoethanogenum were circumvented through the use of a plasmid that is conditional for replication coupled with the routine implementation of an Illumina library preparation protocol that eliminates plasmid-based reads. A transposon library was then used to determine the essential genes needed for growth using carbon monoxide as a sole carbon and energy source.IMPORTANCEAlthough microbial genome sequences are relatively easily determined, assigning gene function remains a bottleneck. Consequently, relatively few genes are well characterised, leaving the function of many as either hypothetical or entirely unknown. High-throughput, transposon sequencing can help remedy this deficiency, but is generally only applicable to microbes with efficient DNA-transfer procedures. These exclude many microorganisms of importance to humankind either as agents of disease or as industrial process organisms. Here we developed approaches to facilitate transposon-insertion sequencing in the acetogen Clostridium autoethanogenum, a chassis being exploited to convert single-carbon waste gases, CO and CO2, into chemicals and fuels at an industrial scale. This allowed the determination of gene essentiality under heterotrophic and autotrophic growth providing insights into the utilisation of CO as a sole carbon and energy source. The strategies implemented are translatable and will allow others to apply transposon-insertion sequencing to other microbes where DNA-transfer has until now represented a barrier to progress.
Implementation of a qPCR assay coupled with genomic surveillance for real-time monitoring of SARS-CoV-2 variants of concern
Authors: Rego Natalia , Costábile Alicia , Paz Mercedes , Salazar Cecilia , Perbolianachis Paula , Spangenberg Lucía , Ferrés Ignacio , Arce Rodrigo , Fajardo Alvaro , Arleo Mailen , Possi Tania , Bellini Inés , Bilbao Lucia , Reyes Natalia , Bentancor Ma Noel , Lizasoain Andrés , Benítez María José , Castells Matías , Victoria Matías , Maya Leticia , Bortagaray Viviana , Moller Ana , Bello Gonzalo , Arantes Ighor , Brandes Mariana , Smircich Pablo , Chappos Odhille , Duquía Melissa , González Belén , Griffero Luciana , Méndez Mauricio , Techera Ma Pía , Zanetti Juan , Rivera Bernardina , Maidana Matías , Alonso Martina , Alonso Cecilia , Medina Julio , Albornoz Henry , Colina Rodney , Noya Veronica , Iraola Gregorio , Fernández-Calero Tamara , Moratorio Gonzalo , Moreno Pilar 
Published: May 2021

AbstractWe developed a genomic surveillance program for real-time monitoring of SARS-CoV-2 variants of concern in Uruguay. Here, we present the first results, including the proposed qPCR-VOC method, the general workflow and the report of the introduction and community transmission of the VOC P.1 in Uruguay in multiple independent events.
Clinical and experimental factors that affect the reported performance characteristics of rapid testing for SARS-CoV-2
Authors: Parvu Valentin , Gary Devin S. , Mann Joseph , Lin Yu-Chih , Mills Dorsey , Cooper Lauren , Andrews Jeffrey C. , Manabe Yukari C. , Pekosz Andrew , Cooper Charles K. 
Published: May 2021

ABSTRACTTests that detect the presence of SARS-CoV-2 antigen in clinical specimens from the upper respiratory tract can provide a rapid means of COVID-19 disease diagnosis and help identify individuals that may be infectious and should isolate to prevent SARS-CoV-2 transmission. This systematic review assesses the diagnostic accuracy of SARS-CoV-2 antigen detection in COVID-19 symptomatic and asymptomatic individuals compared to RT-qPCR, and summarizes antigen test sensitivity using meta-regression. In total, 83 studies were included that compared SARS-CoV-2 rapid antigen lateral flow testing (RALFT) to RT-qPCR for SARS-CoV-2. Generally, the quality of the evaluated studies was inconsistent, nevertheless, the overall sensitivity for RALFT was determined to be 75.0% (95% confidence interval [CI]: 71.0-78.0). Additionally, RALFT sensitivity was found to be higher for symptomatic versus asymptomatic individuals and was higher for a symptomatic population within 7 days from symptom onset (DSO) compared to a population with extended days of symptoms. Viral load was found to be the most important factor for determining SARS-CoV-2 antigen test sensitivity. Other design factors, such as specimen storage and anatomical collection type, also affect the performance of RAFLT. RALFT and RT-qPCR testing both achieve high sensitivity when compared to SARS-CoV-2 viral culture.
Exploring Patients’ Needs & Desires for Quality Prenatal Care in Florida
Authors: Fryer Kimberly , Reid Chinyere N. , Cabral Naciely , Marshall Jennifer , Menon Usha 
Published: May 2021

