bluuebunny/crossref_metadata_2025 huggingface dataset:
SMMARTS
Authors: Lampotang Samsun , Bigos André K. , Avari Kaizad , Johnson William T. , Mei Vincent , Lizdas David E.
Published: September 2020

Introduction

Different simulators often share elements, resulting in different laboratories doing redundant work. This can lead to higher development and acquisition costs, proprietary, incompatible technology, lack of interoperability, and large inventories that reduce accessibility to the benefits of simulation. Simulation technology can become more affordable and scalable with open architecture and modular design. We describe the System of Modular Mixed and Augmented Reality Tracking Simulators (SMMARTS) open architecture, rapid development platform for designing and building modular procedural and guided-intervention simulators.

Methods

A modular stand provides mechanical indexing (registration) of a modular anatomical block representing the anatomy relevant to the simulated intervention. A software development kit (SDK) integrated with the hardware (stand and hand-held tracked tools such as a needle and ultrasound probe) facilitates software development. The SMMARTS SDK at https://github.com/UF-CSSALT/SMMARTS-SDK developed in Unity Technologies' Unity game engine includes Arduino microcontroller and NDI's 6 degrees of freedom tracking connectivity along with software tools such as a replayer, user interface templates, 3D visualization of the virtual counterparts of physical elements, scoring monitors, cognitive aids, common error messages, and Experience Application Programming Interface compatibility.

Results

We used SMMARTS to develop 9 different simulators internally (instructor-less central venous access currently deployed to Iraq, prostate biopsy, epidural loss-of-resistance, ventriculostomy, pterygopalatine fossa block, lumbar/chronic pain blocks, chest tube insertion) and externally (intravenous access).

Discussion

As a living tool, SMMARTS now has sufficient functionality and benefits that we can share it to help clinicians and engineers focus more on content specific to learning objectives rather than back-end tasks.
Baseline Brain Segmental Volumes in Responders and Nonresponders to Anticholinergic Therapy for Overactive Bladder Syndrome
Authors: Sheyn David , Martin Nicole M. , Walden Lucas , Roberts Kasey M. , El-Nashar Sherif , Hijaz Adonis K. , Prescott Jeffrey W.
Published: September 2020

Objective

Evaluate structural differences in brains of responders (R) and nonresponders (NR) to anticholinergic (AC) therapy for overactive bladder (OAB).

Materials and Methods

This was a retrospective cohort study of age matched women treated with an AC medication for OAB and underwent magnetic resonance imaging within 12 months before treatment. Data on pretreatment demographic and clinical variables and symptom severity was also collected.

T1-weighted magnetic resonance images of the brain for each subject were segmented using FreeSurfer software. Structures included for analysis were cerebral cortex, white matter, subcortical gray matter, cerebellum, and brain stem.

Nonresponders were defined as patients who reported less than 50% improvement after a minimum of 4 weeks on the maximum dose of the prescribed medication. Pairwise analysis between groups was performed using the Wilcoxon-Rank Sum test and Fisher exact test where appropriate. Spearman ρ was used to evaluate for correlations between neurologic structures and symptom severity.

Results

There were no differences in pretreatment characteristics or symptom severity between the 21 R and 18 NR. Nonresponders had lower volumes of the right caudal anterior cingulate gyrus white matter (1919 mm3 vs 2416 mm3, P = 0.008) and right parahippocampal gyrus white matter (1008 mm3 vs 1469 mm3, P = 0.001). Incontinence episode frequency showed a negative moderate correlation with the anterior cingulate gyrus white matter volume (ρ = −0.4228, P = 0.007). The right and left cerebellar cortices showed weak and moderate negative correlations to frequency of nocturia (ρ = −0.384, P = 0.02 and ρ −0.443, P = 0.005, respectively).

Conclusion

There are measurable volumetric differences in brain structures in R and NR to AC therapy.
Scarring and Selection in the Great Irish Famine
Authors: Blum Matthias , Colvin Christopher L. , McLaughlin Eoin
Published: September 2020

What is the health impact of famines on survivors? We use a population exposed to severe famine conditions during infancy to document two opposing effects. The first: exposure leads to poor health into adulthood, a scarring effect. The second: survivors do not themselves suffer health consequences, a selection effect. Anthropometric evidence on over 21,000 subjects born before, during and after the Great Irish Famine (1845-52), among modern history’s most severe famines, suggests selection is strongest where mortality is highest. Individuals born in heavily-affected areas experienced no measurable stunted growth; scarring was found only where excess mortality was low.
Influenza vaccination coverage among healthcare workers during the first two seasons of data collection, Finland, 2017-2019
Authors: Hammer Charlotte C , Lyytikäinen Outi , Arifulla Dinah , Toura Saija , Nohynek Hanna
Published: September 2020

Background

Influenza can cause severe illness among high-risk groups such as elderly and immunocompromised patients. Mandatory influenza vaccination of healthcare workers (HCWs) has been viewed as means to improve patient and HCW protection.

Methods

We analyzed data collected by a web-based survey sent annually to all Finnish acute care hospitals and described the influenza vaccination coverage among HCWs during seasons 2017/18 (without mandate) and 2018/19 (mandate enforced).

