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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 161,163 papers from 673,089 authors.

Most tweeted biology preprints, last 24 hours

*There are gaps in historical Twitter data, most notably in spring 2020. This may result in some preprints appearing with less tweets than they should.

112 results found. For more information, click each entry to expand.

21: Automatic identification and annotation of MYB gene family members in plants
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Posted 16 Oct 2021

Automatic identification and annotation of MYB gene family members in plants
9 tweets bioRxiv plant biology

Boas Pucker

Background: MYBs are among the largest transcription factor families in plants. Consequently, members of this family are involved in a plethora of processes including development and specialized metabolism. The MYB families of many plant species were investigated in the last two decades since the first investigation looked at Arabidopsis thaliana. This body of knowledge and characterized sequences provide the basis for the identification, classification, and functional annotation of candidate sequences in new genome and transcriptome assemblies. Results: A pipeline for the automatic identification and functional annotation of MYBs in a given sequence data set was implemented in Python. MYB candidates are identified, screened for the presence of a MYB domain and other motifs, and finally placed in a phylogenetic context with well characterized sequences. In addition to technical benchmarking based on existing annotation, the transcriptome assembly of Croton tiglium and the annotated genome sequence of Castanea crenata were screened for MYBs. Results of both analyses are presented in this study to illustrate the potential of this application. The analysis of one species takes only a few minutes depending on the number of predicted sequences and the size of the MYB gene family. This pipeline, the required bait sequences, and reference sequences for a classification are freely available on github: https://github.com/bpucker/MYB_annotator. Conclusions: This automatic annotation of the MYB gene family in novel assemblies makes genome-wide investigations consistent and paves the way for comparative studies in the future. Candidate genes for in-depth analyses are presented based on their orthology to previously characterized sequences which allows the functional annotation of the newly identified MYBs with high confidence. The identification of orthologs can also be harnessed to detect duplication and deletion events.

22: SARS-Cov-2 Infection versus Vaccine-Induced Immunity among Veterans
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Posted 29 Sep 2021

SARS-Cov-2 Infection versus Vaccine-Induced Immunity among Veterans
8 tweets medRxiv infectious diseases

Yinong Young-Xu, Jeremy Smith, Caroline Korves

Background: With over 40 million cases of SARS-CoV-2 infection reported in the US and discussion of both vaccine mandates as well as boosters ongoing, we aim to examine protection conferred by previous infection compared with vaccination so that citizens and policy makers can make informed decisions. Objectives: To compare mRNA COVID-19 vaccine-induced immunity against immunity induced by previous infection with SARS-CoV-2 between June and August 2021 when the Delta variant became dominant in the US. We conducted a retrospective observational study comparing two groups whose incident vaccination or infection occurred within the first two months of 2021: (1) SARS-CoV-2-naive individuals who received a full mRNA vaccination - 2 doses of either Pfizer or Moderna vaccine, (2) newly infected individuals who were subdivided into those have not been vaccinated and those have been vaccinated after their infection. Matched multivariable Cox proportional hazards model was applied. We evaluated laboratory (RT-PCR) confirmed SARS-CoV-2 infection during follow-up, COVID-related hospitalization, and deaths. Setting: Veterans Health Administration (VHA). Main outcomes: Positive SARS-CoV-2 PCR test, COVID-related hospitalization, and deaths. Protection was estimated from hazard ratios with 95% confidence intervals (CI). Results: A total of 9,539 patients with SARS-CoV-2 infection during the first two months of 2021 were matched to 14,458 and 23,105 patients fully vaccinated with Moderna and Pfizer mRNA vaccines, during the same two months. 3,917 (41%) of patients with SARS-CoV-2 infection were subsequently vaccinated. We plan to study this group separately. Consequently, protections were estimated among those with infection but were not subsequently vaccinated and those vaccinated with a mRNA vaccine. Among seniors, Moderna and Pfizer mRNA vaccines offered stronger protection against infection, lowering the risk by an additional 66% [HR: 0.34 (95% CI, 0.14-0.78)] and 68% [HR: 0.32 (95% CI, 0.14-0.70)]; stronger protection against hospitalization, lowering the risk by an additional 61% [HR: 0.34 (95% CI, 0.14-0.78)] and 45% [HR: 0.34 (95% CI, 0.14-0.78)]; and stronger protection against deaths lowering the risk by an additional 95% [HR: 0.05 (95% CI, 0.004-0.62)] and 99% [HR: 0.01 (95% CI, 0.001-0.44)]. Among young adults (age < 65), the protections offered by vaccines were statistically equivalent to that provided by previous infection, especially in terms of absolute incidence rate. Conclusions Among the elderly (age 65 or older), two-dose mRNA vaccines provided stronger protection against infection, hospitalization, and death, compared to natural immunity. Among young adults (age < 65), the protections offered between natural immunity and vaccine-induced immunity were similar.

