bluuebunny/crossref_metadata_2025_split huggingface dataset:
The BioNTech / Pfizer vaccine BNT162b2 induces class-switched SARS-CoV-2-specific plasma cells and potential memory B cells as well as IgG and IgA serum and IgG saliva antibodies upon the first immunization
Authors: Lixenfeld Anne S. , Künsting Inga , Martin Emily L. , Kopylow Vera von , Lehrian Selina , Lunding Hanna B. , Buhre Jana S. , Quack Janna , Steinhaus Moritz , Graf Tobias , Ehlers Marc , Rahmöller Johann 
Published: March 2021

AbstractTo treat the SARS-CoV-2 virus, that enters the body through the respiratory tract, different vaccines in particular against the SARS-CoV-2 spike (S)-protein have been developed or are in the development process. For the BioNTech / Pfizer mRNA vaccine BNT162b2, which is injected twice, protection against COVID-19 has been described for the first weeks after the second vaccination. The underlying mechanisms of defense and the long-term effectiveness of this vaccine against COVID-19 are currently under investigation.In addition to the induction of systemic antibodies (Abs), Ab responses in the respiratory tract would help to form a first line of defense against SARS-CoV-2. Furthermore, protection depends on Fab-part-dependent neutralizing capacities, however, Fc-part-mediated effector mechanisms might also be important. Long-term defense would be based on the induction of long-lived antibody-producing plasma cells (PCs) and memory B cells.Here, we established different assays to analyze anti-SARS-CoV-2-S IgG and IgA Abs in blood serum and saliva as well as SARS-CoV-2-S1-reactive IgG and IgA PCs and potential memory B cells in the blood of individuals upon their first immunization with BNT162b2.We show that the vaccine induces in particular anti-SARS-CoV-2-S IgG1 and IgG3 as well as IgA1 and in some individuals also IgG2 and IgA2 serum Abs. In the saliva, we found no anti-SARS-CoV-2-S IgA, but instead IgG Abs. Furthermore, we found SARS-CoV-2-S reactive IgG+ blood PCs and potential memory B cells as well as SARS-CoV-2-S reactive IgA+ PCs and/or potential memory B cells in some individuals.Our data suggest that the vaccine induces a promising CD4+ T cell-dependent systemic IgG1 and IgG3 Ab response with IgG+ PCs and potential memory B cells. In addition to the systemic IgG response, the systemic IgA and saliva IgG response might help to improve a first line of defense in the respiratory tract against SARS-CoV-2 and its mutants.
KAP survey of practicing doctors on antimicrobial stewardship based on openWHO course
Authors: Kaur Simerdeep , Sethi Prativa , Panda Prasan Kumar 
Published: March 2021

SynopsisBackgroundThe overwhelming, irrational behaviour of using antimicrobial (AM) has added to the amplification and spread of antimicrobial resistance (AMR) burden. Healthcare professionals can curtail the AMR by practicing antimicrobial stewardship (AMS). Keeping this in view WHO has laid down a global action plan to combat AMR including free online availability of openWHO course. So, our study aimed at accessing the knowledge, attitude, and practice (KAP) of practicing doctors towards AMS based on this course in a tertiary care hospital.MethodsThe study was conducted among practitioners (faculty, senior residents, junior residents) in different clinical departments. The study was designed as a KAP survey. A validated self-administered questionnaire consisting of 29 questions was designed and shared among 200 participants through the mail and physically. Apart from observing knowledge/attitude/practice gaps, the difference in response to questions was evaluated among various groups (surgeon vs physician, faculty vs senior resident vs junior resident, openWHO course participant vs openWHO course aware non-participant vs openWHO course unaware non-participants.ResultsResponse rate was 62.5% (n=200). Knowledge on AMS was observed among doctors’ with >50% near correct responses in each question except for the question asking on IV route of AM administration. A significant knowledge gap was found when a comparison was made between faculty members, senior residents, and junior residents (p <0.001) in the spectrum of activity of AM. Almost all the participants agreed that ASP is a necessity in the hospital and believed that ASP reduces healthcare costs and adverse effects of inappropriate AM prescription. A significant difference between the various groups’ aspects was also observed.ConclusionKnowledge gap on ASP is observed among all HCPs but significant differences among faculty, senior residents, and junior residents, among openWHO course vs unaware openWHO course participant. This shows faculty has to take the lead including more and more practice and education in ASP. The openWHO course may help in achieving this.
Acceptability of a nurse-led non-pharmacological complex intervention for knee pain: Nurse and patient views and experiences
Authors: Nomikos Polykarpos Angelos , Hall Michelle C , Fuller Amy , Ogollah Reuben , Valdes Ana M , Doherty Michael , Walsh David Andrew , Nair Roshan das , Abhishek Abhishek 
Published: March 2021

