bluuebunny/crossref_metadata_2025 huggingface dataset:
What Underlies a Greater Reversal in Tactile Temporal Order Judgment When the Hands Are Crossed? A Structural MRI Study
Authors: Moharramipour Ali , Kitazawa Shigeru
Published: April 2021

Our subjective temporal order of two successive tactile stimuli, delivered one to each hand, is often inverted when our hands are crossed. However, there is great variability among different individuals. We addressed the question of why some show almost complete reversal, but others show little reversal. To this end, we obtained structural magnetic resonance imaging data from 42 participants who also participated in the tactile temporal order judgment (TOJ) task. We extracted the cortical thickness and the convoluted surface area as cortical characteristics in 68 regions. We found that the participants with a thinner, larger, and more convoluted cerebral cortex in 10 regions, including the right pars-orbitalis, right and left postcentral gyri, left precuneus, left superior parietal lobule, right middle temporal gyrus, left superior temporal gyrus, right cuneus, left supramarginal gyrus, and right rostral middle frontal gyrus, showed a smaller degree of judgment reversal. In light of major theoretical accounts, we suggest that cortical elaboration in the aforementioned regions improve the crossed-hand TOJ performance through better integration of the tactile stimuli with the correct spatial representations in the left parietal regions, better representation of spatial information in the postcentral gyrus, or improvement of top-down inhibitory control by the right pars-orbitalis.
Biological Control of Citrus Huanglongbing with EB92-1, a Benign Strain of Xylella fastidiosa
Authors: Hopkins D. L. , Ager K. L.
Published: April 2021

Huanglongbing (HLB), caused by Candidatus Liberibacter asiaticus, is currently the most destructive disease of citrus and threatens production in all affected areas. There is no cure. Benign Xylella fastidiosa strain EB92-1 provided good control of Pierce’s disease of grapevine by inducing host resistance; therefore, we evaluated the strain for the biological control of HLB in citrus. Treatment was by injection into the trunk of the trees. Strain EB92-1 was shown to colonize citrus and provided control of HLB by reducing both the incidence of symptomatic trees and the percentage of trees with severe symptoms in three separate trials. All trees were positive by quantitative PCR (qPCR) for Candidatus Liberibacter asiaticus at the start of the trials, and treatment did not eliminate the bacterium. In a trial of asymptomatic mature trees, a single treatment with EB92-1 reduced the incidence of trees with symptoms through 18 months after treatment and reduced the incidence of trees with severe symptoms through 3 years. In mature trees that had 60% incidence of mild HLB symptoms at trial initiation, percentage of trees with symptoms and trees with severe symptoms continued to develop in both the untreated and in the EB92-1–treated trees for 12 months. However, retreatment at 9 and 20 months prevented the development of additional severe symptoms in the EB92-1–treated trees throughout the remainder of the 5-year trial. In 2-year-old trees, incidence of trees with HLB symptoms was higher in the untreated trees than in the treated trees throughout the 6 years of the trial, reaching 90% in the untreated versus 50% in the treated. After 6 years, severity of symptoms was much lower in the EB92-1–treated trees, only 3% of the treated trees had become unproductive compared with 18% of the untreated. In 2020, the reduction in HLB severity resulted in approximately twice as much yield in the treated trees as in these untreated 8-year-old trees. X. fastidiosa strain EB92-1 proved to be efficacious for the control of HLB symptoms in both mature trees and newly planted young trees, but trees may need to be retreated yearly for at least the first 2 to 3 years.
Detection of SARS-CoV-2 antibodies formed in response to the BNT162b2 and mRNA-1237 mRNA vaccine by commercial antibody tests
Authors: Kanji Jamil N , Bailey Ashley , Fenton Jayne , Ling Sean H , Rivera Rafael , Plitt Sabrina , Sligl Wendy I , Taylor Sean , Turnbull LeeAnn , Tipples Graham , Charlton Carmen L.
Published: April 2021

PURPOSE

With rapid approval of SARS-CoV-2 vaccines, the ability of clinical laboratories to detect vaccine-induced antibodies with available high-throughput commercial assays is unknown. We aimed to determine if commercial serology assays can detect vaccine-induced antibodies (VIAs) and understand the vaccination response.

METHODS

This cohort study recruited healthcare workers and residents of long-term care facilities (receiving the BNT162b2 and mRNA-1273 products, respectively) who underwent serum collection pre-vaccination (BNT162b2 group), 2-weeks post vaccination (both groups), and pre-2nddose (both groups). Sera were tested for the presence of SARS-CoV-2 IgG using four commercial assays (Abbott Architect SARS-CoV-2 IgG, Abbott Architect SARS-CoV-2 IgG II Quant, DiaSorin Liaison Trimeric S IgG, and GenScript cPASS) to detect VIAs. Secondary outcomes included description of post-vaccination antibody response and correlation with neutralising titers.

RESULTS

225 participants (177 receiving BNT162b2 and 48 receiving mRNA-1273) were included (median age 41 years,; 66-78% female). Nucleocapsid IgG was found in 4.1% and 21.9% of the BNT162b2 (baseline) and mRNA-1273 (2-weeks post first dose). All anti-spike assays detected antibodies post-vaccination, with an average increase of 87.2% (range 73.8-94.3%; BNT162b2), and 25.2% (range 23.8-26.7%; mRNA-1273) between the first and last sampling time points (all p<0.05). Neutralising antibodies were detected at all post-vaccine timepoints for both vaccine arms, with increasing titers over time (all p<0.05).