AbstractIntroductionEarly and adequate prenatal care is important for patients to obtain health education, risk reduction, psychosocial support, and necessary medical interventions during the prenatal period. High-quality prenatal care encourages adequate care throughout pregnancy by increasing patients’ desires to return for subsequent visits. This study aims to investigate the prenatal care experiences, desires, and needs of women in Florida.MethodsA mixed-methods study was conducted from April to December 2019 with postpartum women (n=55) who received no or late prenatal care and delivered in [City], Florida. Eligible women completed a survey and a semi-structured interview. The interview contextualized conditions shaping perceptions of the quality of prenatal care. Univariate analysis was conducted on the demographic characteristics and prenatal care locations. Qualitative analysis was performed using MAXQDA software and modified grounded theory. The analysis was based on Donabedian’s quality of care model.ResultsThe participants self-identified as Hispanic (52%), White (48%), and Black (21%). Sixty-nine percent had Medicaid while 22% were self-pay. In the qualitative analysis, three core themes emerged. Clinical care processes included provision of health education and medical assessments. Structural conditions included language barriers, clinic availability, and ancillary staff presence. Lastly, interpersonal communication included impersonal care and multiple providers. The overarching conclusion from this analysis was the desire for patient-centered care. Participants wanted the care they received to be informative, tailored to their needs, and to work within the realities of their everyday lives.DiscussionInvestigating women’s experiences with seeking and receiving prenatal care are necessary to inform future interventions. Fostering a positive and patient-centered healthcare environment is necessary to improve the quality of care.Quick pointsWhat is already known on this subject?Racial and ethnic disparities exist in prenatal care access, utilization and both maternal and infant mortality and morbidity.Timely and adequate prenatal care is an important determinant for maternal and infant birth outcomes.What this study addsThis study identified process, structure, and interpersonal factors associated with prenatal care access and utilization from the perspectives of a diverse group of postpartum women.Specific recommendations for patient-centered prenatal care for diverse women in the context of patient expectations and perceptions of quality are provided.
Release of infectious virus and cytokines in nasopharyngeal swabs from individuals infected with non-B.1.1.7 or B.1.1.7 SARS-CoV-2 variants
Authors: Monel Blandine , Planas Delphine , Grzelak Ludivine , Smith Nikaïa , Robillard Nicolas , Staropoli Isabelle , Goncalves Pedro , Porrot Françoise , Guivel-Benhassine Florence , Guinet Nathalie Demory , Rodary Julien , Puech Julien , Euzen Victor , Bélec Laurent , Orvoen Galdric , Nunes Léa , Moulin Véronique , Fourgeaud Jacques , Wack Maxime , Imbeaud Sandrine , Campagne Pascal , Duffy Darragh , Di Santo James P. , Bruel Timothée , Péré Hélène , Veyer David , Schwartz Olivier 
Published: May 2021

AbstractThe mechanisms that allowed for the SARS-CoV-2 B.1.1.7 variant to rapidly outcompete pre-existing variants in many countries remain poorly characterized. Here, we analyzed viral release, anti-SARS-CoV-2 antibodies and cytokine production in a retrospective series of 427 RT–qPCR+ nasopharyngeal swabs collected in COVID-19 patients harbouring either non-B.1.1.7 or B.1.17 variants. We utilized a novel rapid assay, based on S-Fuse-T reporter cells, to quantify infectious SARS-CoV-2. With both non-B.1.1.7 and B.1.1.7 variants, viral titers were highly variable, ranging from 0 to >106 infectious units, and correlated with viral RNA levels. Lateral flow antigenic rapid diagnostic tests (RDTs) were positive in 96% of the samples harbouring infectious virus. About 67 % of individuals carried detectable infectious virus within the first two days after onset of symptoms. This proportion decreased overtime, and viable virus was detected up to 14 days. Samples containing anti-SARS-CoV-2 IgG or IgA did not generally harbour infectious virus. The proportion of individuals displaying viable virus or being RDT-positive was not higher with B.1.1.7 than with non-B.1.1.7 variants. Ct values were slightly but not significantly lower with B.1.1.7. The variant was characterized by a fast decrease of infectivity overtime and a marked release of 17 cytokines (including IFN-β, IP-10, IL-10 and TRAIL). Our results highlight differences between non-B.1.1.7 and B.1.1.7 variants. B.1.1.7 is associated with modified viral decays and cytokine profiles at the nasopharyngeal mucosae during symptomatic infection.
Public Health and Health Systems Impacts of SARS-CoV-2 Variants of Concern: A Rapid Scoping Review
Authors: Curran J , Dol J , Boulos L , Somerville M , McCulloch H 
Published: May 2021

