bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early immunologic response to mRNA COVID-19 vaccine in patients receiving biologics and/or immunomodulators
Authors: Rodríguez-Martinó Esteban , Medina-Prieto Rafael , Santana-Bagur Jorge , Santé María , Pantoja Petraleigh , Espino Ana M. , Sariol Carlos A. , Torres Esther A. 
Published: September 2021

AbstractPatients with immune conditions and immune-modifying therapies were excluded from the Covid-19 vaccine trials. Studies have shown conflicting response to different vaccines in persons receiving immune suppressors or biologics. The aim of this study is to evaluate humoral and cellular response to Covid-19 vaccines in patients with Inflammatory Bowel Disease (IBD) using biologic and/or immunomodulatory (IMM) therapies.MethodsParticipants are adults with IBD receiving biologics or IMM planning to receive a Covid 19 vaccine. Cellular immunity (CD4+ and CD8+ T cell levels) with flow cytometry are measured at baseline and 2 weeks after each vaccine dose. Humoral immunity (antibody titers and neutralizing capacity,VNT%) is analyzed by ELISA at baseline, 2 weeks after each dose, and 6 and 12 months after vaccine. We present the early results of the first 19 subjects. The study is approved by the IRB.Results19 subjects (18 in biologics and 1 in IMM) who received 2 doses of the Pfizer-BioNTech vaccine are included. Total IgG antibodies increased 21.13 times after the first dose and 90 times after the second dose. VTN% increased 11.92 times after the first dose and 53.79 times after the second dose. When compared with a healthy control cohort, total IgG antibodies and VTN% were lower in the subjects after the first dose. After the second dose, IgG antibodies increased but remained lower than controls, but VTN% were similar to controls. CD4 and CD8 mean levels had an upward trend after vaccination.ConclusionsNeutralizing capacity response to the vaccine in subjects was similar to a healthy cohort in spite of lower increases in total IgG antibodies. The CD4 and CD8 results observed may support the capacity to mount an effective cellular response in patients on biologics. Larger studies are needed to determine vaccine efficacy in these patients.
Identification of rare loss of function variation regulating body fat distribution
Authors: Koprulu Mine , Zhao Yajie , Wheeler Eleanor , Dong Liang , Rocha Nuno , Patel Satish , Van de Streek Marcel , Glastonbury Craig A. , Stewart Isobel D. , Day Felix R. , Luan Jian’an , Bowker Nicholas , Wittemans Laura B. L. , Kerrison Nicola D. , Lucarelli Debora M. E. , Barroso Inês , McCarthy Mark I. , Scott Robert A. , Saudek Vladimir , Small Kerrin S. , Wareham Nicholas J. , Semple Robert K. , Perry John R. B. , O’Rahilly Stephen , Lotta Luca A. , Langenberg Claudia , Savage David B. 
Published: September 2021

ABSTRACTBiological and translational insights from large-scale, array-based genetic studies of fat distribution, a key determinant of metabolic health, have been limited by the difficulty in linking identified predominantly non-coding variants to specific gene targets. Rare coding variant analyses provide greater confidence that a specific gene is involved, but do not necessarily indicate whether gain or loss of function would be of most therapeutic benefit. Here we use a dual approach that combines the power of genome-wide analysis of array-based rare, non-synonymous variants in 184,246 individuals of UK Biobank with exome-sequence-based rare loss of function gene burden testing. The data indicates that loss-of-function (LoF) of four genes (PLIN1, INSR, ACVR1C and PDE3B) is associated with a beneficial impact on WHRadjBMI and increased gluteofemoral fat mass, whereas PLIN4 LoF adversely affects these parameters. This study robustly implicates these genes in the regulation of fat distribution, providing new and in some cases somewhat counter-intuitive insight into the potential consequences of targeting these molecules therapeutically.
Interrogating COVID-19 Vaccine Hesitancy in the Philippines with a Nationwide Open-Access Online Survey
Authors: Caple Alexandria , Dimaano Arnie O. , Sagolili Marc Martin C. , Uy April Anne M. , Aguirre Panjee Mariel G. , Alano Dean Lotus C. , Camaya Giselle Sophia M. , Ciriaco Brent John A. , Clavo Princess Jerah S. , Cuyugan Dominic G. , Fermo Cleinne Florence Geeseler V. , Lanete Paul Jeremy C. , La Torre Ardwayne Jurel D. , Loteyro Thomas Albert T. , Lua Raisa Mikaela , Manansala Nicole Gayle R. , Mosquito Raphael Willard M. , Octaviano Alexa Marie C. , Orfanel Alexandra Erika T. , Pascual Gheyanna Merly U. , Sale Aubrey Joy S. , Tendenilla Sophia Lorraine S. , Trinidad Maria Sofia Lauren R. , Trinidad Nicole Jan S. , Verano Daphne Louise V. , Austriaco Nicanor 
Published: September 2021