CONCLUSION

Anti-spike vaccine-induced SARS-CoV-2 IgG are detectable by commercially available high-throughput assays and increases over time. Prior to second dose of vaccination, neutralising antibodies are detectable in 73-89% of individuals, suggesting the majority of individuals would have some degree of protection from subsequent infection.
Assessment of SARS-CoV-2 infectivity by a Rapid Antigen Detection Test
Authors: Korenkov Michael , Poopalasingam Nareshkumar , Madler Matthias , Vanshylla Kanika , Eggeling Ralf , Wirtz Maike , Fish Irina , Dewald Felix , Gieselmann Lutz , Lehmann Clara , Fätkenheuer Gerd , Gruell Henning , Pfeifer Nico , Heger Eva , Klein Florian
Published: April 2021

The identification and isolation of highly infectious SARS-CoV-2-infected individuals is an important public health strategy. Rapid antigen detection tests (RADT) are promising candidates for large-scale screenings due to timely results and feasibility for on-site testing. Nonetheless, the diagnostic performance of RADT in detecting infectious individuals is yet to be fully determined. Two combined oro- and nasopharyngeal swabs were collected from individuals at a routine SARS-CoV-2 diagnostic center. Side-by-side evaluations of RT-qPCR and RADT as well as live virus cultures of positive samples were performed to determine the sensitivity of the Standard Q COVID-19 Ag Test (SD Biosensor/Roche) in detecting SARS-CoV-2-infected individuals with cultivable virus. A total of 2,028 samples were tested and 118 virus cultures inoculated. SARS-CoV-2 infection was detected in 210 samples by RT-qPCR, representing a positive rate of 10.36%. The Standard Q COVID-19 Ag Test yielded a positive result in 92 (4.54%) samples resulting in an overall sensitivity and specificity of 42.86% and 99.89%. For adjusted Ct values <20, <25, and <30 the RADT reached sensitivities of 100%, 98.15%, and 88.64%, respectively. All 29 culture positive samples were detected by RADT. While overall sensitivity was low, Standard Q COVID-19 RADT reliably detected patients with high RNA loads. Additionally, negative RADT results fully corresponded with the lack of viral cultivability in Vero E6 cells. These results indicate that RADT can be a valuable tool for the detection of individuals that are likely to transmit SARS-CoV-2. RADT testing could therefore guide public health testing strategies to combat the COVID-19 pandemic.

One Sentence Summary

Standard Q COVID-19 Ag test reliably detects individuals with high RNA loads and negative results correspond with lack of viral cultivability of SARS-CoV-2 in Vero E6 cells.
Genomic epidemiology of SARS-CoV-2 in Russia reveals recurring cross-border transmission throughout 2020
Authors: Matsvay Alina , Klink Galya V. , Safina Ksenia R. , Nabieva Elena , Garushyants Sofya K. , Biba Dmitry , Bazykin Georgii A , Mikhaylov Ivan M. , Say Anna V. , Zakamornaya Anastasiya I. , Khakhina Anastasiya O. , Lisitsa Tatiana S. , Ayginin Andrey A. , Abramov Ivan S. , A.Bogdan Sergey , Kolbutova Kseniya B. , Oleynikova Daria U , Avdeenko Tatiana F. , Shipulin German A. , M.Yudin Sergey , Skvortsova Veronika I.
Published: April 2021

SARS-CoV-2 has spread rapidly across the globe, with most nations failing to prevent or substantially delay its introduction. While many countries have imposed some limitations on trans-border passenger traffic, the effect of these measures on the spread of COVID-19 strains remains unclear. Here, we report an analysis of whole-genome sequencing of 3206 SARS-CoV-2 samples from 78 regions of Russia covering the period between March and November 2020. We describe recurring imports of multiple COVID-19 strains throughout this period, giving rise to 457 uniquely Russian transmission lineages, as well as repeated cross-border transmissions of local circulating variants out of Russia.
Tryptophan and arginine metabolism is significantly altered at the time of admission in hospital for severe COVID-19 patients: findings from longitudinal targeted metabolomics analysis
Authors: Ansone Laura , Ustinova Monta , Terentjeva Anna , Perkons Ingus , Birzniece Liga , Rovite Vita , Rozentale Baiba , Viksna Ludmila , Kolesova Oksana , Klavins Kristaps , Klovins Janis
Published: April 2021

The heterogeneity in severity and outcome of COVID-19 cases points out the urgent need for early molecular characterization of patients followed by risk-stratified care. The main objective of this study was to evaluate the fluctuations of serum metabolomic profiles of COVID-19 patients with severe illness during the different disease stages in a longitudinal manner. We demonstrate a distinct metabolomic signature in serum samples of 32 hospitalized patients at the acute phase compared to the recovery period, suggesting the tryptophan (tryptophan, kynurenine, and 3-hydroxy-DL-kynurenine) and arginine (citrulline and ornithine) metabolism as contributing pathways in the immune response to SARS-CoV-2 with a potential link to the clinical severity of the disease. In addition, we provide evidence for glutamine metabolism in M2 macrophages as a complementary process and contribution of phenylalanine and tyrosine in the molecular mechanisms underlying the severe course of the infection. In conclusion, our results provide several functional metabolic markers for disease progression and severe outcome with potential clinical application.

