A Dream

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Pre-endoscopy SARS-CoV-2 testing strategy during COVID-19 pandemic: the care must go on

Background: In response to the COVID-19 pandemic, endoscopic societies initially recommended reduction of endoscopic procedures. In particular non-urgent endoscopies should be postponed. However, this might lead to unnecessary delay in diagnosing gastrointestinal conditions. Methods: Retrospectively we analysed the gastrointestinal endoscopies performed at the Central Endoscopy Unit of Saarland University Medical Center during seven weeks from 23 March to 10 May 2020 and present our real-world single-centre experience with an individualized rtPCR-based pre-endoscopy SARS-CoV-2 testing strategy. We also present our experience with this strategy in 2021. Results: Altogether 359 gastrointestinal endoscopies were performed in the initial period. The testing strategy enabled us to conservatively handle endoscopy programme reduction (44% reduction as compared 2019) during the frst wave of the COVID-19 pandemic. The results of COVID-19 rtPCR from nasopharyngeal swabs were available in 89% of patients prior to endoscopies. Apart from six patients with known COVID-19, all other tested patients were negative. The frequencies of endoscopic therapies and clinically signifcant fndings did not difer between patients with or without SARS-CoV-2 tests. In 2021 we were able to unrestrictedly perform all requested endoscopic procedures (>5000 procedures) by applying the rtPCR-based pre-endoscopy SARS-CoV-2 testing strategy, regardless of next waves of COVID-19. Only two out-patients (1893 out-patient procedures) were tested positive in the year 2021. Conclusion: A structured pre-endoscopy SARS-CoV-2 testing strategy is feasible in the clinical routine of an endoscopy unit. rtPCR-based pre-endoscopy SARS-CoV-2 testing safely allowed unrestricted continuation of endoscopic procedures even in the presence of high incidence rates of COVID-19. Given the low frequency of positive tests, the absolute efect of pre-endoscopy testing on viral transmission may be low when FFP-2 masks are regularly used

Case-Based strategies for argumentation dialogues in agent societies

[EN] In multi-agent systems, agents perform complex tasks that require different levels of intelligence and give rise to interactions among them. From these interactions, conflicts of opinion can arise, especially when these systems become open, with heterogeneous agents dynamically entering or leaving the system. Therefore, agents willing to participate in this type of system will be required to include extra capabilities to explicitly represent and generate agreements on top of the simpler ability to interact. Furthermore, agents in multiagent systems can form societies, which impose social dependencies on them. These dependencies have a decisive influence in the way agents interact and reach agreements. Argumentation provides a natural means of dealing with conflicts of interest and opinion. Agents can reach agreements by engaging in argumentation dialogues with their opponents in a discussion. In addition, agents can take advantage of previous argumentation experiences to follow dialogue strategies and persuade other agents to accept their opinions. Our insight is that case-based reasoning can be very useful to manage argumentation in open multi-agent systems and devise dialogue strategies based on previous argumentation experiences. To demonstrate the foundations of this suggestion, this paper presents the work that we have done to develop case-based dialogue strategies in agent societies. Thus, we propose a case-based argumentation framework for agent societies and define heuristic dialogue strategies based on it. The framework has been implemented and evaluated in a real customer support application.This work is supported by the Spanish Government Grants [CONSOLIDER-INGENIO 2010 CSD2007-00022, and TIN2012-36586-C03-01] and by the GVA project [PROMETEO 2008/051].Heras Barberá, SM.; Jordan Prunera, JM.; Botti, V.; Julian Inglada, VJ. (2013). Case-Based strategies for argumentation dialogues in agent societies. Information Sciences. 223:1-30. doi:10.1016/j.ins.2012.10.007S13022

Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting

MicroRNA (miRNA) regulation clearly impacts animal development, but the extent to which development—with its resulting diversity of cellular contexts—impacts miRNA regulation is unclear. Here, we compared cohorts of genes repressed by the same miRNAs in different cell lines and tissues and found that target repertoires were largely unaffected, with secondary effects explaining most of the differential responses detected. Outliers resulting from differential direct targeting were often attributable to alternative 3′ UTR isoform usage that modulated the presence of miRNA sites. More inclusive examination of alternative 3′ UTR isoforms revealed that they influence ~10% of predicted targets when comparing any two cell types. Indeed, considering alternative 3′ UTR isoform usage improved prediction of targeting efficacy significantly beyond the improvements observed when considering constitutive isoform usage. Thus, although miRNA targeting is remarkably consistent in different cell types, considering the 3′ UTR landscape helps predict targeting efficacy and explain differential regulation that is observed.Korea (South). Ministry of Education, Science and Technology (MEST) (National Research Foundation of Korea. NRF-2013R1A1A1010185)National Institutes of Health (U.S.) (Grant RO1 GM067031)National Institutes of Health (U.S.) (Grant K99 GM102319)National Science Foundation (U.S.). Graduate Research Fellowship Progra