AbstractObjectivesThe overall purpose of this research programme is to develop and test the feasibility of a complex intervention for knee pain delivered by a nurse, and comprising both non-pharmacological and pharmacological interventions. In this first phase, we examined the acceptability of the non-pharmacological component of the intervention, issues faced in delivery, and resolve possible challenges.MethodsEighteen adults with chronic knee pain were recruited from the community. The intervention comprised holistic assessment, education, exercise, weight-loss advice (where appropriate) and advice on adjunctive treatments such as hot/cold treatments, footwear modification and walking aids. After nurse training, the intervention was delivered in four sessions spread over five weeks. Participants had one to one semi-structured interview at the end of the intervention. The nurse was interviewed after the last visit of the last participant. These were audio recorded and transcribed verbatim. Themes were identified by one author through framework analysis of the transcripts, and cross-checked by another.ResultsMost participants found the advice from the nurse easy to follow and were satisfied with the package, though some felt that too much information was provided too soon. The intervention changed their perception of managing knee pain, learning that it can be improved with self-management. However, participants thought that the most challenging part of the intervention was fitting the exercise regime into their daily routine. The nurse found discussion of goal setting to be challenging.ConclusionThe nurse-led package of care is acceptable within a research setting. The results are promising and will be applied in a feasibility randomised-controlled trial.
Analytical and clinical performances of a SARS-CoV-2 S-RBD IgG assay: comparison with neutralization titers
Authors: Padoan Andrea , Bonfante Francesco , Cosma Chiara , Chiara Costanza Di , Sciacovelli Laura , Pagliari Matteo , Bortolami Alessio , Costenaro Paola , Musso Giulia , Basso Daniela , Giaquinto Carlo , Plebani Mario 
Published: March 2021

AbstractBackgroundSARS-CoV-2 serology presents an important role in understanding the virus epidemiology, in vaccine prioritization strategies and in convalescent plasma therapy. Immunoassays performances have to be accurately evaluated and correlated with neutralizing antibodies to be used as a surrogate measure of neutralizing activity. We investigate the analytical and clinical performance of a SARS-CoV-2 RBD IgG assay, automated on a high throughput platform, and the correlation of the antibodies (Ab) levels with the plaque reduction neutralization (PRNT50) Ab titers.MethodsA series of 546 samples were evaluated by SARS-CoV-2 RBD IgG assay (Snibe diagnostics), including 171 negative and 168 positive SARS-CoV-2 subjects and a further group of 207 subjects of the COVID-19 family clusters follow-up cohort.ResultsAssay precision was acceptable at low and medium levels; linearity was excellent in all the measurement range. Considering specimens collected after 14 days post symptoms onset, overall sensitivity and specificity were 99.0% and 92.5%, respectively. A total of 281 leftover samples results of the PRNT50 test were available. An elevated correlation was obtained between the SARS-CoV-2 RBD IgG assay and the PRNT50 titer at univariate (rho = 0.689) and multivariate (rho = 0.712) analyses.ConclusionsSARS-CoV-2 S-RBD IgG assay achieves elevated analytical and clinical performances, and a strong correlation with sera neutralization activity.
The impact of headache disorders on COVID-19 survival: a world population-based analysis
Authors: Shapiro Robert E. , Gallardo Víctor J. , Caronna Edoardo , Pozo-Rosich Patricia 
Published: March 2021

