bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of Tbx3 in mouse eye causes retinal angiogenesis defects reminiscent of human disease
Authors: Derbyshire M. , Akula S. , Wong A. , Rawlins K. , Voura E. , Brunken W.J. , Zuber M.E. , Fuhrmann S. , Moon A.M. , Viczian A.S 
Published: May 2022

AbstractPurposeIn Retinopathy of Prematurity (ROP), infants often have incomplete vascularization, affecting the temporal region. A factor expressed in this region during retinal development is the T-box factor, Tbx3, which has not been studied in the mammalian eye. The purpose of this study was to determine if Tbx3 is required during eye formation for retinal angiogenesis.MethodsConditional removal of Tbx3 from both retinal progenitors and astrocytes was done using the optic cup-Cre recombinase driver, BAC-Dkk3-CRE and analyzed using standard immunohistochemical techniques.ResultsWith Tbx3 loss, the retinas were hypovascular, as seen in patients with ROP and Familial Exudative Vitreoretinopathy (FEVR). Retinal vasculature failed to form the stereotypic tri-layered plexus in the dorsal-temporal region. Astrocyte precursors were reduced in number and failed to form a lattice at the dorsal-temporal edge. We next examined retinal ganglion cells, as they have been shown to play a critical role in retinal angiogenesis. We found that melanopsin expression and Islet1/2-positive retinal ganglion cells were reduced in the dorsal half of the retina. In previous studies, loss of melanopsin has been linked to hyaloid artery persistence, which we also observed in the Tbx3 cKO retina, as well as in infants with ROP or FEVR.ConclusionsTogether, these results show that TBX3 is required for normal mammalian eye formation for the first time. This potentially provides a new genetic model for retinal hypovascular diseases.
BiocMAP: A Bioconductor-friendly, GPU-Accelerated Pipeline for Bisulfite-Sequencing Data
Authors: Eagles Nicholas J , Wilton Richard , Jaffe Andrew E. , Collado-Torres Leonardo 
Published: May 2022

AbstractBackgroundBisulfite sequencing is a powerful tool for profiling genomic methylation, an epigenetic modification critical in the understanding of cancer, psychiatric disorders, and many other conditions. Raw data generated by whole genome bisulfite sequencing (WGBS) requires several computational steps before it is ready for statistical analysis, and particular care is required to process data in a timely and memory-efficient manner. Alignment to a reference genome is one of the most computationally demanding steps in a WGBS workflow, taking several hours or even days with commonly used WGBS-specific alignment software. This naturally motivates the creation of computational workflows that can utilize GPU-based alignment software to greatly speed up the bottleneck step. In addition, WGBS produces raw data that is large and often unwieldy; a lack of memory-efficient representation of data by existing pipelines renders WGBS impractical or impossible to many researchers.ResultsWe present BiocMAP, a Bioconductor-friendly Methylation Analysis Pipeline consisting of two modules, to address the above concerns. The first module performs computationally-intensive read alignment using Arioc, a GPU-accelerated short-read aligner. The extraction module extracts and merges DNA methylation proportions - the fractions of methylated cytosines across all cells in a sample at a given genomic site. Since GPUs are not always available on the same computing environments where traditional CPU-based analyses are convenient, BiocMAP is split into two modules, with just the alignment module requiring an available GPU. Bioconductor-based output objects in R utilize an on-disk data representation to drastically reduce required main memory and make WGBS projects computationally feasible to more researchers.ConclusionsBiocMAP is implemented using Nextflow and available at http://research.libd.org/BiocMAP/. To enable reproducible analysis across a variety of typical computing environments, BiocMAP can be containerized with Docker or Singularity, and executed locally or with the SLURM or SGE scheduling engines. By providing Bioconductor objects, BiocMAP’s output can be integrated with powerful analytical open source software for analyzing methylation data.
Waning of PCV13 vaccine-induced antibody levels within the first year of life, using a 3+0 schedule: an observational population-level serosurveillance study among children under 5 years old in Blantyre, Malawi
Authors: Swarthout Todd D , Henrion Marc Y R , Thindwa Deus , Meiring James E , Mbewe Maurice , Brown Comfort , Msefula Jacquline , Moyo Brewster , Mataya Andrew A , Barnaba Susanne , Pearce Emma , Gordon Melita , Goldblatt David , French Neil , Heyderman Robert S. 
Published: May 2022

ABSTRACTBackgroundPneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibody, effectively reducing vaccine-serotype (VT) carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence of serotype-specific exposure. With uncertainty around correlate of protection (CoP) estimates and with persistent VT carriage and VT-IPD following PCV13 introduction, we undertook population-level immunogenicity profiling among children <5 years in Blantyre, Malawi.MethodsFor 638 children, capsule-specific IgG to PCV13 VTs, two non-VTs, and IgG to three pneumococcal proteins were measured using an enzyme-linked immunosorbent assay and a direct-binding electrochemiluminescence-based multiplex assay. A linear spline regression model estimated population-level, serotype-specific immunogenicity profiles. A linear regression model was used to validate putative CoPs.FindingsImmunogenicity profiles revealed a consistent pattern among VTs except serotype 3: a vaccine-induced IgG peak followed by waning to a nadir and subsequent increase in titre. For serotype 3 there was no apparent vaccine-induced increase. Heterogeneity in parameters included age range at post-vaccination-nadir (11·2 [19F, 23F] to 27·3 [7F] months). Titres dropped below IPD CoPs among 9 VTs and below carriage CoPs for 10 VTs. Study data estimated a range of carriage CoPs (0·50μg/mL to 2·5μg/mL). Increasing antibody among older children and seroincident events were consistent with ongoing VT exposure.InterpretationA 3+0 PCV13 schedule with high uptake has not led to sustained population-level antibody immunity beyond the first year of life. Indeed, post-vaccine antibody concentrations dropped below putative CoPs for several VTs, potentially contributing to persistent VT carriage and residual VT-IPD in Malawi and other similar settings.FundingBill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health & Care Research.
Determinants of SARS-CoV-2 anti-spike antibody levels following BNT162b2 vaccination: cross-sectional analysis of 6,000 SIREN study participants
Authors: Otter Ashley David , D’Arcangelo Silvia , Whitaker Heather , Hewson Jacqueline , Foulkes Sarah , Atti Ana , Cole Michelle , Linley Ezra , Tonge Simon , Hettiarachchi Nipunadi , Sajedi Noshin , Calbraith Davina , Norman Chris , de Lacy Elen , Price Lesley , Stewart Sally , Cromey Lisa , Corrigan Diane ,   SIREN study group, Rowe Cathy , Brown Colin S , Islam Jasmin , Semper Amanda , Hopkins Susan , Hall Victoria , Brooks Tim 
Published: May 2022

AbstractBackgroundUnderstanding immunological responses to SARS-CoV-2 vaccinations is integral to the management of SARS-CoV-2. We aimed to investigate determinants of antibody response to the BNT162b2 vaccine.MethodsA cross-sectional analysis of anti-spike binding antibodies in serum samples from healthcare workers after one or two doses. Post-vaccination interval was restricted to ≥21 days after dose 1, ≥14 days after dose 2. The primary outcome was anti-S titres with explanatory variables dose, previous infection, dosing interval, age, ethnicity, and comorbidities. Multivariable linear regression was also conducted.ResultsParticipants (n=5,871) included 3,989 post-dose 1, 1,882 post-dose 2. In SARS-CoV-2 infection naïve, 99.65% seroconverted after dose 1 and >99.9% seroconverted after dose 2. Geometric mean anti-S titre in the naïve cohort was 75.48 Binding Antibody Units/ml after dose 1, 7,049 BAU/ml after dose 2. Anti-S titres were higher in those with previous infection (2,111 BAU/ml post-dose 1, 16,052 BAU/ml post-dose 2), and increased with time between infection and vaccination: 3 months 1,970 (1,506-2,579) vs 9 months; 13,759 (8,097-23,379). Longer dosing intervals increased antibody response post-dose 2: 11-fold higher with a longer interval (>10 weeks) than those with shorter intervals, across all age-groups. Younger participants had higher mean titres (>2.2-fold higher). Multivariable regression modelling corroborated the above associations, and also found higher titres associated with being female or from an ethnic minority but lower titres among immunocompromised participants.ConclusionThe number of antigen exposures and timing between vaccinations plays a significant role in the magnitude of the post-vaccination antibody response, with implications for long-term protection and post-booster antibody responses.
Epidemiological investigation of the COVID-19 outbreak in Vellore district in South India using Geographic Information Surveillance (GIS)
Authors: Murugesan Malathi , Venkatesan Padmanaban , Kumar Senthil , Thangavelu Premkumar , Rose Winsley , John Jacob , Castro Marx , T Manivannan , Mohan Venkata Raghava , Rupali Priscilla 
Published: May 2022