23: Prevalent uses of exons as regulatory sequences are possible and inevitable
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Posted 07 Sep 2021

Prevalent uses of exons as regulatory sequences are possible and inevitable
7 tweets bioRxiv evolutionary biology

Jing Chen, Pengyu Ni, Meng Niu, Jun-tao Guo, Zhengchang Su

It has long been known that exons can encode transcriptional enhancers. However, the prevalence of such dual-use exons and related questions remain elusive. Our recently predicted highly accurate, large sets of cis-regulatory module candidates (CRMCs) and non-CRMCs in the human genome provide us an opportunity to address these questions. We find that exonic transcription factor binding sites(eTFBSs) occupy at least a third of the total exon lengths, suggesting exonic enhancers(eEHs) are more prevalent than originally thought. Moreover, active eTFBSs significantly overlap experimentally determined active eEHs, and enhance the transcription of nearby genes. Furthermore, both A/T and C/G in eTFBSs are more likely under evolutionary selection than those in non-CRMC exons, indicating the eTFBSs might be in dual-use. Interestingly, eTFBSs in codons tend to encode loops rather than more critical helices and strands in protein structures, while eTFBSs in untranslated regions (UTRs) tend to avoid positions where known UTR-related functions were located. Intriguingly, active eTFBSs are found to be in close physical proximity to distal promoters and involved in the activation of target genes. The close physical proximity between exons and promoters in topologically associating domains might render less critical exons to opt for parts of enhancers when non-exonic sequences are unavailable due to space constraints. It appears that nature avoids the dilemma of evolving a sequence for two unrelated functions by using less-critical, physically available exons for eTFBSs. Therefore, the prevalent dual-use of exons is not only possible but also inevitable.

24: Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers
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Posted 21 Aug 2021

Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers
7 tweets medRxiv infectious diseases

Marc Conrad Shamier, Alma Tostmann, Susanne Bogers, Janet De Wilde, Jeroen IJpelaar, Willemijn Van Der Kleij, Herbert De Jager, Bart Haagmans, Richard Molenkamp, Bas Oude Munnink, Carsten van Rossum, Janette Rahamat-Langendoen, Nannet Van Der Geest, Chantal Bleeker-Rovers, Heiman Wertheim, Marion Koopmans, Corine H Geurts van Kessel

SARS-CoV-2 vaccines are highly effective at preventing COVID-19-related morbidity and mortality. As no vaccine is 100% effective, breakthrough infections are expected to occur. We analyzed the virological characteristics of 161 vaccine breakthrough infections in a population of 24,706 vaccinated healthcare workers (HCWs), using RT-PCR and virus culture. The delta variant (B.1.617.2) was identified in the majority of cases. Despite similar Ct-values, we demonstrate lower probability of infectious virus detection in respiratory samples of vaccinated HCWs with breakthrough infections compared to unvaccinated HCWs with primary SARS-CoV-2 infections. Nevertheless, infectious virus was found in 68.6% of breakthrough infections and Ct-values decreased throughout the first 3 days of illness. We conclude that rare vaccine breakthrough infections occur, but infectious virus shedding is reduced in these cases.

25: Atria: An Ultra-fast and Accurate Trimmer for Adapter and Quality Trimming
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Posted 09 Sep 2021

Atria: An Ultra-fast and Accurate Trimmer for Adapter and Quality Trimming
7 tweets bioRxiv bioinformatics

Jiacheng Chuan, Aiguo Zhou, Lawrence Richard Hale, Miao He, Xiang Li

Background: As Next Generation Sequencing takes a dominant role in terms of output capacity and sequence length, adapters attached to the reads and low-quality bases hinder the performance of downstream analysis directly and implicitly, such as producing false-positive single nucleotide polymorphisms (SNP), and generating fragmented assemblies. A fast trimming algorithm is in demand to remove adapters precisely, especially in read tails with relatively low quality. Findings: We present a trimming program named Atria. Atria matches the adapters in paired reads and finds possible overlapped regions with a super-fast and carefully designed byte-based matching algorithm (O(n) time with O(1) space). Atria also implements multi-threading in both sequence processing and file compression and supports single-end reads. Conclusions: Atria performs favorably in various trimming and runtime benchmarks of both simulated and real data with other cutting-edge trimmers. We also provide an ultra-fast and lightweight byte-based matching algorithm. The algorithm can be used in a broad range of short-sequence matching applications, such as primer search and seed scanning before alignment. Availability & Implementation: The Atria executables, source code, and benchmark scripts are available at https://github.com/cihga39871/Atria under the MIT license.

