bluuebunny/crossref_metadata_2025 huggingface dataset:
Remission in SLE—do DORIS criteria match the treating physician’s judgment? A cross-sectional study to assess reasons for discordance
Authors: Mucke Johanna , Düsing Christina , Klose Nora , Schneider Matthias , Chehab Gamal
Published: January 2021

Objectives

The definition of an accurate target for a treat-to-target approach in SLE has been challenging over past years, and recently the DORIS definitions of remission were presented by the international DORIS task force. It was our aim to assess the frequency of DORIS remission and LLDAS in our SLE cohort and their agreement with the treating physician’s (DORIS-) independent remission judgement. Patient characteristics leading to lack of agreement and incoherence ought to be identified.

Methods

In this monocentric cross-sectional study, patients with SLE were enrolled and assessed between September 2016 and December 2017. DORIS remission definitions were applied and after the clinical consultation, the treating physicians gave his/her opinion on whether the patient was in remission. Regression analyses were performed to identify parameters influencing physician remission.

Results

A total of 233 patients were included (87.6% female); 99 (42.5%) patients fulfilled any of the four DORIS remission definitions, while 126 patients were in remission according to their physician’s judgement. We observed discordance in the assessment of remission in 53 patients (22.7%). Physician remission was influenced by disease activity [odds ratio (OR) 0.76, 95% CI: 0.63, 0.90], disease and/or treatment-related damage (OR 0.78, 95% CI: 0.62, 0.98) and the presence of ds-DNA antibodies (OR 2.47, 95% CI: 1.06, 6.04).

Conclusions

DORIS remission proved an achievable target in our outpatient clinic. Still we found discordance regarding DORIS remission and the treating physician’s judgement with a greater number of patients considered in remission by their physicians.
Meta-analysis of latent tuberculosis in healthcare workers in Iran: a retrospective review
Authors: Sepehri NazaninZahra , Saghanezhad Seyed Mohammad , Khoddami Farshad , Arasteh Amin , Delirakbariazar Marziyeh , Khaledi Azad
Published: January 2021

Background

Here we review the status of latent tuberculosis (LTB) in Iranian healthcare workers (HCWs).

Methods

A literature search was conducted using keywords according to the Preferred Reporting Items for Systematic Review and Meta-Analyses instructions. Cross-sectional studies published from 1 January 2000 through 1 January 2019 were retrieved. Meta-analysis was performed using Comprehensive Meta-Analysis software using the random effects model, Cochran's Q and I2 tests. Publication bias was estimated by funnel plot and Egger's linear regression test.

Results

Among 774 articles retrieved in the primary literature search, 21 studies met the eligibility criteria. No publication bias was observed among the included studies (p=0.07). The prevalence of LTB ranged from 7% to 63% in Iranian HCWs from different geographical areas. The overall combined prevalence of LTB among Iranian HCWs was 30.9% (95% confidence interval 24.2 to 38.5). Also, 52.4% of the included studies showed a significant correlation between occupation and LTB incidence (p<0.05).

Conclusions

The prevalence of LTB was high among Iranian HCWs. This requires developing comprehensive information databases and surveillance systems for detecting LTB among HCWs. It is also essential to periodically screen for LTB in HCWs to provide a timely diagnosis of the infection. It is recommended to perform a tuberculin skin test, a useful tool for screening and treatment of LTB, on an annual basis in HCWs.
A review of models applied to the geographic spread of Zika virus
Authors: Li Sabrina L , Messina Jane P , Pybus Oliver G , Kraemer Moritz U G , Gardner Lauren
Published: January 2021

In recent years, Zika virus (ZIKV) has expanded its geographic range and in 2015–2016 caused a substantial epidemic linked to a surge in developmental and neurological complications in newborns. Mathematical models are powerful tools for assessing ZIKV spread and can reveal important information for preventing future outbreaks. We reviewed the literature and retrieved modelling studies that were developed to understand the spatial epidemiology of ZIKV spread and risk. We classified studies by type, scale, aim and applications and discussed their characteristics, strengths and limitations. We examined the main objectives of these models and evaluated the effectiveness of integrating epidemiological and phylogeographic data, along with socioenvironmental risk factors that are known to contribute to vector–human transmission. We also assessed the promising application of human mobility data as a real-time indicator of ZIKV spread. Lastly, we summarised model validation methods used in studies to ensure accuracy in models and modelled outcomes. Models are helpful for understanding ZIKV spread and their characteristics should be carefully considered when developing future modelling studies to improve arbovirus surveillance.
Reassessing species demarcation criteria in viroid taxonomy by pairwise identity matrices
Authors: Chiumenti Michela , Navarro Beatriz , Candresse Thierry , Flores Ricardo , Di Serio Francesco
Published: January 2021

