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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 156,985 papers from 657,798 authors.

Most tweeted biology preprints, last 24 hours

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

1: Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: A three-month nationwide experience from Israel
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Posted 24 Apr 2021

Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: A three-month nationwide experience from Israel
136 tweets medRxiv epidemiology

Yair Goldberg, Micha Mandel, Yonatan Woodbridge, Ronen Fluss, Ilya Novikov, Rami Yaari, Arnona Ziv, Laurence Freedman, Amit Huppert

Worldwide shortage of vaccination against SARS-CoV-2 infection while the pandemic is still uncontrolled leads many states to the dilemma whether or not to vaccinate previously infected persons. Understanding the level of protection of previous infection compared to that of vaccination is critical for policy making. We analyze an updated individual-level database of the entire population of Israel to assess the protection efficacy of both prior infection and vaccination in preventing subsequent SARS-CoV-2 infection, hospitalization with COVID-19, severe disease, and death due to COVID-19. Vaccination was highly effective with overall estimated efficacy for documented infection of 92.8% (CI: [92.6, 93.0]); hospitalization 94.2% (CI: [93.6, 94.7]); severe illness 94.4% (CI: [93.6, 95.0]); and death 93.7% (CI: [92.5, 94.7]). Similarly, the overall estimated level of protection from prior SARS-CoV-2 infection for documented infection is 94.8% (CI: [94.4, 95.1]); hospitalization 94.1% (CI: [91.9, 95.7]); and severe illness 96.4% (CI: [92.5, 98.3]). Our results question the need to vaccinate previously-infected individuals.

2: 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
73 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 [≥]1000 participants aged [≥]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 [≥]70 years; [≥]65 or [≥]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.

3: 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
72 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.

4: Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 Vaccine in long-term care facility residents and healthcare workers - a Danish cohort study
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Posted 09 Mar 2021

Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 Vaccine in long-term care facility residents and healthcare workers - a Danish cohort study
22 tweets medRxiv epidemiology

Ida Rask Moustsen-Helms, Hanne-Dorthe Emborg, Jens Nielsen, Katrine Finderup Nielsen, Tyra Krause, Kaare Molbak, Karina Lauenborg Moeller, Ann-Sofie Nicole Berthelsen, Palle Valentiner-Branth

Abstract Background At the end of 2020, Denmark launched an immunization program against SARS-CoV-2. The Danish health authorities prioritized persons currently living in long-term care facilities (LTCF residents) and frontline healthcare workers (HCW) as the first receivers of vaccination. Here we present preliminary population based vaccine effectiveness (VE) estimates in these two target groups. Methods The study was designed as a retrospective registry- and population-based observational cohort study including all LTCF residents and all HWC. The outcome was a polymerase chain reaction confirmed SARS-CoV-2, and VE was estimated for different periods following first and second dose. We used Poisson and Cox regressions to estimate respectively crude and calendar time-adjusted VE for the BNT162b2 mRNA Covid-19 Vaccine from Pfizer/BioNTech with 95% confidence intervals (CI) for vaccinated versus unvaccinated. Results A total of 39,040 LTCF residents (median age at first dose; 84 years, Interquartile range (IQR): 77-90) and 331,039 HCW (median age at first dose; 47 years, IQR: 36-57) were included. Among LTCF residents, 95.2% and 86.0% received first and second dose from 27 December 2020 until 18 February 2021, for HWC the proportion was 27.8% and 24.4%. During a median follow-up of 53 days , there were 488 and 5,663 confirmed SARS-CoV-2 cases in the unvaccinated groups, whereas there were 57 and 52 in LTCF residents and HCW within the first 7 days after the second dose and 27 and 10 cases beyond seven days of second dose. No protective effect was observed for LTCF residents after first dose. In HCW, VE was 17% (95% CI; 4-28) in the > 14 days after first dose (before second dose). Furthermore, the VE in LTCF residents at day 0-7 of second dose was 52% (95% CI; 27-69) and 46% (95% CI; 28-59) in HCW. Beyond seven days of second dose, VE increased to 64% (95% CI; 14-84) and 90% (95% CI; 82-95) in the two groups, respectively. Conclusion The results were promising regarding the VE both within and beyond seven days of second vaccination with the BNT162b2 mRNA Covid-19 Vaccine currently used in many countries to help mitigate the global SARS-CoV-2 pandemic. Impact of the research: So far, observational studies of the real-word effectiveness of the mRNA Vaccine BNT162b2 has been limited to the period after the administration of the first dose. This is the first report to date to present vaccine effectiveness (VE) estimates after the second BNT162b2 mRNA Covid-19 Vaccine. We estimated a VE of 52% and 46% in LTCF residents and HCW within seven days, which increased to 64% and 90% in the two groups respectively beyond seven days of immunization. These findings supports maintaining a two-dose schedule of the BNT162b2 mRNA Covid-19 Vaccine.