AbstractObjectivesGeographical Information Surveillance (GIS) is an advanced digital technology tool that maps location-based data and helps in epidemiological modeling. We applied GIS to analyze patterns of spread and hotspots of COVID-19 cases in Vellore district in South India.MethodsLaboratory-confirmed COVID-19 cases from the Vellore district and neighboring taluks from March 2020 to June 2021 were geo-coded and spatial maps were generated. Time trends exploring urban-rural burden with an age-sex distribution of cases and other variables were correlated with outcomes.ResultsA total of 45,401 cases of COVID-19 were detected with 20730 cases during the first wave and 24671 cases during the second wave. The overall incidence rates of COVID-19 were 462.8 and 588.6 per 100,000 populations during the first and second waves respectively. The pattern of spread revealed epicenters in densely populated urban areas with radial spread sparing rural areas in the first wave. The case fatality rate was 1.89% and 1.6% during the first and second waves that increased with advancing age.ConclusionsModern surveillance systems like GIS can accurately predict the trends and pattern of spread during future pandemics. A real-time mapping can help design risk mitigation strategies thereby preventing the spread to rural areas.
How time-scale differences in asymptomatic and symptomatic transmission shape SARS-CoV-2 outbreak dynamics
Authors: Harris Jeremy D. , Park Sang Woo , Dushoff Jonathan , Weitz Joshua S. 
Published: May 2022

AbstractAsymptomatic and symptomatic SARS-CoV-2 infections can have different characteristic time scales of transmission. These time-scale differences can shape outbreak dynamics as well as bias population-level estimates of epidemic strength, speed, and controllability. For example, prior work focusing on the initial exponential growth phase of an outbreak found that larger time scales for asymptomatic vs. symptomatic transmission can lead to under-estimates of the basic reproduction number as inferred from epidemic case data. Building upon this work, we use a series of nonlinear epidemic models to explore how differences in asymptomatic and symptomatic transmission time scales can lead to changes in the realized proportion of asymptomatic transmission throughout an epidemic. First, we find that when asymptomatic transmission time scales are longer than symptomatic transmission time scales, then the effective proportion of asymptomatic transmission increases as total incidence decreases. Moreover, these time-scale-driven impacts on epidemic dynamics are enhanced when infection status is correlated between infector and infectee pairs (e.g., due to dose-dependent impacts on symptoms). Next we apply these findings to understand the impact of time-scale differences on populations with age-dependent assortative mixing and in which the probability of having a symptomatic infection increases with age. We show that if asymptomatic generation intervals are longer than corresponding symptomatic generation intervals, then correlations between age and symptoms lead to a decrease in the age of infection during periods of epidemic decline (whether due to susceptible depletion or intervention). Altogether, these results demonstrate the need to explore the role of time-scale differences in transmission dynamics alongside behavioural changes to explain outbreak features both at early stages (e.g., in estimating the basic reproduction number) and throughout an epidemic (e.g., in connecting shifts in the age of infection to periods of changing incidence).
Snotwatch COVID-Toes: An ecological study of chilblains and COVID-19 diagnoses in Victoria, Australia
Authors: Sawires Rana , Pearce Christopher , Fahey Michael , Clothier Hazel , Gardner Karina , Buttery Jim 
Published: May 2022