With a small, circular and non-protein coding RNA genome, viroids are the smallest infectious agents. They invade plants, which in turn may develop symptoms. Since their discovery about 50 years ago, more than thirty viroids have been reported and classified using as species demarcation less than 90 per cent sequence identity on the overall genome and evidence of biological divergence with respect to the closest related viroids. In the last few years, new viroids have been identified that infect latently their (frequently) woody hosts and have a narrow experimental hosts range, complicating and slowing down studies on their biology. As a consequence, several viroids are still waiting for classification. Moreover, the number of new viroids is expected to increase in the next years due to the use of high-throughput sequencing technologies with diagnostics purposes. Therefore, establishment of reliable species demarcation criteria mainly based on molecular features of viroids is needed. Here, viroid classification is reassessed and a scheme based on pairwise sequence identity matrices is developed. After identifying a threshold pairwise identity score (PWIS) for each viroid genus, to be used as a species demarcation criterion, we show that most of those yet unclassified viroids can be assigned to a known or to a new species, thus limiting the need for additional biological evidence to only a few more complex situations. The advantages of this PWIS-based method are that the proposed identity thresholds for species demarcations are not arbitrarily established and evidence for biological divergence is not mandatory. Importantly, the current classification is not essentially modified. A protocol for a tentative fast classification of new viroids according to the proposed approach is also provided.
Prioritization of putatively detrimental variants in euploid miscarriages
Authors: Buonaiuto Silvia , Di Biase Immacolata , Aleotti Valentina , Ravaei Amin , Marino Adriano De , Damaggio Gianluca , Chierici Marco , Pulijala Madhuri , D’Ambrosio Palmira , Esposito Gabriella , Ayub Qasim , Furlanello Cesare , Greco Pantaleo , Capalbo Antonio , Rubini Michele , Biase Sebastiano Di , Colonna Vincenza
Published: January 2021

Miscarriage is the spontaneous termination of a pregnancy before 24 weeks of gestation. We studied the genome of euploid miscarried embryos from mothers in the range of healthy adult individuals to understand genetic susceptibility to miscarriage not caused by chromosomal aneuploidies. We developed GP, a pipeline that we used to prioritize 439 unique variants in 399 genes, including genes known to be associated with miscarriages. Among the prioritized genes we found STAG2 coding for the cohesin complex subunit, for which inactivation in mouse is lethal, and TLE4 a target of Notch and Wnt, physically interacting with a region on chromosome 9 associated to miscarriages.
Zorro versus Covid-19: fighting the pandemic with face masks
Authors: Damette Olivier
Published: January 2021

To confront the global Covid-19 pandemic and reduce the spread of the virus, we need to better understand if face mask use is effective to contain the outbreak and investigate the potential drivers in favor of mask adoption. It is highly questionable since there is no consensus among the general public despite official recommendations. For the first time, we conduct a panel econometric exercise to assess the dynamic impact of face mask use on both infected cases and fatalities at a global scale. We reveal a negative impact of mask wearing on fatality rates and on the Covid-19 number of infected cases. The delay of action varies from around 7 days to 28 days concerning infected cases but is more longer concerning fatalities. We also document the increasing adoption of mask use over time. We find that population density and pollution levels are significant determinants of heterogeneity regarding mask adoption across countries, while altruism, trust in government and demographics are not. Surprisingly, government effectiveness and income level (GDP) have an unexpected influence. However, strict government policies against Covid-19 have the most significant effect on mask use. Therefore, the most effective way of increasing the level of mask wearing is to enforce strict laws on the wearing of masks.
Landscapes and bacterial signatures of mucosa-associated intestinal microbiota in Chilean and Spanish patients with inflammatory bowel disease
Authors: Chamorro Nayaret , Montero David A. , Gallardo Pablo , Farfán Mauricio , Contreras Mauricio , De la Fuente Marjorie , Dubois Karen , Hermoso Marcela A. , Quera Rodrigo , Pizarro-Guajardo Marjorie , Paredes-Sabja Daniel , Ginard Daniel , Rosselló-Móra Ramon , Vidal Roberto
Published: January 2021

Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn’s disease (CD), cause chronic inflammation of the gut, affecting millions of people worldwide. IBD have been frequently associated with an alteration of the gut microbiota, termed dysbiosis, which is generally characterized by an increase in abundance of Proteobacteria such as Escherichia coli, and a decrease in abundance of Firmicutes such as Faecalibacterium prausnitzii (an indicator of a healthy colonic microbiota). The mechanisms behind the development of the IBD and the dysbiosis are incompletely understood. Using samples from colonic biopsies, we studied the mucosa-associated intestinal microbiota in Chilean and Spanish patients with IBD. In agreement with previous studies, microbiome comparison between IBD patients and non-IBD controls indicated that dysbiosis in these patients is characterized by an increase of pro-inflammatory bacteria (mostly Proteobacteria) and a decrease of commensal beneficial bacteria (mostly Firmicutes). Notably, bacteria typically residing on the mucosa of healthy individuals were mostly obligate anaerobes, whereas in the inflamed mucosa an increase of facultative anaerobe and aerobic bacteria was observed. We also identify potential co-occurring and mutually exclusive interactions between bacteria associated with the healthy and inflamed mucosa, which appear to be determined by the oxygen availability and the type of respiration. Finally, we identify a panel of bacterial biomarkers that allow the discrimination between eubiosis from dysbiosis with a high diagnostic performance (96% accurately), which could be used for the development of non-invasive diagnostic methods. Thus, this study is a step forward toward understanding the landscapes and alterations of mucosa-associated intestinal microbiota in patients with IBD.
Quality Control Metrics for Whole Blood Transcriptome Analysis in the Parkinson’s Progression Markers Initiative (PPMI)
Authors: Hutchins Elizabeth , Craig David , Violich Ivo , Alsop Eric , Casey Bradford , Hutten Samantha , Reimer Alyssa , Whitsett Timothy G. , Crawford Karen L. , Toga Arthur W , Levy Shawn , Robinson Madison , Prasad Nripesh , Gibbs J. Raphael , Cookson Mark R. , Van Keuren-Jensen Kendall ,   Parkinson Progression Marker Initiative
Published: January 2021