Results

In season 2017/2018, 38/39 hospitals provided data and 35/36 hospitals in 2018/2019. The mean coverage in season 2017/18 was 88% (median, 84%; range 48-100%) and in 2018/19 91% (median, 91%; range 57-100%). The mean increase from season 2017/2018 to 2018/2019 was 6.5% (median, 3%; range -11.0-33.0%).

Conclusions

The coverage of influenza vaccinated HCWs in Finnish hospitals was high. However, there were major differences between hospitals which raise the question about data quality as well as implementation of the mandate, and need further evaluation.
Retrospective meta-transcriptomic identification of severe dengue in a traveller returning from Africa to Sweden, 1990
Authors: Alfsnes Kristian , Lagerqvist Nina , Vene Sirkka , Bohlin Jon , Verner-Carlsson Jenny , Ekqvist David , Bråve Andreas , Holmes Edward C. , Shi Weifeng , Pettersson John H.-O.
Published: September 2020

The first imported case of severe haemorrhagic fever in Sweden was reported in 1990. Despite extensive diagnostic study, no aetiological agent was identified. Following retrospective investigation with total RNA-sequencing of plasma and urine samples collected during between 7–36 days from onset of symptoms, we identified dengue virus 3 (DENV-3) and a human pegivirus (HPgV). We conclude that the patient most likely suffered from haemorrhagic symptoms due to a severe dengue infection.
Quantitative particle analysis of particulate matter release during orthodontic procedures: A pilot study
Authors: Din Ahmed Riaz , Hindocha Annika , Patel Tulsi , Sudarshan Sanjana , Cagney Neil , Koched Amine , Mueller Jens-Dominik , Seoudi Noha , Morgan Claire , Shahdad Shakeel , Fleming Padhraig S.
Published: September 2020

Introduction

Transmission of SARS-Cov-2 through aerosol has been implicated particularly in the presence of highly concentrated aerosols in enclosed environments. It is accepted that aerosols are produced during a range of dental procedures, posing potential risks to both dental practitioners and patients. There has been little agreement concerning aerosol transmission associated with orthodontics and associated mitigation.

Methods

Orthodontic procedures were simulated in a closed side-surgery using a dental manikin on an acrylic model using composite-based adhesive. Adhesive removal representing debonding was undertaken using a 1:1 contra-angle handpiece (W&H Synea™ Vision WK-56 LT, Bürmoos, Austria) and fast hand-piece with variation in air and water flow. The removal of acid etch was also simulated with use of combined 3-in-1 air water syringe to remove etch. An Optical Particle Sizer (OPS 3330, TSI Inc. Minnesota, USA) and a portable Scanning Mobility Particle Sizer (NanoScan SMPS Nanoparticle Sizer 3910, TSI Inc Minnesota, USA) were both to assess particulate matter ranging from ‘very small’ (0.08 – 0.26 μm) to ‘large’ (2.7 – 10 μm) particles.

Results

Standard debonding procedure (involving air but no water) was associated with clear increase in the ‘very small’ and ‘small’ (0.26 – 0.9 μm) particles but only for a short period. Debonding procedures without air appeared to produce similar levels of aerosol to standard debonding. Debonding in association with water tended to produce large increase in aerosol levels, producing particles of all sizes throughout the experiment. The use of water and a fast hand-piece led to the most significant increase in particles. Combined use of the 3-in-1 air water syringe did not result in any detectable increase in the aerosol levels.

Conclusions

Particulate matter was released during orthodontic debonding, although the concentration and volume was markedly less than that associated with the use of a fast hand-piece. No increase in particulates was associated with prolonged use of a 3-in-1 air-water syringe. Particulate levels reduced to baseline levels over a short period (approx. 5 minutes). Further research within alternative, open environments and without air exchange systems is required.
SARS-CoV-2 Antibody Prevalence and Association with Routine Laboratory Values in a Life Insurance Applicant Population
Authors: Rigatti Steven J. , Stout Robert
Published: September 2020

Objectives

The prevalence of SARS-CoV-2 antibodies in the general population is largely unknown. Since many infections, even among the elderly and other vulnerable populations, are asymptomatic, the prevalence of antibodies could help determine how far along the path to herd immunity the general population has progressed. Also, in order to clarify the clinical manifestations of current or recent past COVID-19 illness, it may be useful to determine if there are any common alterations in routine clinical laboratory values.

Methods

We performed SARS-CoV-2 antibody tests on 50,130 consecutive life insurance applicants who were having blood drawn for the purpose of underwriting (life risk assessment). Subjects were also tested for lipids, liver function tests, renal function studies, as well as serum proteins. Other variables included height, weight, blood pressure at the time of the blood draw, and history of common chronic diseases (hypertension, heart disease, diabetes, and cancer).

Results

The overall prevalence of SARS-CoV-2 was 3.0%, and was fairly consistent across the age range and similar in males and females. Several of the routine laboratory tests obtained were significantly different in antibody-positive vs. antibody-negative subjects, including albumin, globulins, bilirubin, and the urine albumin:creatinine ratio. The BMI was also significantly higher in the antibody-positive group. Geographical distribution revealed a very high level of positivity in the state of New York compared to all other areas (17.1%). Using state population data from the US Census, it is estimated that this level of seropositivity would correspond to 6.98 million (99% CI: 6.56-7.38 million) SARS-CoV-2 infections in the US, which is 3.8 times the cumulative number of cases in the US reported to the CDC as of June 1, 2020.