AbstractBackgroundThe COVID-19 pandemic has caused widespread illness with varying clinical manifestations. One less-commonly-reported presentation of COVID-19 infection is chilblain-like lesions.AimsWe conducted an ecological analysis of chilblain presentations in comparison with confirmed and suspected COVID-19 infections in a primary care setting to establish that a relationship exists between the two.Study DesignOur study collated data from three Primary Health Networks across Victoria, Australia, from 2017-2021, to understand patterns of chilblain presentations prior to and throughout the pandemic. Using a zero-inflated negative binomial regression analysis, we estimated the relationship between local minimum temperature, COVID-19 infections and the frequency of chilblain presentations.ResultsWe found a 5.72 risk ratio of chilblain incidence in relation to COVID-19 infections and a 3.23 risk ratio associated with suspected COVID-19 infections. COVID-19 infections were also more strongly associated with chilblain presentations in 0-16-year-olds throughout the pandemic in Victoria.ConclusionOur study statistically demonstrates that chilblains are significantly associated with COVID-19 infections in a primary care setting. This has major implications for clinicians aiming to diagnose COVID-19 infections or determine the cause of a presentation of chilblains. Additionally, we demonstrate the utility of large-scale primary care data and its potential application to monitoring the spread of COVID-19 infections across the state, supporting current epidemiological efforts for COVID-19 tracking.
Resilience in soil bacterial communities of the boreal forest from one to five years after wildfire across a severity gradient
Authors: Whitman Thea , Woolet Jamie , Sikora Miranda , Johnson Dana B. , Whitman Ellen 
Published: May 2022

AbstractWildfires can represent a major disturbance to ecosystems, including soil microbial communities belowground. Furthermore, fire regimes are changing in many parts of the world, altering and often increasing fire severity, frequency, and size. The boreal forest and taiga plains ecoregions of northern Canada are characterized by naturally-occurring stand-replacing wildfires on a 40-350 year basis. We previously studied the effects of wildfire on soil microbial communities one year post-fire across 40 sites, spanning a range of burn severity. Here, we return to the same sites five years post-fire to test a series of hypotheses about the effects of fire on bacterial community composition. We ask the following questions: (1a) Do the fundamental factors structuring bacterial community composition remain the same five years post-fire? (1b) Do the effects of fire on bacterial community composition decrease between one and five years post-fire? (1c) Do shifts in bacterial community composition between one and five years post-fire suggest resilience? (2a) Does the importance of fast growth diminish between one and five years post-fire? (2b) Do short-term post-fire responders continue to dominate the community five years post-fire? We find the following: (1a) Five years post-fire, vegetation community, moisture regime, pH, total carbon, texture, and burned/unburned all remained significant predictors of bacterial community composition with similar predictive value (R2). (1b and 1c) Bacterial communities became more similar to unburned sites five years post-fire, across the range of severity, suggesting resilience, while general structure of co-occurrence networks remained similar one and five years post-fire. (2a) Fast growth potential, as estimated using predicted 16S rRNA copy numbers, was no longer significantly correlated with burn severity five years post-fire, indicating the importance of this trait for structuring bacterial community composition may be limited to relatively short timescales. (2b) Many taxa that were enriched in burned sites one year post-fire remained enriched five years post-fire, although the degree to which they were enriched generally decreased. Specific taxa of interest from the generaMassilia, Blastococcus, andArthrobacterall remained significantly enriched, suggesting that they may have traits that allow them to continue to flourish in the post-fire environment, such as tolerance to increased pH or ability to degrade pyrogenic organic matter. This hypothesis-based work expands our understanding of the post-fire recovery of soil bacterial communities and raises new hypotheses to test in future studies.
Isotopic reconstruction of the subsistence strategy for a Central Italian Bronze Age community (Pastena cave, 2nd millennium BCE)
Authors: Cortese F. , De Angelis F. , Achino K.F. , Bontempo L. , Di Cicco M.R. , Gatta M. , Lubritto C. , Salari L. , Silvestri L. , Rickards O. , Rolfo M.F. 
Published: May 2022

