bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diverse Humoral Immune Responses in Younger and Older Adult COVID-19 Patients
Authors: Sasson Jennifer M. , Campo Joseph J. , Carpenter Rebecca M. , Young Mary K. , Randall Arlo Z. , Trappl-Kimmons Krista , Oberai Amit , Hung Christopher , Edgar Joshua , Teng Andy A. , Pablo Jozelyn V. , Liang Xiaowu , Yee Angela , Petri William A. , Camerini David 
Published: January 2021

AbstractWe sought to discover links between antibody responses to SARS-CoV-2 and patient clinical variables, cytokine profiles and antibodies to endemic coronaviruses. Serum from patients of varying ages and clinical severity were collected and used to probe a novel multi-coronavirus protein microarray containing SARS-CoV-2 proteins and overlapping protein fragments of varying length as well as SARS-CoV, MERS-CoV, HCoV-OC43 and HCoV-NL63 proteins. IgG, IgA and IgM antibody responses to specific epitopes within the spike (S), nucleocapsid (N) and membrane proteins (M) were higher in older adult patients. Moreover, the older age group displayed more consistent correlations of antibody reactivity with systemic cytokine and chemokine responses when compared to the younger adult group. A subset of patients, however, had little or no response to SARS-CoV-2 antigens and disproportionately severe clinical outcomes. Further characterization of these serosilent individuals with cytokine analysis revealed significant differences in IL-10, IL-15, IP-10, EGF and sCD40L levels when compared to seroreactive patients in the cohort.
State-of-the-art structural variant calling: What went conceptually wrong and how to fix it?
Authors: Schmidt Markus , Kutzner Arne 
Published: January 2021

AbstractStructural variant (SV) calling belongs to the standard tools of modern bioinformatics for identifying and describing alterations in genomes. Initially, this work presents several complex genomic rearrangements that reveal conceptual ambiguities inherent to the SV representations of state-of-the-art SV callers. We contextualize these ambiguities theoretically as well as practically and propose a graph-based approach for resolving them. Our graph model unifies both genomic strands by using the concept of skew-symmetry; it supports graph genomes in general and pan genomes in specific. Instances of our model are inferred directly from seeds instead of the commonly used alignments that conflict with various types of SV as reported here. For yeast genomes, we practically compute adjacency matrices of our graph model and demonstrate that they provide highly accurate descriptions of one genome in terms of another. An open-source prototype implementation of our approach is available under the MIT license at https://github.com/ITBE-Lab/MA.
Low generalizability of polygenic scores in African populations due to genetic and environmental diversity
Authors: Majara Lerato , Kalungi Allan , Koen Nastassja , Zar Heather , Stein Dan J. , Kinyanda Eugene , Atkinson Elizabeth G. , Martin Alicia R. 
Published: January 2021

AbstractAfrican populations are vastly underrepresented in genetic studies but have the most genetic variation and face wide-ranging environmental exposures globally. Because systematic evaluations of genetic prediction had not yet been conducted in ancestries that span African diversity, we calculated polygenic risk scores (PRS) in simulations across Africa and in empirical data from South Africa, Uganda, and the UK to better understand the generalizability of genetic studies. PRS accuracy improves with ancestry-matched discovery cohorts more than from ancestry-mismatched studies. Within ancestrally and ethnically diverse South Africans, we find that PRS accuracy is low for all traits but varies across groups. Differences in African ancestries contribute more to variability in PRS accuracy than other large cohort differences considered between individuals in the UK versus Uganda. We computed PRS in African ancestry populations using existing European-only versus ancestrally diverse genetic studies; the increased diversity produced the largest accuracy gains for hemoglobin concentration and white blood cell count, reflecting large-effect ancestry-enriched variants in genes known to influence sickle cell anemia and the allergic response, respectively. Differences in PRS accuracy across African ancestries originating from diverse regions are as large as across out-of-Africa continental ancestries, requiring commensurate nuance.
Using a biologically mimicking climbing robot to explore the performance landscape of climbing in lizards
Authors: Schultz Johanna T. , Beck Hendrik K. , Haagensen Tina , Proost Tasmin , Clemente Christofer J. 
Published: January 2021