26: Infection fatality rate of COVID-19 in community-dwelling populations with emphasis on the elderly: An overview
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Posted 13 Jul 2021

Infection fatality rate of COVID-19 in community-dwelling populations with emphasis on the elderly: An overview
7 tweets medRxiv epidemiology

Cathrine Axfors, John Ioannidis

Background: The infection fatality rate (IFR) of Coronavirus Disease 2019 (COVID-19) varies widely according to age and residence status. Purpose: Estimate the IFR of COVID-19 in community-dwelling elderly populations and other age groups from seroprevalence studies. Study protocol: https://osf.io/47cgb. Data Sources: Seroprevalence studies done in 2020 and identified by any of four existing systematic reviews. Study Selection: SARS-CoV-2 seroprevalence studies with [&ge;]1000 participants aged [&ge;]70 years that presented seroprevalence in elderly people; aimed to generate samples reflecting the general population; and whose location had available data on cumulative COVID-19 deaths in elderly (primary cutoff [&ge;]70 years; [&ge;]65 or [&ge;]60 also eligible). Data Extraction: We extracted the most fully adjusted (if unavailable, unadjusted) seroprevalence estimates and sampling procedure details. We also extracted age- and residence-stratified cumulative COVID-19 deaths (until 1 week after the seroprevalence sampling midpoint) from official reports, and population statistics, to calculate IFRs corrected for unmeasured antibody types. Sample size-weighted IFRs were estimated for countries with multiple estimates. Secondary analyses examined data on younger age strata from the same studies. Data Synthesis: Twenty-three seroprevalence surveys representing 14 countries were included. Across all countries, the median IFR in community-dwelling elderly and elderly overall was 2.4% (range 0.3%-7.2%) and 5.5% (range 0.3%-12.1%). IFR was higher with larger proportions of people >85 years. Younger age strata had low IFR values (median 0.0027%, 0.014%, 0.031%, 0.082%, 0.27%, and 0.59%, at 0-19, 20-29, 30-39, 40-49, 50-59, and 60-69 years). Limitations: Biases in seroprevalence and mortality data. Conclusions: The IFR of COVID-19 in community-dwelling elderly people is lower than previously reported. Very low IFRs were confirmed in the youngest populations.

27: Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the San Francisco Bay Area, California
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Posted 25 Aug 2021

Predominance of antibody-resistant SARS-CoV-2 variants in vaccine breakthrough cases from the San Francisco Bay Area, California
7 tweets medRxiv infectious diseases

Venice Servellita, Alicia Sotomayor-Gonzalez, Amelia Gliwa, Erika Torres, Noah Brazer, Alicia Zhou, Katherine Hernandez, Madeline Sankaran, Baolin Wang, Daniel Wong, Candace Wang, Yueyuan Zhang, Kevin Reyes, Dustin Glasner, Wayne Deng, Jessica Streithorst, Steve Miller, Edwin Frias, John Hackett, Susan Philip, Scott Topper, Darpun Sachdev, Charles Y Chiu

Associations between vaccine breakthrough cases and infection by SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analyzed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from February 1 to June 30, 2021, of which 125 (9.1%) were vaccine breakthrough infections. Fully vaccinated were more likely than unvaccinated persons to be infected by variants carrying mutations associated with decreased antibody neutralization (L452R, L452Q, E484K, and/or F490S) (78% versus 48%, p = 1.96e-08), but not by those associated with increased infectivity (L452R and/or N501Y) (85% versus 77%, p = 0.092). Differences in viral loads were non-significant between unvaccinated and fully vaccinated persons overall (p = 0.99) and according to lineage (p = 0.09 - 0.78). Viral loads were significantly higher in symptomatic as compared to asymptomatic vaccine breakthrough cases (p < 0.0001), and symptomatic vaccine breakthrough infections had similar viral loads to unvaccinated infections (p = 0.64). In 5 cases with available longitudinal samples for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to immunocompromised state or infection by an antibody-resistant lineage. These findings suggest that vaccine breakthrough cases are preferentially caused by circulating antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may potentially transmit COVID-19 as efficiently as unvaccinated infections, regardless of the infecting lineage.

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Posted 14 Aug 2021

6 tweets medRxiv infectious diseases

Lydia Horndler, Pilar Delgado, Salvador Romero-Pinedo, Marina Quesada, Ivaylo Balabanov, Rocio Laguna-Goya, Patricia Almendro-Vazquez, Miguel A Llamas, Manuel Fresno, Estela Paz-Artal, Hisse M. van Santen, Stela Alvarez, Asuncion Olmo, Balbino Alarcon

The rapid development of vaccines to prevent infection by SARS-CoV-2 virus causing COVID-19 makes necessary to compare the capacity of the different vaccines in terms of development of a protective humoral response. Here, we have used a highly sensitive and reliable flow cytometry method to measure the titers of antibodies of the IgG1 isotype in blood of healthy volunteers after receiving one or two doses of the vaccines being administered in Spain. We took advantage of the multiplexed capacity of the method to measure simultaneously the reactivity of antibodies with the S protein of the original strain Wuhan and the variants B.1.1.7 (Alpha), B.1.617.2 (Delta) and B.1.617.1 (Kappa). We found significant differences in the titer of anti-S antibodies produced after a first dose of the vaccines ChAdOx1 nCov-19/AstraZeneca, mRNA-1273/Moderna, BNT162b2/Pfizer-BioNTech and Ad26.COV.S/Janssen. Most important, we found a relative reduction in the reactivity of the sera with the Alpha, Delta and Kappa variants, versus the Wuhan one, after the second boosting immunization. These data allow to make a comparison of different vaccines in terms of anti-S antibody generation and cast doubts about the convenience of repeatedly immunizing with the same S protein sequence.