5: Random Forest Factorization Reveals Latent Structure in Single Cell RNA Sequencing Data
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Posted 14 Sep 2021

Random Forest Factorization Reveals Latent Structure in Single Cell RNA Sequencing Data
15 tweets bioRxiv bioinformatics

Boris M Brenerman, Benjamin Shapiro, Michael Schatz, Alexis Battle

Single-cell RNA sequencing data contain patterns of correlation that are poorly captured by techniques that rely on linear estimation or assumptions of Gaussian behavior. We apply random forest regression to scRNAseq data from mouse brains, which identifies the co-regulation of genes within specific cellular contexts. By analyzing the estimators of the random forest, we identify several novel candidate gene regulatory networks and compare these networks in aged and young mice. We demonstrate that cell populations have cell-type specific phenotypes of aging that are not detected by other methods, including the collapse of differentiating oligodendrocytes but not precursors or mature oligodendrocytes.

6: Shedding of Infectious SARS-CoV-2 Despite Vaccination when the Delta Variant is Prevalent - Wisconsin, July 2021
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Posted 31 Jul 2021

Shedding of Infectious SARS-CoV-2 Despite Vaccination when the Delta Variant is Prevalent - Wisconsin, July 2021
15 tweets medRxiv infectious diseases

Kasen K Riemersma, Brittany E Grogan, Amanda Kita-Yarbro, Peter Halfmann, Anna Kocharian, Kelsey R Florek, Ryan Westergaard, Allen Bateman, Gunnar E Jeppson, Yoshihiro Kawaoka, David H O'Connor, Thomas C Friedrich, Katarina M Grande

SARS-CoV-2 variant B.1.617.2 (delta) is associated with higher viral loads [1] and increased transmissibility relative to other variants, as well as partial escape from polyclonal and monoclonal antibodies [2]. The emergence of the delta variant has been associated with increasing case counts and test-positivity rates, indicative of rapid community spread. Since early July 2021, SARS-CoV-2 cases in the United States have increased coincident with delta SARS-CoV-2 becoming the predominant lineage nationwide [3]. Understanding how and why the virus is spreading in settings where there is high vaccine coverage has important public health implications. It is particularly important to assess whether vaccinated individuals who become infected can transmit SARS-CoV-2 to others. In Wisconsin, a large local contract laboratory provides SARS-CoV-2 testing for multiple local health departments, providing a single standard source of data using the same assay to measure virus burdens in test-positive cases. This includes providing high-volume testing in Dane County, a county with extremely high vaccine coverage. These PCR-based tests provide semi-quantitative information about the viral load, or amount of SARS-CoV-2 RNA, in respiratory specimens. Here we use this viral load data to compare the amount of SARS-CoV-2 present in test-positive specimens from people who self-report their vaccine status and date of final immunization, during a period in which the delta variant became the predominant circulating variant in Wisconsin. We find no difference in viral loads when comparing unvaccinated individuals to those who have vaccine "breakthrough" infections. Furthermore, individuals with vaccine breakthrough infections frequently test positive with viral loads consistent with the ability to shed infectious viruses. Our results, while preliminary, suggest that if vaccinated individuals become infected with the delta variant, they may be sources of SARS-CoV-2 transmission to others.

