bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk-factors Associated with Non-Vaccination in Gambian Children: A Population-Based Cohort Study
Authors: Young Benjamin , Sarwar Golam , Hossain Ilias , Mackenzie Grant 
Published: March 2021

AbstractObjectiveWe determined the risk-factors associated with children who remain unvaccinated in rural Gambia.MethodsWe conducted prospective demographic surveillance and recorded immunisations in real-time in the Basse Health and Demographic Surveillance System. Analysis included residents born between January 1, 2012 and December 31, 2016. Demographic data included age, sex, household members and relationships, migrations, births, deaths, ethnicity, residential location, and birth type. Children were defined as unvaccinated at 10-, 15-, and 24-months of age, if they missed all primary series doses (pentavalent, oral polio and pneumococcal conjugate vaccines), secondary series (1st dose measles and yellow-fever vaccines) or both vaccination series, respectively. Multivariate three-level mixed effects logistic regressions measured the strength of association between risk-factors and being unvaccinated at age 10-, 15-, and 24-months.Findings38,090 infants were born during the study period, while 30,832 survived as residents and 1,567 were unvaccinated at age 10 months. Being unvaccinated at 10-months of age was associated with children not residing with their father (adjusted odds ratio [aOR] 1.38, 95% CI 1.22–1.58) or mother (aOR 2.94, 95% CI 1.33–6.46) or both parents (aOR 2.26, 1.60–3.19), whose parents were not the head of household (aOR 1.29 (1.09–1.52), experiencing external in-migration (aOR 2.78, 95% CI 1.52–5.08) and not of Mandinka ethnicity (aOR varied between 1.57 to 1.85 for three other ethnicities).ConclusionUnimmunised children in rural Gambia are more likely to not live with their parents and have migrated into the area. These results may inform strategies to increase vaccine coverage.
Adverse clinical outcomes in people at clinical high-risk for psychosis related to activity and glutamate function in the hippocampus
Authors: Allen Paul , Hird Emily J. , Orlov Natasza , Modinos Gemma , Bossong Matthijs , Antoniades Mathilde , Sampson Carly , Azis Matilda , Howes Oliver , Stone James , Perez Jesus , Broome Matthew , Grace Antony A. , McGuire Philip 
Published: March 2021

AbstractPreclinical models suggest that psychosis involves alterations in activity and glutamate function in the hippocampus, driving dopamine activity through projections to the striatum. The extent to which this model applies to the onset of psychosis in clinical subjects is unclear. We assessed whether interactions between hippocampal glutamatergic function and activity/striatal-connectivity are associated with adverse clinical outcomes in people at clinical high-risk (CHR) for psychosis. We measured functional Magnetic Resonance Imaging of hippocampal activation/connectivity, and 1H-Magnetic Resonance Spectroscopy of hippocampal glutamatergic metabolites in 75 CHR participants and 31 healthy volunteers. At follow-up, 12 CHR participants had transitioned to psychosis and 63 had not. Within the clinical high-risk cohort, at follow-up, 35 and 17 participants had a poor or a good functional outcome, respectively. The onset of psychosis (ppeakFWE =.003, t=4.4, z=4.19) and a poor functional outcome (ppeakFWE <.001, t=5.52, z=4.81 and ppeakFWE <.001, t=5.25, z=4.62) were associated with a negative correlation between hippocampal activation and hippocampal Glx concentration at baseline. In addition, there was a negative association between hippocampal Glx concentration and hippocampo-striatal connectivity (ppeakFWE=.016, t=3.73, z=3.39, ppeakFWE=.014, t=3.78, z=3.42, ppeakFWE=.011, t=4.45, z=3.91, ppeakFWE=.003, t=4.92, z=4.23) in the total CHR sample, not seen in healthy volunteers. As predicted by preclinical models, adverse clinical outcomes in people at risk for psychosis are associated with altered interactions between hippocampal activity and glutamatergic function.
Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection
Authors: Smith Rebecca L. , Gibson Laura L. , Martinez Pamela P. , Ke Ruian , Mirza Agha , Conte Madison , Gallagher Nicholas , Conte Abigail , Wang Leyi , Fredrickson Rick , Edmonson Darci C. , Baughman Melinda E. , Chiu Karen K. , Choi Hannah , Jensen Tor W. , Scardina Kevin R. , Bradley Shannon , Gloss Stacy L. , Reinhart Crystal , Yedetore Jagadeesh , Owens Alyssa N. , Broach John , Barton Bruce , Lazar Peter , Henness Darcy , Young Todd , Dunnett Alastair , Robinson Matthew L. , Mostafa Heba H. , Pekosz Andrew , Manabe Yukari C. , Heetderks William J. , McManus David D. , Brooke Christopher B. 
Published: March 2021

