bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral load dynamics of SARS-CoV-2 Delta and Omicron variants following multiple vaccine doses and previous infection
Authors: Woodbridge Yonatan , Amit Sharon , Huppert Amit , Kopelman Naama M. 
Published: March 2022

AbstractAn important, and often neglected, aspect of vaccine effectiveness is its impact on pathogen transmissibility, harboring major implications for public health policies. As viral load is a prominent factor affecting infectivity, its laboratory surrogate, qRT-PCR cycle threshold (Ct), can be used to investigate the infectivity-related component of vaccine effectiveness. While vaccine waning has previously been observed for viral load, during the Delta wave, it is yet unknown how Omicron viral load is affected by vaccination status, and whether vaccine-derived and natural infection protection are sustainable. By analyzing results of more than 460,000 individuals we show that while recent vaccination reduces Omicron viral load, its effect wanes rapidly. In contrast, a significantly slower waning rate is demonstrated for recovered COVID-19 individuals. Thus, while the vaccine is effective in decreasing morbidity and mortality, their relative minute effect on transmissibility and rapid waning call for reassessment of the scientific justification for “vaccine certificate”, as it may promote false reassurance and promiscuous behavior.
Clinical validation and the evaluation of a colorimetric SARS-CoV-2 RT-LAMP assay identify its robustness against RT-PCR
Authors: Erdem M. , Andac-Ozketen A. , Ozketen AC. , Karahan G. , Tozluyurt A. , Palaz F. , Alp A. , Unal S. 
Published: March 2022

SUMMARYThe novel coronavirus has infected millions of people all around the world and has posed a great risk to global health. Rapid and accurate tests are needed to take early precautions and control the disease. The most routinely used method is real time polymerase chain reaction (RT-PCR) which stands as the gold standard in the detection of SARS-COV-2 viral RNA. However, robust assays as accurate as RT-PCR have been developed for rapid diagnosis and efficient control of the spread of the disease. Reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) is one of the time-saving, accurate and cost-effective alternative methods to RT-PCR. In this study, we study the improved RT-LAMP colorimetric assay (N-Fact) to detect SARS-COV-2 viral RNA within 30 minutes using a primer sets special to N gene. Moreover, RT-LAMP colorimetric assay is subjected to authorized clinical studies to test its ability to detect COVID-19 in its early phases. The results reveal RT-LAMP colorimetric assay is an efficient, robust, and rapid assay to be used as in vitro diagnostic tool display competitiveness compared to RT-PCR.
Accuracy of Rapid Antigen Testing across SARS-CoV-2 Variants
Authors: Drain Paul K. , Bemer Meagan , Morton Jennifer F. , Dalmat Ronit , Abdille Hussein , Thomas Katherine , Uppal Timsy , Hau Derrick , Green Heather R. , Gates-Hollingworth Marcellene A. , AuCoin David P. , Verma Subhash C. 
Published: March 2022

AbstractVariants of SARS-CoV-2 have mutations in the viral genome that may alter the accuracy of rapid diagnostic tests. We conducted analytical and clinical accuracy studies of two FDA-approved rapid antigen tests—SCoV-2 Ag Detect™ Rapid Test (InBios International, Seattle) and BinaxNOW™ COVID-19 Ag CARD; (Abbott Laboratories, Chicago)—using three using replication-competent variants or strains, including Omicron (B.1.1.529/BA.1), Delta (B.1.617.2), and a wild-type of SARS-CoV-2 (USA-WA1/2020). Overall, we found non-significant differences in the analytical limit of detection or clinical diagnostic accuracy of rapid antigen testing across SARS-CoV-2 variants. This study provides analytical and clinical performance data to demonstrate the preserved accuracy of rapid antigen testing across SARS-CoV-2 variants among symptomatic adults.
Undiagnosed COVID-19 in households with a child with mitochondrial disease
Authors: Gordon-Lipkin Eliza M. , Marcum Christopher , Kruk Shannon , Thompson Elizabeth , Kelly Sophie E.M. , Kalish Heather , Sadtler Kaitlyn , McGuire Peter J. 
Published: March 2022