AbstractImportanceCOVID-19 has not impacted people or countries uniformly. This disparity has prompted investigations to identify clinical and genetic predictors of COVID-19 mortality. Headache, a COVID-19 symptom, has been associated with positive disease prognosis. It is logical to consider whether primary headache disorders, among the most prevalent and disabling diseases globally, may also be associated with reduced viral mortality and thereby may have arisen as adaptive host defencesObjectiveTo study the relationship between COVID-19 mortality and primary headache disorders.Main outcome measureUsing a generalized additive model regression (GAM), we analysed data across 171 nations to identify variables which impact COVID-19 mortality rates (demographics, national wealth and government effectiveness, pandemic management indexes, latitude of the country’s capital, prevalence of headache disorders and other diseases). We performed similar analyses of seasonal influenza mortality. Separately, we meta-analysed studies of COVID-19 inpatient survival reporting headache, using PRISMA guidelines.ResultsIn the global population-level analysis, we observed that a higher prevalence of headache disorders was associated with a higher COVID-19 mortality rate, and represented the main variable contributing to differences in COVID-19 mortality rates between countries (37.8%; F value=10.68). By contrast, we observed a negative trend between the prevalence of headache disorders and influenza death rates. Controversially, when considering headache as a symptom of COVID-19, in the 48 meta-analysed studies we observed a significantly higher risk ratio of survival (RR:2.178 [1.882-2.520], p<0.0001) among COVID-19 inpatients with headache.Conclusions and RelevanceHeadache as a primary disorder is more prevalent in nations with higher COVID-19 mortality, whereas headache as a COVID-19 symptom is associated with enhanced survival. Further studies should clarify whether primary headache disorders represent a risk factor for mortality for COVID-19 or, rather, whether this association reflects evolutionary adaptive processes to enhance survival that, in the case of COVID-19, are insufficiently protective.
Specific allelic discrimination of N501Y and other SARS-CoV-2 mutations by ddPCR detects B.1.1.7 lineage in Washington State
Authors: Perchetti Garrett A. , Zhu Haiying , Mills Margaret G. , Shrestha Lasata , Wagner Cassia , Bakhash Shah Mohamed , Lin Michelle , Xie Hong , Huang Meei-Li , Mathias Patrick , Bedford Trevor , Jerome Keith R. , Greninger Alexander L. , Roychoudhury Pavitra 
Published: March 2021

ABSTRACTReal-time epidemiological tracking of variants of interest can help limit the spread of more contagious forms of SARS-CoV-2, such as those containing the N501Y mutation. Typically, genetic sequencing is required to be able to track variants of interest in real-time. However, sequencing can take time and may not be accessible in all laboratories. Genotyping by RT-ddPCR offers an alternative to sequencing to rapidly detect variants of concern through discrimination of specific mutations such as N501Y that is associated with increased transmissibility. Here we describe the first cases of the B.1.1.7 lineage of SARS-CoV-2 detected in Washington State by using a combination of RT-PCR, RT-ddPCR, and next-generation sequencing. We screened 1,035 samples positive for SARS-CoV-2 by our CDC-based laboratory developed assay using ThermoFisher’s multiplex RT-PCR COVID-19 assay over four weeks from late December 2020 to early January 2021. S gene dropout candidates were subsequently assayed by RT-ddPCR to confirm four mutations within the S gene associated with the B.1.1.7 lineage: a deletion at amino acid (AA) 69-70 (ACATGT), deletion at AA 145, (TTA), N501Y mutation (TAT), and S982A mutation (GCA). All four targets were detected in two specimens, and follow-up sequencing revealed a total of 10 mutations in the S gene and phylogenetic clustering within the B.1.1.7 lineage. As variants of concern become increasingly prevalent, molecular diagnostic tools like RT-ddPCR can be utilized to quickly, accurately, and sensitively distinguish more contagious lineages of SARS-CoV-2.
Immunity Depletion, Telomere Imbalance, and Cancer-associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Caloric Restriction
Authors: Maestri Evan , Duszka Kalina , Kuznetsov Vladimir A 
Published: March 2021