7: Structure of a bacterial Rhs effector exported by the type VI secretion system
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Posted 14 Sep 2021

Structure of a bacterial Rhs effector exported by the type VI secretion system
12 tweets bioRxiv biochemistry

Patrick Guenther, Dennis Quentin, Shehryar Ahmad, Kartik Sachar, Christos Gatsogiannis, John Whitney, Stefan Raunser

The type VI secretion system (T6SS) is a widespread protein export apparatus found in Gram-negative bacteria. The majority of T6SSs deliver toxic effector proteins into competitor bacteria. Yet, the structure, function, and activation of many of these effectors remains poorly understood. Here, we present the structures of the T6SS effector RhsA from Pseudomonas protegens and its cognate T6SS spike protein, VgrG1, at 3.3 [A] resolution. The structures reveal that the rearrangement hotspot (Rhs) repeats of RhsA assemble into a closed anticlockwise {beta}-barrel spiral similar to that found in bacterial insecticidal Tc toxins and in metazoan teneurin proteins. We find that the C-terminal toxin domain of RhsA is autoproteolytically cleaved but remains inside the Rhs 'cocoon' where, with the exception of three ordered structural elements, most of the toxin is disordered. The N-terminal 'plug' domain is unique to T6SS Rhs proteins and resembles a champagne cork that seals the Rhs cocoon at one end while also mediating interactions with VgrG1. Interestingly, this domain is also autoproteolytically cleaved inside the cocoon but remains associated with it. We propose that mechanical force is required to remove the cleaved part of the plug, resulting in the release of the toxin domain as it is delivered into a susceptible bacterial cell by the T6SS.

8: Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study
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Posted 31 Jul 2021

Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study
11 tweets medRxiv infectious diseases

Po Ying Chia, Sean Ong, Calvin J Chiew, Li Wei Ang, Jean-marc Gilbert Chavatte, Tze Minn Mak, Lin Cui, Shirin Kalimuddin, Wan Ni Chia, Chee Wah Tan, Louis Yi Ann Chai, Seow Yen Tan, Shuwei Zheng, Raymong Tzer Pin Lin, Linfa Wang, Yee-Sin Leo, Vernon J. Lee, David Chien Lye, Barnaby Edward Young

Objectives Highly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns (VOCs) with mutations in the spike protein are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections. Methods We conducted a multi-centre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared the clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals. Results Of 218 individuals with B.1.617.2 infection, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). PCR cycle threshold (Ct) values were similar between both vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients, however, these titers were significantly lower against B.1.617.2 as compared with the wildtype vaccine strain. Conclusion The mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of COVID-19 pandemic.

9: Long-term symptoms after SARS-CoV-2 infection in school children: population-based cohort with 6-months follow-up. Short Report
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Posted 18 May 2021

Long-term symptoms after SARS-CoV-2 infection in school children: population-based cohort with 6-months follow-up. Short Report
10 tweets medRxiv epidemiology

Thomas Radtke, Agne Ulyte, Milo Alan Puhan, Susi Kriemler

Although nobody doubts the existence of long COVID in children, it is still unclear to what extent children are affected. The Ciao Corona study is a longitudinal cohort investigating SARS-CoV-2 seroprevalence and clustering of cases among around 2500 children from 55 randomly selected primary and secondary schools in the canton of Zurich in Switzerland. Between June 2020 and April 2021, we completed three testing phases where we collected venous blood for serological analysis (ABCORA 2.0 test) and asked about symptoms with online questionnaires. We compared children who tested positive for SARS-CoV-2 antibodies in October/November 2020 with those who tested negative. Children who were seronegative in October/November 2020 and seroconverted or were not retested by March/April 2021 were excluded from the analysis (n=256). In March-May 2021 we assessed the presence of symptoms occurring since October 2020, lasting for at least 4 weeks, and persisting for either >4 weeks or >12 weeks. Overall, 1355 of 2503 children with a serology result in October/November 2020 and follow up questionnaire in March/April 2021 were included. Among seropositive and seronegative 6-to 16-year-old children and adolescents, 9% versus 10% reported at least one symptom beyond 4 weeks, and 4% versus 2% at least one symptom beyond 12 weeks. None of the seropositive children reported hospitalization after October 2020. Seropositive children, all with a history of pauci-symptomatic SARS-CoV-2 infection, did not report long COVID more frequently than seronegative children. This study suggests a very low prevalence of long COVID in a randomly selected population-based cohort of children followed over 6 months after serological testing.

