bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the file management method of data storage system for airborne radar
Authors: Tian Haishan , Ju Fangfang , Nie Hongshan , Yang Qiong , Wu Yuanyu , Li Shuangjian
Published: June 2021

In order to solve the problem that the air-to-ground data transfer rate is much lower than the radar data rate, the onboard system is commonly used for storing the airborne radar data. However, there are two main problems in the data storage using the traditional file management method. The first is that the frequent data updating of the file allocation table (FAT) and the file directory table (FDT) cause a high frequency of address jumps among the discontinuous areas, which leads to a long response time. The second is that the updating frequencies of the FAT, the FDT and the data region are seriously inconsistent, which results in uneven wear of the three areas. To solve these two problems, a file management method, which optimizes the data writing in the three areas of the FAT, the FDT and the data region, is proposed in this study. An actual measurement is carried out on a data storage system of the airborne radar using the proposed file management method. The result shows that the proposed method significantly reduces the updating frequency of FAT and FDT, and achieves the wear levelling of file area and data region.
Optimal governance and implementation of vaccination programmes to contain the COVID-19 pandemic
Authors: Piraveenan Mahendra , Sawleshwarkar Shailendra , Walsh Michael , Zablotska Iryna , Bhattacharyya Samit , Farooqui Habib Hassan , Bhatnagar Tarun , Karan Anup , Murhekar Manoj , Zodpey Sanjay , Rao K. S. Mallikarjuna , Pattison Philippa , Zomaya Albert , Perc Matjaz
Published: June 2021

Since the recent introduction of several viable vaccines for SARS-CoV-2, vaccination uptake has become the key factor that will determine our success in containing the COVID-19 pandemic. We argue that game theory and social network models should be used to guide decisions pertaining to vaccination programmes for the best possible results. In the months following the introduction of vaccines, their availability and the human resources needed to run the vaccination programmes have been scarce in many countries. Vaccine hesitancy is also being encountered from some sections of the general public. We emphasize that decision-making under uncertainty and imperfect information, and with only conditionally optimal outcomes, is a unique forte of established game-theoretic modelling. Therefore, we can use this approach to obtain the best framework for modelling and simulating vaccination prioritization and uptake that will be readily available to inform important policy decisions for the optimal control of the COVID-19 pandemic.
The avian compass can be sensitive even without sustained electron spin coherence
Authors: Jain Rakshit , Poonia Vishvendra S. , Saha Kasturi , Saha Dipankar , Ganguly Swaroop
Published: June 2021

Theoretical studies indicating the presence of long-lived coherence in the radical pair system have engendered questions about its utilitarian role in the avian compass. In this paper, we investigate the role of electron spin coherence in a multinuclear radical pair system including its impact on compass sensitivity. We find that sustenance of long-lived electron spin coherence is unlikely in a multinuclear hyperfine environment. After probing the role of the hyperfine interactions in the compass, we affirm the hyperfine anisotropy to be an essential parameter for the necessary sensitivity required for the compass action. Thereby, we identify a parameter regime where the compass would exhibit good sensitivity even without sustained electron spin coherence.
More views of a one-sided surface: mechanical models and stereo vision techniques for Möbius strips
Authors: Kumar Arun , Handral Poornakanta , Bhandari Darshan , Rangarajan Ramsharan
Published: June 2021

Möbius strips are prototypical examples of ribbon-like structures. Inspecting their shapes and features provides useful insights into the rich mechanics of elastic ribbons. Despite their ubiquity and ease of construction, quantitative experimental measurements of the three-dimensional shapes of Möbius strips are surprisingly non-existent in the literature. We propose two novel stereo vision-based techniques to this end—a marker-based technique that determines a Lagrangian description for the construction of a Möbius strip, and a structured light illumination technique that furnishes an Eulerian description of its shape. Our measurements enable a critical evaluation of the predictive capabilities of mechanical theories proposed to model Möbius strips. We experimentally validate, seemingly for the first time, the developable strip and the Cosserat plate theories for predicting shapes of Möbius strips. Equally significantly, we confirm unambiguous deficiencies in modelling Möbius strips as Kirchhoff rods with slender cross-sections. The experimental techniques proposed and the Cosserat plate model promise to be useful tools for investigating a general class of problems in ribbon mechanics.
Streptomyces coffeae sp. nov., an endophytic actinomycete isolated from the root of Coffea arabica (L.)
Authors: Nammali Achararak , Intaraudom Chakapong , Pittayakhajonwut Pattama , Suriyachadkun Chanwit , Tadtong Sarin , Srabua Phatraya , Thawai Chitti
Published: June 2021

An endophytic actinobacterium, designated strain CA1R205T, was isolated from the surface-sterilized root of Coffea arabica L. collected from Ratchaburi province, Thailand. The taxonomic position of this strain was evaluated using a polyphasic approach. The strain produced light yellowish brown to dark brownish black substrate mycelium and greyish white aerial mycelium. The spiral spore chains were produced directly on aerial mycelium. CA1R205T was found to have
ll
-diaminopimelic acid in the cell peptidoglycan, galactose, glucose, mannose and ribose as whole-cell reducing sugars, MK-10(H4), MK-9(H6), MK-10(H2), MK-9(H4), MK-10(H6) and MK-10(H8) as menaquinones and iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0 and C16 : 0 as major fatty acids. Diphosphatidylglycerol, phosphatidylethanolamine, hydroxyphosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol were detected in the cells. These characteristics were consistent the typical chemotaxonomic properties of members the genus