29: Guidelines for reliable and reproducible functional enrichment analysis
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Posted 07 Sep 2021

Guidelines for reliable and reproducible functional enrichment analysis
5 tweets bioRxiv bioinformatics

Kaumadi Wijesooriya, Sameer A Jadaan, Kaushalya L Perera, Tanuveer Kaur, Mark Ziemann

Gene set enrichment tests (a.k.a. functional enrichment analysis) are among the most frequently used methods in computational biology. Despite this popularity, there are concerns that these methods are being applied incorrectly and the results of some peer-reviewed publications are unreliable. These problems include the use of inappropriate background gene lists, lack of false discovery rate correction and lack of methodological detail. An example analysis of public RNA-seq reveals that these methodological errors alter enrichment results dramatically. To ascertain the frequency of these errors in the literature, we performed a screen of 186 open access research articles describing functional enrichment results. We find that 95% of analyses using over-representation tests did not implement an appropriate background gene list or did not describe this in the methods. Failure to perform p-value correction for multiple tests was identified in 43% of analyses. Many studies lacked detail in the methods section about the tools and gene sets used. Only 15% of studies avoided major flaws, which highlights the poor state of functional enrichment rigour and reporting in the contemporary literature. We provide a set of minimum standards that should act as a checklist for researchers and peer-reviewers.

30: The Specious Art of Single-Cell Genomics
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Posted 26 Aug 2021

The Specious Art of Single-Cell Genomics
5 tweets bioRxiv genomics

Tara Chari, Joeyta Banerjee, Lior Pachter

Dimensionality reduction is standard practice for filtering noise and identifying relevant dimensions in large-scale data analyses. In biology, single-cell expression studies almost always begin with reduction to two or three dimensions to produce 'all-in-one' visuals of the data that are amenable to the human eye, and these are subsequently used for qualitative and quantitative analysis of cell relationships. However, there is little theoretical support for this practice. We examine the theoretical and practical implications of low-dimensional embedding of single-cell data, and find extensive distortions incurred on the global and local properties of biological patterns relative to the high-dimensional, ambient space. In lieu of this, we propose semi-supervised dimension reduction to higher dimension, and show that such targeted reduction guided by the metadata associated with single-cell experiments provides useful latent space representations for hypothesis-driven biological discovery.

31: Principles of resilient coding for plant ecophysiologists
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Posted 12 Sep 2020

Principles of resilient coding for plant ecophysiologists
5 tweets bioRxiv plant biology

Joseph R Stinziano, Cassaundra Roback, Demi Gamble, Bridget K Murphy, Patrick J Hudson, Christopher D Muir

Plant ecophysiology is founded on a rich body of physical and chemical theory, but it is challenging to connect theory with data in unambiguous, analytically rigorous, and reproducible ways. Custom scripts written in computer programming languages (coding) enable plant ecophysiologists to model plant processes and fit models to data reproducibly using advanced statistical techniques. Since many ecophysiologists lack formal programming education, we have yet to adopt a unified set of coding principles and standards that could make coding easier to learn, use, and modify. We identify eight principles to help in plant ecophysiologists without much programming experience to write resilient code: 1) standardized nomenclature, 2) consistency in style, 3) increased modularity/extensibility for easier editing and understanding, 4) code scalability for application to large datasets, 5) documented contingencies for code maintenance, 6) documentation to facilitate user understanding; 7) extensive tutorials, and 8) unit testing. We illustrate these principles using a new R package, {photosynthesis}, which provides a set of analytical and simulation tools for plant ecophysiology. Our goal with these principles is to advance scientific discovery in plant ecophysiology by making it easier to use code for simulation and data analysis, reproduce results, and rapidly incorporate new biological understanding and analytical tools.