10: The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses
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Posted 06 May 2021

The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses
9 tweets medRxiv infectious diseases

F. Konstantin Föhse, Büsranur Geckin, Gijs Overheul, Josephine van de Maat, Gizem Kilic, Ozlem Bulut, Helga Dijkstra, Heidi Lemmers, S. Andrei Sarlea, Maartje Reijnders, Jacobien Hoogerwerf, Jaap ten Oever, Elles Simonetti, Frank L van de Veerdonk, Leo A.B. Joosten, Bart L. Haagmans, Reinout van Crevel, Yang Li, Ronald P. van Rij, Corine GeurtsvanKessel, Marien I. de Jonge, Jorge Domínguez-Andrés, Mihai G. Netea

The mRNA-based BNT162b2 vaccine from Pfizer/BioNTech was the first registered COVID-19 vaccine and has been shown to be up to 95% effective in preventing SARS-CoV-2 infections. Little is known about the broad effects of the new class of mRNA vaccines, especially whether they have combined effects on innate and adaptive immune responses. Here we confirmed that BNT162b2 vaccination of healthy individuals induced effective humoral and cellular immunity against several SARS-CoV-2 variants. Interestingly, however, the BNT162b2 vaccine also modulated the production of inflammatory cytokines by innate immune cells upon stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli. The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2 vaccination, while fungi-induced cytokine responses were stronger. In conclusion, the mRNA BNT162b2 vaccine induces complex functional reprogramming of innate immune responses, which should be considered in the development and use of this new class of vaccines.

11: Multiplexed profiling of kinase interactomes quantifies cellular network plasticity
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Posted 15 Sep 2021

Multiplexed profiling of kinase interactomes quantifies cellular network plasticity
9 tweets bioRxiv biochemistry

Martin Golkowski, Andrea Lius, Tanmay S Sapre, Ho-Tak Lau, Taylor Moreno, Dustin J. Maly, Shao-En Ong

Cells utilize protein-protein interaction (PPI) networks to receive, transduce, and respond to stimuli. Interaction network rewiring drives devastating diseases like cancers, making PPIs attractive targets for pharmacological intervention. Kinases are druggable nodes in PPI networks but high-throughput proteomics approaches to quantify disease-associated kinome PPI rewiring are lacking. We introduce kinobead competition and correlation analysis (Ki-CCA), a chemoproteomics approach to simultaneously map hundreds of endogenous kinase PPIs. We identified 2,305 PPIs of 300 kinases across 18 diverse cancer lines, quantifying the high plasticity of interaction networks between cancer types, signaling, and phenotypic states; this database of dynamic kinome PPIs provides deep insights into cancer cell signaling. We discovered an AAK1 complex promoting epithelial-mesenchymal transition and drug resistance, and depleting its components sensitized cells to targeted therapy. Ki-CCA enables rapid and highly multiplexed mapping of kinome PPIs in native cell and tissue lysates, without epitope tagged baits, protein labeling, or antibodies.

12: Differences in evolutionary accessibility determine which equally effective regulatory motif evolves to generate pulses
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Posted 03 Dec 2020

Differences in evolutionary accessibility determine which equally effective regulatory motif evolves to generate pulses
9 tweets bioRxiv evolutionary biology

Kun Xiong, Mark Gerstein, Joanna Masel

Transcriptional regulatory networks (TRNs) are enriched for certain "motifs". Motif usage is commonly interpreted in adaptationist terms, i.e. that the optimal motif evolves. But certain motifs can also evolve more easily than others. Here, we computationally evolved TRNs to produce a pulse of an effector protein. Two well-known motifs, type 1 incoherent feed-forward loops (I1FFLs) and negative feedback loops (NFBLs), evolved as the primary solutions. Which motif evolves more often depends on selection conditions, but under all conditions, either motif achieves similar performance. I1FFLs generally evolve more often than NFBLs, unless we select for a tall pulse. I1FFLs are more evolutionarily accessible early on, before the effector protein evolves high expression; when NFBLs subsequently evolve, they tend to do so from a conjugated I1FFL-NFBL genotype. In the empirical S. cerevisiae TRN, output genes of NFBLs had higher expression levels than those of I1FFLs. These results suggest that evolutionary accessibility, and not relative functionality, shapes which motifs evolve in TRNs, and does so as a function of the expression levels of particular genes.