Conclusions

The estimated number of total SARS-CoV-2 infections based on positive serology is substantially higher than the total number of cases reported to the CDC. Certain laboratory values, particularly serum protein levels, are associated with positive serology, though these associations are not likely to be clinically meaningful.
TGF-β1 in extracellular vesicles from HIV-infected plasma and macrophages linked to cardiopulmonary dysfunction
Authors: Krishnamachary Balaji , Agarwal Stuti , Mahajan Aatish , Kumar Ashok , Mohan Aradhana , Chen Ling , Hsue Priscilla , Chalise Prabhakar , Morris Alison , Dhillon Navneet K.
Published: September 2020

Rationale

Extracellular vesicles (EVs) have emerged as important mediators in cell-cell communication and disease pathogenesis; however, their relevance in pulmonary hypertension (PH) secondary to HIV infection is yet to be explored.

Objective

To examine the role of circulating small EVs and monocyte-derived macrophage (MDM) EVs in the development of HIV-associated PH

Methods

EVs isolated from plasma of HIV-infected drug users and non-users with/without PH and from supernatants of HIV-infected MDMs treated with/without second hit of cocaine were studied for their effect on vascular dysfunction both in vitro and in vivo.

Measurements and Main Results

We report significantly higher numbers of plasma derived EVs (PEVs) carrying higher levels of TGF-β1 in people living with HIV (PLWH) that had PH compared to non-PH PLWH. Importantly, levels of these TGF-β1 loaded PEVs correlated with pulmonary arterial systolic pressures, CD4 counts, but not with diffusion capacity for carbon monoxide or viral load. Correspondingly, enhanced TGF-β1-dependent pulmonary endothelial injury and smooth muscle hyperplasia was observed. Cocaine treatment of HIV-1 infected-MDMs resulted in increased number of TGF-β1 high-EVs. Intravenous injection of these EVs in rats led to increased right ventricle systolic pressure accompanied with myocardial injury and increased levels of serum endothelin-1, TNF-α, and cardiac Troponin-I. Conversely, pretreatment of rats with TGFβ-Receptor 1 inhibitor prevented these EV-mediated changes.

Conclusion

Findings define the ability of macrophage-derived small EVs to cause pulmonary vascular modeling and PH via modulation of TGF-β signaling and suggest clinical implications of circulating TGF-β high-EVs as a potential biomarker of HIV-PH.
COVID-19Predict – Predicting Pandemic Trends
Authors: Bosch Jürgen , Wilson Austin , O’Neil Karthik , Zimmerman Peter A.
Published: September 2020

Background

Given the global public health importance of the COVID-19 pandemic, data comparisons that predict on-going infection and mortality trends across national, state and county-level administrative jurisdictions are vitally important. We have designed a COVID-19 dashboard with the goal of providing concise sets of summarized data presentations to simplify interpretation of basic statistics and location-specific current and short-term future risks of infection.

Methods

We perform continuous collection and analyses of publicly available data accessible through the COVID-19 dashboard hosted at Johns Hopkins University (JHU github). Additionally, we utilize the accumulation of cases and deaths to provide dynamic 7-day short-term predictions on these outcomes across these national, state and county administrative levels.

Findings

COVID-19Predict produces 2,100 daily predictions [or calculations] on the state level (50 States x3 models x7 days x2 cases and deaths) and 131,964 (3,142 Counties x3 models x7 days x2 cases and deaths) on the county level. To assess how robust our models have performed in making short-term predictions over the course of the pandemic, we used available case data for all 50 U.S. states spanning the period January 20 - August 16 2020 in a retrospective analysis. Results showed a 3.7% to −0.2% mean error of deviation from the actual case predictions to date.

Interpretation

Our transparent methods and admin-level visualizations provide real-time data reporting and forecasts related to on-going COVID-19 transmission allowing viewers (individuals, health care providers, public health practitioners and policy makers) to develop their own perspectives and expectations regarding public life activity decisions.

Funding

Financial resources for this study have been provided by Case Western Reserve University.
A Co-infection model for HPV and Syphilis with Optimal Control and Cost-Effectiveness Analysis
Authors: Omame A. , Okuonghae D. , Nwafor U. E. , Odionyenma B. U.
Published: September 2020

In this work, we develop and present a co-infection model for human papillomavirus (HPV) and syphilis with cost-effectiveness optimal control analysis. The full co-infection model is shown to undergo the phenomenon of backward bifurcation when a certain condition is satisfied. The global asymptotic stability of the disease-free equilibrium of the full model is shown not to exist, when the associated reproduction number is less than unity. The existence of endemic equilibrium of the syphilis-only sub-model is shown to exist and the global asymptotic stability of the disease-free and endemic equilibria of both the syphilis-only sub-model and HPV-only sub-model were established. The global asymptotic stability of disease-free equilibrium of the HPV-only sub-model is also proven. Numerical simulations of the optimal control model showed that the optimal control strategy which implements syphilis treatment controls for singly infected individuals is the most cost-effective of all the control strategies in reducing the burden of HPV and syphilis co-infections.
Oxygen Saturation or breathlessness? – how best to predict pneumonia in patients presenting with a cough to primary care
Authors: Chambers Elspeth , Stuart Beth , Moore Michael , Lown Mark
Published: September 2020

SYNOPSIS

Background

Distinguishing pneumonia from acute bronchitis has an important bearing on treatment decisions. The best validated diagnostic decision rule was derived from the GRACE-09 study. The 3Cs study provides oxygen saturations in addition to clinical signs and symptoms. Oxygen saturation is a predictor in hospital settings and may be beneficial in primary care.

