bluuebunny/crossref_metadata_2025 huggingface dataset:
Does End-Expiratory Occlusion Test Predict Fluid Responsiveness in Mechanically Ventilated Patients? A Systematic Review and Meta-Analysis
Authors: Si Xiang , Song Xiaodong , Lin Qiwen , Nie Yao , Zhang Guanrong , Xu Hailin , Chen Minying , Wu Jianfeng , Guan Xiangdong
Published: May 2020

Background:

We performed a systematic review and meta-analysis of studies investigating the end-expiratory occlusion (EEO) test induced changes in cardiac index (CI) and in arterial pressure as predictors of fluid responsiveness in adults receiving mechanical ventilation.

Methods:

MEDLINE, EMBASE, Cochrane Database, and Chinese database were screened for relevant original and review articles. The meta-analysis determined the pooled sensitivity, specificity, diagnostic odds ratio, area under the receiver operating characteristic curve (AUROC), and threshold for the EEO test assessed with CI and arterial pressure. In addition, heterogeneity and subgroup analyses were performed.

Results:

We included 13 studies involving 479 adult patients and 523 volume expansion. Statistically significant heterogeneity was identified, and meta-regression indicated that prone position was the major sources of heterogeneity. After removal of the study performed in prone position, heterogeneity became nonsignificant. EEO-induced changes in CI (or surrogate) are accurate for predicting fluid responsiveness in semirecumbent or supine patients, with excellent pooled sensitivity of 92% (95% CI, 0.88–0.95, I2 = 0.00%), specificity of 89% (95% CI, 0.83–0.93, I2 = 34.34%), and a summary AUROC of 0.95 (95% CI, 0.93–0.97). The mean threshold was an EEO-induced increase in CI (or surrogate) of more than 4.9 ± 1.5%. EEO test exhibited better diagnostic performance in semirecumbent or supine patients than prone patients, with higher AUROC (0.95 vs. 0.65; P < 0.001). In addition, EEO test exhibited higher specificity (0.93 vs. 0.83, P < 0.001) in patients ventilated with low tidal volume compared with normal or nearly normal tidal volume. However, EEO test was less accurate when its hemodynamic effects were detected on arterial pressure. EEO-induced changes in arterial pressure exhibited a lower sensitivity (0.88 vs. 0.92; P = 0.402), specificity (0.77 vs. 0.90; P = 0.019), and AUROC (0.87 vs. 0.96; P < 0.001) compared with EEO-induced changes in CI (or surrogate).

Conclusions:

EEO test is accurate to predict fluid responsiveness in semirecumbent or supine patients but not in prone patients. EEO test exhibited higher specificity in patients ventilated with low tidal volume, and its accuracy is better when its hemodynamic effects are assessed by direct measurement of CI than by the arterial pressure.
Sepsis Activates the TLR4/MyD88 Pathway in Schwann Cells to Promote Infiltration of Macrophages, Thereby Impeding Neuromuscular Function
Authors: Ye Wanlin , Liu Xueru , Bai Yiping , Tang Ni , Wu Gangming , Wang Xiaobin , Cheng Jinyuan , Liu Li
Published: May 2020

Introduction:

Sepsis is a kind of maladjustment response to bacterial infection and activation of coagulation, which can induce neuromuscular dysfunction. However, there is scarce of experimental evidence about the relationship between Schwann cells (SCs) and sepsis in neuromuscular dysfunction. We therefore set out to identify the potential role of SCs in sepsis-induced neuromuscular dysfunction and to explore the underlying molecular mechanism.

Methods:

Primary SCs were isolated from the left hind limb sciatic nerve of sepsis mice, which was constructed by cecal ligation and puncture. Then, the SCs were infected with adenovirus encoding toll-like receptor 4 (TLR4), MyD88, or IL-1R (with lipopolysaccharide stimulation), and the Raw 264.7 macrophages were injected with adenovirus with CCR2 silencing (with mMCP-1 stimulation). Further investigation of the interleukin 1 beta (IL-1β) and macrophage cationic peptide 1 (MCP-1) expressions, we followed reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay techniques, the F4/80 and Ki67 expressions was observed by immunofluorescence staining, while the expressions of CCR2, FAK/p-FAK, nuclear factor-κB (NFκB)/p-NFκB, and ERK1/2/p-ERK1/2 were determined by Western blot analysis. Last, but not the least, the cell migration ability and cell proliferation ability were detected by Transwell assay and Flow cytometry respectively.

Results:

Our results showed that in sepsis mice, the TLR4/MyD88/ERK pathway was activated in SCs, which triggered the cells to secrete IL-1β and MCP-1. The secreted IL-1β bound with IL-1β receptor on the surface of SCs, thereby activating the IL-1β/IL-1R/MyD88/ERK pathway and further promoting the secretion of MCP-1 by SCs. MCP-1 was found to bind to CCR2 on the surface of Raw264.7 macrophages to activate the TLR4/MyD88/ERK pathway which caused the inhibition of neuromuscular function.