13: ADataViewer: Exploring Semantically Harmonized Alzheimer's Disease Cohort Datasets
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Posted 14 Sep 2021

ADataViewer: Exploring Semantically Harmonized Alzheimer's Disease Cohort Datasets
8 tweets medRxiv health informatics

Yasamin Salimi, Daniel Domingo-Fernandez, Carlos Bobis-Alvarez, Martin Hofmann-Apitius, Alzheimer's Disease Neuroimaging Initiative, Japanese Alzheimer's Disease Neuroimaging Initiative, Aging Brain: Vasculature, Ischemia, and Behavior Study, Alzheimer's Disease Repository Without Borders Investigators, European Prevention of Alzheimer's Disease (EPAD) Consortium, Colin Birkenbihl

INTRODUCTION: Currently, AD cohort datasets are difficult to find, lack across-cohort interoperability, and the content of the shared datasets often only becomes clear to third-party researchers once data access has been granted. METHODS: We accessed and systematically investigated the content of 20 major AD cohort datasets on data-level. A medical professional and a data specialist manually curated and semantically harmonized the acquired datasets. We developed a platform that facilitates data exploration. RESULTS: We present ADataViewer, an interactive platform that facilitates the exploration of 20 cohort datasets with respect to longitudinal follow-up, demographics, ethnoracial diversity, measured modalities, and statistical properties of individual variables. Additionally, we publish a variable mapping catalog harmonizing 1,196 variables across the 20 cohorts. The platform is available under https://adata.scai.fraunhofer.de/. DISCUSSION: ADataViewer supports robust data-driven research by transparently displaying cohort dataset content and suggesting datasets suited for discovery and validation studies based on selected variables of interest.

14: Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence
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Posted 08 Aug 2021

Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence
7 tweets medRxiv public and global health

Arjun Puranik, Patrick Lenehan, Eli Silvert, Michiel JM Niesen, Juan Corchado-Garcia, John C O'Horo, Abinash Virk, Melanie D Swift, John Halamka, Andrew D Badley, AJ Venkatakrishnan, Venky Soundararajan

Although clinical trials and real-world studies have affirmed the effectiveness and safety of the FDA-authorized COVID-19 vaccines, reports of breakthrough infections and persistent emergence of new variants highlight the need to vigilantly monitor the effectiveness of these vaccines. Here we compare the effectiveness of two full-length Spike protein-encoding mRNA vaccines from Moderna (mRNA-1273) and Pfizer/BioNTech (BNT162b2) in the Mayo Clinic Health System over time from January to July 2021, during which either the Alpha or Delta variant was highly prevalent. We defined cohorts of vaccinated and unvaccinated individuals from Minnesota (n = 25,589 each) matched on age, sex, race, history of prior SARS-CoV-2 PCR testing, and date of full vaccination. Both vaccines were highly effective during this study period against SARS-CoV-2 infection (mRNA-1273: 86%, 95%CI: 81-90.6%; BNT162b2: 76%, 95%CI: 69-81%) and COVID-19 associated hospitalization (mRNA-1273: 91.6%, 95% CI: 81-97%; BNT162b2: 85%, 95% CI: 73-93%). However, in July, the effectiveness against infection was considerably lower for mRNA-1273 (76%, 95% CI: 58-87%) with an even more pronounced reduction in effectiveness for BNT162b2 (42%, 95% CI: 13-62%). Notably, the Delta variant prevalence in Minnesota increased from 0.7% in May to over 70% in July whereas the Alpha variant prevalence decreased from 85% to 13% over the same time period. Comparing rates of infection between matched individuals fully vaccinated with mRNA-1273 versus BNT162b2 across Mayo Clinic Health System sites in multiple states (Minnesota, Wisconsin, Arizona, Florida, and Iowa), mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). Our observational study highlights that while both mRNA COVID-19 vaccines strongly protect against infection and severe disease, further evaluation of mechanisms underlying differences in their effectiveness such as dosing regimens and vaccine composition are warranted.