Importance

Although the host defense mechanisms against SARS-CoV-2 infection are still poorly described, they are of central importance in shaping the course of the disease and the possible outcome. Metabolomic profiling may complement the lacking knowledge of the molecular mechanisms underlying clinical manifestations and pathogenesis of COVID-19. Moreover, early identification of metabolomics□based biomarker signatures is proved to serve as an effective approach for the prediction of disease outcome. Here we provide the list of metabolites describing the severe, acute phase of the infection and bring the evidence of crucial metabolic pathways linked to aggressive immune responses. Finally, we suggest metabolomic phenotyping as a promising method for developing personalized care strategies in COVID-19 patients.
Accuracy and performance of the WHO 2015 and WHO 2019 HIV testing strategies across epidemic settings
Authors: Eaton Jeffrey W , Sands Anita , Barr-DiChiara Magdalena , Jamil Muhammad S , Baggaley Rachel , Tippett Barr Beth A , Kalua Thokozani , Jahn Andreas , Maheu-Giroux Mathieu , Johnson Cheryl C
Published: April 2021

Background

WHO 2019 HIV testing guidelines recommended a standard HIV testing strategy consisting of three consecutively HIV-reactive test results on serology assays to diagnose HIV infection. National HIV programmes in high prevalence settings currently using the strategy consisting of only two consecutive HIV-reactive tests should consider when to implement the new guideline recommendations.

Methods and Findings

We implemented a probability model to simulate outcomes of WHO 2019 and the two strategies recommended by WHO 2015 guidelines on HIV testing services. Each assay in the strategy was assumed independently 99% sensitivity and 98% specificity, the minimal thresholds required for WHO prequalification. For each strategy and positivity ranging 20% to 0.2%, we calculated the number of false-negative, false-positive, and inconclusive results; positive and negative predictive value (PPV, NPV); number of each assay used, and testing programme costs. We found that the NPV was above 99.9% for all scenarios modelled. Under the WHO 2015 two-test strategy, the PPV was below the 99% target threshold when positivity fell below 5%. For the WHO 2019 strategy, the PPV was above 99% for all positivity levels. The number reported ‘inconclusive’ was higher under the WHO 2019 strategy. Implementing the WHO 2019 testing strategy in Malawi, would require around 89,000 A3 tests in 2021, compared to 175,000 A2 tests and over 4.5 million A1 tests per year. The incremental cost of the WHO 2019 strategy was less than 2% in 2021 and declined to 0.9% in 2025.

Conclusions

As positivity among persons testing for HIV reduces below 5% in nearly all settings, implementation of the WHO 2019 testing strategy will ensure that positive predictive value remains above the 99% target threshold, averting misdiagnoses and ART initiations among HIV uninfected people. The incremental cost of implementing the WHO 2019 HIV testing strategy compared to the two-test strategy is negligible because the third assay accounts for a small and diminishing share of total HIV tests.
Replication of LZTFL1 gene region as a susceptibility locus for COVID-19 in Latvian population
Authors: Rescenko Raimonds , Peculis Raitis , Ustinova Monta , Ansone Laura , Terentjeva Anna , Litvina Helena Daiga , Birzniece Liga , Megnis Kaspars , Kolesova Oksana , Rozentale Baiba , Viksna Ludmila , Rovite Vita , Klovins Janis
Published: April 2021

The severity of COVID-19 disease is partly determined by host genetic factors that have been reported by GWAS. We evaluated nine previously reported genome-wide significant associations regardless of the disease severity in a representative sample from the population of Latvia. Our cohort consisted of 475 SARS-CoV-2 positive cases, from which 146 were hospitalized individuals and 2217 controls. We found three variants from Neanderthal introgression event at the 3p21.31 region to be significantly associated with increased risk of SARS-CoV-2 infection and hospitalization status. The strongest association was displayed by rs71325088 with Bonferroni adjusted P=0.007, OR=1.46 [95% CI 1.17-1.81]. We performed fine-mapping by exploring 1 Mb region at 3p21.31 locus and identified 9 SNPs with even lower p-values with the strongest association estimated for rs2191031 P=5e-05, OR = 1.40[CI 95% 1.19-1.64] located in the LZTFL1. We show clear replication of 3p.21.31 locus in an independent cohort which favors further functional investigation of leading variants.
Smoking and COVID-19: A two-sample Mendelian randomization study
Authors: Zheng Bing-Kun , Li Na
Published: April 2021

Evidence from observational studies suggested that smokers are at increased risk of coronavirus disease 2019 (COVID-19). We aimed to assess the causal effect of smoking on risk for COVID-19 susceptibility and severity using two-sample Mendelian randomization method. Smoking-associated variants were selected as instrument variables from two largest genetic studies. The latest summary data of COVID-19 that shared on Jan 18, 2021 by the COVID-19 Host Genetics Initiative was used. The present Mendelian randomization study provided genetic evidence that smoking was a causal risk factor for COVID-19 susceptibility and severity. In addition, there may be a dose-effect relationship between smoking and COVID-19 severity.
Risk quantification for SARS-CoV-2 infection through airborne transmission in university settings
Authors: Ambatipudi Mythri , Gonzalez Paola Carrillo , Tasnim Kazi , Daigle Jordan T. , Kulyk Taisa , Jeffreys Nicholas , Sule Nishant , Trevino Rafael , He Emily M. , Mooney David J. , Koh Esther
Published: April 2021