Conclusion:

Sepsis significantly promotes the infiltration of macrophages by activating the TLR4/MyD88 pathway in SCs, thereby impeding neuromuscular function. Consistently, our study provides a novel concept in the area of neuromuscular dysfunction therapeutics following sepsis.
Involvement of NF-κB1 and the Non-canonical NF-κB Signaling Pathway in the Pathogenesis of Acute Kidney Injury in Shiga-toxin-2-induced Hemolytic-uremic Syndrome in Mice
Authors: Sobbe Isabelle V. , Krieg Nadine , Dennhardt Sophie , Coldewey Sina M.
Published: May 2020

The hemolytic-uremic syndrome (HUS) is a thrombotic microangiopathy which can occur as a severe systemic complication after an infection with Shiga-toxin-(Stx)-producing Escherichia coli (STEC). Elevated levels of proinflammatory cytokines associated with the classical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) signaling pathway were detected in the urine of HUS patients. Thus, we hypothesize that the immune response of the infected organism triggered by Stx can affect the kidneys and contributes to acute kidney injury. Hitherto, the role of the classical and non-canonical NF-κB signaling pathway in HUS has not been evaluated systematically in vivo. We aimed to investigate in a murine model of Shiga toxin-induced HUS-like disease, whether one or both pathways are involved in the renal pathology in HUS. In kidneys of mice subjected to Stx or sham-treated mice, protein or gene expression analyses were performed to assess the expression of receptors activating the classical and non-canonical pathway, such as Fn14 and CD40, levels of NF-κB1/RelA and NF-κB2/RelB including its upstream signaling proteins, and expression of cytokines as target molecules of both pathways. In line with a higher expression of Fn14 and CD40, we detected an enhanced translocation of NF-κB1 and RelA as well as NF-κB2 and RelB into the nucleus accompanied by an increased gene expression of the NF-κB1-target cytokines Ccl20, Cxcl2, Ccl2, Cxcl1, IL-6, TNF-α, Cxcl10, and Ccl5, indicating an activation of the classical and non-canonical NF-κB pathway. Thereby, we provide, for the first time, in vivo evidence for an involvement of both NF-κB signaling pathways in renal pathophysiology of STEC-HUS.
Saving Lives and Improving the Quality of Pediatric Resuscitation Across the World
Authors: Kessler David O. , Stone Kimberly P. , Chang Todd P. , Dolby Tom , Gray Rebecca , Shilkofski Nicole A. , Deutsch Ellen , Duval-Arnould Jordan , Nadkarni Vinay M. , Cheng Adam , Pusic Martin , Hunt Elizabeth A.
Published: May 2020

Summary Statement

The International Network for Simulation-based Pediatric Innovation, Research, and Education co-hosted a novel research accelerator meeting with the International Pediatric Simulation Society in May of 2019 in Toronto. The purpose of the meeting was to bring together healthcare simulation scientists with resuscitation stakeholders to brainstorm strategies for accelerating progress in the science of saving pediatric lives from cardiac arrest. This was achieved by working in teams to draft targeted requests for proposals calling the research community to action investigating this topic. During the 1-day meeting, groups were divided into 6 teams lead by experts representing specific domains of simulation research. Teams developed a pitch and presented a sample request for proposals to a panel of expert judges, making a case for why their domain was the most important to create a funding opportunity. The winner of the competition had their specific request for proposal turned into an actual funding opportunity, supported by philanthropy that was subsequently disseminated through International Network for Simulation-based Pediatric Innovation, Research, and Education as a competitive award. An inspired donor supported an award for the second-place proposal as well, evidence of early research acceleration catalyzed from this conference. This article is a summary of the meeting rationale, format, and a description of the requests for proposals that emerged from the meeting. Our goal is to inspire other stakeholders to use this document that leverages simulation and resuscitation science expertise, as the framework to create their own funding opportunities, further accelerating pediatric resuscitation research, ultimately saving the lives of more children worldwide.
Isolating the sources of heterogeneity in nano-engineered particle–cell interactions
Authors: Johnston Stuart T. , Faria Matthew , Crampin Edmund J.
Published: May 2020

Nano-engineered particles have the potential to enhance therapeutic success and reduce toxicity-based treatment side effects via the targeted delivery of drugs to cells. This delivery relies on complex interactions between numerous biological, chemical and physical processes. The intertwined nature of these processes has thus far hindered attempts to understand their individual impact. Variation in experimental data, such as the number of particles inside each cell, further inhibits understanding. Here, we present a mathematical framework that is capable of examining the impact of individual processes during particle delivery. We demonstrate that variation in experimental particle uptake data can be explained by three factors: random particle motion; variation in particle–cell interactions; and variation in the maximum particle uptake per cell. Without all three factors, the experimental data cannot be explained. This work provides insight into biological mechanisms that cause heterogeneous responses to treatment, and enables precise identification of treatment-resistant cell subpopulations.
Elastic recoil action amplifies jaw closing speed in an aquatic feeding salamander
Authors: Rull-Garza Mateo , Solomon Jacob , Konow Nicolai
Published: May 2020