The Michael J. Fox Foundation’s Parkinson’s Progression Markers Initiative (PPMI) is an observational study to comprehensively evaluate Parkinson’s disease (PD) patients using imaging, biologic sampling, clinical and behavioural assessments to identify biomarkers of PD progression. As part of this study, we obtained 4,756 whole blood samples from 1,570 subjects at baseline, 0.5, 1, 2, and 3 years from enrollment in the study. We isolated RNA and performed whole transcriptome sequencing in this longitudinal cohort. Here, we describe and quantify technical variability associated with this dataset through the use of pooled reference samples, including plate distribution, RNA quality, and outliers. This large, uniformly processed dataset is available to researchers at https://www.ppmi-info.org.
A New Sensory Skill Shows Automaticity and Integration Features in Multisensory Interactions
Authors: Negen James , Bird Laura-Ashleigh , Slater Heather , Thaler Lore , Nardini Marko
Published: January 2021

People can learn new sensory skills that augment their perception, such as human echolocation. However, it is not clear to what extent these can become an integral part of the perceptual repertoire. Can they show automatic use, integrated with the other senses, or do they remain cognitively-demanding, cumbersome, and separate? Here, participants learned to judge distance using an echo-like auditory cue. We show that use of this new skill met three key criteria for automaticity and sensory integration: (1) enhancing the speed of perceptual decisions; (2) processing through a non-verbal route and (3) integration with vision in an efficient, Bayes-like manner. We also show some limits following short training: integration was less-than-optimal, and there was no mandatory fusion of signals. These results demonstrate key ways in which new sensory skills can become automatic and integrated, and suggest that sensory augmentation systems may have benefits beyond current applications for sensory loss.
Heat shock protein gene expression is higher and more variable with thermal stress and mutation accumulation inDaphnia
Authors: Scheffer Henry , Coate Jeremy , Ho Eddie K. H. , Schaack Sarah
Published: January 2021

Understanding the genetic architecture of the stress response and its ability to evolve in response to different stressors requires an integrative approach. Here we quantify gene expression changes in response to two stressors associated with global climate change and habitat loss—heat shock and mutation accumulation. We measure expression levels for two Heat Shock Proteins (HSP90 and HSP60)—members of an important family of conserved molecular chaperones that have been shown to play numerous roles in the cell. While HSP90 assists with protein folding, stabilization, and degradation throughout the cell, HSP60 primarily localizes to the mitochondria and mediatesde novofolding and stress-induced refolding of proteins. We perform these assays inDaphnia magnaoriginally collected from multiple genotypes and populations along a latitudinal gradient, which differ in their annual mean, maximum, and range of temperatures. We find significant differences in overall expression between loci (10-fold), in response to thermal stress (~6x increase) and with mutation accumulation (~4x increase). Importantly, stressors interact synergistically to increase gene expression levels when more than one is applied (increasing, on average, >20x). While there is no evidence for differences among the three populations assayed, individual genotypes vary considerably in HSP90 expression. Overall, our results support previous proposals that HSP90 may act as an important buffer against not only heat, but also mutation, and expands this hypothesis to include another member of the gene family acting in a different domain of the cell.
Genomic mating in outbred species: predicting cross usefulness with additive and total genetic covariance matrices
Authors: Wolfe Marnin D. , Chan Ariel W. , Kulakow Peter , Rabbi Ismail , Jannink Jean--Luc
Published: January 2021

Diverse crops are both outbred and clonally propagated. Breeders typically use truncation selection of parents and invest significant time, land and money evaluating the progeny of crosses to find exceptional genotypes. We developed and tested genomicmateselection criteria suitable for organisms of arbitrary homozygosity level where the full-sibling progeny are of direct interest as future parents and/or cultivars. We extended cross variance and covariance variance prediction to include dominance effects and predicted the multivariate selection index genetic variance of crosses based on haplotypes of proposed parents, marker effects and recombination frequencies. We combined the predicted mean and variance into usefulness criteria for parent and variety development. We present an empirical study of cassava (Manihot esculenta), a staple tropical root crop. We assessed the potential to predict the multivariate genetic distribution (means, variances and trait covariances) of 462 cassava families in terms of additive and total value using cross-validation. We were able to predict all genetic variances and most covariances with non-zero accuracy. We also tested a directional dominance model and found significant inbreeding depression for most traits and a boost in total merit accuracy for root yield. We predicted 47,083 possible crosses of 306 parents and contrasted them to those previously tested to show how mate selection can reveal new potential within the germplasm. We enable breeders to consider the potential of crosses to produce future parents (progeny with excellent breeding values) and varieties (progeny with top performance).