AbstractThe life and death of an organism often depends on its ability to perform well at some ecologically relevant task. Yet despite this significance we have little idea how well species are optimised for competing locomotor tasks. Most scientists generally accept that the ability for natural systems to become optimised for a specific task is limited by structural, historic or functional constraints. Climbing lizards provide a good example of constraint where climbing ability requires the optimization of conflicting tasks such as speed, stability, or efficiency. Here we reconstruct multiple performance landscapes of climbing locomotion using a 10-DOF robot based upon the lizard bauplan, including an actuated spine, shoulders, and feet, the latter which interlock with the surface via claws. This design allows us to independently vary speed, foot angles, and range of motion, while simultaneously collecting data on climbed distance, stability and efficiency. We first demonstrate a trade-off between speed and stability with high speeds resulting in decreased stability and low speeds an increased cost of transport. By varying foot orientation of fore and hindfeet independently, we found geckos converge on a narrow optimum for both speed and stability, but avoid a secondary wider optimum highlighting a possible constraint. Modifying the spine and limb range of movement revealed a gradient in performance. Evolutionary modifications in movement among extant species appear to follow this gradient towards areas which promote speed and efficiency. This approach can give us a better understanding about locomotor optimization, and provide inspiration for industrial and search-and-rescue robots.Significance StatementClimbing requires the optimization of conflicting tasks such as speed, stability, or efficiency, but understanding the relative importance of these competing performance traits is difficult.We used a highly modular bio-inspired climbing robot to reconstruct performance landscapes for climbing lizards. We then compared the performance of extant species onto these and show strong congruence with lizard phenotypes and robotic optima.Using this method we can show why certain phenotypes are not present among extant species, illustrating why these would be potentially mal-adaptive.These principles may be useful to compare with relative rates of evolution along differing evolutionary histories. It also highlights the importance of biological inspiration towards the optimization of industrial climbing robots, which like lizards, must negotiate complex environments.
COVID-19: Rapid Antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing
Authors: Peto Tim ,   UK COVID-19 Lateral Flow Oversight Team
Published: January 2021

AbstractLateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Here we report on standardised laboratory evaluations of LFDs, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots (UK COVID-19 testing centres, hospital, schools, armed forces). 4/64 LFDs so far have desirable performance characteristics (Orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1-6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20-0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists (156/198, 95% CI 72.4-84.3) was 78.8%. Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission.FundingDepartment of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research.
Evaluation of Urine SARS-COV-2 RT-PCR as a predictor of Acute Kidney Injury and disease severity in critical COVID-19 patients
Authors: de Souza Sérgio Pinto , Silveira Marcelo Augusto Duarte , de Freitas Souza Bruno Solano , Nonaka Carolina Kymie Vasques , de Melo Erica , Cabral Julia , Coelho Fernanda , da Hora Passos Rogério 
Published: January 2021

AbstractThe novel coronavirus disease (COVID-19) is an emerging infectious disease caused by SARS-CoV-2, which began as an outbreak in Wuhan, China and spread rapidly throughout the globe. Although the majority of infections are mild, severe and critical COVID-19 patients face deterioration of respiratory function, and may also present extrapulmonary manifestations, mostly affecting the kidney, digestive tract, heart and nervous system. Here, we prospectively evaluated the presence of SARS-CoV-2 genetic material by RT-PCR in urine samples obtained from critical care COVID-19 patients. In 51 patients included, we found higher serum creatinine levels, a longer hospital stay and a more frequent dialysis need in urine-positive patients. These findings could suggest that, in predisposed patients, a direct viral cytopathic effect may contribute to a more severe disease phenotype.
Application of Optical Genome Mapping For Comprehensive Assessment of Chromosomal Structural Variants for Clinical Evaluation of Myelodysplastic Syndromes
Authors: Yang Hui , Garcia-Manero Guillermo , Rush Diana , Montalban-Bravo Guillermo , Mallampati Saradhi , Medeiros L. Jeffrey , Levy Brynn , Luthra Rajyalakshmi , Kanagal-Shamanna Rashmi 
Published: January 2021

ABSTRACTStructural chromosomal variants [copy number variants (CNVs): losses/ gains and structural variants (SVs): inversions, balanced and unbalanced fusions/translocations] are important for diagnosis and risk-stratification of myelodysplastic syndromes (MDS). Optical genome mapping (OGM) is a novel single-platform cytogenomic technique that enables high-throughput, accurate and genome-wide detection of all types of clinically important chromosomal variants (CNVs and SVs) at a high resolution, hence superior to current standard-of-care cytogenetic techniques that include conventional karyotyping, FISH and chromosomal microarrays. In this proof-of-principle study, we evaluated the performance of OGM in a series of 12 previously well-characterized MDS cases using clinical BM samples. OGM successfully facilitated detection and detailed characterization of twenty-six of the 28 clonal chromosomal variants (concordance rate: 93% with conventional karyotyping; 100% with chromosomal microarray). These included copy number gains/losses, inversions, inter and intra-chromosomal translocations, dicentric and complex derivative chromosomes; the degree of complexity in latter aberrations was not apparent using standard technologies. The 2 missed aberrations were from a single patient within a composite karyotype, below the limit of detection. Further, OGM uncovered 6 additional clinically relevant sub-microscopic aberrations in 4 (33%) patients that were cryptic by standard-of-care technologies, all of which were subsequently confirmed by alternate platforms. OGM permitted precise gene-level mapping of clinically informative genes such as TP53, TET2 and KMT2A, voiding the need for multiple confirmatory assays. OGM is a potent single-platform assay for high-throughput and accurate identification of clinically important chromosomal variants.
Do antibody positive healthcare workers have lower SARS-CoV-2 infection rates than antibody negative healthcare workers? Large multi-centre prospective cohort study (the SIREN study), England: June to November 2020
Authors: Hall V , Foulkes S , Charlett A , Atti A , Monk EJM , Simmons R , Wellington E , Cole MJ , Saei A , Oguti B , Munro K , Wallace S , Kirwan PD , Shrotri M , Vusirikala A , Rokadiya S , Kall M , Zambon M , Ramsay M , Brooks T ,   SIREN Study Group, Brown CS , Chand MA , Hopkins S 
Published: January 2021