Tendon springs often influence locomotion by amplifying the speed and power of limb joint rotation. However, less is known about elastic recoil action in feeding systems, particularly for small aquatic animals. Here, we ask if elastic recoil amplifies the speed of gape closing during aquatic food processing in the Axolotl (Ambystoma mexicanum). We measure activation of the adductor mandibulae externus via electromyography and strain of the jaw adductor muscle–tendon unit (MTU), and gape kinematics via fluoromicrometry. The muscle is pre-activated coincident with gape opening, which causes MTU stretch. Activation lasts significantly shorter for fish than cricket processing, and muscle shortening during MTU lengthening yields significantly greater elastic strain for cricket processing. The speed of MTU shortening, which dictates the speed of gape closing is 2.5–4.4 times greater than the speed of the initial shortening of the muscle fascicles for fish and cricket gape cycles, respectively. These data demonstrate a clear role for elastic recoil, which may be unexpected for a MTU in a feeding system of a small, aquatic animal. Amplification of jaw-closing speed resulting from elastic recoil likely confers ecological advantages in reducing prey escape risks during food processing in a dense and viscous fluid environment.
COVID-19 in Uganda: Predicting the impact of the disease and public health response on disease burden
Authors: Bell David , Hansen Kristian Schultz , Kiragga Agnes N. , Kambugu Andrew , Kissa John , Mbonye Anthony K.
Published: May 2020

Objective

COVID-19 transmission and the public health ‘lock-down’ response are now established in sub-Saharan Africa, including Uganda. Population structure and prior morbidities differ markedly between these countries from those where outbreaks were previously established. We predicted the relative impact of COVID-19 and the response in Uganda to understand whether the benefits could be outweighed by the costs.

Design and setting

Age-based COVID-19 mortality data from China were applied to the population structures of Uganda and countries with previously established outbreaks, comparing theoretical mortality and disability-adjusted life years (DALYs) lost. Based on recent Ugandan data and theoretical scenarios of programme deterioration, we predicted potential additional disease burden for HIV/AIDS, malaria and maternal mortality.

Main outcome measures

DALYs lost and mortality.

Results

Based on population age structure alone Uganda is predicted to have a relatively low COVID-19 burden compared to equivalent transmission in China and Western countries, with mortality and DALYs lost predicted to be 12% and 19% that of Italy. Scenarios of ‘lockdown’ impact predict HIV/AIDS and malaria equivalent to or higher than that of an extensive COVID-19 outbreak. Emerging HIV/AIDS and maternal mortality data indicate that such deterioration could be occurring.

Conclusions

The results predict a relatively low COVID-19 impact on Uganda associated with its young population, with a high risk of negative impact on non-COVID-19 disease burden from a prolonged lockdown response. The results are likely to reflect the situation in other sub-Saharan populations, underlining the importance of tailoring COVID-19 responses to population structure and potential disease vulnerabilities.

Transparency statement

The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that there are no discrepancies from the study as originally planned.
Preventive behavior of Vietnamese people in response to the COVID-19 pandemic
Authors: Thang Thang Van , Nguyen Nhan Phuc Thanh , Hoang Tuyen Dinh , Tran Vi Thao , Vu Cuc Thi , Nelson Siewe Joseph , Colebunders Robert , Dunne Michael
Published: May 2020

We sought to evaluate the adherence of Vietnamese adults to COVID-19 preventive measures, and gain insight into the effects of the epidemic on the daily lives of Vietnamese people. An online questionnaire survey was organized from March 31 to April 6, 2020. The questionnaire assessed preventive behavior using multiple answer responses to indicate the extent of adherence. In total, 2175 respondents completed the questionnaire (age range: 18-69 years). The mean adherence scores for personal and community preventive measures were 7.23 ± 1.63 (range 1-9) and 9.57 ± 1.12 (range 1-11), respectively. Perceived adaptation of the community to lockdown (β=2.64, 95% CI 1.25 −4.03), fears/worries concerning one′s health (β=2.87, 95% CI 0.04-5.70), residing in large cities (β=19.40, 95% CI 13.78-25.03), access to official COVID19 information sources (β=16.45, 95% CI 6.82-26.08), and belonging to the healthcare sector (β=22.53, 95% CI 16.00-29.07) were associated with a higher adherence score to anti −COVID instructions. The study indicates excellent preventive behavior of the Vietnamese population which explains the low number of COVID-19 infections and zero recorded mortality up to the first week of May 2020. Further monitoring is recommended to assess the sustainability of COVID-19 prevention via behavior change in the medium and long-term.
Assessment of dispersion of airborne particles of oral/nasal fluid by high flow nasal cannula therapy
Authors: Jermy Mark C , Spence Callum JT , Kirton Robert , O'Donnell Jane F , Kabaliuk Natalia , Gaw Sally , Jiang Yannan , Zainol Abidin Zulkhairi , Dougherty Ronald L , Rowe Philip , Mahaliyana Anjula , Gibbs Amelia , Roberts Sally
Published: May 2020