Objectives

This project evaluates whether the data from GRACE-09 and 3Cs studies can be mapped onto each other and be combined dataset to refine the diagnostic accuracy of the GRACE-09 clinical prediction rule for the diagnosis of pneumonia.

Patients and Methods

GRACE-09 included 3106 patients with acute cough in a multicentre European study. 3Cs is a UK based study of 28883 patients with acute cough.

Binary logistic regression was used in the 3Cs dataset to determine which variables significantly predicted low oxygen saturation (<95%). Statistically significant predictors were determined using area under curve (AUC). This equation was used to model the probability of low oxygen saturation in the GRACE-09 dataset and subsequently included in the GRACE-09 model to determine whether low oxygen saturation is a comparable predictor to breathlessness in predicting pneumonia.

Results

For 3Cs, using all seven variables achieved an AUC for low oxygen saturation of 0.73 (95% CI 0.72-0.74). Substituting low oxygen saturation into GRACE-09 model gives AUC 0.75 (95% CI 0.69-0.82) compared to original GRACE-09 using breathlessness and gives AUC 0.77 (95% CI 0.73-0.82).

Conclusions

Low oxygen saturation and breathlessness are similarly predictive and could be used interchangeably in a modified GRACE-09 prediction model.

KEY MESSAGES

Can pulse oximetry replace subjective breathlessness assessment in the GRACE-09 prediction rule? Pulse oximetry gives an objective measurement that can be used to assist the diagnosis of pneumonia in primary care.
Influence of Malaria Edemicity and Standardized TB Prevalence to BCG Coverage on Covid-19 Mortality
Authors: Raham Tareef Fadhil
Published: September 2020

Background

Regarding SARS-CoV-2 it is well known that a substantial percentage of adult population cannot get infected if exposed to this novel coronavirus. Several studies give primary indication of the possible role of preexisting immunity whether cross immunity or not. Possible role of latent TB and BCG and malaria have been already suggested to create innate cross heterogeneous immunity. We look for influence of these factors on Covid-19 mortality in malarious countries.

Material and methods

80 malarious countries are enrolled in this study. Hierarchical multiple regression type of analyses is used for data analyses. TB prevalence/ 100,000 population standardized to BCG coverage rates is taken as direct factor in the test. Malaria incidence /1000 population is considered as intermediate factor and the outcome is COVID-19 mortality/ 1 million (M) population.

Results

TB prevalence is associated with reduced COVID-19 mortality and malaria have an additional effect in reducing COVID-19 mortality. The results show with robust statistical support that TB prevalence was also associated with reduced COVID-19 mortality with additional effect that is also observed in TB and BCG coverage rate.

Conclusions

Malaria and standardized TB prevalence are statistical significant factors predicting COVID-19 mortality in negative associations.
Daytime variation in SARS-CoV-2 infection and cytokine production
Authors: Diallo Aïssatou Bailo , Gay Laetitia , Coiffard Benjamin , Leone Marc , Mezouar Soraya , Mege Jean-Louis
Published: September 2020

S. Ray and A. Reddy recently anticipated the implication of circadian rhythm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of the coronavirus disease (Covid-19). In addition to its key role in the regulation of biological functions, the circadian rhythm has been suggested as a regulator of viral infections. Specifically, the time of day of infection was found critical for illness progression, as has been reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. We analyzed circadian rhythm implication in SARS-CoV-2 virus infection of isolated human monocytes, key actor cells in Covid-19 disease, from healthy subjects. The circadian gene expression ofBmal1andClockgenes was investigated with q-RTPCR. Monocytes were infected with SARS-CoV-2 virus strain and viral infection was investigated by One-Step qRT-PCR and immunofluorescence. Interleukin (IL)-6, IL-1β and IL-10 levels were also measured in supernatants of infected monocytes. Using Cosinor analysis, we showed thatBmal1andClocktranscripts exhibited circadian rhythm in monocytes with an acrophase and a bathyphase at Zeitgeber Time (ZT)6 and ZT17. After forty-eight hours, the amount of SARS-CoV-2 virus increased in the monocyte infected at ZT6 compared to ZT17. The high virus amount at ZT6 was associated with significant increased release in IL-6, IL-1β and IL-10 compared to ZT17. Our results suggest that time day of SARS-CoV-2 infection affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease progression and we propose circadian rhythm as a novel target for managing viral progression.

Importance

The implication of circadian rhythm (CR) in pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been recently anticipated. The time of day of infection is critical for illness progression as reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. In this study, we wondered if SARS-CoV-2 infection and cytokine production by human monocytes, innate immune cells affected by Covid-19, were regulated by CR. Our results suggest that time day of SARS-CoV-2 infection affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease progression and we propose circadian rhythm as a novel target for managing viral progression.
Variants inPRKAR1Bcause a neurodevelopmental disorder with autism spectrum disorder,apraxia, and insensitivity to pain
Authors: Marbach Felix , Stoyanov Georgi , Erger Florian , Rosenfeld Jill A. , Torti Erin , Haldeman-Englert Chad , Sklirou Evgenia , Kessler Elena , Ceulemans Sophia , Nelson Stanley F. , Martinez-Agosto Julian A. , Palmer Christina G.S. , Signer Rebecca H. ,   Undiagnosed Diseases Network, Andrews Marisa V. , Grange Dorothy K. , Willaert Rebecca , Person Richard , Telegrafi Aida , Lichtarge Olivier , Katsonis Panagiotis , Stocco Amber , Schaaf Christian P.
Published: September 2020

Purpose

We characterize the phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder, who carry heterozygous missense-variants of thePRKAR1Bgene.