Author Summary

Breeders typically use truncation selection and invest significant resources evaluating progeny to find exceptional genotypes. We extended genetic variance and trait covariance prediction to include dominance and predicting the multivariate selection index variance. We enable mate selection based on potential to produce future parents (progeny with excellent breeding values) and/or varieties (progeny with top performance). Using cross-validation, we demonstrate that genetic variances and covariances can be predicted with non-zero accuracy in cassava, a staple tropical root crop.
Rhizoliths identified as prehistoric filing tools for fishhook production on San Nicolas Island, California
Authors: Wärmländer Sebastian K.T.S. , Smith Kevin N. , Vellanoweth René L. , Moritz Ryan , Jansson Kjell , Gooding Tim , Kendig William E. , Sholts Sabrina B.
Published: January 2021

Chemical analysis of archeological objects can provide important clues about their purpose and function. In this study, we used scanning electron microscopy (SEM) and chemical spectroscopy (SEM-EDS and XRD) to identify a white residue present on cylindrical rhizoliths from a component at an archaeological site (CA-SNI-25) on San Nicolas Island, California, dated ca. AD 1300 to 1700. The residue was found to consist of biogenic calcite and aragonite particles, different in composition and morphology from the CaCO3 particles in the rhizoliths, but identical to marine shell material. These results, together with observations of surface micro-wear patterning on fishhooks and rhizoliths, replicative experiments,insitu spatial analysis, and other archaeological evidence, show that rhizoliths were used as files in a larger tool kit for crafting shell fishhooks. Our findings shed new light on the technological innovations devised by Native Americans to exploit the rich marine resources surrounding the Channel Islands, and provide the first analytical evidence for the use of rhizoliths as a production tool.
White Matter Alterations in Young Children with Prenatal Alcohol Exposure
Authors: Kar Preeti , Reynolds Jess E. , Grohs Melody N. , Gibbard W. Ben , McMorris Carly , Tortorelli Christina , Lebel Catherine
Published: January 2021

Prenatal alcohol exposure (PAE) can lead to cognitive, behavioural, and social-emotional challenges. Previous neuroimaging research has identified alterations to brain structure in newborns, older children, adolescents, and adults with PAE; however, little is known about brain structure in young children. Extensive brain development takes place during early childhood; therefore, understanding the neurological profiles of young children with PAE is critical for early identification and effective intervention. We studied 54 children (5.21±1.11 years; 27 males) with confirmed PAE compared to 54 age- and sex-matched children without PAE. Children underwent diffusion tensor imaging between 2 and 7 years of age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were obtained for 10 major white matter tracts, along with tract volume, axial and radial diffusivity (AD, RD). A univariate analysis of covariance was conducted to test for group differences (PAE vs. control) controlling for age, sex and tract volume. Our results reveal white matter microstructural differences between young children with PAE and unexposed controls. The PAE group had higher FA and/or lower MD (as well as lower AD and RD) in the genu and the body of the corpus callosum, as well as the bilateral uncinate fasciculus and pyramidal tracts. Our findings align with studies of newborns with PAE finding lower AD, but contrast those in older populations with PAE, which consistently report lower FA and higher MD. These findings may reflect premature development of white matter that may then plateau too early, leading to the lower FA/higher MD observed at older ages.
eDNA in a bottleneck: obstacles to fish metabarcoding studies in megadiverse freshwater systems
Authors: Jackman Jake M. , Benvenuto Chiara , Coscia Ilaria , Carvalho Cintia Oliveira , Ready Jonathan S. , Boubli Jean P. , Magnusson William E. , McDevitt Allan D. , Sales Naiara Guimarães
Published: January 2021

The current capacity of environmental DNA (eDNA) to provide accurate insights into the biodiversity of megadiverse regions (e.g., the Neotropics) requires further evaluation to ensure its reliability for long-term monitoring. In this study, we first evaluated the taxonomic resolution capabilities of a short fragment from the 12S rRNA gene widely used in fish eDNA metabarcoding studies, and then compared eDNA metabarcoding data from water samples with traditional sampling using nets. For the taxonomic discriminatory power analysis, we used a specifically curated reference dataset consisting of 373 sequences from 264 neotropical fish species (including 47 newly generated sequences) to perform a genetic distance-based analysis of the amplicons targeted by the MiFish primer set. We obtained an optimum delimitation threshold value of 0.5% due to lowest cumulative errors. The barcoding gap analysis revealed only a 50.38% success rate in species recovery (133/264), highlighting a poor taxonomic resolution from the targeted amplicon. To evaluate the empirical performance of this amplicon for biomonitoring, we assessed fish biodiversity using eDNA metabarcoding from water samples collected from the Amazon (Adolpho Ducke Forest Reserve and two additional locations outside the Reserve). From a total of 84 identified Molecular Operational Taxonomic Units (MOTUs), only four could be assigned to species level using a fixed threshold. Measures of α-diversity analyses within the Reserve showed similar patterns in each site between the number of MOTUs (eDNA dataset) and species (netting data) found. However, β-diversity revealed contrasting patterns between the methods. We therefore suggest that a new approach is needed, underpinned by sound taxonomic knowledge, and a more thorough evaluation of better molecular identification procedures such as multi-marker metabarcoding approaches and tailor-made (i.e., order-specific) taxonomic delimitation thresholds.
A Unifying Bayesian Framework for Merging X-ray Diffraction Data
Authors: Dalton Kevin M. , Greisman Jack B. , Hekstra Doeke R.
Published: January 2021