ABSTRACTBackgroundThere is an urgent need to better understand whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection.MethodsA large multi-centre prospective cohort was recruited from publicly funded hospital staff in the UK. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2-4 weeks) and completed fortnightly questionnaires on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive or prior PCR/antibody test positive) or negative cohort (antibody negative, not previously known to be PCR/antibody positive). Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, possible (subdivided by symptom-status)) depending on hierarchy of evidence. Individuals in the primary infection were excluded from this analysis if infection was confirmed by antibody only. Reinfection rates in the positive cohort were compared against new PCR positives in the negative cohort using a mixed effective multivariable logistic regression analysis.FindingsBetween 18 June and 09 November 2020, 44 reinfections (2 probable, 42 possible) were detected in the baseline positive cohort of 6,614 participants, collectively contributing 1,339,078 days of follow-up. This compares with 318 new PCR positive infections and 94 antibody seroconversions in the negative cohort of 14,173 participants, contributing 1,868,646 days of follow-up. The incidence density per 100,000 person days between June and November 2020 was 3.3 reinfections in the positive cohort, compared with 22.4 new PCR confirmed infections in the negative cohort. The adjusted odds ratio was 0.17 for all reinfections (95% CI 0.13-0.24) compared to PCR confirmed primary infections. The median interval between primary infection and reinfection was over 160 days.InterpretationA prior history of SARS-CoV-2 infection was associated with an 83% lower risk of infection, with median protective effect observed five months following primary infection. This is the minimum likely effect as seroconversions were not included.FundingDepartment of Health and Social Care and Public Health England, with contributions from the Scottish, Welsh and Northern Irish governments.
Genome-wide functional screen of 3’UTR variants uncovers causal variants for human disease and evolution
Authors: Griesemer Dustin , Xue James R , Reilly Steven K , Ulirsch Jacob C , Kukreja Kalki , Davis Joe , Kanai Masahiro , Yang David K , Montgomery Stephen B , Novina Carl D , Tewhey Ryan , Sabeti Pardis C 
Published: January 2021

Abstract3’ untranslated region (3’UTR) variants are strongly associated with human traits and diseases, yet few have been causally identified. We developed the Massively Parallel Reporter Assay for 3’UTRs (MPRAu) to sensitively assay 12,173 3’UTR variants. We applied MPRAu to six human cell lines, focusing on genetic variants associated with genome-wide association studies (GWAS) and human evolutionary adaptation. MPRAu expands our understanding of 3’UTR function, suggesting that low-complexity sequences predominately explain 3’UTR regulatory activity. We adapt MPRAu to uncover diverse molecular mechanisms at base-pair resolution, including an AU-rich element ofLEPRlinked to potential metabolic evolutionary adaptations in East Asians. We nominate hundreds of 3’UTR causal variants with genetically fine-mapped phenotype associations. Using endogenous allelic replacements, we characterize one variant that disrupts a miRNA site regulating the viral defense geneTRIM14, and one that altersPILRBabundance, nominating a causal variant underlying transcriptional changes in age-related macular degeneration.
Achromobactergenetic adaptation in cystic fibrosis
Authors: Gabrielaite Migle , Nielsen Finn C. , Johansen Helle K. , Marvig Rasmus L. 
Published: January 2021

AbstractAchromobacteris an emerging pathogen in patients with cystic fibrosis (CF) andAchromobactercaused infections are associated with more severe disease outcomes and high intrinsic antibiotic resistance. While conventional CF pathogens are studied extensively, little is known about the genetic determinants leading to antibiotic resistance and the genetic adaptation inAchromobacterinfections.Here, we analyzed 101Achromobactergenomes from 51 patients with CF isolated during the course of up to 20 years of infection to identify within-host adaptation, mutational signatures, and genetic variation associated with increased antibiotic resistance.We found that the same regulatory and inorganic ion transport genes were frequently mutated in persisting clone types within and betweenAchromobacterspecies indicating convergent genetic adaptation. Genome-wide association study (GWAS) of six antibiotic resistance phenotypes revealed the enrichment of associated genes involved in inorganic ion transport genes, transcription gene enrichment in β-lactams, and energy production and translation gene enrichment in the trimethoprim/sulfonamide group.Overall, we provide insights into the pathogenomics ofAchromobacterinfections in patients with CF airways. Since emerging pathogens are increasingly recognised as an important healthcare issue, our findings on evolution of antibiotic resistance and genetic adaptation can facilitate better understanding of disease progression and how mutational changes have implications for patients with CF.
Beeporter: a high-throughput tool for non-invasive analysis of honey bee virus infection
Authors: Evans Jay D. , Banmeke Olubukola , Palmer-Young Evan C. , Chen Yanping , Ryabov Eugene V. 
Published: January 2021