Methods

Variants ofPRKAR1Bwere identified by single-exome or trio-exome analysis. We contacted the families and physicians of the six individuals in order to collect clinical and phenotypic information.

Results

PRKAR1Bencodes the R1β subunit of the cyclic AMP-dependent protein kinase A (PKA), and is predominantly expressed in the central nervous system. Recent studies of patient cohorts with neurodevelopmental disorders found significant enrichment ofde novomissense variants inPRKAR1B, andin vivostudies of the murine ortholog demonstrated altered hippocampal function and reduced neurogenic inflammation and long-term nociceptive pain in R1β-deficient mice.

In our study,de novoorigin of thePRKAR1B-variants could be confirmed in five out of six individuals, and four carried the same heterozygousde novovariant c.1003C>T (p. Arg335Trp; NM_001164760). Global developmental delay, autism spectrum disorder, and apraxia/dyspraxia has been reported in all six, and reduced pain sensitivity was found in three individuals carrying the c.1003C>T variant.

Conclusion

Our study provides strong evidence for a novel,PRKAR1B-related neurodevelopmental disorder.
COVID-19: Mechanistic model calibration subject to active and varying non-pharmaceutical interventions
Authors: Willis Mark J. , Wright Allen , Bramfitt Victoria , Díaz Victor Hugo Grisales
Published: September 2020

Mathematical models are useful in epidemiology to understand the COVID-19 contagion dynamics. Our aim is to demonstrate the effectiveness of parameter regression methods to calibrate an established epidemiological model describing COVID-19 infection rates subject to active and varying non-pharmaceutical interventions (NPIs). To do this, we assess the potential of some established chemical engineering modelling principles and practice for application to modelling of epidemiological systems. This allows us to exploit the sophisticated functionality of a commercial chemical engineering simulator capable of parameter regression with piecewise continuous integration and event and discontinuity management. Our results provide insights into the outcomes of on-going disease suppression measures, while visualisation of reported data also provides up-to-date condition monitoring of the status of the pandemic. We observe that the effective reproduction number response to NPIs is non-linear with variable response rate, magnitude and direction.

Highlights

Modelling COVID-19 contagion dynamics with piecewise continuous integration and event and discontinuity management

Equivalence to kinetic model with time varying stoichiometry

Model calibration and estimation of non-linear variation in Re

Development of prototype demonstrator algorithm for estimation of Re using data with time varying NPIs
Bacterial pulmonary superinfections are associated with unfavourable outcomes in critically ill COVID-19 patients
Authors: Buehler Philipp K. , Zinkernagel Annelies S. , Hofmaenner Daniel A. , García Pedro David Wendel , Acevedo Claudio T. , Gómez-Mejia Alejandro , Shambat Srikanth Mairpady , Andreoni Federica , Maibach Martina A. , Bartussek Jan , Hilty Matthias P. , Frey Pascal M. , Schuepbach Reto A. , Brugger Silvio D.
Published: September 2020

Objectives

While superinfections are associated with unfavourable disease course, their impact on clinical outcomes in critically ill COVID-19 patients remains largely unknown. We aimed to investigate the burden of superinfections in COVID-19 patients.

Methods

In this prospective single centre cohort study in an intensive care setting patients aged ≥ 18 years with COVID-19 acute respiratory distress syndrome were assessed for concomitant microbial infections by longitudinal analysis of tracheobronchial secretions, bronchoalveolar lavages and blood. Our primary outcome was ventilator-free survival on day 28 in patients with and without clinically relevant superinfection. Further outcomes included the association of superinfection with ICU length of stay, incidence of bacteremia, viral reactivations, and fungal colonization.

Results

In 45 critically ill COVID-19 patients, we identified 19 patients with superinfections (42.2%) by longitudinal analysis of 433 TBS, 35 BAL and 455 blood samples, respectively. On average, superinfections were detected on day 10 after ICU admission. The most frequently isolated clinically relevant bacteria were Enterobacteriaceae, Streptococcus pneumoniae, and Pseudomonas aeruginosa.

Ventilator-free survival was substantially lower in patients with superinfection (subhazard ratio 0.37, 95%-CI 0.15-0.90, p=0.028). Patients with pulmonary superinfections more often had bacteraemia, virus reactivations, yeast colonization, and needed ICU treatment for a significantly longer time.