AbstractBackgroundAs of April 2021, three SARS-CoV-2 variants of concern (VOC: B.1.1.7, B.1.351 and P.1) have been detected in over 132 countries. Increased transmissibility of VOC has implications for public health measures and health system arrangements. This rapid scoping review aims to provide a synthesis of current evidence related to public health measures and health system arrangements associated with VOC.MethodsRapid scoping review. Seven databases were searched up to April 7, 2021 for terms related to VOC, transmission, public health and health systems. A grey literature search was conducted up to April 14, 2021. Title, abstracts and full text were screened independently by two reviewers. Data were double extracted using a standardized form. Studies were included if they reported on at least one of the VOC and public health or health system outcomes.ResultsOf the 2487 articles and 59 grey literature sources retrieved, 37 studies and 21 guidance documents were included. Included studies used a wide range of designs and methods. Most of the studies and guidance documents reported on B.1.1.7, and 18 studies and 4 reports provided data for consideration in relation to public health measures. Public health measures, including lockdowns, physical distancing, testing and contact tracing, were identified as critical adjuncts to a comprehensive vaccination campaign. No studies reported on handwashing or masking procedures related to VOC. For health system arrangements, 17 studies were identified. Some studies found an increase in hospitalization due to B.1.1.7 but no difference in length of stay or ICU admission. Six studies found an increased risk of death ranging from 15-67% with B.1.1.7 compared non-B.1.1.7, but three studies reported no change. One study reported on the effectiveness of personal protective equipment in reducing VOC transmission in the hospital. No studies reported on screening staff and visitors, adjusting service provisions, or adjusting patient accommodations and shared spaces, which is a significant gap in the literature. Guidance documents did not tend to cite any evidence and were thus assumed to be based on expert opinion.ConclusionWhile the findings should be interpreted with caution as most of the sources identified were preprints, findings suggest a combination of non-pharmaceutical interventions (e.g., masking, physical distancing, lockdowns, testing) should be employed alongside a vaccine strategy to improve population and health system outcomes. While the findings are mixed on the impact of VOC on health system arrangements, the evidence is trending towards increased hospitalization and death.
Cryptic diversity within thePoecilochirus carabimite species complex phoretic onNicrophorus buryingbeetles: phylogeny, biogeography, and host specificity
Authors: Canitz Julia , Sikes Derek S. , Knee Wayne , Baumann Julia , Haftaro Petra , Steinmetz Nadine , Nave Martin , Eggert Anne-Katrin , Hwang Wenbe , Nehring Volker 
Published: May 2021