ABSTRACTBackgroundThe impact of the COVID-19 pandemic on medically fragile populations, who are at higher risk of severe illness and sequelae, has not been well characterized. Viral infection is a major cause of morbidity in children with mitochondrial disease (MtD), and the COVID-19 pandemic represents an opportunity to study this vulnerable population.MethodsA convenience sampling cross-sectional serology study was conducted (October 2020 to June 2021) in households (N = 20) containing a child with MtD (N = 22). Samples (N = 83) were collected in the home using a microsampling apparatus and shipped to investigators. Antibodies against SARS-CoV-2 nucleocapsid (IgG), spike protein (IgG, IgM, IgA), and receptor binding domain (IgG, IgM, IgA) were determined by enzyme linked immunosorbent assay.ResultsWhile only 4.8% of participants were clinically diagnosed for SARS-CoV-2 infection, 75.9% of study participants were seropositive for SARS-CoV-2 antibodies. Most samples were IgM positive for spike or RBD (70%), indicating that infection was recent. This translated to all 20 families showing evidence of infection in at least one household member. For the children with MtD, 91% had antibodies against SARS-CoV-2 and had not experienced any adverse outcomes at the time of assessment. For children with recent infections (IgM+ only), serologic data suggest household members as a source.ConclusionsCOVID-19 was highly prevalent and undiagnosed in households with a child with MtD through the 2020-2021 winter wave of the pandemic. In this first major wave, children with MtD tolerated SARS-CoV-2 infection well, potentially due to household adherence to CDC recommendations for risk mitigation.FundingThis study was funded by the Intramural Research Program of the National Institutes of Health (HG200381-03).Clinical trial numberNCT04419870
Altered microRNA expression in severe COVID-19: potential prognostic and pathophysiological role
Authors: Garnier Nathalie , Pollet Kato , Fourcot Marie , Caplan Morgan , Marot Guillemette , Goutay Julien , Labreuche Julien , Soncin Fabrice , Boukherroub Rabah , Hober Didier ,   Lille COVID Research Network (LICORNE), Szunerits Sabine , Poissy Julien , Engelmann Ilka 
Published: March 2022

AbstractBackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is ongoing. The pathophysiology of SARS-CoV-2 infection is beginning to be elucidated but the role of microRNAs (miRNAs), small non-coding RNAs that regulate gene expression, remains incompletely understood. They play a role in the pathophysiology of viral infections with potential use as biomarkers. The objective of this study was to identify miRNAs as biomarkers of severe COVID-19 and to analyze their role in the pathophysiology of SARS-CoV-2 infection.MethodsmiRNA expression was measured in nasopharyngeal swabs from 20 patients with severe COVID-19, 21 patients with non-severe COVID-19 and 20 controls. Promising miRNAs to differentiate non-severe from severe COVID-19 patients were identified by differential expression analysis and sparse Partial Least Squares-Discriminant Analysis (sPLS-DA). ROC analysis, target prediction, GO enrichment and pathway analysis were used to analyze the role and the pertinence of these miRNAs in severe COVID-19.ResultsThe number of expressed miRNAs was lower in severe COVID-19 patients compared to non-severe COVID-19 patients and controls. Among the differentially expressed miRNAs between severe COVID-19 and controls, 5 miRNAs were also differentially expressed between severe and non-severe COVID-19. sPLS-DA analysis highlighted 8 miRNAs, that allowed to discriminate the severe and non-severe COVID-19 cases. Target and functional analysis revealed enrichment for genes involved in viral infections and the cellular response to infection as well as one miRNA, hsa-miR-15b-5p, that targeted the SARS-CoV-2 RNA.The comparison of results of differential expression analysis and discriminant analysis revealed three miRNAs, namely hsa-miR-125a-5p, hsa-miR-491-5p and hsa-miR-200b-3p. These discriminated severe from non-severe cases with areas under the curve ranging from 0.76 to 0.80.ConclusionsOur analysis of miRNA expression in nasopharyngeal swabs revealed several miRNAs of interest to discriminate severe and non-severe COVID-19. These miRNAs represent promising biomarkers and possibly targets for antiviral or anti-inflammatory treatment strategies.
Sequential appearance and isolation of a SARS-CoV-2 recombinant between two major SARS-CoV-2 variants in a chronically infected immunocompromised patient
Authors: Burel Emilie , Colson Philippe , Lagier Jean-Christophe , Levasseur Anthony , Bedotto Marielle , Lavrard Philippe , Fournier Pierre-Edouard , La Scola Bernard , Raoult Didier 
Published: March 2022