Streptomyces

. The taxonomic affiliation at the genus level of this strain could be confirmed using its 16S rRNA gene sequence data. CA1R205T showed the highest 16S rRNA gene sequence similarity value to

Streptomyces rapamycinicus

NRRL B-5491T (98.9 %), followed by

Streptomyces iranensis

HM 35T (98.8 %). Digital DNA–DNA hybridization and average nucleotide identity-by blast (ANIb) values between CA1R205T and

S. rapamycinicus

NRRL B-5491T were 27.2 and 81.5 %, respectively. The DNA G+C content of genomic DNA was 70.7 mol%. Due to the differences in physiological, biochemical and genotypic data, CA1R205T could be discriminated from its closest neighbour. Thus, CA1R205T should be recognized as representing a novel species of the genus

Streptomyces

, for which the name Streptomyces coffeae sp. nov. is proposed. The type strain is CA1R205T (=TBRC 11244T=NBRC 114295T).
Robustness and bias of European excess death estimates in 2020 under varying model specifications
Authors: Schöley Jonas
Published: June 2021

Various procedures are in use to calculate excess deaths during the ongoing COVID-19 pandemic. Using weekly death counts from 20 European countries, we evaluate the robustness of excess death estimates to the choice of model for expected deaths and perform a cross-validation analysis to assess the error and bias in each model’s predicted death counts. We find that the different models produce very similar patterns of weekly excess deaths but disagree substantially on the level of excess. While the exact country ranking along percent excess death in 2020 is sensitive to the choice of model the top and bottom ranks are robustly identified. On the country level, the 5-year average death rate model tends to produce the lowest excess death estimates, whereas high excess deaths are produced by the popular 5-year average death count and Euromomo-style Serfling models. Cross-validation revealed these estimates to be biased under a causal interpretation of “expected deaths had COVID-19 not happened.”
The mental health impact of COVID-19 racial and ethnic discrimination against Asian American and Pacific Islanders
Authors: Zhou Sasha , Banawa Rachel , Oh Hans
Published: June 2021

Hate crimes against Asian American/ Pacific Islanders (AAPIs) have surged in the United States during the COVID-19 pandemic to alarming new levels. We analyzed data from the Healthy Minds Study, and found that COVID-19 related racial/ethnic discrimination was associated with greater odds of having depression, anxiety, non-suicidal self-injury, binge drinking, and suicidal ideation among AAPI university students (N=1697). Findings suggest that the COVID-19 pandemic precipitated discrimination, which has been linked to mental health problems, calling for more preventive interventions to address the AAPI population, especially given their low rates of formal treatment utilization.
Post-COVID-19 Perceived Stigma-Discrimination Scale: Psychometric Development and Evaluation
Authors: Cassiani-Miranda Carlos Arturo , Pedrozo-Pupo John Carlos , Campo-Arias Adalberto
Published: June 2021

The COVID-19 survivors face social stigmatization, even with negative tests. Valid and reliable instruments are required to quantify the stigma-discrimination complex associated with COVID-19 (COVID-19-CED). The study aimed to adapt and evaluate a scale to measure COVID-19-CED in COVID-19 survivors. A validation study was done with 330 COVID-19 survivors between 18 and 89 years. The COVID-19 Perceived Discrimination Scale (C-19-PDS) was used, which was adapted from the Tuberculosis Perceived Discrimination Scale. An exploratory factor analysis (EFA), confirmatory factor analysis (CFA), internal consistency, and differential item functioning (DIF) were performed using the classical theory of tests. EFA showed a one-dimensional solution for the items of C-19-PDS; however, CFA showed poor goodness-of-fit indicators. The 5-item version of the C-19-PDS showed better goodness-of-fit indicators, high internal consistency, and non-gender DIF. In conclusion, the 5-item version of the C-19-PDS is one-dimensional, with high internal consistency, and without gender DIF. This instrument is recommended to evaluate COVID-19-CED in the Colombian population.
Antipsychotic Drugs and the Risk of Breast Cancer
Authors: Rahman Tahir , Sahrmann John M. , Olsen Margaret A. , Nickel Katelin B. , Miller J. Phillip , Ma Cynthia , Grucza Richard A.
Published: June 2021

Objective

Antipsychotic drugs are well established to alter circulating prolactin levels by blocking dopamine D-2 receptors in the pituitary. Prolactin activates many genes important in the development of breast cancer. The aim of this study was to evaluate the risk of breast cancer in women exposed to antipsychotic drugs, stratified by prolactin elevating potential (high, mid, and low), compared to women taking anticonvulsants and/or lithium.

Methods

The IBM MarketScan Commercial and Medicaid Databases were used to establish a large, observational cohort of women taking antipsychotics drugs compared to control drugs. Invasive breast cancer was identified using diagnostic codes. Bivariable and multivariable Cox proportional hazards models were used to evaluate the risk of breast cancer by antipsychotic drug exposure, both as pooled antipsychotics and by prolactin specific categories.

Results

A total of 2,708 (0.2%) cases of invasive breast cancer were identified among 1,562,839 women. Exposure to antipsychotics with high prolactin elevating potential was associated with a 23% increased risk of breast cancer (aHR 1.23; 95% CI, 1.11-1.35), whereas mid and low prolactin categories of antipsychotics were not significant.