Abstract

Novel X-ray methods are transforming the study of the functional dynamics of biomolecules. Key to this revolution is detection of often subtle conformational changes from diffraction data. Diffraction data contain patterns of bright spots known as reflections. To compute the electron density of a molecule, the intensity of each reflection must be estimated, and redundant observations reduced to consensus intensities. Systematic effects, however, lead to the measurement of equivalent reflections on different scales, corrupting observation of changes in electron density. Here, we present a modern Bayesian solution to this problem, which uses deep learning and variational inference to simultaneously rescale and merge reflection observations. We successfully apply this method to monochromatic and polychromatic single-crystal diffraction data, as well as serial femtosecond crystallography data. We find that this approach is applicable to the analysis of many types of diffraction experiments, while accurately and sensitively detecting subtle dynamics and anomalous scattering.
Explaining Deep Neural Networks for Knowledge Discovery in Electrocardiogram Analysis
Authors: Hicks Steven A. , Isaksen Jonas L. , Thambawita Vajira , Ghouse Jonas , Ahlberg Gustav , Linneberg Allan , Grarup Niels , Strümke Inga , Ellervik Christina , Olesen Morten Salling , Hansen Torben , Graff Claus , Holstein-Rathlou Niels-Henrik , Halvorsen Pål , Maleckar Mary M. , Riegler Michael A. , Kanters Jørgen K.
Published: January 2021

Deep learning-based tools may annotate and interpret medical tests more quickly, consistently, and accurately than medical doctors. However, as medical doctors remain ultimately responsible for clinical decision-making, any deep learning-based prediction must necessarily be accompanied by an explanation that can be interpreted by a human. In this study, we present an approach, called ECGradCAM, which uses attention maps to explain the reasoning behind AI decision-making and how interpreting these explanations can be used to discover new medical knowledge. Attention maps are visualizations of how a deep learning network makes, which may be used in the clinic to aid diagnosis, and in research to identify novel features and characteristics of diagnostic medical tests. Here, we showcase the use of ECGradCAM attention maps using a novel deep learning model capable of measuring both amplitudes and intervals in 12-lead electrocardiograms.
Impact of B.1.1.7 variant mutations on antibody recognition of linear SARS-CoV-2 epitopes
Authors: Haynes Winston A. , Kamath Kathy , Lucas Carolina , Shon John , Iwasaki Akiko
Published: January 2021

In 579 COVID patients’ samples collected between March and July of 2020, we examined the effects of non-synonymous mutations harbored by the circulating B.1.1.7 strain on linear antibody epitope signal for spike glycoprotein and nucleoprotein. At the antigen level, the mutations only substantially reduced signal in 0.5% of the population. Although some epitope mutations reduce measured signal in up to 6% of the population, these are not the dominant epitopes for their antigens. Given dominant epitope patterns observed, our data suggest that the mutations would not result in immune evasion of linear epitopes for a large majority of these COVID patients.
SARS-CoV-2 patient self-testing with an antigen-detecting rapid test: a head-to-head comparison with professional testing
Authors: Lindner Andreas K. , Nikolai Olga , Rohardt Chiara , Kausch Franka , Wintel Mia , Gertler Maximilian , Burock Susen , Hörig Merle , Bernhard Julian , Tobian Frank , Gaeddert Mary , Lainati Federica , Corman Victor M. , Jones Terry C. , Sacks Jilian A. , Seybold Joachim , Denkinger Claudia M. , Mockenhaupt Frank P.
Published: January 2021

Background

Antigen-detecting rapid diagnostic tests (Ag-RDTs) have been widely recommended as a complement to RT-PCR. Considering the possibility of nasal self-sampling and the ease-of-use in performing the test, self-testing may be an option.

Methods and Findings

We performed a manufacturer-independent, prospective diagnostic accuracy study of nasal mid-turbinate self-sampling and self-testing when using a WHO-listed SARS-CoV-2 Ag-RDT. Symptomatic participants suspected to have COVID-19 received written and illustrated instructions. Procedures were observed without intervention. For comparison, Ag-RDTs with nasopharyngeal sampling were professionally performed. Estimates of agreement, sensitivity, and specificity relative to RT-PCR on a combined oro-/nasopharyngeal sample were calculated. Feasibility was evaluated by observer and participant questionnaires.

Among 146 symptomatic adults, 40 (27.4%) were RT-PCR-positive for SARS-CoV-2. Sensitivity with self-testing was 82.5% (33/40 RT-PCR positives detected; 95% CI 68.1-91.3), and 85.0% (34/40; 95% CI 70.9-92.9) with professional testing. The positive percent agreement between self-testing and professional testing on Ag-RDT was 91.4% (95% CI 77.6-97.0), and negative percent agreement 99.1% (95% CI 95.0-100). At high viral load (>7.0 log10 SARS-CoV-2 RNA copies/ml), sensitivity was 96.6% (28/29; 95% CI 82.8-99.8) for both self- and professional testing. Deviations in sampling and testing (incomplete self-sampling or extraction procedure, or imprecise volume applied on the test device) were observed in 25 out of the 40 PCR-positives. Participants were rather young (mean age 35 years) and educated (59.6% with higher education degree). Most participants (80.9%) considered the Ag-RDT as rather easy to perform.