Background
Nasal High Flow (NHF) therapy delivers flows of heated humidified gases up to 60 LPM (litres per minute) via a nasal cannula. Particles of oral/nasal fluid released by patients undergoing NHF therapy may pose a cross-infection risk, which is a potential concern for treating COVID-19 patients.
Methods
Liquid particles within the exhaled breath of healthy participants were measured with two protocols: (1) high speed camera imaging and counting exhaled particles under high magnification (6 participants) and (2) measuring the deposition of a chemical marker (riboflavin-5-monophosphate) at a distance of 100 and 500 mm on filter papers through which air was drawn (10 participants). The filter papers were assayed with HPLC. Breathing conditions tested included quiet (resting) breathing and vigorous breathing (which here means nasal snorting, voluntary coughing and voluntary sneezing). Unsupported (natural) breathing and NHF at 30 and 60 LPM were compared.
Results
(1) Imaging: During quiet breathing, no particles were recorded with unsupported breathing or 30 LPM NHF (detection limit for single particles 33 microns). Particles were detected in 2 of 6 participants at 60 LPM quiet breathing at approximately 10% of the rate caused by unsupported vigorous breathing. Unsupported vigorous breathing released the greatest numbers of particles. Vigorous breathing with NHF at 60 LPM, released half the number of particles compared to vigorous breathing without NHF.
(2) Chemical marker tests: No oral/nasal fluid was detected in quiet breathing without NHF (detection limit 0.28 microlitres/m3). In quiet breathing with NHF at 60 LPM, small quantities were detected in 4 out of 29 quiet breathing tests, not exceeding 17 microlitres/m3. Vigorous breathing released 200-1000 times more fluid than the quiet breathing with NHF. The quantities detected in vigorous breathing were similar whether using NHF or not.
Conclusion
During quiet breathing, 60 LPM NHF therapy may cause oral/nasal fluid to be released as particles, at levels of tens of microlitres per cubic metre of air.
Vigorous breathing (snort, cough or sneeze) releases 200 to 1000 times more oral/nasal fluid than quiet breathing. During vigorous breathing, 60 LPM NHF therapy caused no statistically significant difference in the quantity of oral/nasal fluid released compares to unsupported breathing.

NHF use does not increase the risk of dispersing infectious aerosols above the risk of unsupported vigorous breathing. Standard infection prevention and control measures should apply when dealing with a patient who has an acute respiratory infection, independent of which, if any, respiratory support is being used.
Monitoring and predicting SARS-CoV-2 epidemic in France after deconfinement using a multiscale age-stratified rate model
Authors: Reingruber Juergen , Papale Andrea , holcman David
Published: May 2020

The entire world and France were strongly impacted by the SARS-COV-2 epidemic. Finding appropriate measures that effectively contain the spread of the epidemic without putting a too severe pressure on social and economic life is major challenge for modern predictive approaches. To assess the impact of confinement (March 17th till May 11th) and deconfinement, we develop a novel rate model to monitor and predict the spread of the epidemic and its impact on the health care system. The model accounts for age-dependent interactions between population groups and predicts consequences for various infection categories such as number of infected, hospitalized, load of intensive care units (ICU), number of death, recovered and more. We use online health care data for the five most infected regions of France to calibrate the model. At day of deconfinement (May 11th), we find that 13% (around 4.8M) of the population is infected in the five most affected regions of France (extrapolating to 5.8M for France). The model predicts that if the reproduction rate R0 is reduced by at least a factor of 2.5-3 for all age groups, which could be achieved by wearing masks and social distancing, a significant second peak could be prevented. However, if the reduction in R0 for the age group 0-25 would be less and below 2 (school openings), a second peak is unavoidable in which case the ICU will be saturated. In that context testing should be focused on children, but it will nevertheless have a limited impact on reducing the spread.
Income-based inequalities in self-reported moderate-to-vigorous physical activity among adolescents in England and the United States: a cross-sectional study
Authors: Scholes Shaun , Mindell Jennifer S
Published: May 2020

Objective

Quantify inequalities in self-reported moderate-to-vigorous physical activity (MVPA) in England and the United States (US).

Design

Population-based cross-sectional study.

Participants

4019 adolescents aged 11–15 years in England (Health Survey for England 2008, 2012, 2015) and 4312 aged 12–17 years in the US (National Health and Nutrition Examination Survey 2007–16).

Main outcome measures

Three aspects of MVPA: (1) doing any, (2) average min/day (MVPA: including those who did none), and (3) average min/day conditional on participation (MVPA-active). Using hurdle models, inequalities were quantified using the absolute difference in marginal means (average marginal effects: AMEs).

Results

In England, adolescents in high-income households were more likely than those in low-income households to have done any formal sports/exercise in the last seven days (boys: 11%; 95% CI: 4% to 17%; girls: 13%; 95% CI: 6% to 20%); girls in high-income households did more than their low-income counterparts (MVPA: 6 min/day, 95% CI: 2 to 9). Girls in low-income households spent more time in informal activities than girls in high-income households (MVPA: 21 min/day; 95% CI: 10 to 33), whilst boys in low-income versus high-income households spent longer in active travel (MVPA: 21 min/week; 95% CI: 8 to 34). In the US, in a typical week, recreational activity was greater among high-income versus low-income households (boys: 15 min/day; 95% CI: 6 to 24; girls: 19 min/day; 95% CI: 12 to 27). In contrast, adolescents in low-income versus high-income households were more likely to travel actively (boys: 11%; 95% CI: 3% to 19%; girls: 10%; 95% CI: 3% to 17%) and do more.

Conclusions

Policy actions and interventions are required to increase MVPA across all income groups in England and the US. Differences in formal sports/exercise (England) and recreational (US) activities suggest that additional efforts are required to reduce inequalities.
Social heterogeneity and the COVID-19 lockdown in a multi-group SEIR model
Authors: Dolbeault Jean , Turinici Gabriel
Published: May 2020