The COVID-19 pandemic has significantly impacted learning as many institutions switched to remote or hybrid instruction. An in-depth assessment of the risk of infection that takes into account environmental setting and mitigation strategies is needed to make safe and informed decisions regarding reopening university spaces. A quantitative model of infection probability that accounts for space-specific parameters is presented to enable assessment of the risk in reopening university spaces at given densities. The model uses local positivity rate, room capacity, mask filtration efficiency, air exchange rate, room volume, and time spent in the space as parameters to calculate infection probabilities in teaching spaces, dining halls, dorms, and shared bathrooms. The model readily calculates infection probabilities in various university spaces, with mask filtration efficiency and air exchange rate being among the dominant variables. When applied to university spaces, this model demonstrated that, under specific conditions that are feasible to implement, in-person classes could be held in large lecture halls with an infection risk over the semester < 1%. Meal pick-ups from dining halls and the use of shared bathrooms in residential dormitories among small groups of students could also be accomplished with low risk. The results of applying this model to spaces at Harvard University (Cambridge and Allston campuses) and Stanford University are reported. Finally, a user-friendly web application was developed using this model to calculate infection probability following input of space-specific variables. The successful development of a quantitative model and its implementation through a web application may facilitate accurate assessments of infection risk in university spaces. In light of the impact of the COVID-19 pandemic on universities, this tool could provide crucial insight to students, faculty, and university officials in making informed decisions.
Racial Disparities in the SOFA Score Among Patients Hospitalized with COVID-19
Authors: Tolchin Benjamin , Oladele Carol , Galusha Deron , Kashyap Nitu , Showstark Mary , Bonito Jennifer , Salazar Michelle C. , Herbst Jennifer L. , Martino Steve , Kim Nancy , Nash Katherine A. , Nguemeni Tiako Max Jordan , Roy Shireen , Jubanyik Karen
Published: April 2021

Background

Sequential Organ Failure Assessment (SOFA) score predicts probability of in-hospital mortality. Many crisis standards of care use SOFA score to allocate medical resources during the COVID-19 pandemic.

Research Question

Are SOFA scores disproportionately elevated among Non-Hispanic Black and Hispanic patients hospitalized with COVID-19, compared to Non-Hispanic White patients?

Study Design and Methods

Retrospective cohort study conducted in Yale New Haven Health System, including 5 hospitals with total of 2681 beds. Study population drawn from consecutive patients aged ≥18 admitted with COVID-19 from March 29thto August 1st, 2020. Patients excluded from the analysis if not their first admission with COVID-19, if they did not have SOFA score recorded within 24 hours of admission, if race and ethnicity data were not Non-Hispanic Black, Non-Hispanic White, or Hispanic, or if they had other missing data. The primary outcomes was SOFA score, with peak score within 24 hours of admission dichotomized as <6 or ≥6.

Results

Of 2982 patients admitted with COVID-19, 2320 met inclusion criteria and were analyzed, of whom 1058 (45.6%) were Non-Hispanic White, 645 (27.8%) were Hispanic, and 617 (26.6%) were Non-Hispanic Black. Median age was 65.0 and 1226 (52.8%) were female. In univariate logistic screen and in full multivariate model, Non-Hispanic Black patients but not Hispanic patients had greater odds of an elevated SOFA score ≥6 when compared to Non-Hispanic White patients (OR 1.49, 95%CI 1.11-1.99).

Interpretation

Crisis standards of care utilizing the SOFA score to allocate medical resources would be more likely to deny these resources to Non-Hispanic Black patients.
Global-scale analysis and longitudinal assessment of COVID-19 incidence in the first six months
Authors: Ghosh Sujoy , Roy Saikat Sinha
Published: April 2021

Studies examining factors responsible for COVID-19 incidence have mostly focused at the national or sub-national level. Here we undertake an analysis of COVID-19 cases at the global scale to identify key factors associated with disease incidence. A regression modeling framework was used to identify key variables associated with COVID-19 incidence, and to assess longitudinal trends in reported incidence at the country-level. New COVID-19 case dynamics in response to lockdowns was characterized via cluster analysis. Eleven variables were found to be independently associated with COVID-19 infections (p<1e-05) and a 4-variable model adequately explained global variations in COVID-19 cases (p<0.01). COVID-19 case trajectories for most countries followed the log-logistic curve. Six predominant country clusters summarized the differences in individual country’s response to lockdowns. Globally, economic and meteorological factors are important determinants of COVID-19 incidence. Analysis of longitudinal trends and lockdown effects on COVID-19 caseloads further highlights important nuances in country-specific responses to the pandemic. These findings on the first six months of the pandemic has important implications for additional phases of the disease currently underway in many countries.
Increasing concentration of COVID-19 by socioeconomic determinants and geography in Toronto, Canada: an observational study
Authors: Mishra Sharmistha , Ma Huiting , Moloney Gary , Yiu Kristy CY , Darvin Dariya , Landsman David , Kwong Jeffrey C. , Calzavara Andrew , Straus Sharon , Chan Adrienne K , Gournis Effie , Rilkoff Heather , Xia Yiqing , Katz Alan , Williamson Tyler , Malikov Kamil , Kustra Rafal , Maheu-Giroux Mathieu , Sander Beate , Baral Stefan D
Published: April 2021

Background

Inequities in the burden of COVID-19 observed across Canada suggest heterogeneity within community transmission.

Objectives

To quantify the magnitude of heterogeneity in the wider community (outside of long-term care homes) in Toronto, Canada and assess how the magnitude in concentration evolved over time (January 21 to November 21, 2020).

Design

Retrospective, population-based observational study using surveillance data from Ontario’s Case and Contact Management system.