Decline of emergency admissions for cardiovascular and cerebrovascular events after the outbreak of COVID-19

Background The spread of the novel coronavirus SARS-CoV-2 and the guidance from authorities for social distancing and media reporting lead to significant uncertainty in Germany. Concerns have been expressed regarding the underdiagnosing of harmful diseases. We explored the rates of emergency presentations for acute coronary syndrome (ACS) and acute cerebrovascular events (ACVE) before and after spread of SARS-CoV-2. Methods We analyzed all-cause visits at a tertiary university emergency department and admissions for ACS and ACVE before (calendar weeks 1–9, 2020) and after (calendar weeks 10–16, 2020) the first coronavirus disease (COVID-19) case in the region of the Saarland, Germany. The data were compared with the same period of the previous year. Results In 2020 an average of 346 patients per week presented at the emergency department whereas in 2019 an average of 400 patients presented up to calendar week 16 (p = 0.018; whole year 2019 = 395 patients per week). After the first COVID-19 diagnosis in the region, emergency department visit volume decreased by 30% compared with the same period in 2019 (p = 0.0012). Admissions due to ACS decreased by 41% (p = 0.0023 for all; Δ − 71% (p = 0.007) for unstable angina, Δ − 25% (p = 0.42) for myocardial infarction with ST-elevation and Δ − 17% (p = 0.28) without ST-elevation) compared with the same period in 2019 and decreased from 142 patients in calendar weeks 1–9 to 62 patients in calendar weeks 10–16. ACVE decreased numerically by 20% [p = 0.25 for all; transient ischemic attack: Δ − 32% (p = 0.18), ischemic stroke: Δ − 23% (p = 0.48), intracerebral haemorrhage: Δ + 57% (p = 0.4)]. There was no significant change in ACVE per week (p = 0.7) comparing calendar weeks 1–9 (213 patients) and weeks 10–16 (147 patients). Testing of 3756 samples was performed to detect 58 SARS-CoV-2 positive patients (prevalence 1,54%, thereof one patient with myocardial and two with cerebral ischemia) up to calendar week 16 in 2020. Conclusions The COVID-19 pandemic was associated with a significant decrease in all-cause admission and admissions due to cardiovascular events in the emergency department. Regarding acute cerebrovascular events there was a numerical decrease but no significant difference

The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes

Background: All mRNAs are bound in vivo by proteins to form mRNA-protein complexes (mRNPs), but changes in the composition of mRNPs during posttranscriptional regulation remain largely unexplored. Here, we have analyzed, on a transcriptome-wide scale, how microRNA-mediated repression modulates the associations of the core mRNP components eIF4E, eIF4G, and PABP and of the decay factor DDX6 in human cells. Results: Despite the transient nature of repressed intermediates, we detect significant changes in mRNP composition, marked by dissociation of eIF4G and PABP, and by recruitment of DDX6. Furthermore, although poly(A)-tail length has been considered critical in post-transcriptional regulation, differences in steady-state tail length explain little of the variation in either PABP association or mRNP organization more generally. Instead, relative occupancy of core components correlates best with gene expression. Conclusions: These results indicate that posttranscriptional regulatory factors, such as microRNAs, influence the associations of PABP and other core factors, and do so without substantially affecting steady-state tail length.National Institutes of Health (U.S.) (Grant K99GM102319)National Institutes of Health (U.S.) (Grant T32GM007753)National Institutes of Health (U.S.) (Grant R01GM067031)National Institutes of Health (U.S.) (Grant R35GM118135)Natural Sciences and Engineering Research Council of Canada (Discovery Grant

Model-Based Analysis of SARS-CoV-2 Infections, Hospitalization and Outcome in Germany, the Federal States and Districts