SUMMARYWhat is already known about this topic?Diagnostic tests and sample types for SARS-CoV-2 vary in sensitivity across the infection period.What is added by this report?We show that both RTqPCR (from nasal swab and saliva) and the Quidel SARS Sofia FIA rapid antigen tests peak in sensitivity during the period in which live virus can be detected in nasal swabs, but that the sensitivity of RTqPCR tests rises more rapidly in the pre-infectious period. We also use empirical data to estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency.What are the implications for public health practice?RTqPCR tests will be more effective than rapid antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (provided results reporting is timely). All modalities, including rapid antigen tests, showed >94% sensitivity to detect infection if used at least twice per week. Regular surveillance/screening using rapid antigen tests 2-3 times per week can be an effective strategy to achieve high sensitivity (>95%) for identifying infected individuals.
Factors Associated with Intention to Vaccinate against COVID-19 in Puerto Rico
Authors: Melin Kyle , Zhang Cheyu , Zapata Juan Pablo , Rivera Yonaira M. , Fernandez Katie , Shacham Enbal , Malavé-Rivera Souhail M. , Rodríguez-Díaz Carlos E. 
Published: March 2021

AbstractCOVID-19 has been particularly devastating to Black and Latinx communities in the U.S. However, data on acceptability of the COVID-19 vaccines among minority populations are limited. We conducted an online survey among adults in Puerto Rico to identify factors associated with intention to vaccinate against COVID-19. Sociodemographic variables were analyzed independently for association with intention to vaccinate. Significant associations were included in the multivariate logistic regression analysis. A total of 1016 responses were available for analysis. In the bivariate analysis, younger age, higher education, pre-covid employment, male sex, gay/bisexual identity, and single marital status were associated with increased intention to vaccinate. In the multivariate logistic regression, younger, male respondents who had higher educational attainment reported higher intention to vaccinate. Lower-income and living outside the San Juan metro region were associated with lower intention to vaccinate. National and international health organizations were identified as the most reliable sources of information, followed by healthcare professionals. These findings highlight the importance of considering sociodemographic characteristics identified with low intention to vaccinate as well as using trusted sources of information when designing public messaging related to increasing COVID-19 vaccinations.
Analysis of Thrombotic Adverse Reactions of COVID-19 AstraZeneca Vaccine reported to EudraVigilance database
Authors: Tobaiqy Mansour , Elkout Hajer , MacLure Katie 
Published: March 2021

AbstractThe development of safe, effective, affordable vaccines against COVID-19 remains the cornerstone to mitigating this pandemic. Early December 2020, multiple research groups had designed potential vaccines. From 11 March 2021, several European countries temporarily suspended the use of the Oxford-AstraZeneca vaccine amid reports of blood clot events and death of a vaccinated person, despite the European Medicines Agency and the World Health Organization assurance that there was no indication that vaccination was linked. This study aimed to identify and analyse the thrombotic adverse reactions associated with Oxford-AstraZeneca vaccine. This was a retrospective descriptive study using spontaneous reports submitted to the EudraVigilance database in the period from 17 February to 12 March 2021. There were 54,571 adverse reaction reports of which 28 were associated with thrombotic adverse reactions. Three fatalities were related to Pulmonary Embolism; 1 fatality to Thrombosis. With 17 million people having had the AstraZeneca vaccine, these are extremely rare events. The EMA’s Pharmacovigilance Risk Assessment Committee (18 March 2021) concluded that the vaccine was safe, effective and the benefits outweighed the risks. Conducting further analyses based on more detailed thrombotic adverse event reports, including patients’ characteristics and comorbidities, may enable assessment of the causality with higher specificity.
Low levels of protective humoral immunity following mild or asymptomatic infection with SARS-CoV-2 in a community-based serological study
Authors: McDade Thomas W. , Sancilio Amelia , D’Aquila Richard , Mustanski Brian , Vaught Lauren A. , Reiser Nina L. , Velez Matthew P. , Hsieh Ryan R. , Ryan Daniel T. , Saber Rana , McNally Elizabeth M. , Demonbreun Alexis R. 
Published: March 2021