Conclusion

In the largest study of antipsychotics taken by women, a modest risk between antipsychotic drug use and the risk for breast cancer was observed, with a differential higher association with high prolactin elevating drugs. Residual confounding factors included incomplete information on parity, race and socioeconomic status, and differential outpatient visits. Clinicians should consider monitoring serum prolactin levels and adopting vigilant mammography screening practices, especially in older women taking category one antipsychotics.
g-CXR-Net: A Graphic Application for the Rapid Recognition of SARS-CoV-2 from Chest X-Rays
Authors: Gatti Domenico L.
Published: June 2021

g-CXR-Net is a graphic application for the rapid recognition of SARS-CoV-2 from Antero/Posterior chest X-rays. It employs the Artificial Intelligence engine of CXR-Net (arXiv:2103.00087) to generate masks of the lungs overlapping the heart and large vasa, probabilities for Covid vs. non-Covid assignment, and high resolution heat maps that identify the SARS associated lung regions.
WHAT ABOUT USING SNIFFIN’ STICKS 12 SCREENING TEST TO IDENTIFY POST-COVID-19 OLFACTORY DISORDERS?
Authors: Vandersteen Clair , Payne Magali , Dumas Louise-Émilie , Plonka Alexandra , D’Andrea Grégoire , Chirio David , Demonchy Élisa , Risso Karine , Askenazy-Gittard Florence , Guevara Nicolas , Castillo Laurent , Manera Valeria , Gros Auriane
Published: June 2021

Background

Olfactory impairment is a major sequela of SARS-CoV-2 infection and has a negative impact on daily life quality. Olfactory loss can be assessed in many ways but seems to be little realized in a daily clinical practice. The sniffin Sticks test – 12 items (SST-12) can be used in quick olfactory disorders screening. Its use in a post-covid19 situation was the main objective of this work.

Methodology

Consecutive patients consulting to the ENT department with post-Covid-19 olfactory loss were included. The clinical examination included an analog scale for the self-assessment of olfactory recovery (VAS), self-reported salt and sugar intake, a nasofibroscopy, the complete Sniffin’ Stick Test (SST) and the SST-12.

Results

Among the 54 patients included, based on the SST-12, 14,8% (n=8) of the patients could be classified as normosmic (SST-12≥11), 48,1% (n=26) as hyposmic (6< SST-12<10) and 37% (n=20) as functional anosmic (SST-12≤6). We report excellent and significant correlations between SST-12 and SST or VAS assessments. Salt and Sugar increased intake seems significantly related to SST-12 results.

Conclusions

SST-12 is a reliable way to screen post-COVID-19 olfactory disorders could be used in a daily clinical practice and might be used to prevent bad diet habits and so cardiovascular risk.
Operationalizing a routine wastewater monitoring laboratory for SARS-CoV-2
Authors: Kantor Rose S. , Greenwald Hannah D. , Kennedy Lauren C. , Hinkle Adrian , Harris-Lovett Sasha , Metzger Matthew , Thornton Melissa M. , Paluba Justin M. , Nelson Kara L.
Published: June 2021

Wastewater-based testing for SARS-CoV-2 is a novel tool for public health monitoring, but additional laboratory capacity is needed to provide routine monitoring at all locations where it has the potential to be useful. Few standardization practices for SARS-CoV-2 wastewater analysis currently exist, and quality assurance/quality control procedures may vary across laboratories. Alongside counterparts at many academic institutions, we built out a laboratory for routine monitoring of wastewater at the University of California, Berkeley. Here, we detail our group’s establishment of a wastewater testing laboratory including standard operating procedures, laboratory buildout and workflow, and a quality assurance plan. We present a complete data analysis pipeline and quality scoring framework and discuss the data reporting process. We hope that this information will aid others at research institutions, public health departments, and wastewater agencies in developing programs to support wastewater monitoring for public health decision-making.
Financial Meltdown in “Swing Hospitals” during the COVID-19 Outbreak
Authors: Takaku Reo , Yokoyama Izumi
Published: June 2021

Hospitals in Japan have complete autonomy in deciding whether to admit COVID-19 patients, similar to that of the US. Taking this into account, we estimated the effect of admitting COVID-19 patients on hospital profits, using instrumental variable (IV) regression. Using IVs related to government intervention enabled us to not only estimate the effect of admitting COVID-19 patients among “swing hospitals,” where both options (to admit or to not admit COVID-19 patients) could potentially be realized but to also evaluate the effect of government intervention on such hospitals. Our empirical results revealed that monthly profits per bed decreased by approximately JPY 600,000 (≈USD 6,000) among swing hospitals, which is 15 times the average monthly profits in 2019. This overwhelming financial damage indicates that it would be costly for swing hospitals to treat COVID-19 patients because of their low suitability for admitting such patients. Given the implications of our main results, we propose an alternative strategy to handling surges in patients with new infectious diseases.
Genetic and environmental determinants of diastolic heart function
Authors: Thanaj Marjola , Mielke Johanna , McGurk Kathryn A. , Bai Wenjia , Savioli Nicoló , de Marvao Antonio , Meyer Hannah V. , Zeng Lingyao , Sohler Florian , Wilkins Martin R. , Ware James S. , Bender Christian , Rueckert Daniel , MacNamara Aidan , Freitag Daniel F. , O’Regan Declan P.
Published: June 2021

Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends on myocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processes and is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiac motion analysis to measure diastolic functional traits in 39,559 participants of UK Biobank and perform a genome-wide association study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomeric function under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes were independent predictors of diastolic function and we found a causal relationship between ventricular stiffness and heart failure. Our results provide novel insights into the genetic and environmental factors influencing diastolic function that are relevant for identifying causal relationships and tractable targets in heart failure.
Neutralizing anti-DNase1L3 antibodies derive from autoreactive VH4-34+-B cells and associate with the interferon signature in SLE
Authors: Yu Yikai , Gomez-Bañuelos Eduardo , Li Jessica , Cashman Kevin S. , Paz Merlin , Trejo-Zambrano Maria Isabel , Bugrovsky Regina , Wang Youliang , Chida Asiya Seema , Sherman-Baust Cheryl A. , Ferris Dylan P. , Goldman Daniel W. , Darrah Erika , Petri Michelle , Sanz Iñaki , Andrade Felipe
Published: June 2021

DNase1L3 deficiency is an inborn error of immunity that causes monogenic systemic lupus erythematosus (SLE) in humans. Here, we identified that one third of patients with sporadic SLE have antibodies to DNase1L3. Like DNase1L3 deficiency, we found that patients with anti-DNase1L3 antibodies have features associated with immune pathways activated by immunogenic self-DNA, including elevated antibodies to dsDNA and prominent expression of the interferon and myeloid/neutrophil signatures. Interestingly, 40-80% of anti-DNase1L3 antibodies in SLE serum contain the 9G4 idiotype, which is encoded by the autoreactive heavy-chain gene segment VH4-34. Sequence and functional analysis of four anti-DNase1L3 monoclonal antibodies generated from SLE patients experiencing disease-associated flares showed that these antibodies were derived from self-reactive 9G4+switched memory B cells. These antibodies are highly enriched in somatic hypermutations, indicating that they originated from antigen-experienced cells, and have neutralizing activity against DNase1L3. Together, the data demonstrate that autoantibodies to DNase1L3 phenocopy pathogenic mechanisms associated with DNase1L3 deficiency. Moreover, the finding that autoreactive B cells bearing the 9G4 idiotype produce dominant serum autoantibodies, including antibodies to DNase1L3, underscores VH4-34+B cells as sensible therapeutic targets for specific depletion of pathogenic B cells in SLE.
Context-aware genomic surveillance reveals hidden transmission of a carbapenemase-producing Klebsiella pneumoniae
Authors: Viehweger Adrian , Blumenscheit Christian , Lippmann Norman , Wyres Kelly L. , Brandt Christian , Hans Jörg B. , Hölzer Martin , Irber Luiz , Gatermann Sören , Lübbert Christoph , Pletz Mathias , Holt Kathryn E. , König Brigitte
Published: June 2021

Genomic surveillance can inform effective public health responses to pathogen outbreaks. However, integration of non-local data is rarely done. We investigate two large hospital outbreaks of a carbapenemase-carrying Klebsiella pneumoniae strain in Germany and show the value of contextual data. By screening more than ten thousand genomes, 500 thousand metagenomes, and two culture collections using in silico and in vitro methods, we identify a total of 415 closely related genomes reported in 28 studies. We identify the relationship between the two outbreaks through time-dated phylogeny, including their respective origin. One of the outbreaks presents extensive hidden transmission, with descendant isolates only identified in other studies. We then leverage the genome collection from this meta-analysis to identify genes under positive selection. We thereby identify an inner membrane transporter (ynjC) with a putative role in colistin resistance. Contextual data from other sources can thus enhance local genomic surveillance at multiple levels and should be integrated by default when available.
Emergence of Severe Metastatic Hypervirulent Klebsiella pneumoniae infections in Texas
Authors: Alam Junaid M. , Ahmed Haris , Thai Hong M. , Garnepudi Kevin , Kesavan Ramesh B. , Jayaraman Gnananandh , Sangster Anna , Curry Dylan , Butz Heidi A. , Smith Lori , Vowles Maureen , Oakeson Kelly F. , Young Erin L. , Sarva Siva T.
Published: June 2021

Background

Hypervirulent Klebsiella pneumoniae (hvKp) infections have mainly been described in Asia. Two patients in the age group of 30 to 50 years presented within a two month period to a tertiary referral hospital in Texas with septic shock, hepatic abscess and septic thrombophlebitis. Blood cultures were positive for Klebsiella pneumoniae (isolates 2020CK-00441 and 2021CK-00720 respectively).

Methods

Whole genome sequencing was performed using paired-end Illumina MiSeq reads for both isolates. Nanopore sequencing to obtain a closed genome was performed for 2020CK-00441.

Results

2020CK-00441 belonged to ST23 type while 2021CK-00720 was a ST65 type isolate. Kleborate analyses predicted with high confidence that both the isolates were hvKp. Phylogenetic analyses showed that the two strains are not closely related to each other or to any other known hvKp isolates. Both the isolates had yersiniabactin, colibactin, aerobactin and salmochelin producing loci which likely confer these isolates hvKp phenotype. 2020CK-00441 had a unique pK2044 like plasmid.

