bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a new automated chemiluminescent anti-SARS-CoV-2 IgM and IgG antibody assay system detecting both N and S proteins in Japan
Authors: Yokoyama Rin , Kurano Makoto , Morita Yoshifumi , Shimura Takuya , Nakano Yuki , Qian Chungen , Xia Fuzhen , He Fan , Kishi Yoshiro , Okada Jun , Yoshikawa Naoyuki , Nagura Yutaka , Okazaki Hitoshi , Moriya Kyoji , Seto Yasuyuki , Kodama Tatsuhiko , Yatomi Yutaka 
Published: July 2020

AbstractPCR methods are presently the standard for the diagnosis of Coronavirus disease 2019 (COVID-19), but additional methodologies are needed to complement PCR methods, which have some limitations. Here, we validated and investigated the usefulness of measuring serum antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the iFlash3000 CLIA analyzer. We measured IgM and IgG titers against SARS-CoV-2 in sera collected from 26 PCR-positive COVID-19 patients, 53 COVID-19-suspected but PCR-negative patients, and 20 and 100 randomly selected non-COVID-19 patients who visited our hospital in 2020 and 2017, respectively. The within-day and between-day precisions were regarded as good, since the coefficient variations were below 5%. Linearity was also considered good between 0.6 AU/mL and 112.7 AU/mL for SARS-CoV-2 IgM and between 3.2 AU/mL and 55.3 AU/mL for SARS-CoV-2 IgG, while the linearity curves plateaued above the upper measurement range. We also confirmed that the seroconversion and no-antibody titers were over the cutoff values in all 100 serum samples collected in 2017. These results indicate that this measurement system successfully detects SARS-CoV-2 IgM/IgG. We observed four false-positive cases in the IgM assay and no false-positive cases in the IgG assay when 111 serum samples known to contain autoantibodies were evaluated. The concordance rates of the antibody test with the PCR test were 98.1% for SARS-CoV-2 IgM and 100% for IgG among PCR-negative cases and 30.8% for SARS-CoV-2 IgM and 73.1% for SARS-CoV-2 IgG among PCR-positive cases. In conclusion, the performance of this measurement system is sufficient for use in laboratory testing.
SARS-Cov-2 cysteine-like protease (Mpro) is immunogenic and can be detected in serum and saliva of COVID-19-seropositive individuals
Authors: Martínez-Fleta Pedro , Alfranca Arantzazu , González-Álvaro Isidoro , Casasnovas Jose M , Fernández-Soto Daniel , Esteso Gloria , Cáceres-Martell Yaiza , Gardeta Sofía , Prat Salomé , Mateu-Albero Tamara , Gabrie Ligia , López-Granados Eduardo , Sánchez-Madrid Francisco , Reyburn Hugh T. , Rodríguez Frade José M. , Valés-Gómez Mar 
Published: July 2020

AbstractCurrently, there is a need for reliable tests that allow identification of individuals that have been infected with SARS-CoV-2 even if the infection was asymptomatic. To date, the vast majority of the serological tests for SARS-CoV-2 specific antibodies are based on serum detection of antibodies to either the viral spike glycoprotein (the major target for neutralising antibodies) or the viral nucleocapsid protein that are known to be highly immunogenic in other coronaviruses. Conceivably, exposure of antigens released from infected cells could stimulate antibody responses that might correlate with tissue damage and, hence, they may have some value as a prognostic indicator. We addressed whether other non-structural viral proteins, not incorporated into the infectious viral particle, specifically the viral cysteine-like protease, might also be potent immunogens. Using ELISA tests, coating several SARS-CoV-2 proteins produced in vitro, we describe that COVID-19 patients make high titre IgG, IgM and IgA antibody responses to the Cys-like protease from SARS-CoV-2, also known as 3CLpro or Mpro, and it can be used to identify individuals with positive serology against the coronavirus. Higher antibody titres in these assays associated with more severe disease and no cross-reactive antibodies against prior betacoronavirus were found. Remarkably, IgG antibodies specific for Mpro and other SARS-CoV-2 antigens can also be detected in saliva. In conclusion, Mpro is a potent antigen in infected patients that can be used in serological tests and its detection in saliva could be the basis for a rapid, non-invasive test for COVID-19 seropositivity.
Oral colonization by Entamoeba gingivalis and Trichomonas tenax: PCR-based study in health, gingivitis, and periodontitis
Authors: Yaseen Alaa’ , Mahafzah Azmi , Dababseh Deema , Tayem Duaa , Hamdan Ahmad A. , Al-Fraihat Esraa , Hassona Yazan , Şahin Gülşen Özkaya , Santi-Rocca Julien , Sallam Malik 
Published: July 2020