AbstractCoevolution is often considered a major driver of speciation, but evidence for this claim is not always found because diversity might be cryptic. When morphological divergence is low, molecular data are needed to uncover diversity. A taxon for which this holds true are the mites, which are known for their extensive and often cryptic diversity. We studied mites of the genusPoecilochirusthat are phoretic on burying beetles (Silphidae:Nicrophorus).Poecilochirustaxonomy is poorly understood. Most studies on this genus focus on the evolutionary ecology ofPoecilochirus carabi sensu lato, a complex of at least two biological species. Based on molecular data of 230 specimens from 43 locations worldwide, we identified 24 genetic clusters that may represent species. We estimate that these mites began to diversify during the Paleogene, when the clade containingP. subterraneusbranched off and the remaining mites diverged into two further clades. One clade resemblesP. monospinosusandP. austroasiaticus. The other clade contains 17 genetic clusters resemblingP. carabi s.l.. Among these areP. carabi sensu stricto, P. necrophori, and potentially many additional cryptic species. Our analyses suggest that these clades were formed in the miocene by large-scale geographic separation. Diversification also seems to have happened on a smaller scale, potentially due to adaptation to specific hosts or local abiotic conditions, causing some clusters to specialize on certain beetle species. Our results suggest that biodiversity in this genus was generated by multiple interacting forces shaping the tangled webs of life.
SOD2 in Skeletal Muscle: New Insights from an Inducible Deletion Model
Authors: Zhuang Aowen , Yang Christine , Liu Yingying , Tan Yanie , Bond Simon T. , Walker Shannen , Sikora Tim , Sharma Arpeeta , de Haan Judy B. , Meikle Peter J. , Coughlan Melinda T. , Calkin Anna C. , Drew Brian G. 
Published: May 2021

AbstractMetabolic conditions such as obesity, insulin resistance and glucose intolerance are frequently associated with impairments in skeletal muscle function and metabolism. This is often linked to dysregulation of homeostatic pathways including an increase in reactive oxygen species (ROS) and oxidative stress. One of the main sites of ROS production is the mitochondria, where the flux of substrates through the electron transport chain (ETC) can result in the generation of oxygen free radicals. Fortunately, several mechanisms exist to buffer bursts of intracellular ROS and peroxide production, including the enzymes Catalase, Glutathione Peroxidase and Superoxide Dismutase (SOD). Of the latter there are two intracellular isoforms; SOD1 which is mostly cytoplasmic, and SOD2 which is found exclusively in the mitochondria. Developmental and chronic loss of these enzymes has been linked to disease in several studies, however the temporal effects of these disturbances remain largely unexplored. Here, we induced a post-developmental (8-week old mice) deletion of SOD2 in skeletal muscle (SOD2-iMKO) and demonstrate that 16 weeks of SOD2 deletion leads to no major impairment in whole body metabolism, despite these mice displaying alterations in aspects of mitochondrial abundance and voluntary ambulatory movement. Furthermore, we demonstrated that SOD2 deletion impacts on specific aspects of muscle lipid metabolism, including the abundance of phospholipids and phosphatidic acid (PA), the latter being a key intermediate in several cellular signaling pathways. Thus, our findings suggest that post-developmental deletion of SOD2 induces a more subtle phenotype than previous embryonic models have shown, allowing us to highlight a previously unrecognized link between SOD2, mitochondrial function and bioactive lipid species including PA.
An optimized protocol for dual RNA-Seq of human macrophages infected with Mycobacterium avium
Authors: Schildkraut Jodie A , Koeken Valerie ACM , Coolen Jordy PM , van Crevel Reinout , van Ingen Jakko 
Published: May 2021

AbstractRecently, dual RNA-sequencing (RNA-Seq) has been identified as a powerful tool to study host-pathogen interactions, which is particularly interesting for intracellular pathogens such as mycobacteria. However, due to the complexity of obtaining human host cells, many models rely on the usage of host cells derived from animals or cell lines, which does not accurately mimic the situation in the patient. Furthermore, due to the severe disbalance in host and pathogen RNA content, it is difficult to obtain sufficient sequencing depth for the infecting pathogen. Here, we present an optimized method to perform dual RNA-sequencing on human monocyte-derived macrophages (hMDMs) infected with Mycobacterium avium (M. avium). It is likely that, with slight modifications in multiplicity of infection (MOI) to account for differences in virulence, this methodology will be applicable for other difficult-to-lyse intracellular mycobacteria.
Universal allometry from empirical parameters
Authors: McKerral Jody C. , Kleshnina Maria , Bartle Louise , Mitchell James G. , Filar Jerzy A. 
Published: May 2021

AbstractAllometric settings of population dynamics models are appealing due to their parsimonious nature and broad utility when studying system level effects. Here, we parameterise the size-scaled Rosenzweig-Macarthur ODEs to eliminate prey-mass dependency. We define the functional response term to match experiments, and examine situations where metabolic theory derivations and observation diverge. We produce dynamics consistent with observation. Our parameterisation of the Rosenzweig-Macarthur system is an accurate minimal model across 15+ orders of mass magnitude.