15: COVID-19: Rapid Antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing
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Posted 15 Jan 2021

COVID-19: Rapid Antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing
7 tweets medRxiv infectious diseases

UK COVID-19 Lateral Flow Oversight Team, Tim Peto

Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Here we report on standardised laboratory evaluations of LFDs, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots (UK COVID-19 testing centres, hospital, schools, armed forces). 4/64 LFDs so far have desirable performance characteristics (Orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1-6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20-0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists (156/198, 95% CI 72.4-84.3) was 78.8%. Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding: Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research.

16: Ecological constraints on highly evolvable olfactory receptor genes and morphology
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Posted 06 Sep 2021

Ecological constraints on highly evolvable olfactory receptor genes and morphology
7 tweets bioRxiv evolutionary biology

Laurel R Yohe, Matteo Fabbri, Daniela Lee, Kalina Davies, Thomas P Yohe, Miluska KR Sanchez, Edgar Rengifo, Ronald Hall, Gregory Mutumi, Brandon P. Hedrick, Alexa Aline Sadier, Nancy B Simmons, Karen E. Sears, Elizabeth Dumont, Stephen Rossiter, Bhart-Anjan Bhullar, Liliana Davalos

While evolvability of genes and traits may promote specialization during species diversification, how ecology subsequently restricts such variation remains unclear. Chemosensation requires animals to decipher a complex chemical background to locate fitness-related resources, and thus the underlying genomic architecture and morphology must cope with constant exposure to a changing odorant landscape; detecting adaptation amidst extensive chemosensory diversity is an open challenge. Phyllostomid bats, an ecologically diverse clade that evolved plant-visiting from an insectivorous ancestor, suggests the evolution of novel food detection mechanisms is a key innovation: phyllostomids behaviorally rely strongly on olfaction, while echolocation is supplemental. If this is true, exceptional variation of underlying olfactory genes and phenotypes may have preceded dietary diversification. We compared olfactory receptor (OR) genes sequenced from olfactory epithelium transcriptomes and olfactory epithelium surface area of bats with differing diets. Surprisingly, although OR evolution rates were quite variable and generally high, they are largely independent of feeding ecology. olfactory epithelial surface area, however, is greater in plant-visiting bats and there is an inverse relationship between OR evolution rates and surface area. Larger surface areas suggest greater reliance on olfactory detection and stronger ecological constraint on maintaining an already diverse OR repertoire. Instead of the typical case in which specialization and elaboration is coupled with rapid diversification of associated genes, here the relevant genes are already evolving so quickly that increased reliance on smell has led to stabilizing selection, presumably to maintain the ability to consistently discriminate among specific odorants - an ecological constraint on sensory evolution.

17: Rapid initiation of nasal saline irrigation to reduce morbidity and mortality in COVID+ outpatients: a randomized clinical trial compared to a national dataset
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Posted 17 Aug 2021

Rapid initiation of nasal saline irrigation to reduce morbidity and mortality in COVID+ outpatients: a randomized clinical trial compared to a national dataset
6 tweets medRxiv infectious diseases

Amy L. Baxter, Kyle R. Schwartz, Ryan W. Johnson, Taylor Giller, Kevin M. Swartout, Arni Rao, Ann M Kuchinski, Robert W Gibson, Houlton Boomer, Erica Cherian, Matthew Lyon, Richard B Schwartz