Conclusions

Ambulatory participants suspected for SARS-CoV-2 infection were able to reliably perform the Ag-RDT and test themselves. Procedural errors might be reduced by refinement of the Ag-RDTs for self-testing, such as modified instructions for use or product design/procedures. Self-testing may result in more wide-spread and more frequent testing. Paired with the appropriate information and education of the general public about the benefits and risks, self-testing may therefore have significant impact on the pandemic.
Folate (MTHFRC677T andMTRRA66G) gene polymorphisms and risk of prostate cancer: a case-control study with an updated meta-analysis
Authors: Yadav Upendra , Kumar Pradeep , Dwivedi Shailendra , Singh Bhupendra Pal , Rai Vandana
Published: January 2021

Introduction

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are the key enzymes of the folate pathway, which involved in the DNA methylation. DNA methylation may affect the stability and integrity of DNA, that supposed to play a pivotal role in carcinogenesis. So, we aimed to investigate the association ofMTHFRC677T andMTRRA66G gene polymorphisms with susceptibility to prostate cancer in North Indian population. We also performed meta-analyses of published literatures on these polymorphisms to evaluate their association with prostate cancer.

Methods

We genotypedMTHFRC677T andMTRRA66G gene polymorphisms in 147 prostate cancer cases and 147 healthy controls using PCR-RFLP methods. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for risk estimation. For meta-analysis different databases were searched and all statistical analysis were performed using Open Meta-Analyst software.

Results

The present case control study revealed that the T allele (OR= 1.67; 95% CI: 0.99-2.84, p= 0.05), CT genotype (OR= 1.92; 95% CI: 1.06-3.48, p= 0.02), and dominant (TT+CT) model (OR= 1.85; 95% CI: 1.05-3.30, p= 0.03) ofMTHFRC677T gene polymorphism and G allele (OR= 1.92; 95% CI: 1.35-2.73, p= 0.0002) ofMTRRA66G gene polymorphism were significantly associated with prostate cancer susceptibility. Meta-analyses ofMTHFRC677T andMTRRA66G gene polymorphisms showed no significant association between these polymorphisms and prostate cancer risk in overall or in subgroup meta-analysis stratified by ethnicity.

Conclusion

MTHFRC677T andMTRRA66G gene polymorphisms seem to play a significant role in prostate cancer susceptibility in North Indian population, while results of meta-analysis revealed no association betweenMTHFRC677T andMTRRA66G gene polymorphisms and prostate cancer susceptibility.
Mobilefuge: A low-cost, portable, open source, 3D-printed centrifuge that can be used for purification of saliva samples for SARS-CoV2 detection
Authors: Bhupathi Mohini , Devarapu Ganga Chinna Rao
Published: January 2021

One of the best ways to contain the spread of COVID-19 is frequent testing of as many people as possible and timely isolation of uninfected personnel from infected personnel. However, the cost of massive testing is affordable in many countries. The existing technologies might not be scalable to offer affordable testing for millions of people. To address this issue, novel testing methods based on Loop-Mediated Isothermal Amplification (LAMP) were proposed that are more sensitive, require less reagents and can work with saliva samples instead of more tedious nasal swabs. As a result, LAMP based protocols can make it possible to drive the cost down to one dollar per test. These LAMP based methods require a centrifuge device, mostly for separation of viral particles from reaction inhibitors in saliva samples. However, centrifuge is neither accessible nor affordable in many resource limited settings, especially during this pandemic situation when normal supply chains are heavily disrupted. To overcome these challenges, we invented a low-cost centrifuge that can be useful for carrying out low-cost LAMP based detection of SARS-Cov2 virus in saliva. The 3D printed centrifuge (Mobilefuge) is portable, robust, stable, safe, easy to build and operate. The Mobilefuge doesn’t require soldering or programming skills and can be built without any specialised equipment, yet practical enough for high throughput use. More importantly, Mobilefuge can be powered from widely available USB ports, including mobile phones and associated power supplies. This allows the Mobilefuge to be used even in off-grid and resource limited settings. We believe that our invention will aid the efforts to contain the spread of COVID-19 by lowering the costs of testing equipment. Apart from the COVID-19 testing, the Mobilefuge can have applications in the field of biomedical research and diagnostics.
COVID-19 Rapid Antigen Test at hospital admission associated to the knowledge of individual risk factors allow overcoming the difficulty of managing suspected patients in hospitals COVID-19 Rapid Antigen Test facilitates the management of suspected patients on hospital admission
Authors: Filgueiras Priscilla S , Corsini Camila A , Almeida Nathalie BF , Assis Jessica V , Pedrosa Maria Luysa C , de Oliveira Alana K , Amorim Raquel NH , de Miranda Daniel AP , Coutinho Lucélia A , Gomes Sarah VC , Custódio Natália G , da Silva Douglas H , Santos Gabriela PV , Silva Raphael A , Medeiros Maria Izabella VARC , Reis Priscila VCC , Lourenço Adelina J , Bicalho Cecília MF , Vilela Raquel VR , Neves Hércules P , Fernandes Gabriel R , Grenfell Rafaella FQ
Published: January 2021