The goal of the lockdown is to mitigate and if possible prevent the spread of an epidemic. It consists in reducing social interactions. This is taken into account by the introduction of a factor of reduction of social interactions q, and by decreasing the transmission coefficient of the disease accordingly. Evaluating q is a difficult question and one can ask if it makes sense to compute an average coefficient q for a given population, in order to make predictions on the basic reproduction rate ℛ0, the dynamics of the epidemic or the fraction of the population that will have been infected by the end of the epidemic. On a very simple example, we show that the computation of ℛ0 in a heterogeneous population is not reduced to the computation of an average q but rather to the direct computation of an average coefficient ℛ0. Even more interesting is the fact that, in a range of data compatible with the Covid-19 outbreak, the size of the epidemic is deeply modified by social heterogeneity, as is the height of the epidemic peak, while the date at which it is reached mainly depends on the average ℛ0 coefficient. This paper illustrates more technical results that can be found in [4], with new numerical computations. It is intended to draw the attention on the role of heterogeneities in a population in a very simple case, which might be difficult to apprehend in more realistic but also more complex models.
Data-driven analysis on the simulations of the spread of COVID-19 under different interventions of China
Authors: Tian Ting , Zhang Jingwen , Lin Shiyun , Jiang Yukang , Tan Jianbin , Li Zhongfei , Wang Xueqin
Published: May 2020

Since February 2020, COVID-19 has spread rapidly to more than 200 countries in the world. During the pandemic, local governments in China have implemented different interventions to efficiently control the spread of the epidemic. Characterizing transmission of COVID-19 under some typical interventions is essential to help countries develop appropriate interventions. Based on the pre-symptomatic transmission patterns of COVID-19, we established a novel compartmental model: Baysian SIHR model with latent Markov structure, which treated the numbers of infected and infectious individuals without isolation to be the latent variables and allowed the effective reproduction number to change over time, thus the effects of policies could be reasonably estimated. By using the epidemic data of Wuhan, Wenzhou and Shenzhen, we migrated the corresponding estimated policy modes to South Korea, Italy, and the United States and simulated the potential outcomes for these countries when they adopted similar policy strategies of three cities in China. We found that the mild interventions implemented in Shenzhen were effective to control the epidemic in the early stage, while more stringent policies which were issued in Wuhan and Wenzhou were necessary if the epidemic was more severe and needed to be controlled in a short time.
Association of Giardia lamblia Infection with Child Growth Impairment
Authors: Chowdhury Afrin Sultana , Ahmed Emtiaz , Islam Nazneen Nahar
Published: May 2020

The authors have withdrawn this manuscript because the study was part of a bigger project and there is a possibility that the data shown in the manuscript may represent a different conclusion than the whole study. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Monitoring the evolution of the COVID-19 pandemic in China, South Korea, Italy and USA through the net relative rate of infection of the total number of confirmed cases
Authors: Moreira Joao Manoel Losada
Published: May 2020

Managing the COVID-19 pandemic in the middle of the events requires real-time monitoring of its evolution to perform analyses of containment actions and to project near future scenarios. This work proposes a scheme to monitor the temporal evolution of the COVID-19 pandemic using the time series of its total number of confirmed cases in a given region. The monitored parameter is the spread rate obtained from this time series (day-1) expressed in %/day. The scheme's capability is verified using the epidemic data from China and South Korea. Its projection capability is shown for Italy and United States with scenarios for the ensuing 30 days from April 2nd, 2020. The spread rate (relative rate of change of the time series) is very sensitive to sudden changes in the epidemic evolution and can be used to monitor in real-time the effectiveness of containment actions. The logarithm of this variable allows identifying clear trends of the evolution of the COVID-10 epidemic in these countries. The spread rate calculated from the number of confirmed cases of infection is interpreted as a probability per unit of time of virus infection and containment actions. Its product with the number of confirmed cases of infections yields the number of new cases per day. The stabilization and control of the epidemic for China and South Korea appear to occur for values of this parameter below 0.77 %/day (doubling time of 90 days).
Quantifying antibody kinetics and RNA shedding during early-phase SARS-CoV-2 infection
Authors: Borremans Benny , Gamble Amandine , Prager K C , Helman Sarah K , McClain Abby M , Cox Caitlin , Savage Van , Lloyd-Smith James O
Published: May 2020

Our ability to understand and mitigate the spread of SARS-CoV-2 depends largely on antibody and viral RNA data that provide information about past exposure and shedding. Five months into the outbreak there is an impressive number of studies reporting antibody kinetics and RNA shedding dynamics, but extensive variation in detection assays, study group demographics, and laboratory protocols has presented a challenge for inferring the true biological patterns. Here, we combine existing data on SARS-CoV-2 IgG, IgM and RNA kinetics using a formal quantitative approach that enables integration of 3,214 data points from 516 individuals, published in 22 studies. This allows us to determine the mean values and distributions of IgG and IgM seroconversion times and titer kinetics, and to characterize how antibody and RNA detection probabilities change during the early phase of infection. We observe extensive variation in antibody response patterns and RNA detection patterns, explained by both individual heterogeneity and protocol differences such as targeted antigen and sample type. These results provide a robust reference for clinical management of individual patients, and a foundation for the mathematical models and serological surveys that underpin public health policies.
Epidemic Models with Random Infectious Period
Authors: Riaño Germán
Published: May 2020

In this paper, we present an extension to the classical SIR epidemic transmission model that uses any general probability distribution for the length of the infectious period. The classical SIR model implicitly requires an exponential distribution for the length of this period of time. We will show how a general distribution can be easily taken into account using the Transient Little Law and present numerical methods to solve the model in an efficient way. Our numerical experiments show that in the presence of a more realistic distribution, with lower variability than the exponential distribution, the size of peak of infected individuals on the graph will be higher and occur earlier. Conversely, a higher-variability distribution will lead to a lower peak that takes longer to dissipate. We also discuss some extensions to the basic model, to include variants like SEIRD and SIS. These findings should have profound and important consequences in the design of public policy.
The specificity of Japanese PCR assays for SARS-CoV-2 exceeds 99.7%
Authors: Tsukadaira Akihiro , Nishie Kenichi
Published: May 2020