Conclusions

The detection of superinfections was frequent and associated with reduced ventilator-free survival. Despite empirical antibiotic therapy, superinfections lead to an extended ICU stay in COVID 19 patients. Longitudinal microbiological sampling in COVID-19 patients could allow targeted antimicrobial therapy, and therefore minimize the use of broad-spectrum and reserve antibiotics.
Productivity loss associated with physical impairment in a contemporary small-scale subsistence population
Authors: Stieglitz Jonathan , Hooper Paul L. , Trumble Benjamin C. , Kaplan Hillard , Gurven Michael D.
Published: September 2020

Humans experience unique physical impairments with potentially severe economic consequences. Quantifying the burden of impairment in subsistence populations is critical for understanding selection pressures underlying strategies that minimize risk of production deficits. We examine among forager-horticulturalists whether compromised bone strength (indicated by vertebral fracture and lower bone mineral density, BMD) is associated with diminished subsistence involvement. We estimate the magnitude of productivity losses associated with compromised bone strength. Fracture is associated with cessation of hunting, tree chopping and walking long distances, but not tool manufacture. Age-specific productivity losses from hunting cessation related to fracture and lower BMD are substantial: ∼397 lost kcals/day, with expected future losses of up to 1.88 million kcals (22% of expected production). Productivity loss is thus substantial for high strength and endurance tasks. Determining the extent to which impairment obstructs productivity in contemporary subsistence populations improves the ability to infer consequences of impairment over human evolution.
Modeling the dynamics of SARS-CoV-2 immunity waning, antigenic drifting, and population serology patterns
Authors: Koopman James S. , Simon Carl P.
Published: September 2020

Reinfection with SARS-CoV-2 can result from either waning immunity, a drift in the virus that escapes previously stimulated immunity, or both. The nature of such reinfection risks will affect the choice of control tactics and vaccines. We constructed an SIR transmission model of waning and drifting that can be fitted to cross-neutralization serological data. In this model, waning occurs in individuals who have recovered from previous infections while drifting occurs during transmission to a previously infected individual. Interactions at the population level generate complex dynamics that cause drifting to occur in unanticipated but explainable ways across waning and drifting parameter sets. In particular, raising the fraction of transmissions where drifting occurs slows the rise of drifted strains to high levels and changes the equilibrium distribution of strains from ∪ shaped (extreme strains dominate) to ∩ shaped (central strains dominate). In ∪ shaped parameter regimes, endemic infection levels can rise after many years to above the original epidemic peak. The model simulates results from cross-neutralization assays given sera from previously infected individuals when multiple drifted strains are used in the assays. Fitting the model to such assay data can estimate waning and drifting parameters. Given the parameters, the model predicts infection patterns. We propose a process for using fits of our model to serological and other data called Decision Robustness and Identifiability Analysis (DRIA). This can inform decisions about vaccine options such as whether to prepare for changes in vaccine composition because the virus is changing to escape immunity.

Highlights

We construct and analyze a transmission system model that integrates immunity waning and antigenic drifting. We found no other model that integrates both.

The model reveals strong joint effects of waning and drifting. For example, waning is essential for drifting. But once drifting starts, it generates its own momentum.

The model generates unexpected but explainable phenomena such as: A) Given low drifting parameters, strains become increasingly different from each other, but given high drifting parameters, they merge together. B) Higher drifting rates accelerate the appearance of new strains but slow the expansion of those new strains.

The model generates assay data for neutralization across drifted strains. This enables population serological analyses to estimate waning and drifting parameters.

Predicting drifting through population serology analyzed by fitting models to the data has potential to better inform vaccine strain choices than the approach taken for influenza which focuses on analysis of large numbers of virus strains over time.

Model elaboration using a strategy of Decision Robustness and Identifiability Analysis will inform decisions about vaccine design and use and provides insights on resistance to infection by age.
Evaluating ten commercially-available SARS-CoV-2 rapid serological tests using the STARD (Standards for Reporting of Diagnostic Accuracy Studies) method
Authors: Dortet Laurent , Ronat Jean-Baptiste , Vauloup-Fellous Christelle , Langendorf Céline , Mendels David-Alexis , Emeraud Cécile , Oueslati Saoussen , Girlich Delphine , Chauvin Anthony , Afdjei Ali , Bernabeu Sandrine , Pape Samuel le , Kallala Rim , Rochard Alice , Verstuyft Celine , Fortineau Nicolas , Roque-Afonso Anne-Marie , Naas Thierry
Published: September 2020

Numerous SARS-CoV-2 rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially-available SARS-CoV2 rapid serological tests using the STARD methodology (Standards for Reporting of Diagnostic Accuracy Studies). 250 sera from 159 PCR-confirmed SARS-CoV-2 patients (collected from 0 to 32 days after onset of symptoms) were tested with rapid serological tests. Control sera (N=254) were retrieved from pre-COVID periods from patients with other coronavirus infections (N=11), positive rheumatoid factors (N=3), IgG/IgM hyperglobulinemia (N=9), malaria (n=5), or no documented viral infection (N=226). All samples were tested using rapid lateral flow immunoassays (LFIA) from ten manufacturers. Only four tests achieved ≥98% specificity, with other tests ranging from 75.7%-99.2%. Sensitivities varied by the day of sample collection, from 31.7%-55.4% (Days 0-9), 65.9%92.9% (Days 10-14), and 81.0%-95.2% (>14 days) after the onset of symptoms, respectively. Only three tests evaluated met French Health Authorities’ thresholds for SARS-CoV-2 serological tests (≥90% sensitivity + ≥98% specificity). Overall, the performances between tests varied greatly, with only a third meeting acceptable specificity and sensitivity thresholds. Knowing the analytical performance of these tests will allow clinicians to use them with more confidence, could help determine the general population’s immunological status, and may diagnose some patients with false-negative RT-PCR results.
Lessons from the COVID-19 pandemic: People’s experiences and satisfaction with telehealth during the COVID-19 pandemic in Australia
Authors: Isautier JMJ , Copp T , Ayre J , Cvejic E , Meyerowitz-Katz G , Batcup C , Bonner C , Dodd RH , Nickel B , Pickles K , Cornell S , Dakin T , McCaffery K
Published: September 2020

Objectives

To determine how participants perceived telehealth consults in comparison to traditional in-person visits, and to investigate whether people believe that telehealth services would be useful beyond the pandemic.