ABSTRACTGenetic recombination is a major evolutionary mechanism among RNA viruses, and it is common in coronaviruses, including those infecting humans. A few SARS-CoV-2 recombinants have been reported to date whose genome harbored combinations of mutations from different mutants or variants, but a single patient’s sample was analyzed, and the virus was not isolated. Here, we re-port the gradual creation of a hybrid genome of B.1.160 and Alpha variants in a lymphoma patient chronically infected for 14 months, and we isolated the recombinant virus. The hybrid genome was obtained by next-generation sequencing, and recombination sites were confirmed by PCR. This consisted of a parental B.1.160 backbone interspersed with two fragments, including the spike gene, from an Alpha variant. Analysis of seven sequential samples from the patient decoded the recombination steps, including the initial infection with a B.1.160 variant, then a concurrent infec-tion with this variant and an Alpha variant, the generation of hybrid genomes, and eventually the emergence of a predominant recombinant virus isolated at the end of the patient’s follow-up. This case exemplifies the recombination process of SARS-CoV-2 in real life, and it calls for intensifying genomic surveillance in patients coinfected with different SARS-CoV-2 variants, and more gener-ally with several RNA viruses, as this may lead to the creation of new viruses.
Another doubling of excess mortality in the United States relative to its European peers between 2017 and 2021
Authors: Heuveline Patrick 
Published: March 2022

AbstractA mortality gap between the United States and other high-income nations emerged before the pandemic. International comparisons of Covid-19 mortality suggest this gap might have increased during the pandemic.Applying average mortality rates of the five largest West European countries to the US population shows that the number of “excess deaths” attributable to this mortality gap continues to increase year after year in the United States. The annual number of such excess deaths has doubled between 2017 and 2021, with most of the increase occurring during the pandemic (+89.1% between 2019 and 2021). In 2021, excess mortality in the United States relative to its European peers contributed 892,491 excess deaths, amounting to 25.8% of all US deaths that year, up from 15.7% in 2017.Of the 450,224 excess deaths added between 2017 and 2021, 42,317 are attributable to population change (9.4%), 230,672 to differential rates of Covid-19 mortality (51.2%), and the remaining 177,235 to differential rates of mortality from other causes (39.4%, possibly including misclassified deaths due to Covid-19). The contribution of Covid-19 mortality to excess mortality in the United States (relative to its European peers) grew between 2020 and 2021 due to diverging trends in Covid-19 mortality, especially towards the end of 2021 as US vaccination rates plateaued at lower levels than in European countries. While this contribution might be transient, divergent trends in mortality from other causes persistently separates the United States from West European countries. Excess mortality is particularly high between ages 15 and 64. In 2021, nearly half of all US deaths in this age range are excess deaths (48.0%).
Eye drift during fixation predicts visual acuity
Authors: Clark Ashley M. , Intoy Janis , Rucci Michele , Poletti Martina 
Published: March 2022