The Japanese government arranged a total of three charter flights to evacuate Japanese residents out of Wuhan Jan 29, 30, and 31, 2020. The project to rescue Japanese residents can be recognized as a randomized sampling study for the COVID-19 epidemic in Wuhan at that time. Jan 23, Jonathan MR et al stated in the medRxiv, in 14 days’ time (Feb 4, 2020), the number of infected people in Wuhan is estimated to be greater than 190 thousand (prediction interval, 132,751 to 273,649). In our study, the estimation of the COVID-19 cases in Wuhan around Jan 29, 30 and 31, 2020 exceeds the lower prediction 132,751 in the prior probability: 0.0134. Our statistical analysis is consistent with Jonathan MR et al, if the specificity of SARS–CoV–2 PCR assays in Japan exceeds 99.7%.
IL-6 inhibition in critically ill COVID-19 patients is associated with increased secondary infections
Authors: Kimmig Lucas M. , Wu David , Gold Matthew , Pettit Natasha N , Pitrak David , Mueller Jeffery , Husain Aliya N. , Mutlu Ece A. , Mutlu Gökhan M.
Published: May 2020

Background

Anti-inflammatory therapies such as IL-6 inhibition have been proposed for COVID-19 in a vacuum of evidence-based treatment. However, abrogating the inflammatory response in infectious diseases may impair a desired host response and predispose to secondary infections.

Methods

We retrospectively reviewed the medical record of critically ill COVID-19 patients during an 8-week span and compared the prevalence of secondary infection and outcomes in patients who did and did not receive tocilizumab. Additionally, we included representative histopathologic post-mortem findings from several COVID-19 cases that underwent autopsy at our institution.

Results

111 patients were identified, of which 54 had received tocilizumab while 57 had not. Receiving tocilizumab was associated with a higher risk of secondary bacterial (48.1% vs. 28.1%, p=0.029 and fungal (5.6% vs. 0%, p=0.112) infections. Consistent with higher number of infections, patients who received tocilizumab had higher mortality (35.2% vs. 19.3%, p=0.020). Seven cases underwent autopsy. In 3 cases who received tocilizumab, there was evidence of pneumonia on pathology. Of the 4 cases that had not been given tocilizumab, 2 showed evidence of aspiration pneumonia and 2 exhibited diffuse alveolar damage.

Conclusions

Experimental therapies are currently being applied to COVID-19 outside of clinical trials. Anti-inflammatory therapies such as anti-IL-6 therapy have the potential to impair viral clearance, predispose to secondary infection, and cause harm. We seek to raise physician awareness of these issues and highlight the need to better understand the immune response in COVID-19.
Declined functional connectivity of white matter during rest and working memory tasks associates with cognitive impairments in schizophrenia
Authors: Gao Yurui , Li Muwei , Huang Anna S , Anderson Adam W , Ding Zhaohua , Heckers Stephan H , Woodward Neil D , Gore John C
Published: May 2020

BACKGROUND: Schizophrenia, characterized by cognitive impairments, arises from a disturbance of brain network. Pathological changes in white matter (WM) have been indicated as playing a role in disturbing neural connectivity in schizophrenia. However, deficits of functional connectivity (FC) in individual WM bundles in schizophrenia have never been explored; neither have cognitive correlates with those deficits.
METHODS: Resting-state and spatial working memory task fMRI images were acquired on 67 healthy subjects and 84 patients with schizophrenia. The correlations in blood-oxygenation-level-dependent (BOLD) signals between 46 WM and 82 gray matter regions were quantified, analyzed and compared between groups under three scenarios (i.e., resting state, retention period and entire time of a spatial working memory task). Associations of FC in WM with cognitive assessment scores were evaluated for three scenarios.
RESULTS: FC deficits were significant (p<.05) in external capsule, cingulum, uncinate fasciculus, genu and body of corpus callosum under all three scenarios. Deficits were also present in the anterior limb of the internal capsule and cerebral peduncle in task scenario. Decreased FCs in specific WM bundles associated significantly (p<.05) with cognitive impairments in working memory, processing speed and/or cognitive control.
CONCLUSIONS: Decreases in FC are evident in several WM bundles in patients with schizophrenia and are significantly associated with cognitive impairments during both rest and working memory tasks. Furthermore, working memory tasks expose FC deficits in more WM bundles and more cognitive associates in schizophrenia than resting state does.
Using the shock index to rule out stroke in patients with impaired consciousness in the emergency department: a single-centre retrospective study
Authors: Kato Kosuke , Sagisaka Shogo , Ueda Masayuki , Tamune Hidetaka
Published: May 2020

Objectives: Stroke is a significant cause of impaired consciousness. During a stroke, intracranial pressure increases, resulting in hypertension and bradycardia, also known as the Cushing response. Previous studies showed that systolic blood pressure (sBP) was useful for diagnosing stroke. We hypothesized that stroke patients would show a low Shock Index (SI, pulse rate divided by sBP), and that a high SI would therefore be also useful for ruling out stroke in patients with impaired consciousness.