Setting

Toronto, Canada.

Participants

Laboratory-confirmed cases of COVID-19 (N=33,992).

Measurements

We generated epidemic curves by SDOH and crude Lorenz curves by neighbourhoods to visualize inequities in the distribution of COVID-19 cases by social determinants of health (SDOH) and estimated the crude Gini coefficient. We examined the correlation between SDOH using Pearson correlation coefficients.

Results

The Gini coefficient of cumulative cases by population size was 0.41 (95% CI: 0.36-0.47) and were estimated for: household income (0.20, 95%CI: 0.14-0.28); visible minority (0.21, 95%CI: 0.16-0.28); recent immigration (0.12, 95%CI: 0.09-0.16); suitable housing (0.21, 95%CI: 0.14-0.30); multi-generational households (0.19, 95%CI: 0.15-0.23); and essential workers (0.28, 95% CI: 0.23-0.34). Most SDOH were highly correlated.

Locally acquired cases were concentrated in higher income neighbourhoods in the early phase of the epidemic, and then concentrated in lower income neighbourhoods. Mirroring the trajectory of epidemic curves by income, the Lorenz curve shifted over time from below to above the line of equality with a similar pattern across SDOH.

Limitations

Study relied on area-based measures of the SDOH and individual case counts of COVID-19. We cannot infer concentration of cases by specific occupational exposures given limitation to broad occupational categories.

Conclusion

COVID-19 is increasingly concentrated by SDOH given socioeconomic inequities and structural racism.

Primary Funding Source

Canadian Institutes of Health Research.
The association of ABO blood group with the asymptomatic COVID-19 cases in India
Authors: Singh Prajjval Pratap , Srivastava Abhishek K , Upadhyay Sudhir K , Singh Ashish , Gupta Pranav , Maurya Sanjeev , Upadhyay Shashank , Pandey Rudra Kumar , Srivastava Anshika , Dev Priya , Singh Vanya , Mishra Rahul , Shukla Manoj Kumar , Chaubey Govind , Kumar Pradeep , Rai Vandana , Tripathi Yamini B , Pathak Abhishek , Mishra Vijay Nath , Mallick Chandana Basu , Shrivastava Pankaj , Chaubey Gyaneshwer
Published: April 2021

The COVID-19 pandemic has resulted several waves of infection in many countries worldwide. The large variations in case fatality ratio among different geographical regions suggests that the human susceptibility against this virus varies substantially. Several studies from different parts of the world showed a significant association of ABO blood group and COVID-19 susceptibility. It was shown that individuals with blood group O are at the lower risk of coronavirus infection. To establish the association of ABO blood group in SARS-CoV-2 susceptibility, we for the first time analysed SARS-CoV-2 neutralising antibodies as well as blood groups among 509 random individuals from three major districts of Eastern Uttar Pradesh region of India.. Interestingly, we found neutralising antibodies in significantly higher percentage of people with blood group AB (0.36) followed by B (0.31), A (0.22) and lowest in people with blood group O (0.11). This indicates that people with blood group AB are at comparatively higher risk of infection than other blood groups. Further, in line to previous reports we too observed that people with blood group O have significantly decreased risk of SARS-CoV-2 infection. Thus, among the asymptomatic SARS-CoV-2 infected individuals with blood group AB has highest, whilst blood group O has lowest risk of infection.
A randomised control trial of the effects of home-based online attention training and working memory training on cognition and everyday function in a community stroke sample
Authors: Peers Polly V. , Punton Sarah F. , Murphy Fionnuala C. , Watson Peter , Bateman Andrew , Duncan John , Astle Duncan E. , Hampshire Adam , Manly Tom
Published: April 2021

Cognitive difficulties are common following stroke and can have widespread impacts on everyday functioning. Technological advances offer the possibility of individualised cognitive training for patients at home, potentially providing a low-cost, low-intensity adjunct to rehabilitation services. Using this approach, we have previously demonstrated post-training improvements in attention and everyday functioning in fronto-parietal stroke patients. Here we examine whether these benefits are observed more broadly in a community stroke sample. Patients were randomised to either 4 weeks of online adaptive attention training (SAT), working memory training (WMT) or waitlist (WL). Cognitive and everyday function measures were collected before and after intervention, and after 3months. During training, weekly measures of patients’ subjective functioning were collected. The training was well received and compliance good. No differences in standardised cognitive tests were observed for either intervention relative to controls. However, on patient reported outcomes, SAT participants showed greater levels of improvement in everyday functioning than WMT or WL participants. In line with our previous work, everyday functioning improvements were greatest for patients with spatial impairments and those who received SAT training. Whether attention training can be recommended for stroke survivors depends on whether cognitive test performance or everyday functioning is considered more relevant.
DRUL for School: Opening Pre-K with safe, simple, sensitive saliva testing for SARS-CoV-2
Authors: Frank Mayu O. , Blachere Nathalie E. , Parveen Salina , Hacisuleyman Ezgi , Fak John , Luna Joseph M. , Michailidis Eleftherios , Wright Samara , Stark Pamela , Campbell Ann , Foo Ashley , Sakmar Thomas P. , Huffman Virginia , Bergh Marissa , Goldfarb Audrey , Mansisidor Andres , Patriotis Agata L. , Palmquist Karl H. , Poulton Nicolas , Leicher Rachel , Vargas César D. M. , Duba Irene , Hurley Arlene , Colagreco Joseph , Pagane Nicole , Orange Dana E. , Mora Kevin , Rakeman Jennifer L. , Fowler Randall C. , Fernandes Helen , Lamendola-Essel Michelle F. , Didkovsky Nick , Silvera Leopolda , Masci Joseph , Allen Machelle , Rice Charles M. , Darnell Robert B.
Published: April 2021