AbstractVisual acuity is commonly assumed to be determined by the eye optics and spatial sampling in the retina. Unlike a camera, however, the eyes are never stationary during the acquisition of visual information, a jittery motion known as ocular drift, incessantly displaces stimuli over many photoreceptors. Previous studies have shown that acuity is impaired in the absence of retinal image motion caused by eye drift. However, the relation between individual drift characteristics and acuity remains unknown. Here we show that (a) healthy emmetropes exhibit a large variability in their amount of drift; and (b) that these differences profoundly affect the structure of spatiotemporal signals to the retina. We further show that (c) the spectral distribution of the resulting luminance modulations strongly correlates with individual visual acuity; and (d) that natural inter-trial fluctuations in the amount of drift modulate acuity. As a consequence, in healthy emmetropes acuity can be predicted from the motor behavior elicited by a simple fixation task, without directly measuring it. These results shed new light on how oculomotor behavior contributes to fine spatial vision.SignificanceHealthy humans can visually resolve extremely fine patterns, in some cases with the relevant features spanning less than a single photoreceptor on the retina. This accomplishment is particularly remarkable considering that the eyes are never stationary. Ocular drift—a motion that eludes human awareness—shifts the stimulus across many photoreceptors during the acquisition of visual information. Here we show that visual acuity depends on ocular drift. Natural variations in the amount of drift are associated with acuity both within and across subjects, so that individual acuity limits can be directly inferred from the amount of motion during fixation on a marker. Results closely follow the strength of the luminance modulations caused by ocular drift, providing support to long-standing dynamic theories of visual acuity.
Brain iron and mental health symptoms in youth with and without prenatal alcohol exposure
Authors: Nakhid Daphne , McMorris Carly A. , Sun Hongfu , Gibbard William B. , Tortorelli Christina , Lebel Catherine 
Published: March 2022

AbstractPrenatal alcohol exposure (PAE) negatively affects brain development and increases the risk of poor mental health. We investigated if brain susceptibility, measuring iron, or volume were associated with internalizing or externalizing symptoms in youth with and without PAE. T1-weighted and quantitative susceptibility mapping (QSM) MRI scans were collected for 19 PAE and 40 unexposed participants aged 7.5-15 years. Magnetic susceptibility and volume of basal ganglia and limbic structures were extracted using FreeSurfer. Internalizing and externalizing problems were assessed using the Behavioural Assessment System for Children (BASC-2-PRS). Susceptibility in the nucleus accumbens was negatively associated with internalizing problems, while amygdala susceptibility was positively associated with internalizing problems across groups. In the PAE group, thalamus susceptibility was negatively associated with internalizing problems, and putamen susceptibility was positively associated with externalizing problems. Brain volume was not related to internalizing or externalizing symptoms. These findings highlight that brain iron is related to internalizing and externalizing symptoms differently in some brain regions for youth with and without PAE. Atypical iron levels (high or low) may indicate mental health problems across individuals, and iron in the thalamus and putamen may be particularly important for behaviour in individuals with PAE.
Application of Digital Twin and Heuristic Computer Reasoning to Workflow Management: Gastroenterology Outpatient Centers Study
Authors: Garbey Marc , Joerger Guillaume , Furr Shannon 
Published: March 2022

AbstractThe workflow in a large medical procedural suite is characterized by high variability of input and suboptimum throughput. Today, Electronic Health Record systems do not address the problem of workflow efficiency: there is still high frustration from medical staff who lack real-time awareness and need to act in response of events based on their personal experiences rather than anticipating. In a medical procedural suite, there are many nonlinear coupling mechanisms between individual tasks that could wrong and therefore is difficult for any individual to control the workflow in real-time or optimize it in the long run. We propose a system approach by creating a digital twin of the procedural suite that assimilates Electronic Health Record data and supports the process of making rational, data-driven, decisions to optimize the workflow on a continuous basis. In this paper, we focus on long term improvements of gastroenterology outpatient centers as a prototype example and use six months of data acquisition in two different clinical sites to validate the artificial intelligence algorithms.
Seasonality of Common Human Coronaviruses in the United States, 2014-2021
Authors: Shah Melisa M. , Winn Amber , Dahl Rebecca M. , Kniss Krista L. , Silk Benjamin J. , Killerby Marie E. 
Published: March 2022

