bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTBackgroundOlfactory 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.MethodologyConsecutive 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.ResultsAmong 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.ConclusionsSST-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

AbstractWastewater-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

AbstractHospitals 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

ABSTRACTDiastole 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

AbstractDNase1L3 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

AbstractGenomic 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

ABSTRACTBackgroundHypervirulent 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).MethodsWhole 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.Results2020CK-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.ConclusionsHvKp 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

AbstractSevere 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.SignificanceSARS-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

AbstractOn 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

AbstractBackgroundCOVID-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.MethodsA 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.ResultsThe 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%).ConclusionThe 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

AbstractProgrammed 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

AbstractDendritic 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

ABSTRACTThe 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.