32: Airpart: Interpretable statistical models for analyzing allelic imbalance in single-cell datasets
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Posted 16 Oct 2021

Airpart: Interpretable statistical models for analyzing allelic imbalance in single-cell datasets
5 tweets bioRxiv bioinformatics

Wancen Mu, Hirak Sarkar, Avi Srivastava, Kwangbom Choi, Rob Patro, Michael I Love

Motivation: Allelic expression analysis aids in detection of cis-regulatory mechanisms of genetic variation which produce allelic imbalance (AI) in heterozygotes. Measuring AI in bulk data lacking time or spatial resolution has the limitation that cell-type-specific (CTS), spatial-, or time-dependent AI signals may be dampened or not detected. Results: We introduce a statistical method airpart for identifying differential CTS AI from single-cell RNA-sequencing (scRNA-seq) data, or other spatially- or time-resolved datasets. airpart outputs discrete partitions of data, pointing to groups of genes and cells under common mechanisms of cis-genetic regulation. In order to account for low counts in single-cell data, our method uses a Generalized Fused Lasso with Binomial likelihood for partitioning groups of cells by AI signal, and a hierarchical Bayesian model for AI statistical inference. In simulation, airpart accurately detected partitions of cell types by their AI and had lower RMSE of allelic ratio estimates than existing methods. In real data, airpart identified differential AI patterns across cell states and could be used to define trends of AI signal over spatial or time axes. Availability: The airpart package is available as a R/Bioconductor package at https://bioconductor.org/packages/airpart.

33: Genomic insights into the population history and biological adaptation of Southwestern Chinese Hmong-Mien people
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Posted 16 Oct 2021

Genomic insights into the population history and biological adaptation of Southwestern Chinese Hmong-Mien people
4 tweets bioRxiv genetics

Yan Yan Liu, Mengge Wang, Changhui Liu, Jingrong Zhu, Xing Zou, Wenshan Li, Lin Lin Wang, Cuo Leng, Quyi Xu, Hui-Yuan Yeh, Chuan-Chao Wang, Xiaohong Wen, Chao Liu, Guanglin He

Hmong-Mien-speaking (HM) populations, widely distributed in South China, North of Thailand, Laos and Vietnam, have experienced different settlement environments, dietary habits and pathogen exposure. However, their specific biological adaptation also remained largely uncharacterized, which is important in the population evolutionary genetics and Trans-Omics for regional Precision Medicine. Besides, the origin and genetic diversity of HM people and their phylogenetic relationship with surrounding modern and ancient populations are unknown. Here, we reported genome-wide SNPs in 52 representative Miao people and combined them with 144 HM people from 13 geographically representative populations to characterize the full genetic admixture and adaptive landscape of HM speakers. We found that obvious genetic substructures existed in geographically different HM populations and also identified one new ancestral lineage specifically exited in HM people, which spatially distributed from Sichuan and Guizhou in the North to Thailand in the South and temporally dated to at least 500 years. The sharing patterns of the newly-identified homogeneous ancestry component combined the estimated admixture times via the decay of Linkage Disequilibrium and haplotype sharing in GLOBETROTTER suggested that the modern HM-speaking populations originated from Southwest China and migrated southward recently, which is consistent with the reconstructed phenomena of linguistic and archeological documents. Additionally, we identified specific adaptive signatures associated with several important human nervous system biological functions. Our pilot work emphasized the importance of anthropologically-informed sampling and deeply genetic structure reconstruction via whole-genome sequencing in the next step in the deep Chinese population genomic diversity project (CPGDP), especially in the ethnolinguistic regions.

34: Brain imaging before and after COVID-19 in UK Biobank
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Posted 15 Jun 2021

Brain imaging before and after COVID-19 in UK Biobank
4 tweets medRxiv neurology

Gwenaƫlle Douaud, Soojin Lee, Fidel Alfaro-Almagro, Christoph Arthofer, Chaoyue Wang, Paul McCarthy, Frederik Lange, Jesper L.R. Andersson, Ludovica Griffanti, Eugene Duff, Saad Jbabdi, Bernd Taschler, Anderson M Winkler, Thomas E. Nichols, Rory Collins, Paul M. Matthews, Naomi Allen, Karla Miller, Stephen M. Smith