AbstractThe degree of protective humoral immunity after mild or asymptomatic SARS-CoV-2 infection is not known. We measured antibody-mediated neutralization of spike protein-ACE2 receptor binding—a surrogate measure of protection against SARS-CoV-2 infection—in a large and diverse community-based seroprevalence study. Comparisons were made across three groups of seropositive participants that differed in the severity of infection and engagement with clinical care (N=790). The clinical group was seropositive for prior infection, symptomatic, and diagnosed with COVID-19 by a healthcare provider. The symptomatic group was seropositive and reported one or more symptoms of infection but received no clinical care. The asymptomatic group was seropositive but reported no symptoms. 86.2% of all infections were mild or asymptomatic; 13.8% received clinical care. Of the clinical cases, 96.3% were outpatient; only 3.7% required hospitalization. Moderate or high levels of neutralizing activity were detected following 27.5% of clinical infections, in comparison with 5.4% of symptomatic and 1.5% of asymptomatic infections. The majority of infections in the general population are mild or asymptomatic and likely result in low levels of antibody-mediated protective immunity.
Differential CTCF binding in motor neurons and lymphocytes
Authors: Arslan Belkis Atasever , Brady Scott T , Sadik Gamze Gunal 
Published: March 2021

ABSTRACTTranscriptional regulation of protein-coding genes is a primary control mechanism of cellular function. Similarities in regulation of expression for select genes between lymphocytes and neurons have led to proposals that such genes may be useful biomarkers for some neurological disorders that can be monitored via patient lymphocyte populations. Examination of shared molecular mechanisms underlying neurogenesis and lymphocyte differentiation may give help to identify relevant pathways and suggest additional biomarkers in lymphocytes that are relevant to neurological disorders. In this study, we analysed similarities and conserved regions in several genes regulated by CCCTC-binding factor (CTCF) during lymphocyte and neuronal developmental stages. We performed epigenetic analysis of CTCF binding Trak1, Gabpa, Gabpb1, Gabpb2, Gfi1, Gfi1b gene loci at T and B lymphocytes at different developmental stages, as well as in neural progenitor cells and motor neurons. Common and shared CTCF binding events at Trak1 gene suggest additional transcriptional regulatory factors that control Trak1 gene expression levels differ in neurons and lymphocytes. Gabpb1 gene includes a common CTCF binding site shared with neurons and lymphocytes. Correlation of CTCF binding analysis and gene expression profile suggests that CTCF binding plays a role in epigenetic regulation of Gabpb1 gene. In contrast, while Gfi1a gene is phylogenetically well-conserved and CTCF sites are occupied in lymphocytes, there are no CTCF binding occupied in neurons and neural progenitor cells. Low expression levels of Gfi1s in neurons indicate that regulation of this gene is CTCF-independent in neurons. Although Gfi1b is highly homologous to Gfi1, differences in expression levels suggest that Gfi1b is critical for both lymphogenesis and neurogenesis. Neurons and lymphocytes have multiple common CTCF binding sites in the Gfi1b gene, although lineage specific transcriptional regulators that play a role in their different expression levels still need to be identified. The partial overlap in CTCF regulatory sites for some genes in neurons and lymphocytes suggest that there may be markers that can exhibit parallel changes in these cells and serve as biomarkers.
Validating the automation of different measures of high temperature tolerance of small terrestrial insects
Authors: MacLean Heidi J. , Hansen Jonas Hjort , Sørensen Jesper G. 
Published: March 2021