To address the need for simple, safe, sensitive, and scalable SARS-CoV-2 tests, we validated and implemented a PCR test that uses a saliva collection kit use at home. Individuals self-collected 300 µl saliva in vials containing Darnell Rockefeller University Laboratory (DRUL) buffer and extracted RNA was assayed by RT-PCR (the DRUL saliva assay). The limit of detection was confirmed to be 1 viral copy/µl in 20 of 20 replicate extractions. Viral RNA was stable in DRUL buffer at room temperature up to seven days after sample collection, and safety studies demonstrated that DRUL buffer immediately inactivated virus at concentrations up to 2.75×106 PFU/ml. Results from SARS-CoV-2 positive nasopharyngeal (NP) swab samples collected in viral transport media and assayed with a standard FDA Emergency Use Authorization (EUA) test were highly correlated with samples placed in DRUL buffer. Direct comparison of results from 162 individuals tested by FDA EUA oropharyngeal (OP) or NP swabs with co-collected saliva samples identified four otherwise unidentified positive cases in DRUL buffer. Over six months, we collected 3,724 samples from individuals ranging from 3 months to 92 years of age. This included collecting weekly samples over 10 weeks from teachers, children, and parents from a pre-school program, which allowed its safe reopening while at-risk pods were quarantined. In sum, we validated a simple, sensitive, stable, and safe PCR-based test using a self-collected saliva sample as a valuable tool for clinical diagnosis and screening at workplaces and schools.
An ecological niche model to predict the geographic distribution of Haemagogus janthinomys, Dyar, 1921 the yellow fever and Mayaro virus vector, in South America
Authors: Celone Michael , Pecor David , Potter Alexander , Richardson Alec , Dunford James , Pollet Simon
Published: April 2021

Yellow fever virus (YFV) has a long history of impacting human health in South America. Mayaro virus (MAYV) is an emerging arbovirus of public health concern in the Neotropics and its full impact is yet unknown. Both YFV and MAYV are primarily maintained via a sylvatic transmission cycle but can be opportunistically transmitted to humans by the bites of infected forest dwelling Haemagogus janthinomys Dyar, 1921. To better understand the potential risk of YFV and MAYV transmission to humans, a more detailed understanding of this vector species’ distribution is critical. This study compiled a comprehensive database of 170 unique Hg. janthinomys collection sites retrieved from the published literature, digitized museum specimens and publicly accessible mosquito surveillance data. Covariate analysis was performed to optimize a selection of environmental (topographic and bioclimatic) variables associated with predicting habitat suitability, and species distributions modelled across South America using a maximum entropy (MaxEnt) approach. Our results indicate that suitable habitat for Hg. janthinomys can be found across forested regions of South America including the Atlantic forests and interior Amazon.

Author Summary

Mayaro virus is a neglected tropical disease and there is insufficient evidence to define its geographic range. The mosquito Haemagogus janthinomys is a primary vector of Mayaro and its distribution is largely unknown at a sub-country scale. Building compendiums of collection data and creating ecological niche models provides a more precise estimation vector species potential habitat. Our dataset stands as one of the most expansive existing for collection data of this species combining data published in literature, publicly available data repositories and digitized museum specimen records. Comparing results of niche models with near real time environmental data can give even better predictions of areas where Mayaro virus exposure could occur. The methods and results of this study can be replicated for any disease/vector of interest so long as there is data discoverable through the scientific literature, public repositories, or other civilian and governmental agencies willing to share.
Feedback-related potentials and oscillations during trial and error learning in Parkinson’s disease
Authors: Viñales Laura , Procyk Emmanuel , Quilodran René
Published: April 2021

Electrophysiological markers of performance monitoring are thought to reflect functioning of dedicated neural networks and neuromodulatory systems. Whether and how these markers are altered in neurological diseases and whether they can reflect particular cognitive deficits remains to be confirmed. Here we first tested whether the frontal medial feedback-related potential, evoked during a trial and error learning task, is changed in early Parkinson’s disease patients compared to control subjects. The potential was not changed in amplitude and discriminated negative and positive feedback as in controls. Feedback-related markers in Parkinson’s patients also appeared in time-frequency analyses, unaltered in theta (3-7 Hz) band but reduced in beta (20-30 Hz) oscillations for positive feedback. Beta oscillations power appeared to be dramatically globally reduced during the task. Overall, our results show that Beta oscillation markers of performance monitoring captured by EEG are selectively altered in Parkinson’s disease patients, and that they are accompanied by changes in task-related oscillatory dynamics.

