bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance and Operational Evaluation of the Access Bio CareStart Rapid Antigen Test in a High-throughput Drive-through Community Testing Site in Massachusetts
Authors: Pollock Nira R. , Tran Kristine , Jacobs Jesica R. , Cranston Amber E. , Smith Sita , O’Kane Claire Y. , Roady Tyler J. , Moran Anne , Scarry Alison , Carroll Melissa , Volinsky Leila , Perez Gloria , Patel Pinal , Gabriel Stacey , Lennon Niall J. , Madoff Lawrence C. , Brown Catherine , Smole Sandra C. 
Published: March 2021

AbstractBackgroundTo facilitate deployment of point-of-care testing for SARS-CoV-2, we evaluated the Access Bio CareStart COVID-19 Antigen test in a high-throughput, drive-through, free community testing site using anterior nasal (AN) swab RT-PCR for clinical testing.MethodsConsenting symptomatic and asymptomatic children (≤18 years) and adults received dual AN swabs. CareStart testing was performed with temperature/humidity monitoring. All tests had two independent reads to assess inter-operator agreement. Patients with positive CareStart results were called and instructed to isolate pending RT-PCR results. The paired RT-PCR result was the reference for sensitivity and specificity calculations.ResultsOf 1603 participants, 1245 adults and 253 children had paired RT-PCR/CareStart results and complete symptom data. 83% of adults and 87% of children were asymptomatic. CareStart sensitivity/specificity were 84.8% (95% confidence interval [CI] 71.1-93.7)/97.2% (92.0-99.4) and 85.7% (42.1-99.6)/89.5% (66.9-98.7) in adults and children, respectively, within 5 days of symptoms. Sensitivity/specificity were 50.0% (41.0-59.0)/99.1% (98.3-99.6) in asymptomatic adults and 51.4% (34.4-68.1)/97.8% (94.5-99.4) in asymptomatic children. Sensitivity in all 234 RT-PCR-positive people was 96.3% with cycle threshold (Ct) ≤25, 79.6% with Ct ≤30, and 61.4% with Ct ≤35. All 21 false positive CareStart tests had faint but normal bands. Inter-operator agreement was 99.5%. Operational challenges included identification of faint test bands and inconsistent swab elution volumes.ConclusionsCareStart had high sensitivity in people with Ct ≤25 and moderate sensitivity in symptomatic people overall. Specificity was unexpectedly lower in symptomatic versus asymptomatic people. Excellent inter-operator agreement was observed, but operational challenges indicate that operator training is warranted.
Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 Vaccine in long-term care facility residents and healthcare workers – a Danish cohort study
Authors: Moustsen-Helms Ida Rask , Emborg Hanne-Dorthe , Nielsen Jens , Nielsen Katrine Finderup , Krause Tyra Grove , Mølbak Kåre , Møller Karina Lauenborg , Berthelsen Ann-Sofie Nicole , Valentiner-Branth Palle 
Published: March 2021