Conclusions

HvKp strains capable of causing devastating metastatic septic infections have emerged in Texas. These isolates are unique when compared to other hvKp strains of the world. Country wide surveillance and whole genome sequencing of these strains is essential to prevent a major public health emergency in USA.
Bovine Colostrum Derived Antibodies Against SARS-CoV-2 Show Great Potential to Serve as a Prophylactic Agent
Authors: Kangro Kadri , Kurašin Mihhail , Gildemann Kiira , Sankovski Eve , Žusinaite Eva , Lello Laura Sandra , Pert Raini , Kavak Ants , Poikalainen Väino , Lepasalu Lembit , Kuusk Marilin , Pau Robin , Piiskop Sander , Rom Siimu , Oltjer Ruth , Tiirik Kairi , Kogermann Karin , Plaas Mario , Tiirats Toomas , Aasmäe Birgit , Plaas Mihkel , Krinka Dagni , Talpsep Ene , Kadaja Meelis , Gerhold Joachim M. , Planken Anu , Tover Andres , Merits Andres , Männik Andres , Ustav Mart , Ustav Mart
Published: June 2021

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) until now imposes a serious burden to health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of the virus is still ongoing. One of the mechanisms how neutralizing antibodies (NAbs) block virus entry into cells encompasses interaction inhibition between the cell surface receptor angiotensin-converting enzyme 2 (ACE2) and the spike (S) protein of SARS-CoV-2. SARS-CoV-2 specific NAb development can be induced in the blood of cattle. Pregnant cows produce NAbs upon immunization, and antibodies move into the colostrum just before calving. Here we immunized cows with SARS-CoV-2 S1 receptor binding domain (RBD) protein in proper adjuvant solutions, followed by one boost with SARS-CoV-2 trimeric S protein, and purified immunoglobulins from colostrum. We demonstrate that this preparation indeed blocks interaction between the trimeric S protein and ACE2 in different in vitro assays. Moreover, we describe the formulation of purified immunoglobulin preparation into a nasal spray. When administered to human subjects, the formulation persists on the nasal mucosa for at least 4 hours as determined by a clinical study. Therefore, we are presenting a solution that shows great potential to serve as a prophylactic agent against SARS-CoV-2 infection as an additional measure to vaccination and wearing masks. Moreover, our technology allows for a rapid and versatile adaption for preparing prophylactic treatments against other diseases by using the defined characteristics of antibody movement into the colostrum.

Significance

SARS-CoV-2 infections continue to be a high-risk factor for mankind. Antibodies with the potential to neutralize the virus and thus its entry into the host cell have been shown to impose a potent measure against the infection. Human derived neutralizing antibodies are therapeutics and thus fall under the legislation of drugs. However, an alternative could be the purification of efficient neutralizing antibodies from other species. Here, we present immunization of pregnant cows with spike protein of SARS-CoV-2 which results in high quantities of colostrum immunoglobulins that can be easily harvested and safely purified within a remarkably short time. The colostrum immunoglobulin preparation has a great potential to serve in formulations that can be used as prophylactic agent against SARS-CoV-2 infection.
Response of Unvaccinated US Adults to Official Information About the Pause in Use of the Johnson & Johnson-Janssen COVID-19 Vaccine
Authors: Mishra Vishala , Dexter Joseph P.
Published: June 2021

On April 13, 2021 the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) recommended in a pause in use of the Johnson & Johnson (J&J)-Janssen COVID-19 vaccine due to reports of cerebral venous sinus thrombosis (CVST) in recently vaccinated individuals. The announcement of the pause required development of a coordinated communication strategy under extreme time pressure and careful messaging by stakeholders to mitigate reduced public confidence in COVID-19 vaccines, as was observed following the temporary suspension of the Oxford-AstraZeneca vaccine in many countries. In this survey study, we evaluated understanding and impressions of the CDC’s public online information about the J&J-Janssen pause among unvaccinated US adults.
Assessing the Impact of Mask Usage on COVID-19 Transmission Using a Computer Simulation
Authors: Lacson Roger , Veldkamp Peter , Zapanta Conrad
Published: June 2021

Background

COVID-19, caused by SARS-CoV-2, is highly contagious and causes substantial morbidity and mortality. Mask usage has been advocated by health professionals to minimize its spread. Thus, it is important to develop a simulation that models SARS-CoV-2 spread in indoor environments to evaluate mask usage effectiveness.

Methods

A visual computer simulation was developed with Pygame in Python 3. A virtual indoor supermarket is simulated by a given flow of customers with an initial infection percentage and mask usage percentage who enter, move around, and exit a supermarket with shelves, tables and cashiers to demonstrate a system’s dynamic complexity, i.e. nonlinear interactions of system elements over time. A supermarket was simulated with initial infection rates of 5%, 10%, and 20% and mask use percentages of 0%, 25%, 50% 75%, and 100%. The environmental settings (e.g. shelf number and location) and total customers (N=200) were kept constant.

Results

The number of infected customers increased as the percentage of mask usage decreased (p < 0.01). At 5% initial infection, almost no infections were observed at 50% mask usage, with a logarithmic best-fit model (R2 = 0.947). At 10% initial infection, the association between mask usage and decrease in number of infections was best fit with a linear model (R2 = 0.924). For 20% initial infection, a quadratic model was the best fit (R2 = 0.934). While a linear model suggests proportional decreases in infection, the quadratic model suggests more significant reductions in infections at higher rates of mask use (i.e. increasing mask usage from 5% to 10% is less impactful than from 65% to 70%).