Significance Statement

Frontal neural activity evoked by outcomes reveal the functioning of neural systems devoted to flexible behaviours. Modulations of such activity in Parkinson’s disease (PD) patients could reflect specific alterations of neural systems and cognitive processing. The goal is to evaluate whether such activity can serve as markers of the disease. Here, using EEG and a trial and error learning protocol, we show that mid-frontal midline performance feedback-related potentials for different types of feedback were similar in controls and early diagnosed PD patients. However, task-related oscillations revealed alterations in the beta range accompanied by more global beta activity alteration in PD compared to controls subjects. This study provides data relevant to the search for non-motor biomarkers in early stages of PD.
Large-Scale Deep Multi-Layer Analysis of Alzheimer’s Disease Brain Reveals Strong Proteomic Disease-Related Changes Not Observed at the RNA Level
Authors: Johnson Erik C.B. , Carter E. Kathleen , Dammer Eric B. , Duong Duc M. , Gerasimov Ekaterina S. , Liu Yue , Liu Jiaqi , Betarbet Ranjita , Ping Lingyan , Yin Luming , Serrano Geidy E. , Beach Thomas G. , Peng Junmin , De Jager Philip L. , Haroutunian Vahram , Zhang Bin , Gaiteri Chris , Bennett David A. , Gearing Marla , Wingo Thomas S. , Wingo Aliza P. , Lah James J. , Levey Allan I. , Seyfried Nicholas T.
Published: April 2021

The biological processes that are disrupted in the Alzheimer’s disease (AD) brain remain incompletely understood. We recently performed a proteomic analysis of >2000 brains to better understand these changes, which highlighted alterations in astrocytes and microglia as likely key drivers of disease. Here, we extend this analysis by analyzing >1000 brain tissues using a tandem mass tag mass spectrometry (TMT-MS) pipeline, which allowed us to nearly triple the number of quantified proteins across cases. A consensus protein co-expression network analysis of this deeper dataset revealed new co-expression modules that were highly preserved across cohorts and brain regions, and strongly altered in AD. Nearly half of the protein co-expression modules, including modules significantly altered in AD, were not observed in RNA networks from the same cohorts and brain regions, highlighting the proteopathic nature of AD. Two such AD-associated modules unique to the proteomic network included a module related to MAPK signaling and metabolism, and a module related to the matrisome. Analysis of paired genomic and proteomic data within subjects showed that expression level of the matrisome module was influenced by theAPOE ε4allele, but was not related to the rate of cognitive decline after adjustment for neuropathology. In contrast, the MAPK/metabolism module was strongly associated with the rate of cognitive decline. Disease-associated modules unique to the proteome are sources of promising therapeutic targets and biomarkers for AD.
Inversions maintain differences between migratory phenotypes of a songbird
Authors: Lundberg Max , Mackintosh Alexander , Petri Anna , Bensch Staffan
Published: April 2021

Long-distance migration requires adaptations in a suite of behavioral, physiological and morphological traits. However, almost nothing is known about the genetic basis of these adaptations. The willow warblerPhylloscopus trochilusoccurs in Europe with a northern and southern subspecies that show drastically different migration routes and wintering areas. Previous studies have demonstrated that the subspecies are genetically extremely similar except for three divergent chromosome regions, of which two are associated with the differences in migratory phenotypes and one is associated with an environmental gradient. Here we use a combination of long-read sequencing, linked-read sequencing and optical mapping to construct more complete and contiguous assemblies for both of the subspecies. We find evidence for inversions in each of the three divergent regions, which range from 0.4 to 13 Mb in size, and that breakpoints are associated with tandem repeat arrays or segmental duplications. The divergence times between inverted and non-inverted haplotypes are similar across the regions (∼1.2 Myrs), which is compatible with a scenario where the inversions arose in either of two allopatric populations that subsequently hybridized. The improved genome assemblies and annotation also allowed us to detect additional functional differences in the divergent regions that provide candidate genes for migration and local adaptations to environmental gradients.
Introducing conflict resolution and negotiation training into a biomedical sciences graduate curriculum
Authors: Schaller Michael D. , Gatesman-Ammer Amanda
Published: April 2021

Analysis of the biomedical workforce and graduate education have produced recommendations for modifications of pre-doctoral training to broadly prepare trainees for wider ranging scientific careers. Increased exposure to career opportunities and development of training in professional skills is widely recommended, but details of implementation are not widely available. In alignment with these recommendations, we have incorporated professional skills training into the biomedical science graduate curriculum at West Virginia University. An important component of the training is developing conflict resolution and negotiation skills. This training will provide useful skills for academic careers, non-academic careers and life situations outside of the workplace. Conflict resolution/negotiation skills are also relevant in managing issues in diversity, equity and inclusivity. We report our experience in developing this component of the training program, provide an overview of the approach to delivery and practice of skills, and provide an analysis of the reception and effectiveness of the training.
GNPS Dashboard: Collaborative Analysis of Mass Spectrometry Data in the Web Browser
Authors: Petras Daniel , Phelan Vanessa V. , Acharya Deepa , Allen Andrew E. , Aron Allegra T. , Bandeira Nuno , Bowen Benjamin P. , Belle-Oudry Deirdre , Boecker Simon , Cummings Dale A. , Deutsch Jessica M , Fahy Eoin , Garg Neha , Gregor Rachel , Handelsman Jo , Navarro-Hoyos Mirtha , Jarmusch Alan K. , Jarmusch Scott A. , Louie Katherine , Maloney Katherine N. , Marty Michael T. , Meijler Michael M. , Mizrahi Itzhak , Neve Rachel L , Northen Trent R. , Molina-Santiago Carlos , Panitchpakdi Morgan , Pullman Benjamin , Puri Aaron W. , Schmid Robin , Subramaniam Shankar , Thukral Monica , Vasquez-Castro Felipe , Dorrestein Pieter C , Wang Mingxun
Published: April 2021