ABSTRACTTo mitigate the unprecedented health, social, and economic damage of COVID-19, the Philippines is undertaking a nationwide vaccination program to mitigate the effects of the global pandemic. In this study, we interrogated COVID-19 vaccine hesitancy in the country by deploying a nationwide open-access online survey, two months before the rollout of the national vaccination program. The Health Belief Model (HBM) posits that people are likely to adopt disease prevention behaviors and to accept medical interventions like vaccines if there is sufficient motivation and cues to action. A majority of our 7,193 respondents (62.5%) indicated that they were willing to be vaccinated against COVID-19. Moreover, multivariable analysis revealed that HBM constructs were associated with vaccination intention in the Philippines. Perceptions of high susceptibility, high severity, and significant benefits were all good predictors for vaccination intent. We also found that external cues to action were important. Large majorities of our respondents would only receive the COVID-19 vaccines after many others had received it (72.8%) or after politicians had received it (68.2%). Finally, our study revealed that most (21%) were willing to pay an amount of PHP1,000 [USD20] for the COVID-19 vaccines with an average willing-to-pay amount of PHP1,892 [USD38].
Early life predictors of late life cerebral small vessel disease in four prospective cohort studies
Authors: Backhouse Ellen V , Shenkin Susan D , McIntosh Andrew M , Bastin Mark E , Whalley Heather C , Hernandez Maria Valdez , Maniega Susana Muñoz , Harris Mat , Stolicyn Aleks , Campbell Archie , Steele Douglas , Waiter Gordon D , Sandu Anca-Larisa , Waymont Jennifer MJ , Murray Alison D , Cox Simon R , de Rooij Susanne R. , Roseboom Tessa J. , Wardlaw Joanna M 
Published: September 2021

AbstractDevelopment of cerebral small vessel disease, a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socioeconomic status or of vascular risk factor exposures.We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, socioeconomic status), adult small vessel disease, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n=1080; mean age=59 years); The Dutch Famine Birth cohort (n=118; mean age=68 years); the Lothian Birth Cohort 1936 (LBC1936; n=617; mean age=73 years), and the Simpson’s cohort (n=110; mean age=78 years). We analysed each small vessel disease feature individually and summed to give a total small vessel disease score (range 1-4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult socioeconomic status.Higher birth weight was associated with fewer lacunes (OR per 100g, 0.93 95%CI=0.88-0.99), fewer infarcts (OR=0.94 95%CI=0.89-0.99), and fewer perivascular spaces (OR=0.95 95%CI=0.91-0.99). Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point=0.99 95%CI 0.98-0.998), fewer infarcts (OR=0.98, 95%CI=0.97-0.998), fewer lacunes (OR=0.98, 95%CI=0.97-0.999), and lower total small vessel disease burden (OR=0.98, 95%CI=0.96-0.999). Low education was associated with more microbleeds (OR=1.90 95%CI=1.33-2.72) and lower total brain volume (MD=-178.86cm3, 95%CI=-325.07- -32.66). Low childhood socioeconomic status was associated with fewer lacunes (OR=0.62, 95%CI=0.40-0.95).Early life factors are associated with worse small vessel disease in later life, independent of each other, vascular risk factors and adult socioeconomic status. Risk for small vessel disease may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may contribute to improve lifelong brain health to prevent dementia and stroke in older age.
Efficacy of two doses of COVID-19 vaccine against severe COVID-19 in those with risk conditions and residual risk to the clinically extremely vulnerable: the REACT-SCOT case-control study
Authors: McKeigue Paul M , McAllister David A , Robertson Chris , Hutchinson Sharon , McGurnaghan Stuart , Stockton Diane , Colhoun Helen M ,   for the PHS COVID-19 Epidemiology and Research Cell
Published: September 2021