Design

A national cross-sectional community survey.

Participants

Australian adults aged 18 years and over (n=1369).

Main outcome measures

Telehealth experiences.

Results

Of the 596 telehealth users, the majority of respondents (62%) rated their telehealth experience as “just as good” or “better” than a traditional in-person medical appointment. On average, respondents perceived that telehealth would be moderately to very useful for medical appointments after the COVID-19 pandemic is over (M=3.67 out of 5, SD=1.1). Being male (p=0.007), having a history of both depression and anxiety (p=0.037), or lower patient activation (individuals’ willingness to take on the role of managing their health/healthcare) (p=0.037) were associated with a poorer telehealth experience. Six overarching themes were identified from free-text responses of why telehealth experience was poorer than a traditional in-person medical appointment: communication is not as effective; limitations with technology; issues with obtaining prescriptions and pathology; reduced confidence in doctor; additional burden for complex care; and inability to be physically examined.

Conclusions

Telehealth appointments were reported to be comparable to traditional in-person medical appointments by most of our sample. Telehealth should continue to be offered as a mode of healthcare delivery while the pandemic continues and may be worthwhile beyond the pandemic.

The known

The COVID-19 pandemic has resulted in an increase in telehealth services.

The new

The majority of telehealth users (62%) perceived their experience to be just as good or better than traditional in-person medical care; and that telehealth would be at least somewhat useful beyond the pandemic.

Having a history of both depression and anxiety was associated with a poorer telehealth experience and in-person visits were frequently preferred over telehealth visits for mental health appointments.

The implication

Telehealth should continue to be offered while the COVID-19 pandemic continues and may be worthwhile beyond the pandemic, however, telehealth may be less effective for mental health services.
SARS-CoV-2 NSP1 C-terminal region (residues 130-180) is an intrinsically disordered region
Authors: Kumar Amit , Kumar Ankur , Kumar Prateek , Garg Neha , Giri Rajanish
Published: September 2020

Nonstructural protein 1 (NSP1) of SARS-CoV-2 plays a key role in downregulation of RIG-I pathways and interacts with 40 S ribosome. Recently, the cryo-EM structure in complex with 40S ribosome is deciphered. However, the structure of full length NSP1 without any partner has not been studies. Also, the conformation of NSP1-C terminal region in isolation is not been studied. In this study, we have investigated the conformational dynamics of NSP1C-terminal region (NSP1-CTR; amino acids 130-180) in isolation and under different solvent environments. The NSP1-CTR is found to be intrinsically disordered in aqueous solution. Further, we used alpha helix inducer, trifluoroethanol, and found induction of alpha helical conformation using CD spectroscopy. Additionally, in the presence of SDS, NSP1-CTR is showing a conformational change from disordered to ordered, possibly gaining alpha helix in part. But in presence of neutral lipid DOPC, a slight change in conformation is observed. This implies the possible role of hydrophobic interaction and electrostatic interaction on the conformational changes of NSP1. The changes in structural conformation were further studied by fluorescence-based studies, which showed significant blue shift and fluorescence quenching in the presence of SDS and TFE. Lipid vesicles also showed fluorescence-based quenching. In agreement to these result, fluorescence lifetime and fluorescence anisotropy decay suggests a change in conformational dynamics. The zeta potential studies further validated that the conformational dynamics is mostly because of hydrophobic interaction. In last, these experimental studies were complemented through Molecular Dynamics (MD) simulation which have also shown a good correlation and testify our experiments. We believe that the intrinsically disordered nature of the NSP1-CTR will have implications in disorder based binding promiscuity with its interacting proteins.
Proteomics of autophagy deficient macrophages reveals enhanced antimicrobial immunity via the oxidative stress response
Authors: Maculins Timurs , Verschueren Erik , Hinkle Trent , Chang Patrick , Chalouni Cecile , Lim Junghyun , Katakam Anand Kumar , Kunz Ryan C. , Erickson Brian K. , Huang Ting , Choi Meena , Tsai Tsung-Heng , Vitek Olga , Reichelt Mike , Rohde John , Dikic Ivan , Kirkpatrick Donald S. , Murthy Aditya
Published: September 2020

Defective autophagy is associated with chronic inflammation. Loss-of-function of the core autophagy gene Atg16l1 increases risk for Crohn’s disease by enhancing innate immunity in macrophages. However, autophagy also mediates clearance of intracellular pathogens. These divergent observations prompted a re-evaluation of ATG16L1 in antimicrobial immunity. In this study, we found that loss of Atg16l1 in macrophages enhanced the killing of virulentShigella flexneri(S.flexneri), an enteric bacterium that resides within the cytosol by escaping all membrane-bound compartments. Quantitative multiplexed proteomics revealed that ATG16L1 deficiency significantly upregulated proteins involved in the glutathione-mediated antioxidant response to compensate for elevated oxidative stress, which also promotedS.flexnerikilling. Consistently, myeloid cell-specific deletion of Atg16l1 accelerated bacterial clearancein vivo. Finally, pharmacological modulation of oxidative stress by suppression of cysteine import conferred enhanced microbicidal properties to wild type macrophages. These findings demonstrate that control of oxidative stress by ATG16L1 regulates antimicrobial immunity against intracellular pathogens.