There is strong evidence for brain-related pathologies in COVID-19, some of which could be a consequence of viral neurotropism, or of neuroinflammation following viral infection. Most brain imaging studies have focused on qualitative, gross pathology in moderate to severe cases, most typically carried out on hospitalised patients. It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, in a quantitative and automated manner, and whether this can reveal possible mechanisms for the spread of the disease. UK Biobank scanned over 40,000 participants before the start of the COVID-19 pandemic, making it possible in 2021 to invite back hundreds of previously-imaged participants for a second imaging visit. Here, we studied the possible brain changes associated with the coronavirus infection using multimodal MRI data from 785 adult participants (aged 51-81) from the UK Biobank COVID-19 re-imaging study, including 401 adult participants who tested positive for SARS-CoV-2 infection between their two scans. We used structural, diffusion and functional brain scans from before and after infection, to compare longitudinal changes between these 401 SARS-CoV-2 cases and 384 controls who had either tested negative to rapid antibody testing or had no COVID-19 medical and public health record, and who were matched to the cases for age, sex, ethnicity and interval between scans. The controls and cases did not differ in blood pressure, body mass index, diabetes diagnosis, smoking, alcohol consumption, or socio-economic status. Using both hypothesis-driven and exploratory approaches, with false discovery rate multiple comparison correction, we identified respectively 68 and 67 significant longitudinal effects associated with SARS-CoV-2 infection in the brain, including, on average: (i) a more pronounced reduction in grey matter thickness and contrast in the lateral orbitofrontal cortex (min P=1.7x10-4, r=-0.14) and parahippocampal gyrus (min P=2.7x10-4, r=-0.13), (ii) a relative increase of diffusion indices, a marker of tissue damage, in the regions of the brain functionally-connected to the piriform cortex, anterior olfactory nucleus and olfactory tubercle (min P=2.2x10-5, r=0.16), and (iii) greater reduction in global measures of brain size and increase in cerebrospinal fluid volume suggesting an additional diffuse atrophy in the infected participants (min P=4.0x10-6, r=-0.17). When looking over the entire cortical surface, these grey matter thickness results covered the parahippocampal gyrus and the lateral orbitofrontal cortex, and extended to the anterior insula and anterior cingulate cortex, supramarginal gyrus and temporal pole. The increase of a diffusion index (mean diffusivity) meanwhile could be seen voxel-wise mainly in the medial and lateral orbitofrontal cortex, the anterior insula, the anterior cingulate cortex and the amygdala. These results were not altered after excluding cases who had been hospitalised. We further compared hospitalised (n=15) and non-hospitalised (n=386) infected participants, resulting in similar findings to the larger cases vs control group comparison, with, in addition, a marked reduction of grey matter thickness in fronto-parietal and temporal regions (all FDR-significant, min P=4.0x10-6). The 401 SARS-CoV-2 infected participants also showed larger cognitive decline between the two timepoints in the Trail Making Test compared with the controls (both FDR-significant, min P=1.0x10-4, r=0.17; and still FDR-significant after excluding the hospitalised patients: min P=1.0x10-4, r=0.17), with the duration taken to complete the alphanumeric trail correlating post hoc with the cognitive and olfactory-related crus II of the cerebellum (FDR-significant, P=2.0x10-3, r=-0.19), which was also found significantly atrophic in the SARS-CoV-2 participants (FDR-significant, P=6.1x10-5, r=-0.14). Our findings thus relate to longitudinal abnormalities in limbic cortical areas with direct neuronal connectivity to the primary olfactory system. Unlike in post hoc cross-sectional studies, the availability of pre-infection imaging data mitigates to some extent the issue of pre-existing risk factors or clinical conditions being misinterpreted as disease effects. We were therefore able to demonstrate that the regions of the brain that showed longitudinal differences post-infection did not already show any difference between (future) cases and controls in their initial, pre-infection scans. These brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease -- or of the virus itself -- via olfactory pathways (a possible entry point of the virus to the central nervous system being via the olfactory mucosa), or of neuroinflammatory events due to the infection, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, for instance after improvement of the hyposmic symptoms, or whether these are effects that will persist in the long term, remains to be investigated with additional follow up.

35: Necessity of COVID-19 Vaccination in Previously Infected Individuals: A Retrospective Cohort Study
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Posted 04 Jun 2021

Necessity of COVID-19 Vaccination in Previously Infected Individuals: A Retrospective Cohort Study
4 tweets medRxiv infectious diseases

Nabin Shrestha, Patrick C. Burke, Amy S. Nowacki, Paul Terpeluk, Steven M. Gordon

Background: There are good reasons to expect natural infection to provide protection against future infection with SARS-CoV-2. The purpose of this study was to evaluate the necessity of COVID-19 vaccination in persons previously infected with SARS-CoV-2. Methods: Employees of the Cleveland Clinic Health System working in Ohio on Dec 16, 2020, the day COVID-19 vaccination was started, were included. Any subject who tested positive for SARS-CoV-2 at least 42 days earlier was considered previously infected. One was considered vaccinated 14 days after receipt of the second dose of a SARS-CoV-2 mRNA vaccine. The cumulative incidence of SARS-CoV-2 infection over the next four months, among previously infected subjects who received the vaccine, was compared with those of previously infected subjects who remained unvaccinated, previously uninfected subjects who received the vaccine, and previously uninfected subjects who remained unvaccinated. Results: Among the 52238 included employees, 1220 (47%) of 2579 previously infected subjects received the vaccine, compared with 29461 (59%) of 49659 not previously infected. The cumulative incidence of SARS-CoV-2 infection did not differ among previously infected unvaccinated subjects, previously infected subjects who were vaccinated, and previously uninfected subjects who were vaccinated, and was much lower than that of previously uninfected subjects who remained unvaccinated. Not one of the 1359 previously infected subjects who remained unvaccinated had a SARS-CoV-2 infection over the duration of the study. Conclusion: Individuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination, and vaccines can be safely prioritized to those who have not been infected before.