AbstractThe four common human coronaviruses (HCoVs), including two alpha (HCoV-NL63 and HCoV-229E) and two beta (HCoV-HKU1 and HCoV-OC43) types, generally cause mild, upper respiratory illness. HCoVs are known to have seasonal patterns and variation in predominant types each year, but defined measures of seasonality are needed. We defined seasonality of HCoVs during July 2014 to November 2021 in the United States using a retrospective method applied to National Respiratory and Enteric Virus Surveillance System (NREVSS) data. In the six HCoV seasons prior to 2020-2021, onsets ranged from October to November, peaks from January to February, and offsets from April to June; most (>93%) HCoV detections occurred within the defined seasonal onsets and offsets. The 2020-2021 HCoV season onset was delayed by 11 weeks compared to prior seasons, likely due to COVID-19 mitigation efforts. Better defining HCoV seasonality can inform clinical preparedness and the expected patterns of emerging HCoVs.Article Summary LineThe typical common HCoV season in the United States starts between October and November, peaks towards the end of January, and ends between April and June, but the 2020-2021 season was markedly delayed compared to prior seasons.
Identification of deleterious neutrophil states and altered granulopoiesis in sepsis
Authors: Kwok Andrew J. , Allcock Alice , Ferreira Ricardo C. , Smee Madeleine , Cano-Gamez Eddie , Burnham Katie L. , Zurke Yasemin-Xiomara ,   Oxford acute medicine/ED research, McKechnie Stuart , Monaco Claudia , Udalova Irina , Hinds Charles J. , Davenport Emma E. , Todd John A. , Knight Julian C. 
Published: March 2022

AbstractSepsis is a condition of high mortality arising from dysregulation of the host immune response. Gene expression studies have identified multiple immune endotypes but gaps remain in our understanding of the underlying biology and heterogeneity. We used single-cell multi-omics to profile 272,993 cells across 48 whole blood samples from 26 sepsis patients (9 with paired convalescent samples), 6 healthy controls and 7 post-surgery patients. We identified immature neutrophil populations specific to sepsis and demonstrated the immunosuppressive nature of sepsis neutrophils in vitro. An IL1R2+ neutrophil state was expanded in a transcriptomic sepsis endotype associated with increased early mortality (sepsis response signature 1, SRS1), together with enrichment of the response to IL-1 pathway in mature neutrophils, marking IL-1 out as a potential target for immunotherapy in SRS1 sepsis patients. We confirmed the expansion of immature neutrophils, specifically IL1R2+ neutrophils, in SRS1 in additional cohorts of patients (n = 906 RNA-sequencing samples, n = 41 CyTOF samples). Neutrophil changes persisted in convalescence, implicating disrupted granulopoiesis. Our findings establish a cellular immunological basis for transcriptomically defined sepsis endotypes and emphasise the relevance of granulopoietic dysfunction in sepsis, identifying opportunities for precision medicine approaches to the condition.
Mathematical modelling of COVID-19 transmission dynamics with vaccination: A case study in Ethiopia
Authors: Sharbayta Sileshi Sintayehu , Desta Henok Desalegn , Abdi Tadesse 
Published: March 2022

AbstractMathematical modelling is important for better understanding of disease dynamics and developing strategies to manage rapidly spreading infectious diseases. In this work, we consider a mathematical model of COVID-19 transmission with double-dose vaccination strategy to control the disease. For the analytical analysis purpose we divided the model into two, model with vaccination and without vaccination. Analytical and numerical approach is employed to investigate the results. In the analytical study of the model we have shown the local and global stability of disease-free equilibrium, existence of the endemic equilibrium and its local stability, positivity of the solution, invariant region of the solution, transcritical bifurcation of equilibrium and sensitivity analysis of the model is conducted. From these analyses, for the full model (model with vaccination) we found that the disease-free equilibrium is globally asymptotically stable forRv< 1 and is unstable forRv> 1. A locally stable endemic equilibrium exists forRv> 1, which shows the persistence of the disease if the reproduction parameter is greater than unity. The model is fitted to cumulative daily infected cases and vaccinated individuals data of Ethiopia from May 01, 2021 to January 31, 2022. The unknown parameters are estimated using the least square method with the MATLAB built-in function ‘lsqcurvefit’. The basic reproduction number,R0and controlled reproduction numberRvare calculated to beR0= 1.17 andRv= 1.15 respectively. Finally, we performed different simulations using MATLAB. From the simulation results, we found that it is important to reduce the transmission rate, infectivity factor of asymptomatic cases and, increase the vaccination coverage and quarantine rate to control the disease transmission.