Design: This was a single-centre retrospective medical record review conducted between 2015 and 2016.

Participants: We identified 194 patients with stroke and 588 patients without stroke. We included all out-patients with impaired consciousness who underwent cranial computed tomography (CT) and allocated them to the stroke (cerebral infarction, intracerebral haemorrhage, and subarachnoid haemorrhage) and non-stroke groups.

Measures: For both the sBP and SI, we calculated the sensitivity and specificity of each cut-off value and compared their diagnostic value.

Results: The area under the receiver operating characteristic curve was 0.801 (95% Confidence Interval: 0.761-0.840) for the sBP and 0.764 (0.729-0.799) for the SI. For an sBP higher than 90 mmHg and an SI lower than 1, the sensitivity was 99.5% for both. The specificity was 10.9% and 15.1%, respectively, and the negative likelihood ratio was 0.045 and 0.034, respectively. Subgroup analyses suggested that predictive value of SI was enough high regardless of the subtype of stroke, patient′s past history of hypertension, or level of consciousness.

Conclusion: SI may be useful for excluding stroke in patients with impaired consciousness. This study suggested that when the pulse rate exceeds sBP, stroke can be ruled out. In these cases, we suggest that physicians focus on non-neurological examinations and treatments rather than diagnostic examinations for stroke.
Feasibility of Reusing Surgical Mask Under Different Disinfection Treatments
Authors: SUEN Chin Yan , LEUNG Hong Hang , LAM Ka Wo , HUNG Karen P , CHAN Mei Yan , KWAN Joseph Kai Cho
Published: May 2020

The possibility to extend the lifespan or even reuse one-off personal protective equipment, especially for N95 respirator and surgical mask become critical during pandemic. World Health Organization has confirmed that wearing surgical mask is effective in controlling the spread of respiratory diseases in the community, but the supply may not be able to satisfy all the demands created all over the world in a short period of time. This investigation found that dry heat and UVC irradiance could effectively disinfect the mask material without creating significant damage to surgical mask.
COVID-19 in London, a Case Series Demonstrating Late Improvement in Survivors
Authors: Al-Hindawi Ahmed , Sokhi Jagdish , Cuddihy Joshua , Lockie Christopher , Christie Linsey , Davies Roger , Singh Suveer , Vizcaychipi Marcela , Hayes Michelle , Sisson Alice , Keays Richard
Published: May 2020

Objective
To determine whether the trajectories of survivors and non-survivors are different in patients admitted to intensive care in London.
Design
In this case series of 15 survivors and 16 non-survivors, data from admission to discharge was collected and aligned to lowest PaO2/FiO2 ratio where aggregation and trends were demonstrated.
Setting
Single centre case-series in London, Intensive Care.
Participants
All non-survivors were included (n=16). A biased set of survivors (n=15) who were demonstrated an unexpected and rapid recovery after a prolonged period of mechanical ventilatory support.
Results
Respiratory failure trajectories of survivors and non-survivors were similar once aligned indicating, from a respiratory function perspective, it is difficult to identify survivors from non-survivors with some survivors improving late in their disease (day 20 - 30 from symptom onset)
Non-survivors are admitted earlier in their disease (p < 0.05) and had worse organ failure requirements prior to the nadir of their respiratory funciton (p < 0.05) compard to survivors.
Conclusion
Analysis of multiple factors fails to differentiate between survivors and non-survivors.
Even when faced with multiorgan failure, perseverance until discharge must be advocated as late improvements do occur in survivors.
Causal Modeling of Twitter Activity During COVID-19
Authors: Gencoglu Oguzhan , Gruber Mathias
Published: May 2020

Understanding the characteristics of public attention and perception is an essential prerequisite for appropriate crisis management during adverse health events. This is even more crucial during a pandemic such as COVID-19, as primary responsibility of risk management is not centralized to a single institution, but distributed across society. While numerous studies utilize Twitter data in descriptive or predictive context during COVID-19 pandemic, causal modeling of public attention has not been investigated. In this study, we propose a causal inference approach to discover and quantify causal relationships between pandemic characteristics (e.g. number of infections and deaths) and Twitter activity as well as public sentiment. Our results show that the proposed method can successfully capture the epidemiological domain knowledge and identify variables that affect public attention and perception. We believe our work contributes to the field of infodemiology by distinguishing events that correlate with public attention from events that cause public attention.
Predicting the COVID-19 positive cases in India with concern to Lockdown by using Mathematical and Machine Learning based Models
Authors: Pasayat Ajit Kumar , Pati Satya Narayan , Maharana Aashirbad
Published: May 2020

In this study, we analyze the number of infected positive cases of COVID-19 outbreak with concern to lockdown in India in the time window of February 11th 2020 to Jun 30th 2020. The first case in India was reported in Kerala on January 30th 2020. To break the chain of spreading, Government announced a nationwide lockdown on March 24th 2020, which is increased two times. The Ongoing lockdown 3.0 is over on May 18th, 2020. We derived how the lockdown relaxation is going to impact on containment of the outbreak. Here the Exponential Growth Model has been used to derive the epidemic curve based on the data collected from February 11th 2020, to May 11th 2020, and the Machine Learning based Linear Regression model that gives the epidemic curve to predict the cases with the continuous flow of the lockdown. We estimate that if the lockdown is continuing with more relaxation, then the estimated infected cases reach up to 1.16 crores by June 30th 2020, and the lockdown would persist with current restriction, then the expected predicted infected cases are 5.69 lacs. The Exponential Growth Model and the Linear Regression Model are advantageous to predict the number of affected cases of COVID-19. These models can be used for forecasting in long term intervals. It shows from our result that lockdown with certain restriction has a vital role in preventing the spreading of this epidemic in this current situation.
Is Nigeria really on top of COVID-19? Message from effective reproduction number
Authors: Adekunle Adeshina Israel , Adegboye Oyelola , Gayawan Ezra , McBryde Emma
Published: May 2020