Impact statement

Maculinset alutilize multiplexed mass spectrometry to show that loss of the autophagy geneAtg16l1in macrophages enhances antimicrobial immunity against intracellular pathogens via the oxidative stress response.
The impact of the Covid-19 pandemic on emergency and elective hip surgeries in Norway
Authors: Magnusson Karin , Helgeland Jon , Grøsland Mari , Telle Kjetil
Published: September 2020

Objective

To assess the effects of Covid-19 pandemic lockdown restrictions on the number of emergency and elective hip joint surgeries, and explore whether these procedures are more/less affected by lockdown restrictions than other hospital care.

Methods

In 1.344.355 persons aged ≥35 years in the Norwegian emergency preparedness (BEREDT C19) register, we studied the daily number of persons having 1) emergency surgeries due to hip fractures, and 2) electively planned surgeries due to hip osteoarthritis before and after Covid-19 lockdown restrictions were implemented nationally on March 13th 2020, for different age and sex groups. Incidence Rate Ratios [IRR] reflect the after-lockdown number of surgeries divided by the before-lockdown number of surgeries.

Results

After-lockdown elective hip surgeries were one third the number of before-lockdown (IRR ∼0.3), which is a greater drop than the drop seen in all-cause elective hospital care (IRR ∼0.6) (no age/sex differences). Men aged 35-69 had half the number of emergency hip fracture surgeries (IRR ∼0.6), whereas women aged ≥70 had the same number of emergency hip fracture surgeries after lockdown (IRR ∼1). Only women aged 35–69 and men aged ≥70 had emergency hip fracture surgery rates after lockdown comparable to what may be expected based on analyses of all-cause acute care (IRR ∼0.80)

Conclusion

Important to note for future pandemics management is that lockdown restrictions may impact more on scheduled joint surgery than other scheduled hospital care. Lockdown may also impact on the number of emergency joint surgeries for men aged ≥35 but not for women aged ≥70.
Increased extravascular lung water index (EVLWI) reflects rapid inflammatory oedema and mortality in COVID-19 associated ARDS
Authors: Rasch Sebastian , Schmidle Paul , Sancak Sengül , Herner Alexander , Huberle Christina , Schulz Dominik , Mayr Ulrich , Schneider Jochen , Spinner Christoph , Geisler Fabian , Schmid Roland M. , Lahmer Tobias , Huber Wolfgang
Published: September 2020

OBJECTIVE

Nearly 5 % of the patients with COVID-19 develop an acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to controls and whether EVLWI has the potential to monitor disease progression.

METHODS

From the day of intubation, EVLWI, cardiac function were monitored by transpulmonary thermodilution in n=25 patients with COVID-19 and compared to a control group of 49 non-COVID-19 ARDS-patients.

RESULTS

EVLWI in COVID-19-patients was noticeably elevated and significantly higher than in the control group (17 (11-38) vs. 11 (6-26) mL/kg; p<0.001). High pulmonary vascular permeability index values (2.9 (1.0-5.2) versus 1.9 (1.0-5.2); p=0.003) suggest inflammatory oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and mortality (23.2±6.7% vs. 30.3±6.0%, p=0.025).

CONCLUSIONS

Compared to the control group, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 associated ARDS and could serve as parameter to monitor ARDS progression.
Socio-demographic correlate of knowledge and practice toward novel coronavirus among people living in Mosul-Iraq: A cross-sectional study
Authors: Qubais Saeed Balsam , Al-Shahrabi Rula , Bolarinwa Obasanjo Afolabi
Published: September 2020

Background

Since the World Health Organization (WHO) announced that the 2019 novel coronavirus (2019-nCoV) is a worldwide pandemic, as the Iraqi authorities have started responding and taking action to control the spread of the pandemic. The knowledge and practices of the public play an important role in curbing the spreading of the virus by following the health guidelines. This study aimed to assess the socio-demographic correlate of knowledge and practices of Iraqi living in Mosul-Iraq towards novel coronavirus during its rapid rise.

Methods

A cross-sectional online survey of 909 participants was conducted among Mosul-Iraq between 20th June to 1st July 2020. The survey included three parts: 1) socio-demographic characteristics, 2) participants' knowledge, 3) participants' practices. T-test, ANOVA, chi-square, and binary logistic regression were used. A p-value less than 0.05 (p < 0.05) was considered statistically significant.

Results

The results showed knowledge and practice mean score of (12.91±1.67) and (21.56± 2.92) with cumulative knowledge and practice of 86% and 76% respectively towards 2019-nCoV. Socio-demographic characteristics such as age, marital status, gender, level of education and employment were statistically related with a higher mean score of knowledge and practice towards the virus as P<0.05.

Conclusions

We concluded that the majority of the respondents demonstrate a high level of knowledge and practices towards 2019-nCoV except respondents with socio-demographic characteristics such as those who were younger, male respondents, those with lower education and those unemployed as such campaigns that will increase the knowledge and encourage adequate preventive practice towards 2019-nCoV should be targeted towards this group.