Conclusion

The results suggest that mask usage has a significant impact on decreasing COVID-19 transmission. Ideally, mask usage should be as high as possible to achieve more significant reductions in COVID-19 infections. Various parameters can be adjusted during simulation as we learn more about SARS-CoV-2 to guide policies for minimizing COVID-19 transmission.
Convergent loss of the necroptosis pathway in disparate mammalian lineages shapes virus countermeasures
Authors: Águeda-Pinto Ana , Alves Luís Q. , Neves Fabiana , McFadden Grant , Jacobs Bertram L , Castro L. Filipe C. , Rahman Masmudur M. , Esteves Pedro J.
Published: June 2021

Programmed cell death is a vital process in the life cycle of an organism. Necroptosis, an evolutionary restricted form of programmed necrosis, contributes to the innate immune response by killing pathogen-infected cells. This virus-host interaction pathway is organized around two key components: the receptor-interacting protein kinase 3 (RIPK3), which recruits and phosphorylates the mixed lineage kinase-like protein (MLKL), thus inducing cellular plasma membrane rupture and cell death. Critically, the presence of necroptotic inhibitors in viral genomes validates necroptosis as an important host defense mechanism. Here, we show, counterintuitively, that in different mammalian lineages of mammalian, central components of the necroptotic pathway, such as RIPK3 and MLKL genes, are deleted or display inactivating mutations. Frameshifts or premature stop codons are observed in all the studied species of cetaceans and leporids. In carnivores’ genomes, the MLKL gene is deleted, while in a small number of species from afrotheria and rodentia premature stop codons are observed in RIPK3 and/or MLKL. Interestingly, we also found a strong correlation between the disruption of necroptosis in leporids and cetaceans and the absence of the C-terminal domain of E3-like homologs (responsible for necroptosis inhibition) in their naturally infecting poxviruses. Overall, our study provides the first comprehensive picture of the molecular evolution of necroptosis in mammals. The loss of necroptosis multiple times during mammalian evolution highlights the importance of gene/pathway loss for species adaptation and suggests that necroptosis is not required for normal mammalian development. Moreover, this study highlights a co-evolutionary relationship between poxviruses and their hosts, emphasizing the role of host adaptation in shaping virus evolution.
Nanoscale molecular architecture controls calcium diffusion and ER replenishment in dendritic spines
Authors: Basnayake Kanishka , Mazaud David , Kushnireva Lilia , Bemelmans Alexis , Rouach Nathalie , Korkotian Eduard , Holcman David
Published: June 2021

Dendritic spines are critical components of the neuronal synapse as they receive and transform the synaptic input into a succession of biochemical events regulated by calcium signaling. The spine apparatus (SA), an extension of smooth endoplasmic reticulum (ER), regulates slow and fast calcium dynamics in spines. Calcium release events from SA result in a rapid depletion of calcium ion reservoir, yet the next cycle of signaling requires replenishment of SA calcium stores. How dendritic spines achieve this without triggering calcium release remains unclear. Using computational modeling, calcium and STED super-resolution imaging, we showed that the refilling of calcium-deprived SA involves store-operated calcium entry during spontaneous calcium transients in spine heads. We identified two main conditions that guarantee SA replenishment without depletion: (1) a small amplitude and slow timescale for calcium influx, and (2) a close proximity between SA and plasma membranes. Thereby, molecular nano-organization creates the conditions for a clear separation between SA replenishment and depletion. We further conclude that the nanoscale organization of SA receptors underlies the specificity of calcium dynamics patterns during the induction of long-term synaptic changes.
Implementing the reuse of public DIA proteomics datasets: from the PRIDE database to Expression Atlas
Authors: Walzer Mathias , García-Seisdedos David , Prakash Ananth , Brack Paul , Crowther Peter , Graham Robert L. , George Nancy , Mohammed Suhaib , Moreno Pablo , Papathedourou Irene , Hubbard Simon J. , Vizcaíno Juan Antonio
Published: June 2021

The number of mass spectrometry (MS)-based proteomics datasets in the public domain keeps increasing, particularly those generated by Data Independent Acquisition (DIA) approaches such as SWATH-MS. Unlike Data Dependent Acquisition datasets, the re-use of DIA datasets has been rather limited to date, despite its high potential, due to the technical challenges involved. We introduce a (re-)analysis pipeline for public SWATH-MS datasets which includes a combination of metadata annotation protocols, automated workflows for MS data analysis, statistical analysis, and the integration of the results into the Expression Atlas resource. Automation is orchestrated with Nextflow, using containerised open analysis software tools, rendering the pipeline readily available and reproducible. To demonstrate its utility, we reanalysed 10 public DIA datasets from the PRIDE database, comprising 1,278 SWATH-MS runs. The robustness of the analysis was evaluated, and the results compared to those obtained in the original publications. The final expression values were integrated into Expression Atlas, making SWATH-MS experiments more widely available and combining them with expression data originating from other proteomics and transcriptomics datasets.
RiboReport - Benchmarking tools for ribosome profiling-based identification of open reading frames in bacteria
Authors: Gelhausen Rick , Müller Teresa , Svensson Sarah L. , Alkhnbashi Omer , Sharma Cynthia M. , Eggenhofer Florian , Backofen Rolf
Published: June 2021