36: COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis
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Posted 25 Sep 2021

COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis
4 tweets medRxiv infectious diseases

Lorenz Borsche, Bernd Glauner, Julian von Mendel

Background Much research shows that blood calcidiol (25(OH)D3) levels correlate strongly with SARS-CoV-2 infection severity. There is open discussion regarding whether low D3 is caused by the infection or if deficiency negatively affects immune defense. The aim of this study was to collect further evidence on this topic. Methods Systematic literature search was performed to identify retrospective cohort as well as clinical studies on COVID-19 mortality rates vs. D3 blood levels. Mortality rates from clinical studies were corrected for age, sex and diabetes. Data was analyzed using correlation and linear regression. Results One population study and seven clinical studies were identified, which reported D3 blood levels pre-infection or on the day of hospital admission. They independently showed a negative Pearson correlation of D3 levels and mortality risk (r(17)=-.4154, p=.0770/r(13)=-.4886, p=.0646). For the combined data, median (IQR) D3 levels were 23.2 ng/ml (17.4 - 26.8), and a significant Pearson correlation was observed (r(32)=-.3989, p=.0194). Regression suggested a theoretical point of zero mortality at approximately 50 ng/ml D3. Conclusions The two datasets provide strong evidence that low D3 is a predictor rather than a side effect of the infection. Despite ongoing vaccinations, we recommend raising serum 25(OH)D levels to above 50 ng/ml to prevent or mitigate new outbreaks due to escape mutations or decreasing antibody activity.

37: Neuronal activity drives pathway-specific depolarization of astrocyte distal processes
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Posted 04 Jul 2021

Neuronal activity drives pathway-specific depolarization of astrocyte distal processes
4 tweets bioRxiv neuroscience

Moritz Armbruster, Saptarnab Naskar, Jacqueline Garcia, Mary Sommer, Elliot Kim, Yoav Adam, Philip G Haydon, Edward S Boyden, Adam E. Cohen, Chris G. Dulla

Astrocytes are glial cells that interact with neuronal synapses via their distal processes, where they remove glutamate and potassium (K+) from the extracellular space following neuronal activity. Astrocyte clearance of both glutamate and K+ is voltage-dependent, but astrocyte membrane potential (Vm) has been thought to be largely invariant. As a result, these voltage-dependencies have not been considered relevant to astrocyte function. Using genetically encoded voltage indicators enabling the measurement of Vm at distal astrocyte processes (DAPs), we report large, rapid, focal, and pathway-specific depolarizations in DAPs during neuronal activity. These activity-dependent astrocyte depolarizations are driven by action potential-mediated presynaptic K+ efflux and electrogenic glutamate transporters. We find that DAP depolarization inhibits astrocyte glutamate clearance during neuronal activity, enhancing neuronal activation by glutamate. This represents a novel class of sub-cellular astrocyte membrane dynamics and a new form of astrocyte-neuron interaction.

38: SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis
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Posted 08 Sep 2021

SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis
4 tweets medRxiv epidemiology

Tracy Beth Hoeg, Allison Krug, Josh Stevenson, John Mandrola

Objectives: Establishing the rate of post-vaccination cardiac myocarditis in the 12-15 and 16-17-year-old population in the context of their COVID-19 hospitalization risk is critical for developing a vaccination recommendation framework that balances harms with benefits for this patient demographic. Design, Setting and Participants: Using the Vaccine Adverse Event Reporting System (VAERS), this retrospective epidemiological assessment reviewed reports filed between January 1, 2021, and June 18, 2021, among adolescents ages 12-17 who received mRNA vaccination against COVID-19. Symptom search criteria included the words myocarditis, pericarditis, and myopericarditis to identify children with evidence of cardiac injury. The word troponin was a required element in the laboratory findings. Inclusion criteria were aligned with the CDC working case definition for probable myocarditis. Stratified cardiac adverse event (CAE) rates were reported for age, sex and vaccination dose number. A harm-benefit analysis was conducted using existing literature on COVID-19-related hospitalization risks in this demographic. Main outcome measures: 1) Stratified rates of mRNA vaccine-related myocarditis in adolescents age 12-15 and 16-17; and 2) harm-benefit analysis of vaccine-related CAEs in relation to COVID-19 hospitalization risk. Results: A total of 257 CAEs were identified. Rates per million following dose 2 among males were 162.2 (ages 12-15) and 94.0 (ages 16-17); among females, rates were 13.0 and 13.4 per million, respectively. For boys 12-15 without medical comorbidities receiving their second mRNA vaccination dose, the rate of CAE is 3.7-6.1 times higher than their 120-day COVID-19 hospitalization risk as of August 21, 2021 (7-day hospitalizations 1.5/100k population) and 2.6-4.3-fold higher at times of high weekly hospitalization risk (2.1/100k), such as during January 2021. For boys 16-17 without medical comorbidities, the rate of CAE is currently 2.1-3.5 times higher than their 120-day COVID-19 hospitalization risk, and 1.5-2.5 times higher at times of high weekly COVID-19 hospitalization. Conclusions: Post-vaccination CAE rate was highest in young boys aged 12-15 following dose two. For boys 12-17 without medical comorbidities, the likelihood of post vaccination dose two CAE is 162.2 and 94.0/million respectively. This incidence exceeds their expected 120-day COVID-19 hospitalization rate at both moderate (August 21, 2021 rates) and high COVID-19 hospitalization incidence. Further research into the severity and long-term sequelae of post-vaccination CAE is warranted. Quantification of the benefits of the second vaccination dose and vaccination in addition to natural immunity in this demographic may be indicated to minimize harm.