AbstractAccurately phenotyping numerous test subjects is essential for most experimental research. Collecting such data can be tedious or time-consuming, and can be biased or limited by manual observations. The thermal tolerance of small ectotherms is a good example of this type of phenotypic data, and it is widely used to investigate thermal adaptation, acclimation capacity and climate change resilience of small ectotherms. Here, we present the results of automatically generated thermal tolerance data using motion tracking on video recordings using twoDrosophilaspecies and temperature acclimation to create variation in thermal tolerances and two different heat tolerance assays. We find similar effect sizes of acclimation and hardening responses between manual and automated approaches, but different absolute tolerance estimates. This discrepancy likely reflects both technical differences and the behavioral cessation of movement rather than physiological failure measured in other assays. We conclude that both methods generate biological meaningful results, which reflect different aspects of the thermal biology, find no evidence of inflated variance in the manually scored assays, but find that automation can increase throughput without compromising quality. Further we show that the method can be applied to a wide range of arthropod taxa. We suggest that our automated method is a useful example of through-put phenotyping, and suggest this approach might be applied to other tedious laboratory traits, such as desiccation or starvation tolerance, with similar benefits to through-put. However, the interpretation and potential comparison to results using different methodology rely on thorough validation of the assay and the involved biological mechanism.
A versatile genetic toolbox forPrevotella coprienables studying polysaccharide utilization systems
Authors: Li Jing , Gálvez Eric J.C. , Amend Lena , Almasi Éva , Iljazovic Aida , Lesker Till R. , Bielecka Agata A. , Strowig Till 
Published: March 2021

AbstractPrevotella copriis a prevalent inhabitant of the human gut and has been associated with plant-rich diet consumption and diverse health states. The underlying genetic basis of these associations remains enigmatic due to the lack of genetic tools. Here, we developed a novel versatile genetic toolbox for rapid and efficient genetic insertion and allelic exchange applicable toP. copristrains from multiple clades. Enabled by the genetic platform, we systematically investigated the specificity of polysaccharide utilization loci (PULs), and identified four highly conserved PULs for utilizing arabinan, pectic galactan, arabinoxylan and inulin, respectively. Further genetic and functional analysis of arabinan utilization systems illustrate thatP. coprihas evolved two distinct types of arabinan-processing PULs (PULAra) and that the type-II PULArais significantly enriched in individuals consuming a vegan diet compared to other diets. In summary, this genetic toolbox will enable functional genetic studies forP. copriin the future.
Identification and assessment of cardiolipin interactions withE. coliinner membrane proteins
Authors: Corey Robin A. , Song Wanling , Duncan Anna L. , Ansell T. Bertie , Sansom Mark S.P. , Stansfeld Phillip J. 
Published: March 2021

AbstractIntegral membrane proteins are localised and/or regulated by lipids present in the surrounding bilayer. Whilst bacteria such asE. colihave relatively simple membranes when compared to eukaryotic cells, there is ample evidence that many bacterial proteins bind to specific lipids, especially the anionic lipid cardiolipin. Here, we apply molecular dynamics simulations to assess lipid binding to 42 differentE. coliinner membrane proteins. Our data reveals a strong asymmetry between the membrane leaflets, with a marked increase of anionic lipid binding to the inner leaflet regions of membrane proteins, particularly for cardiolipin. From our simulations we identify over 700 independent cardiolipin binding sites, allowing us to identify the molecular basis of a prototypical cardiolipin binding site, which we validate against structures of bacterial proteins bound to cardiolipin. This allows us to construct a set of metrics for defining a high affinity cardiolipin binding site on (bacterial) membrane proteins, paving the way for a heuristic approach to defining more complex protein-lipid interactions.
Medium optimization for biomass production of three peat moss (SphagnumL.) species using fractional factorial design and response surface methodology
Authors: Heck Melanie A. , Melková Ingrida , Posten Clemens , Decker Eva L. , Reski Ralf 
Published: March 2021

AbstractPeat moss (Sphagnum) biomass is a promising bioresource to substitute peat in growing media with a renewable material. For sustainable production on a large scale, the productivity ofSphagnummosses has to be increased by optimizing culture conditions. Optimization was achieved using fractional factorial design and response surface methodology based on central composite design to determine concentrations of eight factors leading to highest biomass yield. We improved a standard Sphagnum medium by reducing the concentrations of NH4NO3, KH2PO4, KCl, MgSO4, Ca(NO3)2, FeSO4and a microelement solution up to 50 %. Together with a reduced sucrose concentration forSphagnum fuscum, while it remained unchanged forSphagnum palustreandSphagnum squarrosum, moss productivities were enhanced for all tested species in shake flasks. Further upscaling to 5 L photobioreactors increased the biomass yield up to nearly 50-fold forS. fuscum, 40-fold forS. palustreand 25-fold forS. squarrosumin 24 days.
Exploring an experiment-split method to estimate the generalization ability in new data: DeepKme as an example
Authors: Zou Guoyang , Li Lei 
Published: March 2021