ABSTRACTThe etiology of periodontitis needs further investigation, as is the place of gingivitis in its pathophysiology. A few studies linked the oral colonization by parasites (Entamoeba gingivalis and Trichomonas tenax) to the disease and its severity. The aim of this study was to estimate the prevalence of these oral parasites among healthy individuals, gingivitis and periodontitis patients in Jordan. The study was conducted by active enrolment of participants at Jordan University Hospital. The participants answered a questionnaire that included items related to possible risk factors for periodontal disease. Saliva and dental plaque samples were collected. The detection of oral parasites was done using conventional PCR and microscopic examination of wet mounts. The study population comprised a total of 237 individuals divided into three groups: healthy (n=94), gingivitis (n=53), and periodontitis (n=90). PCR results revealed that the overall prevalence of E. gingivalis was 71.7% compared to 12.2% for T. tenax. The periodontal disease group had higher prevalence of E. gingivalis and T. tenax compared to the healthy group (p<0.001). Increasing age was associated with higher prevalence of E. gingivalis (p=0.008) and T. tenax (p=0.019), in the entire study population. The number of cases of colonization detected by microscopic observation was lower for any of the oral parasites, as compared to diagnosis by PCR (40.7% vs. 71.7%, p<0.001 for E. gingivalis and 4.3% vs. 12.2%, p=0.007 for T. tenax). The higher prevalence of oral parasites among patients with periodontal disease might point to their potential contribution in the disease and its severity.IMPORTANCEPeriodontal disease has a high prevalence globally, with adverse effects on the quality of life for affected individuals. Despite the presence of several studies that investigated the role of oral parasites in periodontal disease, reliable conclusions about this matter remained elusive mainly due to utilization of microscopy in parasite detection. The current study provides new insights into the epidemiology and prevalence of the two oral parasites (Entamoeba gingivalis and Trichomonas tenax) in patients with various stages of periodontal disease in comparison to healthy adults. In addition, we describe the potential role of oral colonization by parasites as a risk factor for development of periodontal disease and its severity using a molecular-based approach.
Identification of SARS-CoV2-mediated suppression of NRF2 signaling reveals a potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate
Authors: Olagnier David , Farahani Ensieh , Thyrsted Jacob , Cadanet Julia B. , Herengt Angela , Idorn Manja , Hait Alon , Hernaez Bruno , Knudsen Alice , Iversen Marie Beck , Schilling Mirjam , Jørgensen Sofie E. , Thomsen Michelle , Reinert Line , Lappe Michael , Hoang Huy-Dung , Gilchrist Victoria H. , Hansen Anne Louise , Ottosen Rasmus , Gunderstofte Camilla , Møller Charlotte , van der Horst Demi , Peri Suraj , Balachandran Siddarth , Huang Jinrong , Jakobsen Martin , Svenningsen Esben B. , Poulsen Thomas B. , Bartsch Lydia , Thielke Anne L. , Luo Yonglun , Alain Tommy , Rehwinkel Jan , Alcamí Antonio , Hiscott John , Mogensen Trine , Paludan Søren R. , Holm Christian K. 
Published: July 2020

AbstractAntiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here we demonstrate that the NRF2 anti-oxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular anti-viral program, which potently inhibits replication of SARS-CoV2 across cell lines. The anti-viral program extended to inhibit the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, induction of NRF2 by 4-OI and DMF limited host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2.One Sentence SummaryNRF2 agonists 4-octyl-itaconate (4-OI) and dimethyl fumarate inhibited SARS-CoV2 replication and virus-induced inflammatory responses, as well as replication of other human pathogenic viruses.
Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors
Authors: F. Oliveira A. Sofia , Ibarra Amaurys Avila , Bermudez Isabel , Casalino Lorenzo , Gaieb Zied , Shoemark Deborah K. , Gallagher Timothy , Sessions Richard B. , Amaro Rommie E. , Mulholland Adrian J. 
Published: July 2020

AbstractChangeuxet al. recently suggested that the SARS-CoV-2 spike (S) protein may interact with nicotinic acetylcholine receptors (nAChRs). Such interactions may be involved in pathology and infectivity. Here, we use molecular simulations of validated atomically detailed structures of nAChRs, and of the S protein, to investigate this ‘nicotinic hypothesis’. We examine the binding of the Y674-R685 loop of the S protein to three nAChRs, namely the human α4β2 and α7 subtypes and the muscle-like αβγd receptor fromTetronarce californica. Our results indicate that Y674-R685 has affinity for nAChRs and the region responsible for binding contains the PRRA motif, a four-residue insertion not found in other SARS-like coronaviruses. In particular, R682 has a key role in the stabilisation of the complexes as it forms interactions with loops A, B and C in the receptor’s binding pocket. The conformational behaviour of the bound Y674-R685 region is highly dependent on the receptor subtype, adopting extended conformations in the α4β2 and α7 complexes and more compact ones when bound to the muscle-like receptor. In the α4β2 and αβγd complexes, the interaction of Y674-R685 with the receptors forces the loop C region to adopt an open conformation similar to other known nAChR antagonists. In contrast, in the α7 complex, Y674-R685 penetrates deeply into the binding pocket where it forms interactions with the residues lining the aromatic box, namely with TrpB, TyrC1 and TyrC2. Estimates of binding energy suggest that Y674-R685 forms stable complexes with all three nAChR subtypes. Analyses of the simulations of the full-length S protein show that the Y674-R685 region is accessible for binding, and suggest a potential binding orientation of the S protein with nAChRs.
Association between consumption of vegetables and COVID-19 mortality at a country level in Europe
Authors: Fonseca Susana C , Rivas Ioar , Romaguera Dora , Quijal-Zamorano Marcos , Czarlewski Wienczyslawa , Vidal Alain , Fonseca Joao A , Ballester Joan , Anto Josep M , Basagana Xavier , Cunha Luis M , Bousquet Jean 
Published: July 2020

AbstractBackgroundMany foods have an antioxidant activity, and nutrition may mitigate COVID-19. To test the potential role of vegetables in COVID-19 mortality in Europe, we performed an ecological study.MethodsThe European Food Safety Authority (EFSA) Comprehensive European Food Consumption Database was used to study the country consumption of Brassica vegetables (broccoli, cauliflower, head cabbage (white, red and savoy cabbage), leafy brassica) and to compare them with spinach, cucumber, courgette, lettuce and tomato. The COVID-19 mortality per number of inhabitants was obtained from the Johns Hopkins Coronavirus Resource Center. EuroStat data were used for potential confounders at the country level including Gross Domestic Product (GDP) (2019), population density (2018), percentage of people over 64 years (2019), unemployment rate (2019) and percentage of obesity (2014, to avoid missing values). Mortality counts were analyzed with quasi-Poisson regression models to model the death rate while accounting for over-dispersion.ResultsOf all the variables considered, including confounders, only head cabbage and cucumber reached statistical significance with the COVID-19 death rate per country. For each g/day increase in the average national consumption of some of the vegetables (head cabbage and cucumber), the mortality risk for COVID-19 decreased by a factor of 11, down to 13.6 %. Lettuce consumption increased COVID-19 mortality. The adjustment did not change the point estimate and the results were still significant.DiscussionThe negative ecological association between COVID-19 mortality and the consumption of cabbage and cucumber supports the a priori hypothesis previously reported. The hypothesis needs to be tested in individual studies performed in countries where the consumption of vegetables is common.
A phenome-wide association study identifying risk factors for pediatric post-concussion syndrome
Authors: Yengo-Kahn Aaron M. , Hibshman Natalie , Bonfield Christopher M. , Torstenson Eric S. , Gifford Katherine A. , Belikau Daniil , Davis Lea K. , Zuckerman Scott L. , Dennis Jessica K. 
Published: July 2020