ABSTRACTHoney bees face numerous pests and pathogens but arguably none are as devastating as Deformed wing virus (DWV). Development of antiviral therapeutics and virus-resistant honey bee lines to control DWV in honey bees is slowed by the lack of a cost-effective high-throughput screening of DWV infection. Currently, analysis of virus infection and screening for antiviral treatments in bees and their colonies is tedious, requiring a well-equipped molecular biology laboratory and the use of hazardous chemicals. Here we utilize a cDNA clone of DWV tagged with green fluorescent protein (GFP) to develop the Beeporter assay, a method for detection and quantification of DWV infection in live honey bees. The assay involves infection of honey bee pupae by injecting a standardized DWV-GFP inoculum, followed by incubation for up to 44 hours. GFP fluorescence is recorded at intervals via commonly available long-wave UV light sources and a smartphone camera or a standard ultraviolet transilluminator gel imaging system. Nonlethal DWV monitoring allows high-throughput screening of antiviral candidates and a direct breeding tool for identifying honey bee parents with increased antivirus resistance. For even more rapid drug screening, we also describe a method for screening bees using 96-well trays and a spectrophotometer.
The Relationship between Chronological Age, Dental Age, and Salivary Alkaline Phosphatase in Indonesian Children Aged 8-14 Years: A Cross-Sectional Study
Authors: Nelwan Sindy Cornelia , Wahluyo Soegeng , Khairani Firli Cahaya , Nugraha Ricardo Adrian , Utomo Haryono , Tedjosasongko Udijanto 
Published: January 2021

BackgroundInability to predict dental age accurately has long been the Achilles heel of pediatric dentistry. Whilst dental age has an important aspect in clinical practice, saliva can be one of the most practically important diagnostic tools to estimate biological age.AimsThis study was aimed to analyze a correlation between chronological age, dental age, and salivary alkaline phosphatase in Indonesian children aged 8-14 years.MethodsThis study was an observational study with cross-sectional design. Twenty healthy children (10 boys; age 10.504 ± 1.895 years) were selected by a consecutive sampling. Chronological age was assessed by recording date of birth. Dental age was assessed by orthopantamogram following Demirjian’s method. Salivary samples were collected by passive drool method and estimation of alkaline phosphatase was done by autoanalyzer.ResultsNormality test was assessed using Kolmogorov-Smirnov and Shapiro-Wilk test. Statistical analyses were assessed using Spearman’s rank-order correlation coefficients. Results are presented as mean ± standard deviation (SD). Mean chronological age was10.504 ± 1.895 years, mean Demirjian’s score was 91.74 ± 5.972, and mean salivary alkaline phosphatase was 291.563 ± 115.135 pg/ml. There is a very strong positive correlation between chronological age and dental age (r=+0.804; p<0.001). On the contrary, levels of salivary alkaline phosphatase was negatively correlated to dental age (r=-0.780; p<0.001) and chronological age (r=-0.508; p=0.022).ConclusionsThis study showed a strong correlation between dental age, chronological age, and salivary alkaline phosphatase; hence, estimation of dental age and salivary alkaline phosphatase in Indonesian children during early and late childhood has significant meaning to chronological age.
Evaluating the effects of re-opening plans on dynamics of COVID-19 in São Paulo, Brazil1
Authors: Rubio F.A. , Vilches T.N. 
Published: January 2021

AbstractCoronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in early March 2020. In Brazil, São Paulo is the most affected state, comprising about 20% of the country’s cases. With no vaccine available to date, distancing measures have been taken to reduce virus transmission. To reduce the pandemic’s effect on the economy, the government of São Paulo has proposed a plan consisting of five phases of the gradual re-opening of activities. In this context, we have developed a mathematical model to simulate the gradual re-opening plan on the transmission dynamics of COVID-19, in the city of São Paulo. The model shows that a precipitous reopening can cause a higher peak of the disease, which may compromise the local health system. Waiting for the reduction in the incidence of infected individuals for at least 15 days to phase transition is the most efficient strategy compared to the fixed-period scenario at each phase of the re-opening plan.