AbstractBackgroundAt the end of 2020, Denmark launched an immunization program against SARS-CoV-2. The Danish health authorities prioritized persons currently living in long-term care facilities (LTCF residents) and frontline healthcare workers (HCW) as the first receivers of vaccination. Here we present preliminary population based vaccine effectiveness (VE) estimates in these two target groups.MethodsThe study was designed as a retrospective registry- and population-based observational cohort study including all LTCF residents and all HWC. The outcome was a polymerase chain reaction confirmed SARS-CoV-2, and VE was estimated for different periods following first and second dose. We used Poisson and Cox regressions to estimate respectively crude and calendar time-adjusted VE for the BNT162b2 mRNA Covid-19 Vaccine from Pfizer/BioNTech with 95% confidence intervals (CI) for vaccinated versus unvaccinated.ResultsA total of 39,040 LTCF residents (median age at first dose; 84 years, Interquartile range (IQR): 77-90) and 331,039 HCW (median age at first dose; 47 years, IQR: 36-57) were included. Among LTCF residents, 95.2% and 86.0% received first and second dose from 27 December 2020 until 18 February 2021, for HWC the proportion was 27.8% and 24.4%. During a median follow-up of 53 days, there were 488 and 5,663 confirmed SARS-CoV-2 cases in the unvaccinated groups, whereas there were 57 and 52 in LTCF residents and HCW within the first 7 days after the second dose and 27 and 10 cases beyond seven days of second dose. No protective effect was observed for LTCF residents after first dose. In HCW, VE was 17% (95% CI; 4-28) in the > 14 days after first dose (before second dose). Furthermore, the VE in LTCF residents at day 0-7 of second dose was 52% (95% CI; 27-69) and 46% (95% CI; 28-59) in HCW. Beyond seven days of second dose, VE increased to 64% (95% CI; 14-84) and 90% (95% CI; 82-95) in the two groups, respectively.ConclusionThe results were promising regarding the VE both within and beyond seven days of second vaccination with the BNT162b2 mRNA Covid-19 Vaccine currently used in many countries to help mitigate the global SARS-CoV-2 pandemic.Impact of the researchSo far, observational studies of the real-word effectiveness of the mRNA Vaccine BNT162b2 has been limited to the period after the administration of the first dose. This is the first report to date to present vaccine effectiveness (VE) estimates after the second BNT162b2 mRNA Covid-19 Vaccine. We estimated a VE of 52% and 46% in LTCF residents and HCW within seven days, which increased to 64% and 90% in the two groups respectively beyond seven days of immunization. These findings supports maintaining a two-dose schedule of the BNT162b2 mRNA Covid-19 Vaccine.
Transmission of SARS-CoV-2 by children to contacts in schools and households: a prospective cohort and environmental sampling study in London
Authors: Cordery Rebecca , Reeves Lucy , Zhou Jie , Rowan Aileen , Watber Patricia , Rosadas Carolina , Crone Michael , Storch Marko , Freemont Paul , Mosscrop Lucy , Cowley Alice , Zelent Gina , Bisset Kate , Blond Holly Le , Regmi Sadie , Buckingham Christian , Junaideen Ramlah , Abdulla Nadia , Eliahoo Joseph , Mindlin Miranda , Lamagni Theresa , Barclay Wendy , Taylor Graham P. , Sriskandan Shiranee 
Published: March 2021

AbstractBackgroundAssessing transmission of SARS-CoV-2 by children in schools is of critical importance to inform public health action. We assessed frequency of acquisition of SARS-CoV-2 by contacts of children with COVID-19 in schools and households, as well as the amount of virus shed into the air and onto fomites in both settings.MethodsCases of COVID-19 in children in London schools were identified via notification. Weekly sampling for 3-4 weeks and PCR testing for SARS-CoV-2 of immediate classroom contacts (the “bubble”), non-bubble school contacts, and household contacts was undertaken supported by genome sequencing, along with surface and air sampling in the school and home environment.ResultsWithin schools, secondary transmission was not detected in 28 individual bubble contacts, representing 10 distinct bubble classes. Across 8 non-bubble classes, 3/62 pupils tested positive– all three were asymptomatic and tested positive in one setting on the same day, unrelated to the original index case. In contrast, the secondary attack rate in naïve household contacts was 14.3% (5/35) rising to 19.1% (9/47) when considering all household contacts. Environmental contamination with SARS-CoV-2 was rare in schools, regardless of school type; fomite SARS-CoV-2 RNA was identified in 4/189 (2.1%) samples in bubble classrooms, 2/127 (1.6%) samples in non-bubble classrooms, and 5/130 (3.8%) samples in washrooms. This contrasted with fomites in households, where SARS-CoV-2 RNA was identified in 60/248 (24.2%) bedroom samples, 66/241 (27.4%) communal room samples, and 21/188 (11.2%) bathroom samples. Air sampling identified SARS-CoV-2 RNA in just 1/68 (1.5%) of school air samples, compared with 21/85 (24.7%) of air samples taken in homes.SummaryThe low levels of environmental contamination in schools are consistent with low transmission frequency and adequate levels of cleaning and ventilation in schools during the period of study. Secondary transmission in schools was rare. The high frequency of secondary transmission in households associated with evident viral shedding throughout the home suggests a need to improve advice to households with infection in children in order to prevent onward community spread by sibling and adult contacts. The data highlight that transmission from children is very likely to occur when precautions are reduced.
Localization of muscarinic acetylcholine receptor dependent rhythm generating modules in theDrosophilalarval locomotor network
Authors: Jonaitis Julius , MacLeod James , Pulver Stefan R. 
Published: March 2021