Small proteins, those encoded by open reading frames, with less than or equal to 50 codons, are emerging as an important class of cellular macromolecules in all kingdoms of life. However, they are recalcitrant to detection by proteomics or in silico methods. Ribosome profiling (Ribo-seq) has revealed widespread translation of sORFs in diverse species, and this has driven the development of ORF detection tools using Ribo-seq read signals. However, only a handful of tools have been designed for bacterial data, and have not yet been systematically compared. Here, we have performed a comprehensive benchmark of ORF prediction tools which handle bacterial Ribo-seq data. For this, we created a novel Ribo-seq dataset for E. coli, and based on this plus three publicly available datasets for different bacteria, we created a benchmark set by manual labeling of translated ORFs using their Ribo-seq expression profile. This was then used to investigate the predictive performance of four Ribo-seq-based ORF detection tools we found are compatible with bacterial data (Reparation_blast, DeepRibo, Ribo-TISH and SPECtre). The tool IRSOM was also included as a comparison for tools using coding potential and RNA-seq coverage only. DeepRibo and Reparation_blast robustly predicted translated ORFs, including sORFs, with no significant difference for those inside or outside of operons. However, none of the tools was able to predict a set of recently identified, novel, experimentally-verified sORFs with high sensitivity. Overall, we find there is potential for improving the performance, applicability, usability, and reproducibility of prokaryotic ORF prediction tools that use Ribo-Seq as input.

Key points

Created a benchmark set for Ribo-seq based ORF prediction in bacteria

DeepRibo the first choice for bacterial ORF prediction tasks

Tool performance is comparable between operon vs single gene regions

Identification of novel sORF with DeepRibo is, with restrictions, possible, by using the top 100 novel sORFs sorted by rank.

Experimental results show that considering translation initiation site data could boost the detection of novel small ORFs

Determination of novel sORFs in E. coli using a new experimental protocol to enrich for translation initiation site. These data-set shows that still a significant part (here 8 out 24, so 1/3) are not detected dispute sufficient Ribo-seq signal. An additional 7 could be recovered using translation initiation site protocols.

Tools should embrace the use of replicate data and improve packaging, usability and documentation.
Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis
Authors: Singh Tej Pratap , Carvalho Augusto M. , Grice Elizabeth A. , Scott Phillip
Published: June 2021

Innate lymphoid cells (ILCs) comprise a heterogeneous population of immune cells that maintain barrier function and can initiate a protective or pathological immune response upon infection. Here we show the involvement of IL-17A-producing ILCs in microbiota-driven immunopathology in cutaneous leishmaniasis. IL-17A-producing ILCs were RORγt+ and were enriched in Leishmania major infected skin, and topical colonization with Staphylococcus epidermidis before L. major infection exacerbated the skin inflammatory responses and IL-17A-producing RORγt+ ILC accumulation without impacting type 1 immune responses. IL-17A responses in ILCs were directed by Batf3 dependent CD103+ dendritic cells, and experiments using ILC deficient Rag1-/- mice established that IL-17A+ ILCs were sufficient in driving the inflammatory responses. As depletion of ILCs or neutralization of IL-17A diminished the microbiota mediated immunopathology. Taken together, this study indicates that the skin microbiota promotes RORγt+ IL-17A-producing ILCs, which augment the skin inflammation in cutaneous leishmaniasis.
An atomistic model of the coronavirus replication-transcription complex as a hexamer assembled around nsp15
Authors: Perry Jason K. , Appleby Todd C. , Bilello John P. , Feng Joy Y. , Schmitz Uli , Campbell Elizabeth A.
Published: June 2021

Using available cryo-EM and x-ray crystal structures of the nonstructural proteins that are responsible for SARS-CoV-2 viral RNA replication and transcription, we have constructed an atomistic model of how the proteins assemble into a functioning superstructure. Our principal finding is that the complex is hexameric, centered around nsp15. The nsp15 hexamer is capped on two faces by trimers of nsp14/nsp16/(nsp10)2, where nsp14 is seen to undergo a large conformational change between its two domains. This conformational change facilitates binding of six nsp12/nsp7/(nsp8)2 polymerase subunits to the complex. To this, six subunits of nsp13 are arranged around the superstructure, but not evenly distributed. Two of the six polymerase subunits are each proposed to carry dimers of nsp13, while two others are proposed to carry monomers. The polymerase subunits that coordinate nsp13 dimers also bind the nucleocapsid, which positions the 5’-UTR TRS-L RNA over the polymerase active site, a state distinguishing transcription from replication. Analyzing the path of the viral RNA indicates the dsRNA that exits the polymerase passes over the nsp14 exonuclease and nsp15 endonuclease sites before being unwound by a convergence of zinc fingers from nsp10 and nsp14. The template strand is then directed away from the complex, while the nascent strand is directed to the sites responsible for mRNA capping (the nsp12 NiRAN and the nsp14 and nsp16 methyltransferases). The model presents a cohesive picture of the multiple functions of the coronavirus replication-transcription complex and addresses fundamental questions related to proofreading, template switching, mRNA capping and the role of the endonuclease. It provides a platform to guide biochemical and structural research to address the stoichiometric and spatial configuration of the replication-transcription complex.