Access to web-based platforms has enabled scientists to perform research remotely. A critical aspect of mass spectrometry data analysis is the inspection, analysis, and visualization of the raw data to validate data quality and confirm statistical observations. We developed the GNPS Dashboard, a web-based data visualization tool, to facilitate synchronous collaborative inspection, visualization, and analysis of private and public mass spectrometry data remotely.
Multi-Scale Coarse Grained Model for the Stepping of Molecular Motors with application to Kinesin
Authors: Goldtzvik Yonathan , Thirumalai D.
Published: April 2021

Conventional kinesin, a motor protein that transports cargo within cells, walks by taking multiple steps towards the plus end of the microtubule (MT). While significant progress has been made in understanding the details of the walking mechanism of kinesin there are many unresolved issues. From a computational perspective, a central challenge is the large size of the system, which limits the scope of time scales accessible in standard computer simulations. Here, we create a general multi-scale coarse-grained model for motors that enables us to simulate the stepping process of motors on polar tracks (actin and MT) with focus on kinesin. Our approach greatly shortens the computation times without a significant loss in detail, thus allowing us to better describe the molecular basis of the stepping kinetics. The small number of parameters, which are determined by fitting to experimental data, allows us to develop an accurate method that may be adopted to simulate stepping in other molecular motors. The model enables us to simulate a large number of steps, which was not possible previously. We show in agreement with experiments that due to the docking of the neck linker (NL) of kinesin, sometimes deemed as the power stroke, the space explored diffusively by the tethered head is severely restricted allowing the step to be in a tens of microseconds. We predict that increasing the interaction strength between the NL and the motor head, achievable by mutations in the NL, decreases the stepping time but reaches a saturation value. Furthermore, the full 3-dimensional dynamics of the cargo are fully resolved in our model, contributing to the predictive power and allowing us to study the important aspects of cargo-motor interactions.
SARS-CoV-2 Vaccines Elicit Durable Immune Responses in Infant Rhesus Macaques
Authors: Garrido Carolina , Curtis Alan D. , Dennis Maria , Pathak Sachi H. , Gao Hongmei , Montefiori David , Tomai Mark , Fox Christopher B. , Kozlowski Pamela A. , Scobey Trevor , Munt Jennifer E. , Mallroy Michael L. , Saha Pooja T. , Hudgens Michael G. , Lindesmith Lisa C. , Baric Ralph S. , Abiona Olubukola M. , Graham Barney , Corbett Kizzmekia S. , Edwards Darin , Carfi Andrea , Fouda Genevieve , Van Rompay Koen K. A. , De Paris Kristina , Permar Sallie R.
Published: April 2021

Early life SARS-CoV-2 vaccination has the potential to provide lifelong protection and achieve herd immunity. To evaluate SARS-CoV-2 infant vaccination, we immunized two groups of 8 infant rhesus macaques (RMs) at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein, either encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or mixed with 3M-052-SE, a TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. High magnitude S-binding IgG and neutralizing infectious dose 50 (ID50) >103were elicited by both vaccines. S-specific T cell responses were dominated by IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines are promising pediatric SARS-CoV-2 vaccine candidates to achieve durable protective immunity.

One-Sentence Summary

SARS-CoV-2 vaccines are well-tolerated and highly immunogenic in infant rhesus macaques
CRISPRpas: Programmable regulation of alternative polyadenylation by dCas9
Authors: Shin Jihae , Ding Qingbao , Baljinnyam Erdene , Wang Ruijia , Tian Bin
Published: April 2021

Well over half of human mRNA genes produce alternative polyadenylation (APA) isoforms that differ in mRNA metabolism due to 3’ UTR size changes or have variable coding potentials when coupled with alternative splicing. Aberrant APA is implicated in a growing number of human diseases. A programmable tool for APA regulation, hence, would be instrumental for understanding how APA events impact biological processes. Here, using a catalytically dead Cas9 (dCas9), we developed a method, named CRISPRpas, to alter cleavage and polyadenylation site (PAS) usage in 3’ UTRs or introns. We present key features that facilitate CRISPRpas, including targeting DNA strand, distance between PAS and targeting sequence, and strength of the PAS. For intronic PAS, we additionally analyze strengths of 5’ splice site and target location in intron. Our analyses implicate a dynamic competition between PAS usage and nascent RNA decay when RNA polymerase II elongation is blocked. We show modulation of APA of multiple endogenous genes including a gene that contains a single nucleotide polymorphism (SNP) that affects APA in the human population. CRISPRpas expands the CRISPR toolkit for perturbation of gene expression.
Joint representation of working memory and uncertainty in human cortex
Authors: Li Hsin-Hung , Sprague Thomas C. , Yoo Aspen H. , Ma Wei Ji , Curtis Clayton E.
Published: April 2021

Neural representations of visual working memory (VWM) are noisy, and thus, decisions based on VWM are inevitably subject to uncertainty. However, the mechanisms by which the brain simultaneously represents the content and uncertainty of memory remain largely unknown. Here, inspired by the theory of probabilistic population codes, we test the hypothesis that the human brain represents an item maintained in VWM as a probability distribution over stimulus feature space, thereby capturing both its content and uncertainty. We used a neural generative model to decode probability distributions over memorized locations from fMRI activation patterns. We found that the mean of the probability distribution decoded from retinotopic cortical areas predicted memory reports on a trial-by-trial basis. Moreover, in several of the same mid-dorsal stream areas the spread of the distribution predicted subjective trial-by-trial uncertainty judgments. These results provide evidence that VWM content and uncertainty are jointly represented by probabilistic neural codes.