Early diagnosis of SARS-CoV-2 is essential to limiting the spread of the virus and managing infected patients during hospitalization. The sensitivity of RT-qPCR is contested by the fact that it is time-consuming, executed by trained technicians in proper environment for material extraction. Here, we evaluated the first SARS-CoV-2 antigen test recommended by the World Health Organization at September, 2020 as an alternative for immediate diagnosis of symptomatic and suspected patients at a hospital in Brazil during the epidemic peak. All patients were submitted to RT-qPCR and rapid antigen test using nasopharyngeal swabs rigorously collected at the same time. Demographics, baseline comorbidities, symptoms and outcomes were considered. Prediction analysis revealed that previous stroke, chronic obstructive pulmonary disease, desaturation and tachypnea were the most relevant determinants of the death of COVID-19 patients. Comparison between the rapid antigen test and RT-qPCR revealed an overall PPV of 97%, extended to 100% when performed between 4 and 15 days of symptoms, with an accuracy of 90-91% from days 1 to 7 and a ‘Substantial’ agreement. The rapid antigen test presented no inconclusive result. Among the discordant results and RT-qPCR inconclusives, 72% presented bilateral multifocal ground-glass opacities on imaging and other exams alterations. The median time to obtain RT-qPCR results was 83.6 hours, against 15 minutes for the rapid test, precious time for deciding on patient isolation and management. Knowledge of the risk factors and a rapid diagnosis upon patient admission is critical to reduce mortality of COVID-19 patients, hospital internal costs and in-hospital transmission.
Clinical Validation of a Novel T-cell Receptor Sequencing Assay for Identification of Recent or Prior SARS-CoV-2 Infection
Authors: Dalai Sudeb C. , Dines Jennifer N. , Snyder Thomas M. , Gittelman Rachel M. , Eerkes Tera , Vaney Pashmi , Howard Sally , Akers Kipp , Skewis Lynell , Monteforte Anthony , Witte Pam , Wolf Cristina , Nesse Hans , Herndon Megan , Qadeer Jia , Duffy Sarah , Svejnoha Emily , Taromino Caroline , Kaplan Ian M. , Alsobrook John , Manley Thomas , Baldo Lance
Published: January 2021

Background

While diagnostic, therapeutic, and vaccine development in the COVID-19 pandemic has proceeded at unprecedented speed and scale, critical gaps remain in our understanding of the immune response to SARS-CoV-2. Current diagnostic strategies, including serology, have numerous limitations in addressing these gaps. Here we describe clinical performance of T- Detect™ COVID, the first reported assay to determine recent or prior SARS-CoV-2 infection based on T-cell receptor (TCR) sequencing and immune repertoire profiling from whole blood samples.

Methods

Methods for high-throughput immunosequencing of the TCRβ gene from blood specimens have been described1. We developed a statistical classifier showing high specificity for identifying prior SARS-CoV-2 infection2, utilizing >4,000 SARS-CoV-2-associated TCR sequences from 784 cases and 2,447 controls across 5 independent cohorts. The T-Detect COVID Assay comprises immunosequencing and classifier application to yield a qualitative positive or negative result. Several retrospective and prospective cohorts were enrolled to assess assay performance including primary and secondary Positive Percent Agreement (PPA; N=205, N=77); primary and secondary Negative Percent Agreement (NPA; N=87, N=79); PPA compared to serology (N=55); and pathogen cross-reactivity (N=38).

Results

T-Detect COVID demonstrated high PPA in subjects with prior PCR-confirmed SARS-CoV-2 infection (97.1% 15+ days from diagnosis; 94.5% 15+ days from symptom onset), high NPA (∼100%) in presumed or confirmed SARS-CoV-2 negative cases, equivalent or higher PPA than two commercial EUA serology tests, and no evidence of pathogen cross-reactivity.

Conclusion

T-Detect COVID is a novel T-cell immunosequencing assay demonstrating high clinical performance to identify recent or prior SARS-CoV-2 infection from standard blood samples. This assay can provide critical insights on the SARS-CoV-2 immune response, with potential implications for clinical management, risk stratification, surveillance, assessing protective immunity, and understanding long-term sequelae.
Automatic Gender Detection in Twitter Profiles for Health-related Cohort Studies
Authors: Yang Yuan-Chi , Al-Garadi Mohammed Ali , Love Jennifer S. , Perrone Jeanmarie , Sarker Abeed
Published: January 2021

Objective

Biomedical research involving social media (SM) data is gradually moving from population-level to targeted, cohort-level data analysis. Though crucial for biomedical studies, SM user’s demographic information (e.g., gender) is often not explicitly known from profiles. Here we present an automatic gender classification system for SM and we illustrate how gender information can be incorporated into a SM-based health-related study.

Materials and Methods

We used two large Twitter datasets: (i) public, gender-labeled users (Dataset-1), and (ii) users who have self-reported nonmedical use of prescription medications (Dataset-2). Dataset-1 was used to train and evaluate the gender detection pipeline. We experimented with machine-learning algorithms including support vector machines (SVMs) and deep-learning models, and released packages including M3. We considered user’s information including profile and tweets for classification. We also developed a meta-classifier ensemble that strategically uses the predicted scores from the classifiers. We applied the best-performing pipeline to Dataset-2 to assess the system’s utility.

Results and Discussion

We collected 67,181 and 176,683 users for Dataset-1 and Dataset-2, respectively. A meta-classifier involving SVM and M3 performed the best (Dataset-1 accuracy: 94.4% [95%-CI: 94.0%-94.8%]; Dataset-2: 94.4% [95%-CI: 92.0%-96.6%]. Including automatically-classified information in the analyses of Dataset-2 revealed gender-specific trends— proportions of females closely resemble data from the National Survey of Drug Use and Health 2018 (tranquilizers: 0.50 vs. 0.50; stimulants: 0.50 vs. 0.45), and the overdose Emergency Room Visit due to Opioids by CDC (pain relievers: 0.38 vs. 0.37).