AbstractA Large number of predictors have been built based on different data sets for predicting different post-translational modification sites. However, limited to our knowledge, most of them gave an overfitting estimation of their generalization ability in new data because of the intrinsic trait—not considering the experimental sources of the new data—of the cross-validation method. Thus, we proposed and explored a new method—the experiment-split method—imitating the blinded assessment to deal with the overfitting problem in the new data. The experiment-split method logically split the training and test data based on the data’s different experimental sources, and the new data can be regarded as the data from different experimental sources. To specifically illustrate the experiment-split method, we combined an actual application, DeepKme—a predictor built by us for the lysine methylation sites, to demonstrate how it be used in the true scenarios. We compared the cross-validation method with the experiment-split method. The result suggested the experiment-split method could effectively relieve the overfitting compared with the cross-validation method and may be widely used in the field of identification participated by multiple experiments. We believe DeepKme would facilitate the related researchers’ deep thought of the experiment-split method and the overfitting phenomenon, and of course, advance the study of the lysine methylation and similar fields.
Aniridia-related Keratopathy Relevant Cell Signaling Pathways in Human Fetal Corneas
Authors: Vicente André , Sloniecka Marta , Byström Berit , Liu Jing-Xia , Domellöf Fátima Pedrosa 
Published: March 2021

AbstractBackgroundTo study aniridia-related keratopathy (ARK) relevant cell signaling pathways (Notch1, Wnt/β-catenin, Sonic hedgehog (SHH) and mTOR) in normal human fetal corneas in comparison with normal human adult corneas.Results20 wg fetal and normal adult corneas showed similar staining patterns for Notch1, however 10-11 wg fetal corneas showed increased presence of Notch1. Numb and Dlk1 had an enhanced presence in the fetal corneas compared to the adult corneas. Fetal corneas showed stronger immunolabeling with antibodies against β-catenin, Wnt5a and Wnt7a, Gli1, Hes1, p-rpS6, and mTOR when compared to the adult corneas. Gene expression of Notch1, Wnt5A, Wnt7A, β-catenin, Hes1, mTOR and rps6 was higher in the 9-12 wg fetal corneas when compared to adult corneas.ConclusionsThe cell signaling pathway differences found between human fetal and adult corneas were similar to those previously found in ARK corneas with the exception of Notch1. Analogous profiles of cell signaling pathway activation between human fetal corneas and ARK corneas suggests that there is a less differentiated host milieu in ARK.
Visualising formation of the ribosomal active site in mitochondria
Authors: Chandrasekaran Viswanathan , Desai Nirupa , Burton Nicholas O. , Yang Hanting , Price Jon , Miska Eric A. , Ramakrishnan V. 
Published: March 2021

SummaryRibosome assembly is an essential and complex process that is regulated at each step by specific biogenesis factors. Using cryo-electron microscopy, we identify and order major steps in the formation of the highly conserved peptidyl transferase centre (PTC) and tRNA binding sites in the large subunit of the human mitochondrial ribosome (mitoribosome). The conserved GTPase GTPBP7 regulates the folding and incorporation of core 16S ribosomal RNA (rRNA) helices and the ribosomal protein bL36m, and ensures that the PTC base U3039 has been 2′-O-methylated. Additionally, GTPBP7 binds the RNA methyltransferase NSUN4 and MTERF4, which facilitate earlier steps by sequestering H68-71 of the 16S rRNA and allowing biogenesis factors to access the maturing PTC. Consistent with the central role of NSUN4•MTERF4 and GTPBP7 during mitoribosome biogenesis,in vivomutagenesis designed to disrupt binding of theirCaenorhabditis elegansorthologs to the large subunit potently activates mitochondrial stress responses and results in severely reduced viability, developmental delays and sterility. Next-generation RNA sequencing reveals widespread gene expression changes in these mutant animals that are indicative of mitochondrial stress response activation. We also answer the long-standing question of why NSUN4 but not its enzymatic activity, is indispensable for mitochondrial protein synthesis in metazoans.