The coronavirus disease 2019 (COVID-19) pandemic challenged many national health care systems, with hospitals reaching capacity limits of intensive care units (ICU). Thus, the estimation of acute local burden of ICUs is critical for appropriate management of health care resources. In this work, we applied non-linear mixed effects modeling to develop an epidemiological SARS-CoV-2 infection model for Germany, with its 16 federal states and 400 districts, that describes infections as well as COVID-19 inpatients, ICU patients with and without mechanical ventilation, recoveries, and fatalities during the first two waves of the pandemic until April 2021. Based on model analyses, covariates influencing the relation between infections and outcomes were explored. Non-pharmaceutical interventions imposed by governments were found to have a major impact on the spreading of SARS-CoV-2. Patient age and sex, the spread of variant B.1.1.7, and the testing strategy (number of tests performed weekly, rate of positive tests) affected the severity and outcome of recorded cases and could reduce the observed unexplained variability between the states. Modeling could reasonably link the discrepancies between fine-grained model simulations of the 400 German districts and the reported number of available ICU beds to coarse-grained COVID-19 patient distribution patterns within German regions

IgG seroprevalence of COVID-19 among people living with HIV or at high risk of HIV in south-west Germany: A seroprevalence study

Objectives: Seroprevalence studies of SARS-CoV-2 have shown that there is a high number of undiagnosed missing cases. Seroprevalence of SARS-CoV-2 in people living with HIV (PLWH) is lacking. Therefore, we conducted a prospective cross-sectional study to estimate the seroprevalence of SARS-CoV-2 among PLWH without known diagnosis of COVID-19 in the south-west of Germany. Methods: Serological testing for SARS-CoV-2 immunoglobulin G (IgG) antibodies based on two assays was performed in PLWH who visited the outpatient HIV centre of two hospitals from April to June 2020. Additionally, patients had to answer questionnaires about possible COVID-19-related symptoms and predefined risk factors. Moreover, we tested 50 non-HIV-infected patients receiving post- or pre-exposure (PEP/PrEP) HIV prophylaxis. Results: In all, 594 (488 male, 106 female) PLWH (median age 51 years) and 50 PEP/PrEP-users were included in the study. The estimated seroprevalence of the PLWH cohort was 1.85% (11/594), with 11 positive tested cases in the cohort. Among all patients, only five had COVID-19-related symptoms. One PCRpositive patient did not show any antibody response in repeatedly carried out tests. None of the patients was hospitalized due to COVID-19. Three PrEP users were tested positive. Three patients had been previously diagnosed with SARSCOV-2 infection before inclusion. The used questionnaire did not help to detect SARS-CoV-2 positive patients. Conclusions: Despite the limitation of being only a snapshot in time because of the ongoing pandemic, to our knowledge this is the largest study so far on seroprevalence of SARS-CoV-2 in PLWH in Germany. Our study suggests that the seroprevalence of SARS-CoV-2 in PLWH is comparable to those previously reported for parts of the general German population and that the questionnaire used here might not be the best tool to predict COVID-19 diagnosis

Expression of TRAIL, IP-10, and CRP in children with suspected COVID-19 and real-life impact of a computational signature on clinical decision-making: a prospective cohort study

Purpose We evaluated the host-response marker score “BV” and its components TRAIL, IP-10, and CRP in SARS-CoV-2 positive children, and estimated the potential impact on clinical decision-making. Methods We prospectively analyzed levels of TRAIL, IP-10, CRP, and the BV score, in children with suspected COVID19. Classifcation of infectious etiology was performed by an expert panel. We used a 5-point-questionnaire to evaluate the intention to treat with antibiotics before and after receiving test results. Results We screened 111 children, of whom 6 (5.4%) were positive for SARS-CoV-2. A total of 53 children were included for the exploratory analysis. Median age was 3.1 years (interquartile range [IQR] 1.3–4.3), and 54.7% (n=29) were girls. A viral and a bacterial biomarker pattern was found in 27/53 (50.9%) and 15/53 (28.3%), respectively. BV scores difered between COVID-19, children with other viral infections, and children with bacterial infections (medians 29.5 vs. 9 vs. 66; p=0.0006). Similarly, median TRAIL levels were diferent (65.5 vs. 110 vs. 78; p=0.037). We found no diferences in IP-10 levels (555 vs. 504 vs. 285; p=0.22). We found a concordance between physicians’ “unlikely intention to treat” children with a viral test result in most cases (n=19/24, 79.2%). When physicians expressed a “likely intention to treat” (n=15), BV test revealed 5 bacterial, viral, and equivocal scores each. Antibiotics were withheld in three cases (20%). Overall, 27/42 (64%) of pediatricians appraised the BV test positively, and considered it helpful in clinical practice. Conclusion Host-response based categorization of infectious diseases might help to overcome diagnostic uncertainty, support clinical decision-making and reduce unnecessary antibiotic treatment