AbstractThe Pastena cave is located in central Italy and its best-preserved sector is Grotticella W2, which is dated radiometrically to the Early-Middle Bronze Age. The aim of this paper is to explore human diet, animal husbandry, and plant management analyzing the findings there discovered. Carbon and nitrogen stable isotope analysis have been carried out on 40 charred seeds, 6 faunal remains and 4 human specimens, investigating the whole bio-archaeological samples available. To the best of our knowledge, this is one of the first papers presenting stable isotope analysis on carpological remains dated to the Italian Early-Middle Bronze Age. The obtained results are consistent with a diet based on terrestrial protein, mainly on plants and secondly on meat and animal products. The data suggest that plants, especially broad beans, were partially subjected to human management, while livestock was managed through different husbandry strategies. The cooperation between archaeological studies and molecular analysis allows us to contribute to clarify the economic strategies for a Central Italian community in a scenario that is still poor in published data.
Oral rabies vaccination of dogs – experiences from a field trial in Namibia
Authors: Freuling Conrad M. , Busch Frank , Vos Ad , Ortmann Steffen , Lohr Frederic , Hedimbi Nehemia , Peter Josephat , Nelson Herman Adimba , Shoombe Kenneth , Shilongo Albertina , Gorejena Brighton , Kaholongo Lukas , Khaiseb Siegfried , van der Westhuizen Jolandie , Dietze Klaas , Geurtse Goi , Müller Thomas 
Published: May 2022

AbstractDog-mediated rabies is responsible for tens of thousands of human deaths annually, and in resource-constrained settings, vaccinating dogs to control the disease at source remains challenging. Currently, rabies elimination efforts rely on mass dog vaccination by the parenteral route. To increase the herd immunity, free-roaming and stray dogs need to be specifically addressed in the vaccination campaigns, with oral rabies vaccination (ORV) of dogs being a possible solution. Using a third-generation vaccine and a standardized egg-flavoured bait, bait uptake and vaccination was assessed under field conditions in Namibia. During this trial, both veterinary staff as well as dog owners expressed their appreciation to this approach of vaccination. Of 1,115 dogs offered a bait, 90% (n=1,006, 95%CI:91-94) consumed the bait and 72.9% (n=813, 95%CI:70.2-75.4) of dogs were assessed as being vaccinated, while for (11.7%, n=130, 95%CI:9.9-17.7) the status was recorded as “unkown” and 15.4% (n=172, 95%CI: 13.4-17.7) were considered as being not vaccinated. Smaller dogs and dogs offered a bait with multiple other dogs had significantly higher vaccination rates, while other factors, e.g. sex, confinement status and time had no influence.The favorable results of this first large-scale field trial further support the strategic integration of ORV into dog rabies control programmes. Given the acceptance of the egg-flavored bait under various settings worldwide, ORV of dogs could become a game-changer in countries, where control strategies using parenteral vaccination alone failed to reach sufficient vaccination coverage in the dog population.
Maintenance of quantitative genetic variance in complex, multi-trait phenotypes: The contribution of rare, large effect variants in two Drosophila species
Authors: Hine Emma , Runcie Daniel E. , Allen Scott L. , Wang Yiguan , Chenoweth Stephen F. , Blows Mark W. , McGuigan Katrina 
Published: May 2022

AbstractThe interaction of evolutionary processes to determine quantitative genetic variation has implications for contemporary and future phenotypic evolution, as well as for our ability to detect causal genetic variants. While theoretical studies have provided robust predictions to discriminate among competing models, empirical assessment of these has been limited. In particular, theory highlights the importance of pleiotropy in resolving observations of selection and mutation, but empirical investigations have typically been limited to few traits. Here, we applied high dimensional Bayesian Sparse Factor Genetic modelling to 3,385 gene expression traits fromDrosophila melanogasterand fromD. serratato explore how genetic variance is distributed across high-dimensional phenotypic space. Surprisingly, most of the heritable trait covariation was due to few lines (genotypes) with extreme (>3 IQR from the median) values. This observation, in the two independently sampled species, suggests that the House of Cards (HoC) model might apply not only to individual expression traits, but also to emergent co-expression phenotypes. Intriguingly, while genotypes extreme for a multivariate factor also tended to have a higher proportion of individual traits that were extreme, we also observed genotypes that were outliers for multivariate factors but not for any individual traits. We observed other consistent differences between heritable multivariate factors with outlier lines versus those factors that conformed to a Gaussian distribution of genetic effects, including differences in gene functions. We use these observations to identify further data required to advance our understanding of the evolutionary dynamics and nature of standing genetic variation for quantitative traits.