AbstractObjectivesTo determine whether COVID-19 efficacy varies with clinical risk category and to investigate risk factors for severe COVID-19 in those who have received two doses of vaccine.DesignMatched case-control study (REACT-SCOT).SettingPopulation of Scotland from 1 December 2020 to 8 September 2021.Main outcome measureSevere COVID-19, defined as cases with entry to critical care or fatal outcome.ResultsEfficacy against severe COVID-19 of two doses of vaccine was 94% (95 percent CI 93% to 96%) in those without designated risk conditions, 89% (95 percent CI 86% to 91%) in those with moderate risk conditions, but only 73% (95 percent CI 64% to 79%) in those designated as clinically extremely vulnerable (CEV) and eligible for shielding. Of the 641 cases of severe COVID-19 in double-vaccinated individuals, 47% had moderate risk conditions and 38% were CEV. In the double-vaccinated CEV group, the rate ratio for severe disease (with no risk condition as reference category) was highest in solid organ transplants at 101 (95% CI 47 to 214) but even in this subgroup the absolute risk of severe COVID-19 was low (35 cases in 23678 person-months of follow-up).ConclusionsTwo doses of vaccine protect against severe COVID-19 in CEV individuals but the residual risk in double-vaccinated individuals remains far higher in those who are CEV than in those who are not. These results lay a basis for determining eligibility for additional measures including passive immunization to protect those at highest risk.
Visual Processing During the Interictal Period Between Migraines: A Meta-Analysis
Authors: Sezai Timucin , Nguyen Vinh , Riddell Nina , Murphy Melanie J. , Crewther Sheila G. 
Published: September 2021

AbstractMigraine is a poorly understood neurological disorder and a leading cause of disability in young adults. Migraines are characterized by severe pulsating unilateral headache and visual symptoms. Whether visual function is also impaired in the interictal period between migraines remains controversial. Thus, this meta-analysis investigated the evidence for altered visual function as measured electrophysiologically via pattern-reversal visual evoked potential (VEP) amplitudes and habituation in adult migraineurs with or without visual aura and control in the interictal period. Twenty-three studies were selected for random effects meta-analysis, demonstrating slightly diminished VEP amplitudes and substantially reduced habituation in the early P100 component in migraineurs without aura and with aura compared to controls. No differences were found between migraineurs with and without aura. Although heterogeneity between studies and insufficient published data for VEP latencies and the earlier N75 VEP component data was observed and require further testing, P100 anomalies may indicate abnormal functioning of the fast-conducting magnocellular visual pathway, in episodic migraineurs.
The Paradox of the Plankton: Coexistence of Structured Microbial Communities
Authors: Scarampi Alberto 
Published: September 2021

AbstractIn the framework of resource-competition models, it has been argued that the number of species stably coexisting in an ecosystem cannot exceed the number of shared resources. However, plankton seems to be an exception of this so-called “competitive-exclusion principle”. In planktic ecosystems, a large number of different species stably coexist in an environment with limited resources. This contradiction between theoretical expectations and empirical observations is often referred to as “The Paradox of the Plankton”. This project aims to investigate biophysical models that can account for the large biodiversity observed in real ecosystems in order to resolve this paradox. A model is proposed that combines classical resource competition models, metabolic trade-offs and stochastic ecosystem assembly. Simulations of the model match empirical observations, while relaxing some unrealistic assumptions from previous models.Paradox: from Greek para: “distinct from”, and doxa: opinion. Sainsbury (1995) defines a paradox as “an apparently unacceptable conclusion derived by apparently acceptable reasoning from apparently acceptable premises”. Paradoxes are useful research tools as they suggest logical inconsistencies. In order to spot the flaw, the validity of all the premises has to be carefully assessed.Plankton: refers to the collection of organisms that spend part or all of their lives in suspension in water (Reynolds 2006). Plankton, or plankters, are “organisms that have velocities significantly smaller than oceanic currents and thus are considered to travel with the water parcel they occupy” (Lombard et al. 2019). Phytoplankters refer to the members of the plankton that perform photosynthesis.
Installation and imaging of thousands of minirhizotrons to phenotype root systems of field-grown plants
Authors: Rajurkar Ashish B. , McCoy Scott M. , Ruhter Jeremy , Mulcrone Jessica , Freyfogle Luke , Leakey Andrew D. B. 
Published: September 2021

AbstractBackgroundRoots are vital to plant performance because they acquire resources from the soil and provide anchorage. However, it remains difficult to assess root system size and distribution because roots are inaccessible in the soil. Existing methods to phenotype entire root systems range from slow, often destructive, methods applied to relatively small numbers of plants in the field to rapid methods that can be applied to large numbers of plants in controlled environment conditions. Much has been learned recently by extensive sampling of the root crown portion of field-grown plants. But, information on large-scale genetic and environmental variation in the size and distribution of root systems in the field remains a key knowledge gap. Minirhizotrons are the only established, non-destructive technology that can address this need in a standard field trial. Prior experiments have used only modest numbers of minirhizotrons, which has limited testing to small numbers of genotypes or environmental conditions. This study addressed the need for methods to install and collect images from thousands of minirhizotrons and thereby help break the phenotyping bottleneck in the field.ResultsOver three growing seasons, methods were developed and refined to install and collect images from up to3038 minirhizotrons per experiment. Modifications were made to four tractors and hydraulic soil corers mounted to them. High quality installation was achieved at an average rate of up to 84.4 minirhizotron tubes per tractor per day. A set of four commercially available minirhizotron camera systems were each transported by wheelbarrow to allow collection of images of mature maize root systems at an average rate of up to 65.3 tubes per day per camera. This resulted in over 300,000 images being collected in as little as 11 days for a single experiment.ConclusionThe scale of minirhizotron installation was increased by two orders of magnitude by simultaneously using four tractor-mounted, hydraulic soil corers with modifications to ensure high quality, rapid operation. Image collection can be achieved at the corresponding scale using commercially available minirhizotron camera systems. Along with recent advances in image analysis, these advances will allow use of minirhizotrons at unprecedented scale to address key knowledge gaps regarding genetic and environmental effects on root system size and distribution in the field.
Genome-wide association mapping within a single Arabidopsis thaliana population reveals a richer genetic architecture for defensive metabolite diversity
Authors: Gloss Andrew D. , Vergnol Amélie , Morton Timothy C. , Laurin Peter J. , Roux Fabrice , Bergelson Joy 
Published: September 2021