Following the importation of Covid-19 into Nigeria on the 27 February 2020 and then the outbreak, the question is: how do we anticipate the progression of the ongoing epidemics following all the intervention measures put in place? This kind of question is appropriate for public health responses and it will depend on the early estimates of the key epidemiological parameters of the virus in a defined population.
In this study, we combined a likelihood-based method using a Bayesian framework and compartmental model of the epidemic of Covid-19 in Nigeria to estimate the effective reproduction number (R(t)) and basic reproduction number (R_0). This also enables us to estimate the daily transmission rate (β) that determines the effect of social distancing. We further estimate the reported fraction of symptomatic cases. The models are applied to the NCDC data on Covid-19 symptomatic and death cases from 27 February 2020 and 7 May 2020.
In this period, the effective reproduction number is estimated with a minimum value of 0.18 and a maximum value of 1.78. Most importantly, the R(t) is strictly greater than one from April 13 till 7 May 2020. The R_0 is estimated to be 2.42 with credible interval: (2.37, 2.47). Comparing this with the R(t) shows that control measures are working but not effective enough to keep R(t) below one. Also, the estimated fractional reported symptomatic cases are between 10 to 50%.
Our analysis has shown evidence that the existing control measures are not enough to end the epidemic and more stringent measures are needed.
A Computer Simulation Study on novel Corona Virus Transmission among the People in a Queue
Authors: Mathews Santhosh Samuel
Published: May 2020

The World Health Organization (WHO) on March 11, 2020, has declared the novel Corona virus (COVID-19) outbreak a global pandemic. It is essential to understand how coronavirus transmits from one person to another and this knowledge will help protect the vulnerable and limit the spread of the Corona virus. The mode of respiratory transmission of Corona virus is not completely understood as of date. Using a computer simulation, this paper analyses the probability of spreading of Corona virus through air among the people who are standing in a queue. The parameters such as the diameter of the virus particle, room temperature, relative humidity, height of the person, distance between the people and the waiting time in the queue are considered in the computer model to determine the distribution of Corona virus and hence identify the risk factor of spreading the Covid-19. This paper describes the possibilities of getting infectious when a Covid-19 infected person present in a queue and the impact on the waiting time and the position in the queue on the transmission of Corona virus.
dadasnake, a Snakemake implementation of DADA2 to process amplicon sequencing data for microbial ecology
Authors: Weiβbecker Christina , Schnabel Beatrix , Heintz-Buschart Anna
Published: May 2020

Background

Amplicon sequencing of phylogenetic marker genes, e.g. 16S, 18S or ITS rRNA sequences, is still the most commonly used method to determine the composition of microbial communities. Microbial ecologists often have expert knowledge on their biological question and data analysis in general, and most research institutes have computational infrastructures to employ the bioinformatics command line tools and workflows for amplicon sequencing analysis, but requirements of bioinformatics skills often limit the efficient and up-to-date use of computational resources.

Results

dadasnake wraps pre-processing of sequencing reads, delineation of exact sequence variants using the favorably benchmarked, widely-used the DADA2 algorithm, taxonomic classification and post-processing of the resultant tables, and hand-off in standard formats, into a user-friendly, one-command Snakemake pipeline. The suitability of the provided default configurations is demonstrated using mock-community data from bacteria and archaea, as well as fungi.

Conclusions

By use of Snakemake, dadasnake makes efficient use of high-performance computing infrastructures. Easy user configuration guarantees flexibility of all steps, including the processing of data from multiple sequencing platforms. dadasnake facilitates easy installation via conda environments. dadasnake is available athttps://github.com/a-h-b/dadasnake.
Feasibility of non-invasive nitric oxide inhalation in acute hypoxic respiratory failure: potential role during the COVID-19 pandemic
Authors: Shekar Kiran , Varkey Sneha , Cornmell George , Parsons Leanne , Tol Maneesha , Siuba Matthew , Ramanan Mahesh
Published: May 2020

Acute hypoxemic respiratory failure (ARF) is characterized by both lower arterial oxygen and carbon dioxide tensions in the blood. First line treatment for ARF includes oxygen therapy,intially admininstered non invasively using nasal prongs, high flow nasal cannulae or masks. Invasive mechancial ventilation (IMV) is usually reserved for patients who are unable to maintain their airway, those with worsening hypoxemia, or those who develop respiratory muscle fatigue and consequent hypercapnia.

Inhaled nitric oxide (iNO) gas is known to improve oxygenation in patients with ARF by manipulating ventilation-perfusion matching. Addition of iNO may potentially alleviate the need for IMV in selected patients. This article demonstrates the feasibility of this technique based on our experience of patients with hypoxemic ARF. This technique may also be considered for patients with hypoxic ARF in setting of COVID-19.