Author Summary

The replication of the coronavirus genome and the synthesis of subgenomic mRNA is a complex process involving multiple viral proteins. Despite a fairly complete structural picture of the individual proteins that are believed to coalesce into a larger replication-transcription complex, there is no clear model of how these proteins interact. Here we present the first detailed atomistic model of a complete replication-transcription complex for SARS-CoV-2, made up of the non-structural proteins nsp7-nsp16, as well as the nucleocapsid. Forming a large, hexameric superstructure centered around nsp15, the model provides new perspective on the function of its individual components, including the exonuclease, the endonuclease, the NiRAN site, the helicase, the multiple zinc fingers, and the nucleocapsid. It offers a cohesive view of replication, proofreading, template switching and mRNA capping, which should serve as a guide for future experimental exploration.
Genetic architecture of natural variation of cardiac performance: from flies to Humans
Authors: Saha Saswati , Spinelli Lionel , Castro-Mondragon Jaime A , Kervadec Anaïs , Lynott Michaela , Kremmer Laurent , Roder Laurence , Krifa Sallouha , Torres Magali , Brun Christine , Vogler Georg , Bodmer Rolf , Colas Alexandre R. , Ocorr Karen , Perrin Laurent
Published: June 2021

Deciphering the genetic architecture of human cardiac disorders is of fundamental importance but their underlying complexity is a major hurdle. We investigated the natural variation of cardiac performance in the sequenced inbred lines of the Drosophila Genetic Reference Panel (DGRP). Genome Wide Associations Studies (GWAS) identified genetic networks associated with natural variation of cardiac traits which were used to gain insights as to the molecular and cellular processes affected. Non-coding variants that we identified were used to map potential regulatory non-coding regions, which in turn were employed to predict Transcription Factors (TFs) binding sites. Cognate TFs, many of which themselves bear polymorphisms associated with variations of cardiac performance, were also validated by heart specific knockdown. Additionally, we showed that the natural variations associated with variability in cardiac performance affect a set of genes overlapping those associated with average traits but through different variants in the same genes. Furthermore, we showed that phenotypic variability was also associated with natural variation of gene regulatory networks. More importantly, we documented correlations between genes associated with cardiac phenotypes in both flies and humans, which supports a conserved genetic architecture regulating adult cardiac function from arthropods to mammals. Specifically, roles for PAX9 and EGR2 in the regulation of the cardiac rhythm were established in both models, illustrating that the characteristics of natural variations in cardiac function identified in Drosophila can accelerate discovery in humans.
A mechano-osmotic feedback couples cell volume to the rate of cell deformation
Authors: Venkova Larisa , Vishen Amit Singh , Lembo Sergio , Srivastava Nishit , Duchamp Baptiste , Ruppel Artur , Vassilopoulos Stéphane , Deslys Alexandre , Arcos Juan Manuel Garcia , Diz-Muñoz Alba , Balland Martial , Joanny Jean-François , Cuvelier Damien , Sens Pierre , Piel Matthieu
Published: June 2021

Mechanics has been a central focus of physical biology in the past decade. In comparison, the osmotic and electric properties of cells are less understood. Here we show that a parameter central to both the physics and the physiology of the cell, its volume, depends on a mechano-osmotic coupling. We found that cells change their volume depending on the rate at which they change shape, when they spread, migrate or are externally deformed. Cells undergo slow deformation at constant volume, while fast deformation leads to volume loss. We propose a mechano-sensitive pump and leak model to explain this phenomenon. Our model and experiments suggest that volume modulation depends on the state of the actin cortex and the coupling of ion fluxes to membrane tension. This mechano-osmotic coupling defines a membrane tension homeostasis module constantly at work in cells, causing volume fluctuations associated with fast cell shape changes, with potential consequences on cellular physiology.
Hypoxia induced carbonic anhydrase mediated dorsal horn sensory neuron activation and induction of neuropathic pain
Authors: Lobo M.E. Da Vitoria , Weir N. , Hardowar L. , Ojaimi Y. Al , Madden R. , Gibson Alex , Bestall S.M. , Schaffer C , Hirashima M. , Donaldson L.F , Bates D.O. , Hulse R.P.
Published: June 2021

Neuropathic pain such as that seen in diabetes mellitus, results in part from central sensitisation in the spinal cord dorsal horn. However, the mechanisms responsible for such sensitisation remain unclear. There is evidence that disturbances in the integrity of the spinal vascular network can be a causative factor in the development of neuropathic pain. Here we show that reduced blood flow and vascularity of the dorsal horn leads to the onset of neuropathic pain. Using rodent models (type 1 diabetes and an inducible endothelial specific vascular endothelial growth factor receptor 2 knockout mouse) that result in degeneration of the endothelium in the dorsal horn we show that spinal cord vasculopathy results in nociceptive behavioural hypersensitivity. This also results in increased hypoxia in dorsal horn sensory neurons, depicted by increased expression of hypoxia markers hypoxia inducible factor 1α, glucose transporter 3 and carbonic anhydrase 7. Furthermore, inducing hypoxia via intrathecal delivery of dimethyloxalylglycine leads to the activation of dorsal horn sensory neurons as well as mechanical and thermal hypersensitivity. This shows that hypoxic signalling induced by reduced vascularity results in increased hypersensitivity and pain. Inhibition of carbonic anhydrase activity, through intraperitoneal injection of acetazolamide, inhibited hypoxia induced pain behaviours. This investigation demonstrates that induction of a hypoxic microenvironment in the dorsal horn, as occurs in diabetes, is an integral process by which sensory neurons are activated to initiate neuropathic pain states. This leads to the conjecture that reversing hypoxia by improving spinal cord microvascular blood flow could reverse or prevent neuropathic pain.