AbstractSystematic analysis of calorie restriction (CR) mechanisms and pathways in cancer biology has not been carried out, leaving therapeutic benefits unclear. Using a systems biology approach and metadata analysis, we studied gene expression changes in the response of normal mouse duodenum mucosa (DM) to short-term (2-weeks) 25% CR as a biological model. We found a high similarity of gene expression profiles in human and mouse DM tissues. Surprisingly, 26% of the 467 CR responding differential expressed genes (DEGs) in mice consist of cancer-associated genes—most never studied in CR contexts. The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways (MRP) that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest a misbalance in telomere maintenance and activation of metabolic pathways playing dual (anti-cancer and pro-oncogenic) roles. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor immune evasion controls. Thus, CR induces MRP suppressing multiple immune mechanics and activating oncogenic pathways, potentially driving pre-malignant and cancer states. These findings change the paradigm regarding the anti-cancer role of CR and may initiate specific treatment target development.
Probable omnigenic effect and evolutionary insights of aerobic adaptation allele OsNCED2Ton qDTY12.1 effecting grain yield under reproductive stage drought stress in rice
Authors: Parameswaran C , Cayalvizhi B , Sanghamitra S , Anandan N , Lal K Jawahar , Devanna BN , Awadhesh K , Kishor J , Bandita S , Niranjana B , Biswaranjan B 
Published: March 2021

AbstractYield associated quantitative trait loci (qDTY) under drought stress provides significant advantage for grain yield in rice. The major, stable qDTY12.1 was identified in a mapping population developed from upland cultivars Vandana and Way Rarem. Further, introgression line comprising of qDTY12.1 genomic region was characterized to have multiple genes (NAM, DECUSSATE) regulating the drought tolerance under severe drought stress substantiated through recently proposed omnigenic model for complex traits. Recently, plastid localized NCED2Tallele present within the qDTY12.1 genomic region was characterized for conferring aerobic adaptation in lowland varieties. Since, NCED2Tis evolutionary fixed in upland cultivars and Vandana was found to have the favorable allele of NCED2T, we hypothesized that this favorable allele might confer omnigenic effect on qDTY12.1 genes. Our evolutionary analysis using non synonymous SNPs present in genes namely NCED, NAM, and DECUSSATE and qDTY12.1 genomic regions showed specific grouping of Vandana with upland cultivars only for NCED gene and its adjoining genomic regions. However, non synonymous SNPs in NAM and DECUSSATE genes and its adjoining genomic regions of drought tolerant varieties were closely related and grouped together in the phylogenetic analysis. Moreover, ecotype specific differentiation and greater nucleotide difference with wild relatives was also observed for DECUSSATE gene in rice. This finding indicates differential evolution of qDTY12.1 regions for upland and drought tolerance and omnigenic effect of NCED2Tgene in qDTY12.1. Further, we propose a breeding model for enhancing genetic gain for yield under severe drought stress by incorporation of NCEDT, qDTY12.1 and other drought tolerant QTLs for membrane stability in rice.
Single-Cell Spatial Proteomics Analyses of Head and Neck Squamous Cell Carcinoma Reveal Tumor Heterogeneity and Immune Architectures Associated with Clinical Outcome
Authors: Blise Katie E. , Sivagnanam Shamilene , Banik Grace L. , Coussens Lisa M. , Goecks Jeremy 
Published: March 2021

ABSTRACTThere is increasing evidence that the spatial organization of cells within the tumor-immune microenvironment (TiME) of solid tumors influences survival and response to therapy in numerous cancer types. Here, we report results and demonstrate the applicability of quantitative single-cell spatial proteomics analyses in the TiME of primary and recurrent human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) tumors. Single-cell compositions of a nine patient, primary and recurrent (n=18), HNSCC cohort is presented, followed by deeper investigation into the spatial architecture of the TiME and its relationship with clinical variables and progression free survival (PFS). Multiple spatial algorithms were used to quantify the spatial landscapes of immune cells within TiMEs and demonstrate that neoplastic tumor-immune cell spatial compartmentalization, rather than mixing, is associated with longer PFS. Mesenchymal (αSMA+) cellular neighborhoods describe distinct immune landscapes associated with neoplastic tumor-immune compartmentalization and improved patient outcomes. Results from this investigation are concordant with studies in other tumor types, suggesting that trends in TiME cellular heterogeneity and spatial organization may be shared across cancers and may provide prognostic value in multiple cancer types.
Female fruitflies use gustatory cues to exhibit reproductive plasticity in response to the social environment
Authors: Fowler E.K. , Leigh S. , Rostant W.G. , Thomas A. , Bretman A. , Chapman T. 
Published: March 2021