AbstractObjectiveTo identify risk factors and generate hypotheses for pediatric post-concussion syndrome (PCS) using a phenome-wide association study (PheWAS).MethodsA PheWAS (case-control) was conducted following the development and validation of a novel electronic health record-based algorithm that identified PCS cases and controls from an institutional database of >2.8 million patients. Cases were patients ages 5-18 with PCS codes or keywords identified by natural language processing of clinical notes. Controls were patients with mild traumatic brain injury (mTBI) codes only. Patients with moderate or severe brain injury were excluded. All patients used our healthcare system at least three times 180 days before their injury. Exposures included all pre-injury medical diagnoses assigned at least 180 days prior.ResultsThe algorithm identified 274 pediatric PCS cases (156 females) and 1,096 controls that were age and sex matched to cases. Cases and controls both had a mean of >8 years of healthcare system use pre-injury. Of 202 pre-injury medical, four were associated with PCS after controlling for multiple testing: headache disorders (OR=5.3; 95%CI 2.8-10.1;P=3.8e-7), sleep disorders (OR=3.1; 95%CI 1.8-5.2;P=2.6e-5), gastritis/duodenitis (OR=3.6, 95%CI 1.8-7.0;P=2.1e-4), and chronic pharyngitis (OR=3.3; 95%CI 1.8-6.3;P=2.2e-4).ConclusionsThese results confirm the strong association of pre-injury headache disorders with PCS and provides evidence for the association of pre-injury sleep disorders with PCS. An association of PCS with prior chronic gastritis/duodenitis and pharyngitis was seen that suggests a role for chronic inflammation in PCS pathophysiology and risk. These factors should be considered during the management of pediatric mTBI cases.
Role of intermediate care unit admission and non-invasive respiratory support during the COVID-19 pandemic: a retrospective cohort study
Authors: Grosgurin Olivier , Leidi Antonio , Farhoumand Pauline Darbellay , Carballo Sebastian , Adler Dan , Reny Jean-Luc , Pinto Bernardo Bollen , Rossel Anne , Serratrice Jacques , Agoritsas Thomas , Stirnemann Jérôme , Marti Christophe 
Published: July 2020

BackgroundThe COVID-19 pandemic has led to shortage of Intensive Care Unit (ICU) capacity. We developed a triage strategy including non-invasive respiratory support and admission to the intermediate care unit (IMCU). ICU admission was restricted to patients requiring invasive ventilation.ObjectivesThe aim of this study is to describe the characteristics and outcomes of patients admitted to the intermediate care unit.MethodRetrospective cohort including consecutive patients admitted between March 28th and April 27th 2020. The primary outcome was the proportion of patients with severe hypoxemic respiratory failure avoiding ICU admission. Secondary outcomes included the rate of emergency intubation, 28-days mortality and predictors of ICU admission.ResultsOne hundred fifty seven patients with COVID-19 associated pneumonia were admitted to the IMCU. Among the 85 patients admitted for worsening respiratory failure, 52/85 (61%) avoided ICU admission. In multivariate analysis, PaO2/FiO2 (OR 0.98; 95% CI 0.96 to 0.99) and Body Mass Index (OR 0.88; 95% CI 0.78 to 0.98) were significantly associated with ICU admission. No death or emergency intubation occurred in the intermediate care unit. Among the 72 patients transferred from the ICU, 60/72 (83%) presented neurological complications.ConclusionsNon-invasive respiratory support including High-Flow Nasal Oxygen and continuous positive airway pressure prevents ICU admission for a large proportion of patients with COVID-19 hypoxemic respiratory failure. In the context of the COVID pandemic, intermediate care units may play an important role in preserving ICU capacity by avoiding ICU admission for patients with worsening respiratory failure and allowing early discharge of ICU patients.
Going beyond clinical routine in SARS-CoV-2 antibody testing - A multiplex corona virus antibody test for the evaluation of cross-reactivity to endemic coronavirus antigens
Authors: Becker Matthias , Strengert Monika , Junker Daniel , Kerrinnes Tobias , Kaiser Philipp D. , Traenkle Bjoern , Dinter Heiko , Häring Julia , Zeck Anne , Weise Frank , Peter Andreas , Hörber Sebastian , Fink Simon , Ruoff Felix , Bakchoul Tamam , Baillot Armin , Lohse Stefan , Cornberg Markus , Illig Thomas , Gottlieb Jens , Smola Sigrun , Karch André , Berger Klaus , Rammensee Hans-Georg , Schenke-Layland Katja , Nelde Annika , Märklin Melanie , Heitmann Jonas S. , Walz Juliane S. , Templin Markus , Joos Thomas O. , Rothbauer Ulrich , Krause Gérard , Schneiderhan-Marra Nicole 
Published: July 2020