Conclusion

Our publicly-available, automated gender detection pipeline may aid cohort-specific social media data analyses (https://bitbucket.org/sarkerlab/gender-detection-for-public).
Assessment of fractional anisotropy outcomes in combat sport athletes with mild traumatic brain injury
Authors: Fonseca Jessica Humara , Inguanzo Joe M. Lopez , Hernández Janet Perodin , González Dalmau Evelio
Published: January 2021

Abstract

The practice of combat sports increases the risk of suffering white matter injuries. That is why, it is required the early damage detection to determine to what extent the athlete may be active preserving their performance and health status. The integrity of the white matter can be quantitatively characterized in diffusion tensor images, using fractional anisotropy. This study aims at characterizing the fractional anisotropy of white matter injuries in combat athletes that are exposed to repetitive trauma and also, to detect changes in fractional anisotropy between cerebral hemispheres with and without lesions. It is proposed a global and structural analysis of the hemispheres, as well as the selection of ROI in the lesions. 14 athletes, from Boxing, Karate and Taekwondo sports, participated. The sample was divided into two groups of seven subjects each: Injured (23.428±4.157 years old) and Healthy (24.285±5.023 years old) paired by sport denomination. Diffusion tensor images were used to obtain FA values in the analysis of the hemispheres and lesions. Global and structural analysis of the hemispheres did not detect the presence of white matter lesions; however, the use of ROI selection permitted maximum approximation of the injuries location. It also improved the breakdown of FA values as it allows a local analysis of the lesion. As an additional result, there were found ROIs values, FAmed = 0.454±0.062, which exceed the average fractional anisotropy of the white matter. The cohesion of acute and chronic phase lesions were found in the same subject. The apparently contradictory results in FA values are related to the stage of the lesions.
Glycogen Synthase Kinase 3 regulates the genesis of the rare displaced ganglion cell retinal subtype
Authors: Kisseleff Elena , Vigouroux Robin J , Hottin Catherine , Lourdel Sophie , Shah Parth , Chédotal Alain , Perron Muriel , Swaroop Anand , Roger Jerome E
Published: January 2021

Glycogen Synthase Kinase 3 (GSK) proteins (GSK3α and GSK3β) are key mediators of signaling pathways, with crucial roles in coordinating fundamental biological processes during neural development. Here we show that the complete loss of GSK3 signaling in mouse retinal progenitors leads to microphthalmia with broad morphological defects. Both proliferation of retinal progenitors and neuronal differentiation are impaired and result in enhanced cell death. A single wild-type allele of eitherGsk3αorGsk3βis able to rescue these phenotypes. In this genetic context, all cell types are present with a functional retina. However, we unexpectedly detect a large number of cells in the inner nuclear layer expressing retinal ganglion cell (RGC)-specific markers (called displaced RGCs, dRGCs) when at least one allele ofGsk3αis expressed. Excess dRGCs lead to increased number of axons projecting into the ipsilateral medial terminal nucleus, an area of the brain belonging to the non-image-forming visual circuit and poorly targeted by RGCs in wild-type retina. Transcriptome analysis and optomotor response assay suggest that at least a subset of dRGCs inGsk3mutant mice are direction-selective RGCs. Our study thus uncovers a unique role of GSK3 in controlling the genesis of dRGCs, a rare and poorly characterized retinal cell type.
Defining the Caprin-1 interactome in unstressed and stressed conditions
Authors: Vu Lucas , Ghosh Asmita , Tran Chelsea , Tebung Walters Aji , Sidibé Hadjara , Garcia-Mansfield Krystine , David-Dirgo Victoria , Sharma Ritin , Pirrotte Patrick , Bowser Robert , Velde Christine Vande
Published: January 2021

Cytoplasmic stress granules (SGs) are dynamic non-membranous foci containing translationally arrested mRNA and RNA binding proteins that form in response to a variety of cellular stressors. SGs may evolve into the cytoplasmic inclusions observed in many neurodegenerative diseases. Recent studies have examined the SG proteome by interrogating the interactome of G3BP1, a core SG protein. To gain further insight into the SG proteome, we employed an immunoprecipitation coupled with mass spectrometry approach of endogenous Caprin-1 in HeLa cells under unstressed or stressed conditions. Overall, we identified ~1,500 proteins that interact with Caprin-1. Interactors under stressed conditions were primarily annotated to the ribosome, spliceosome, and RNA transport pathways. We validated four Caprin-1 interactors that localized to arsenite-induced SGs: ANKHD1, Talin-1, GEMIN5, and SNRNP200. We also validated these stress-induced interactions in SH-SY5Y cells and determined that SNRNP200 also associated with osmotic and thermal induced SGs. Finally, we identified SNRNP200 in cytoplasmic aggregates in ALS spinal cord and motor cortex. Collectively, our findings provide the first description of the Caprin-1 protein interactome, identify novel cytoplasmic SG components, and reveal a SG protein in cytoplasmic aggregates in ALS patients. Proteomic data collected in this study are available via ProteomeXchange with identifier PXD023271.