AbstractAnimals can exhibit remarkable reproductive plasticity in response to their social surroundings, with profound fitness consequences. The study of such plasticity in females, particularly in same-sex interactions, has been severely neglected. Here we measured the impact of variation in the pre-mating social environment on reproductive success in females and tested the underlying mechanisms involved. We used theDrosophila melanogastermodel system to test the effect of varying female group size prior to mating and deployed physical and genetic methods to manipulate the perception of different social cues and sensory pathways. We found that socially isolated females were significantly more likely to retain unfertilised eggs before mating, but to show the opposite pattern and lay significantly more fertilised eggs in the 24h after mating, in comparison to grouped females. More than 48h of exposure to other females was necessary for this socially-induced plasticity to be expressed. Neither olfactory nor visual cues were involved in mediating these responses. Instead, we found that females detected other females through direct contact with the deposits they leave behind, even in the absence of eggs. The results demonstrate that females show striking reproductive plasticity in response to their social surroundings and that the nature of their plastic reproductive responses, and the cues they use, differ markedly from those of males. The results emphasise the stark contrasts in how each sex realises reproductive success.
The Genetic Basis of Differential Autodiploidization in Evolving Yeast Populations
Authors: Tung Sudipta , Bakerlee Christopher W. , Phillips Angela M. , Nguyen Ba Alex N. , Desai Michael M. 
Published: March 2021

ABSTRACTSpontaneous whole-genome duplication, or autodiploidization, is a common route to adaptation in experimental evolution of haploid budding yeast populations. The rate at which autodiploids fix in these populations appears to vary across strain backgrounds, but the genetic basis of these differences remains poorly characterized. Here we show that the frequency of autodiploidization differs dramatically between two closely related laboratory strains ofSaccharomyces cerevisiae, BY4741 and W303. To investigate the genetic basis of this difference, we crossed these strains to generate hundreds of unique F1 segregants and tested the tendency of each segregant to autodiplodize across hundreds of generations of laboratory evolution. We find that variants in theSSD1gene are the primary genetic determinant of differences in autodiploidization. We then used multiple laboratory and wild strains ofS. cerevisiaeto show that clonal populations of strains with a functional copy ofSSD1autodiploidize more frequently in evolution experiments, while knocking out this gene or replacing it with the W303 allele reduces autodiploidization propensity across all genetic backgrounds tested. These results suggest a potential strategy for modifying rates of spontaneous whole-genome duplications in laboratory evolution experiments in haploid budding yeast. They may also have relevance to other settings in which eukaryotic genome stability plays an important role, such as biomanufacturing and the treatment of pathogenic fungal diseases and cancers.
Alphaproteobacteria facilitateTrichodesmiumcommunity trimethylamine utilization
Authors: Conover Asa E. , Morando Michael , Zhao Yiming , Semones Jacob , Hutchins David A. , Webb Eric A. 
Published: March 2021

SummaryIn the surface waters of the warm oligotrophic ocean, filaments and aggregated colonies of the nitrogen (N)-fixing cyanobacteriumTrichodesmiumcreate microscale nutrient-rich oases. These hotspots fuel primary productivity and harbor a diverse consortium of heterotrophs. Interactions with associated microbiota can affect the physiology ofTrichodesmium, often in ways that have been predicted to support its growth. Recently, it was found that trimethylamine (TMA), a globally-abundant organic N compound, inhibits N2fixation in cultures ofTrichodesmiumwithout impairing growth rate, suggesting thatTrichodesmiumreceives nitrogen from TMA. In this study,15N-TMA DNA stable isotope probing (SIP) of aTrichodesmiumenrichment was employed to further investigate TMA metabolism and determine if TMA-N is incorporated directly or secondarily via cross-feeding facilitated by microbial associates. Herein we identify two members of the marineRoseobacterclade (MRC) of Alphaproteobacteria as the likely metabolizers of TMA and provide genomic evidence that they converted TMA into a more readily available form of N, e.g., NH4+, which was subsequently used byTrichodesmiumand the rest of the community. The results implicate microbiome-mediated carbon (C) and N transformations in modulating N2fixation, and thus highlight the involvement of host-associated heterotrophs in global biogeochemical cycling.