AbstractGiven the importance of the humoral immune response to SARS-CoV-2 as a global benchmark for immunity, a detailed analysis is needed to monitor seroconversion in the general population, understand manifestation and progression of COVID-19 disease, and ultimately predict the outcome of vaccine development. In contrast to currently available serological assays, which are only able to resolve the SARS-CoV-2 antibody response on an individual antigen level, we developed a multiplex immunoassay, for which we included spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses (NL63, OC43, 229E, HKU1) in an expanded antigen panel. Compared to three commercialin vitrodiagnostic tests, our MULTICOV-AB assay achieved the highest sensitivity and specificity when analyzing a well-characterized sample set of SARS-CoV-2 infected and uninfected individuals. Simultaneously, high IgG responses against endemic coronaviruses became apparent throughout all samples, but no consistent cross-reactive IgG response patterns could be defined. In summary, we have established and validated, a robust, high-content-enabled, and antigen-saving multiplex assay MULTICOV-AB, which is highly suited to monitor vaccination studies and will facilitate epidemiologic screenings for the humoral immunity toward pandemic as well as endemic coronaviruses.
Are we ready when COVID-19 vaccine is available? Study on nurses’ vaccine hesitancy in Hong Kong
Authors: Kwok Kin On , Li Kin Kit , Wei Wan In , Tang Arthur , Wong Samuel Yeung Shan , Lee Shui Shan 
Published: July 2020

ABSTRACTIntroductionNurses are considered a trustworthy source of vaccine-related information to build public confidence in vaccination. This study estimated nurses’ influenza vaccine uptake and intention to receive COVID-19 vaccine when available, and examined the corresponding psychological antecedents.MethodsA cross-sectional online survey among nurses was conducted during the main COVID-19 outbreak in Hong Kong between mid-March and late April 2020. Demographics, influenza vaccination, intention to have COVID-19 vaccine, the 5C vaccine hesitancy components (i.e., confidence, complacency, constraints, calculation, and collective responsibility), work stress and COVID-related work demands (i.e., insufficient supply of personal protective equipment, involvement in isolation rooms, and unfavorable attitudes towards workplace infection control policies) were reported.ResultsThe influenza vaccination coverage and the proportion intending to take COVID-19 vaccine were 49% and 63%, respectively, among 1205 eligible nurses. Influenza vaccine uptake was associated with working in public hospitals and all 5C constructs, whereas stronger COVID-19 vaccination intention was associated with younger age, more confidence, less complacency and more collective responsibility towards the vaccine. COVID-19-related demands were associated with greater work stress, and hence stronger COVID-19 vaccination intention.ConclusionVaccine uptake/intention was well predicted by the 5C constructs. With less work stress among nurses in the post-pandemic period, the intention to take COVID-19 vaccine will likely drop. The 5C constructs should be infused in vaccination campaigns. While a COVID-19 vaccine could be ready soon, communities are not ready to accept it. More research work is needed to boost the uptake.