AbstractMechanisms of rhythm generation have been extensively studied in motor systems that control locomotion over terrain in limbed animals; however, much less is known about rhythm generation in soft-bodied terrestrial animals. Here we explored how muscarinic acetylcholine receptor (mAChR) dependent rhythm generating networks are distributed in the central nervous system (CNS) of soft-bodiedDrosophilalarvae. We measured fictive motor patterns in isolated CNS preparations using a combination of Ca2+imaging and electrophysiology while manipulating mAChR signalling pharmacologically. Bath application of the mAChR agonist oxotremorine potentiated rhythm generation in distal regions of the isolated CNS, whereas application of the mAChR antagonist scopolamine suppressed rhythm generation in these regions. Oxotremorine raised baseline Ca2+levels and potentiated rhythmic activity in isolated posterior abdominal CNS segments as well as isolated anterior brain and thoracic regions, but did not induce rhythmic activity in isolated anterior abdominal segments. Bath application of scopolamine to reduced preparations lowered baseline Ca2+levels and abolished rhythmic activity. These results suggest the presence of a bimodal gradient of rhythmogenicity in the larval CNS, with mAChR dependent rhythm generating networks in distal regions separated by medial segments with severely reduced rhythmogenic abilities. This work furthers our understanding of motor control in soft-bodied locomotion and provides a foundation for study of rhythm generating networks in an emerging genetically tractable locomotor system.
Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis inCandida albicans
Authors: Min Kyunghun , Jannace Thomas F. , Si Haoyu , Veeramah Krishna R. , Haley John D. , Konopka James B. 
Published: March 2021

ABSTRACTMicrobial pathogens grow in a wide range of different morphologies that provide distinct advantages for virulence. In the fungal pathogenCandida albicans, adenylyl cyclase (Cyr1) is thought to be a master regulator of the switch to invasive hyphal morphogenesis and biofilm formation. However, faster growingcyr1Δ/Δ pseudorevertant (PR) mutants were identified that form hyphae in the absence of cAMP. Isolation of additional PR mutants revealed that their improved growth was due to loss of one copy ofBCY1, the negative regulatory subunit of protein kinase (A) from the left arm of chromosome 2. Furthermore, hyphal morphogenesis was improved in some of PR mutants by multigenic haploinsufficiency resulting from loss of large regions of the left arm of chromosome 2, including global transcriptional regulators. Interestingly, hyphal-associated genes were also induced in a manner that was independent of cAMP. This indicates that basal protein kinase A activity is an important prerequisite to induce hyphae, but activation of the cAMP pathway is not needed. Instead, phosphoproteomic analysis indicated that the Cdc28 cyclin-dependent kinase and the casein kinase 1 family member Yck2 play key roles in promoting polarized growth. In addition, integrating transcriptomic and proteomic data reveals hyphal stimuli induce increased production of key transcription factors that contribute to polarized morphogenesis.AUTHOR SUMMARYThe human fungal pathogenCandida albicansswitches between budding and filamentous hyphal morphologies to gain advantages for virulence and survival in the host. Although adenylyl cyclase has been thought to be a master regulator that controls this switch, we identifiedC. albicanspseudorevertant mutants that grow better and form hyphae in the absence of adenylyl cyclase and cAMP. The mutant cells were also able to induce hyphal-associated genes in the absence of cAMP that are needed for virulence. Integrating information from different omics approaches identified cAMP-independent mechanisms that promote hyphal growth. This includes phosphoproteomic studies that revealed key roles for the Cdc28 cyclin-dependent kinase and casein kinase 1 in promoting hyphal growth. In addition, integrating transcriptomic and proteomic data revealed that post-transcriptional mechanisms regulate the levels of a set of key transcription factors that are important for hyphal induction, suggesting a novel form of translational regulation. These studies better define the pathways that stimulateC. albicansto switch from budding to hyphal growth, which is important for invasion into tissues, escape from the immune system, and biofilm formation.
immuneML: an ecosystem for machine learning analysis of adaptive immune receptor repertoires
Authors: Pavlović Milena , Scheffer Lonneke , Motwani Keshav , Kanduri Chakravarthi , Kompova Radmila , Vazov Nikolay , Waagan Knut , Bernal Fabian L. M. , Costa Alexandre Almeida , Corrie Brian , Akbar Rahmad , Al Hajj Ghadi S. , Balaban Gabriel , Brusko Todd M. , Chernigovskaya Maria , Christley Scott , Cowell Lindsay G. , Frank Robert , Grytten Ivar , Gundersen Sveinung , Haff Ingrid Hobæk , Hochreiter Sepp , Hovig Eivind , Hsieh Ping-Han , Klambauer Günter , Kuijjer Marieke L. , Lund-Andersen Christin , Martini Antonio , Minotto Thomas , Pensar Johan , Rand Knut , Riccardi Enrico , Robert Philippe A. , Rocha Artur , Slabodkin Andrei , Snapkov Igor , Sollid Ludvig M. , Titov Dmytro , Weber Cédric R. , Widrich Michael , Yaari Gur , Greiff Victor , Sandve Geir Kjetil 
Published: March 2021