39: Risk of Myocarditis from COVID-19 Infection in People Under Age 20: A Population-Based Analysis
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Posted 27 Jul 2021

Risk of Myocarditis from COVID-19 Infection in People Under Age 20: A Population-Based Analysis
4 tweets medRxiv public and global health

Mendel E Singer, Ira B. Taub, David C. Kaelber

Background There have been recent reports of myocarditis (including myocarditis, pericarditis or myopericarditis) as a side-effect of mRNA-based COVID-19 vaccines, particularly in young males. Less information is available regarding the risk of myocarditis from COVID-19 infection itself. Such data would be helpful in developing a complete risk-benefit analysis for this population. Methods A de-identified, limited data set was created from the TriNetX Research Network, aggregating electronic health records from 48 mostly large U.S. Healthcare Organizations (HCOs). Inclusion criteria were a first COVID-19 diagnosis during the April 1, 2020 - March 31, 2021 time period, with an outpatient visit 1 month to 2 years before, and another 6 months to 2 years before that. Analysis was stratified by sex and age (12-17, 12-15, 16-19). Patients were excluded for any prior cardiovascular condition. Primary outcome was an encounter diagnosis of myocarditis within 90 days following the index date. Rates of COVID-19 cases and myocarditis not identified in the system were estimated and the results adjusted accordingly. Wilson score intervals were used for 95% confidence intervals due to the very low probability outcome. Results For the 12-17-year-old male cohort, 6/6,846 (0.09%) patients developed myocarditis overall, with an adjusted rate per million of 876 cases (Wilson score interval 402 - 1,911). For the 12-15 and 16-19 male age groups, the adjusted rates per million were 601 (257 - 1,406) and 561 (240 - 1,313). For 12-17-year-old females, there were 3 (0.04%) cases of myocarditis of 7,361 patients. The adjusted rate was 213 (73 - 627) per million cases. For the 12-15- and 16-19-year-old female cohorts the adjusted rates per million cases were 235 (64 - 857) and 708 (359 - 1,397). The outcomes occurred either within 5 days (40.0%) or from 19-82 days (~60.0%). Conclusions Myocarditis (or pericarditis or myopericarditis) from primary COVID19 infection occurred at a rate as high as 450 per million in young males. Young males infected with the virus are up 6 times more likely to develop myocarditis as those who have received the vaccine.

40: Intratumoral and extratumoral synapses are required for glioblastoma progression in Drosophila
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Posted 16 Oct 2021

Intratumoral and extratumoral synapses are required for glioblastoma progression in Drosophila
4 tweets bioRxiv neuroscience

Maria Losada-Perez, Mamen Hernandez Garcia-Moreno, Sergio Casas-Tinto

Glioblastoma (GB) is the most aggressive, lethal and frequent primary brain tumor. It originates from glial cells and is characterized by rapid expansion through infiltration. GB cells interact with the microenvironment and healthy surrounding tissues, mostly neurons and vessels. GB cells project tumor microtubes (TMs) that contact with neurons and exchange signaling molecules related to Wingless/WNT, JNK, Insulin or Neuroligin-3 pathways. This cell to cell communication promotes GB expansion and neurodegeneration. Moreover, healthy neurons form glutamatergic functional synapses with GB cells which facilitate GB expansion and premature death in mouse GB xerograph models. Targeting signaling and synaptic components of GB progression may become a suitable strategy against glioblastoma. In a Drosophila GB model, we have determined the post-synaptic nature of GB cells with respect to neurons, and the contribution of post-synaptic genes expressed in GB cells to tumor progression. In addition, we document the presence of intratumoral synapses between GB cells, and the functional contribution of pre-synaptic genes to GB calcium dependent activity and expansion. Finally, we explore the relevance of synaptic genes in GB cells to the lifespan reduction caused by GB advance. Our results indicate that both presynaptic and postsynaptic proteins play a role in GB progression and lethality.

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