AbstractA paradoxical finding from genome-wide association studies (GWAS) in plants is that variation in metabolite profiles typically maps to a small number of loci, despite the complexity of underlying biosynthetic pathways. This discrepancy may partially arise from limitations presented by geographically diverse mapping panels. Properties of metabolic pathways that impede GWAS by diluting the additive effect of a causal variant, such as allelic and genic heterogeneity and epistasis, would be expected to increase in severity with the geographic range of the mapping panel. We hypothesized that a population from a single locality would reveal an expanded set of associated loci. We tested this in a French Arabidopsis thaliana population (< 1 km transect) by profiling and conducting GWAS for glucosinolates, a suite of defensive metabolites that have been studied in depth through functional and genetic mapping approaches. For two distinct classes of glucosinolates, we discovered more associations at biosynthetic loci than previous GWAS with continental-scale mapping panels. Candidate genes underlying novel associations were supported by concordance between their observed effects in the TOU-A population and previous functional genetic and biochemical characterization. Local populations complement geographically diverse mapping panels to reveal a more complete genetic architecture for metabolic traits.
Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach
Authors:   The CRyPTIC Consortium, Carter Joshua J 
Published: September 2021

AbstractThe World Health Organization goal of universal drug susceptibility testing for patients with tuberculosis is most likely to be achieved through molecular diagnostics; however, to date these have focused largely on first-line drugs, and always on predicting binary susceptibilities. Here, we used whole genome sequencing and a quantitative microtiter plate assay to relate genomic mutations to minimum inhibitory concentration in 15,211 Mycobacterium tuberculosis patient isolates from 27 countries across five continents.This work identifies 449 unique MIC-elevating genetic determinants across thirteen drugs, as well as 91 mutations resulting in hypersensitivity for eleven drugs. Our results provide a guide for further implementation of personalized medicine for the treatment of tuberculosis using genetics-based diagnostics and can serve as a training set for novel approaches to predict drug resistance.
Land use change through the lens of macroecology: insights from Azorean arthropods and the Maximum Entropy Theory of Ecology
Authors: Brush Micah , Matthews Thomas J. , Borges Paulo A.V. , Harte John 
Published: September 2021

AbstractHuman activity and land management practices, in particular land use change, have resulted in the global loss of biodiversity. These types of disturbance affect the shape of macroecological patterns, and therefore analyzing these patterns can provide insights into how ecosystems are affected by land use change. We here use arthropod census data from 96 sites at Terceira Island in the Azores archipelago across four different land uses of increasing management intensity: native forest, exotic forest, semi-natural pasture, and intensive pasture, to examine the effects of land use type on three macroecological patterns: the species abundance distribution, the metabolic rate distribution of individuals, and the species–area relationship. The Maximum Entropy Theory of Ecology (METE) has successfully predicted these patterns across habitats and taxa in undisturbed ecosystems, and thus provides a null expectation for their shapes. Across these patterns, we find that the forest habitats are the best fit by METE predictions, while the semi-natural pasture is consistently the worst fit, and the intensive pasture is intermediately well fit. We show that the direction of failure of the METE predictions at the pasture sites is likely due to the hyper-dominance of introduced spider species present there. We hypothesize that the particularly poor fit for the semi-natural pasture is due to the mix of arthropod communities out of equilibrium, leading to greater heterogeneity in composition and complex dynamics that violate METE’s assumption of static state variables. The comparative better fit for the intensive pasture plausibly results from more homogeneous arthropod communities that are well adapted to intensive management, and thus whose state variables are less in flux. Analyzing deviations from theoretical predictions across land use type provides useful information about how land use and disturbance affect ecosystems, and such comparisons could be useful across other habitats and taxa.