AbstractAdaptive immune receptor repertoires (AIRR) are key targets for biomedical research as they record past and ongoing adaptive immune responses. The capacity of machine learning (ML) to identify complex discriminative sequence patterns renders it an ideal approach for AIRR-based diagnostic and therapeutic discovery. To date, widespread adoption of AIRR ML has been inhibited by a lack of reproducibility, transparency, and interoperability. immuneML (immuneml.uio.no) addresses these concerns by implementing each step of the AIRR ML process in an extensible, open-source software ecosystem that is based on fully specified and shareable workflows. To facilitate widespread user adoption, immuneML is available as a command-line tool and through an intuitive Galaxy web interface, and extensive documentation of workflows is provided. We demonstrate the broad applicability of immuneML by (i) reproducing a large-scale study on immune state prediction, (ii) developing, integrating, and applying a novel method for antigen specificity prediction, and (iii) showcasing streamlined interpretability-focused benchmarking of AIRR ML.
Using summary statistics to evaluate the genetic architecture of multiplicative combinations of initially analyzed phenotypes with a flexible choice of covariates
Authors: Wolf Jack , Westra Jason , Tintle Nathan 
Published: March 2021

AbstractWhile the promise of electronic medical record and biobank data is large, major questions remain about patient privacy, computational hurdles, and data access. One promising area of recent development is pre-computing non-individually identifiable summary statistics to be made publicly available for exploration and downstream analysis. In this manuscript we demonstrate how to utilize pre-computed linear association statistics between individual genetic variants and phenotypes to infer genetic relationships between products of phenotypes (e.g., ratios; logical combinations of binary phenotypes using ‘and’ and ‘or’) with customized covariate choices. We propose a method to approximate covariate adjusted linear models for products and logical combinations of phenotypes using only pre-computed summary statistics. We evaluate our method’s accuracy through several simulation studies and an application modeling various fatty acid ratios using data from the Framingham Heart Study. These studies show consistent ability to recapitulate analysis results performed on individual level data including maintenance of the Type I error rate, power, and effect size estimates. An implementation of this proposed method is available in the publicly available R package pcsstools.
A VLP-based vaccine targeting ANGPTL3 lowers plasma triglycerides in mice
Authors: Fowler Alexandra , Sampson Maureen , Remaley Alan T. , Chackerian Bryce 
Published: March 2021

AbstractElevated triglycerides (TGs) are an important risk factor for the development of coronary heart disease (CHD) and in acute pancreatitis. Angiopoietin-like proteins 3 (ANGPTL3) and 4 (ANGPTL4) are critical regulators of TG metabolism that function by inhibiting the activity of lipoprotein lipase (LPL), which is responsible for hydrolyzing triglycerides in lipoproteins into free fatty acids. Interestingly, individuals with loss-of-function mutations in ANGPTL3 and ANGPTL4 have low plasma TG levels, have a reduced risk of CHD, and are otherwise healthy. Consequently, interventions targeting ANGPTL3 and ANGPTL4 have emerged as promising new approaches for reducing elevated TGs. Here, we developed virus-like particle (VLP) based vaccines that target the LPL binding domains of ANGPTL3 and ANGPTL4. ANGPTL3 VLPs and ANGPTL4 VLPs are highly immunogenic in mice and vaccination with ANGPTL3 VLPs, but not ANGPTL4 VLPs, was associated with reduced steady state levels of TGs. Immunization with ANGPTL3 VLPs rapidly cleared circulating TG levels following an oil gavage challenge and enhanced plasma LPL activity. These data indicate that targeting ANGPTL3 by active vaccination is potential alternative to other ANGPTL3-inhibiting therapies.HighlightsANGPTL3 and ANGPTL4 are mediators of lipoprotein metabolism that inhibit lipoprotein lipase (LPL) activity.Vaccination using virus-like particles (VLPs) targeting ANGPTL3 and ANGPTL4 elicits high-titer IgG antibody responses.Immunization with ANGPTL3 VLPs lowers steady-state plasma triglycerides and enhances LPL activity.
Sialic acid-Dependent Binding and Viral Entry of SARS-CoV-2
Authors: Nguyen Linh , McCord Kelli A. , Bui Duong T. , Bouwman Kim M. , Kitova Elena N. , Kumawat Dhanraj , Daskhan Gour C. , Tomris Ilhan , Han Ling , Chopra Pradeep , Yang Tzu-Jing , Willows Steven D. , Mason Andrew L. , Lowary Todd L. , West Lori J. , Hsu Shang-Te Danny , Tompkins S. Mark , Boons Geert-Jan , de Vries Robert P. , Macauley Matthew S. , Klassen John S. 
Published: March 2021