Importance: SARS-CoV-2 enters the nasopharynx to replicate; mechanical debridement with nasal irrigation soon after diagnosis could reduce morbidity and mortality. Objective: To determine whether initiating nasal irrigation after COVID-19 diagnosis reduces hospitalizations and death, and whether irrigant composition impacts severity. Design: Unblinded randomized clinical trial of two nasal irrigation protocols in outpatients PCR positive for SARS-CoV-2, nested in a prospective case:cohort using laboratory-confirmed cases in the CDC COVID-19 Case Surveillance dataset. Setting: Single-lab community testing facility associated with the emergency department (ED) in Augusta, GA. Participants: A consecutive sample of outpatients 55 years and older were contacted from daily COVID-19+ lab reports between September 24 and December 21 of 2020. Patients without supplemental oxygen use or cognitive barriers agreeing to same-day irrigation initiation were remotely consented. Among 826 screened, 321 were unable to be reached, 132 were ineligible, 294 refused participation, and 79 participants were enrolled. Interventions: Participants were randomly assigned adding 2.5 mL povidone-iodine 10% or 2.5 mL sodium bicarbonate to 240ml of isotonic nasal irrigation twice daily for 14 days. Main Outcomes and Measures: The primary outcome was hospitalization or death from COVID-19 within 28 days of enrollment by daily self-report confirmed with phone calls and hospital records, compared to the CDC Surveillance Dataset covering the same time. Secondary outcomes compared symptom resolution by irrigant additive. Results: Seventy-nine participants were enrolled (mean [SD] age, 64 [8] years; 36 [46%] women; 71% Non-Hispanic White). Analyzed by intention-to-treat, by day 28, COVID-19 symptoms resulted in 1/42 hospitalizations in those irrigating with alkalinization, 0/37 in the povidone-iodine group, (1.27%) and no deaths. Of nearly three million CDC cases, 9.14% were known to be hospitalized, with an additional 1.5% mortality in those without hospitalization data. The total risk of hospitalization or death (10.6%) was 8.4 times that of enrolled patients (SE=2.74; P=.006). 62 completed daily surveys (78%), averaging 1.8 irrigations/day. Eleven had irrigation complaints, and four discontinued. There were no significant differences by additive. Conclusion: SARS-CoV-2+ participants initiating nasal irrigation were over 8 times less likely to be hospitalized than the national rate.

18: Structural Basis of Substrate Recognition by the Mitochondrial ADP/ATP Transporter
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Posted 15 Sep 2021

Structural Basis of Substrate Recognition by the Mitochondrial ADP/ATP Transporter
6 tweets bioRxiv biophysics

Shihao Yao, Qiuzi Yi, Boyuan Ma, Xiaoting Mao, Ye Chen, Min-Xin Guan, Xiaohui Cang

Specific import of ADP and export of ATP by ADP/ATP carrier (AAC) across the inner mitochondrial membrane are crucial for sustainable energy supply in all eukaryotes. However, mechanism for highly specific substrate recognition in the dynamic transport process remains largely elusive. Here, unguided MD simulations of 22 microseconds in total reveal that AAC in ground c-state uses the second basic patch (K91K95R187), tyrosine ladder (Y186Y190Y194), F191 and N115 in the upper region of the cavity to specifically recognize ADP and confer selectivity for ADP over ATP. Mutations of these residues in yeast AAC2 reduce ADP transport across the L. lactis membrane and induce defects in OXPHOS and ATP production in yeast. Sequence analyses also suggest that AAC and other adenine nucleotide transporters use the upper region of the cavity, rather than the central binding site to discriminate their substrates. Identification of the new site unveils the unusually high substrate specificity of AAC, and together with central binding site support early biochemical findings about existence of two substrate binding sites. Our results imply that using different sites for substrate recognition and conformational transition could be a smart strategy for transporters to cope with substrate recognition problem in the highly dynamic transport process.

19: Identifying and correcting multiple sources of misspecification in GWAS summary statistics for polygenic scores
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Posted 30 Mar 2021

Identifying and correcting multiple sources of misspecification in GWAS summary statistics for polygenic scores
5 tweets bioRxiv genetics

Florian Privé, Julyan Arbel, Hugues Aschard, Bjarni J. Vilhjálmsson

Are genome-wide association studies (GWAS) summary statistics of good enough quality for performing follow-up analyses? Can we detect possible misspecifications in GWAS summary statistics and correct for them in order to improve predictive performance of polygenic scores?

20: 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
5 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.

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