AbstractEmerging evidence suggests that host glycans influence infection by SARS-CoV-2. Here, we reveal that the receptor-binding domain (RBD) of the spike (S)-protein on SARS-CoV-2 recognizes oligosaccharides containing sialic acid (SA), with preference for the oligosaccharide of monosialylated gangliosides. Gangliosides embedded within an artificial membrane also bind the RBD. The monomeric affinities (Kd= 100-200 μM) of gangliosides for the RBD are similar to heparan sulfate, another negatively charged glycan ligand of the RBD proposed as a viral coreceptor. RBD binding and infection of SARS-CoV-2 pseudotyped lentivirus to ACE2-expressing cells is decreased upon depleting cell surface SA level using three approaches: sialyltransferase inhibition, genetic knock-out of SA biosynthesis, or neuraminidase treatment. These effects on RBD binding and pseudotyped viral entry are recapitulated with pharmacological or genetic disruption of glycolipid biosynthesis. Together, these results suggest that sialylated glycans, specifically glycolipids, facilitate viral entry of SARS-CoV-2.
Multiphasic value biases in fast-paced decisions
Authors: Corbett Elaine A. , Martinez-Rodriguez L. Alexandra , Judd Cian , O’Connell Redmond G. , Kelly Simon P. 
Published: March 2021

AbstractPerceptual decisions are biased toward higher-value options when overall gains can be improved. When stimuli demand immediate reactions, the neurophysiological decision process dynamically evolves through distinct phases of growing anticipation, detection and discrimination, but how value biases are exerted through these phases remains unknown. Here, by parsing motor preparation dynamics in human electrophysiology, we uncovered a multiphasic pattern of countervailing biases operating in speeded decisions. Anticipatory preparation of higher-value actions began earlier, conferring a “starting point”-advantage at stimulus onset, but the delayed preparation of lower-value actions was steeper, conferring a value-opposed buildup rate bias. This, in turn, was countered by a transient deflection toward the higher value action evoked by stimulus detection. A neurally-constrained process model featuring anticipatory urgency, biased detection, and accumulation of growing stimulus-discriminating evidence, successfully captured both behavior and motor preparation dynamics. Thus, an intricate interplay of distinct biasing mechanisms serves to prioritise time-constrained perceptual decisions.
Quantitative Theory for the Diffusive Dynamics of Liquid Condensates
Authors: Hubatsch Lars , Jawerth Louise M. , Love Celina , Bauermann Jonathan , Tang T.-Y. Dora , Bo Stefano , Hyman Anthony A. , Weber Christoph A. 
Published: March 2021

AbstractTo unravel the biological functions of membraneless liquid condensates it is crucial to develop a quantitative understanding of the physics underlying their dynamics. Key processes within such condensates are diffusion and material exchange with their environment. Experimentally, diffusive dynamics are typically probed via fluorescent labels. However, to date we lack a physics-based quantitative framework for the dynamics of labeled condensate components. Here, we derive the corresponding theory, building on the physics of phase separation, and quantitatively validate this framework via experiments. We show that using our theory we can precisely determine diffusion coefficients inside liquid condensates via a spatio-temporal analysis of fluorescence recovery after photobleaching (FRAP) experiments. We showcase the accuracy and precision of our approach by considering space- and time-resolved data of protein condensates and two different polyelectrolyte-coacervate systems. Strikingly, our theory can also be used to determine the diffusion coefficient in the dilute phase and the partition coefficient, without relying on fluorescence measurements in the dilute phase. This bypasses recently described quenching artefacts in the dense phase, which can underestimate partition coefficients by orders of magnitude. Our experimentally verified theory opens new avenues for theoretically describing molecule dynamics in condensates, measuring concentrations based on the dynamics of fluorescence intensities and quantifying rates of biochemical reactions in liquid condensates.