bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic performances and thresholds: the key to harmonization in serological SARS-CoV-2 assays?
Authors: Plebani Mario , Padoan Andrea , Negrini Davide , Carpinteri Benedetta , Sciacovelli Laura
Published: May 2020

Background: The evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody (Ab) assay performances is of the utmost importance in establishing and monitoring virus spread in the community. In this study focusing on IgG antibodies, we compare reliability of three chemiluminescent (CLIA) and two enzyme linked immunosorbent (ELISA) assays.

Methods: Sera from a total of 271 subjects, including 64 reverse transcription-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 patients were tested for specific Ab using Maglumi (Snibe), Liaison (Diasorin), iFlash (Yhlo), Euroimmun (Medizinische Labordiagnostika AG) and Wantai (Wantai Biological Pharmacy) assays. Diagnostic sensitivity and specificity, positive and negative likelihood ratios were evaluated using manufacturers' and optimized thresholds.

Results: Optimized thresholds (Maglumi 2 kAU/L, Liaison 6.2 kAU/L and iFlash 15.0 kAU/L) allowed us to achieve a negative likelihood ratio and an accuracy of: 0.06 and 93.5% for Maglumi; 0.03 and 93.1% for Liaison; 0.03 and 91% for iFlash. Diagnostic sensitivities and specificities were above 93.8% and 85.9%, respectively for all CLIA assays. Overall agreement was 90.3% (Cohen's kappa = 0.805 and SE = 0.041) for CLIA, and 98.4% (Cohen's kappa = 0.962 and SE = 0.126) for ELISA.

Conclusions: The results obtained indicate that, for CLIA assays, it might be possible to define thresholds that improve the negative likelihood ratio. Thus, a negative test result enables the identification of subjects at risk of being infected, who should then be closely monitored over time with a view to preventing further viral spread. Redefined thresholds, in addition, improved the overall inter-assay agreement, paving the way to a better harmonization of serologic tests.
Emergence of Low-density Inflammatory Neutrophils Correlates with Hypercoagulable State and Disease Severity in COVID-19 Patients
Authors: Morrissey Samantha M , Geller Anne E , Hu Xiaoling , Tieri David , Cooke Elizabeth A , Ding Chuanlin , Woeste Matthew , Zhange Huang-ge , Cavallazi Rodrigo , Clifford Sean P , Chen James , Kong Maiying , Watson Corey T , Huang Jiapeng , Yan Jun
Published: May 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Approximately 20% of infected patients experience a severe manifestation of the disease, causing bilateral pneumonia and acute respiratory distress syndrome. Severe COVID-19 patients also have a pronounced coagulopathy with approximately 30% of patients experiencing thromboembolic complications. However, the etiology driving the coagulopathy remains unknown. Here, we explore whether the prominent neutrophilia seen in severe COVID-19 patients contributes to inflammation-associated coagulation. We found in severe patients the emergence of a CD16IntCD44lowCD11bInt low-density inflammatory band (LDIB) neutrophil population that trends over time with changes in disease status. These cells demonstrated spontaneous neutrophil extracellular trap (NET) formation, phagocytic capacity, enhanced cytokine production, and associated clinically with D-dimer and systemic IL-6 and TNF-α levels, particularly for CD40+ LDIBs. We conclude that the LDIB subset contributes to COVID-19-associated coagulopathy (CAC) and could be used as an adjunct clinical marker to monitor disease status and progression. Identifying patients who are trending towards LDIB crisis and implementing early, appropriate treatment could improve all-cause mortality rates for severe COVID-19 patients.
Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia
Authors: Álvarez-Díaz Diego A. , Franco-Muñoz Carlos , Laiton-Donato Katherine , Usme-Ciro José A. , Franco-Sierra Nicolás D. , Flórez Astrid C. , Rangel Sergio Gómez , Rodríguez Luz Dary , Barbosa Juliana , Ospitia Erika , Walteros Diana Marcela , Martínez Martha Lucia Ospina , Mercado-Reyes Marcela
Published: May 2020

The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main inhouse methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3′ end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3’ end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.

HIGHLIGHTS

Colombian SARS-CoV-2 sequences displayed genetic variability in some target regions used for COVID-19 diagnosis.

Mismatches in critical primer regions could impact their performance and the rate of false negative results.
Brain orchestration of pregnancy and maternal behavior in mice
Authors: Barrière David André , Ella Arsène , Szeremeta Frédéric , Adriaensen Hans , Même William , Chaillou Elodie , Migaud Martine , Même Sandra , Lévy Frédéric , Keller Matthieu
Published: May 2020

Reproduction induces changes within the brain to prepare for gestation and motherhood. However, the dynamic of these central changes and their relationships with the development of maternal behavior remain poorly understood. Here, we describe a longitudinal morphometric neuroimaging study in female mice between pre-gestation and weaning, using new magnetic resonance imaging (MRI) resources comprising a high-resolution brain template, its associated tissue priors (60-μm isotropic resolution) and a corresponding mouse brain atlas (1320 regions of interest). Using these tools, we observed transient hypertrophies not only within key regions controlling gestation and maternal behavior (medial preoptic area, bed nucleus of thestria terminalis), but also in the amygdala, caudate nucleus and hippocampus. Additionally, unlike females exhibiting lower levels of maternal care, highly maternal females developed transient hypertrophies in somatosensory, entorhinal and retrosplenial cortices among other regions. Therefore, coordinated and transient brain modifications associated with maternal performance occurred during gestation and lactation.
Dopamine-gated memory selection during slow wave sleep
Authors: Isotalus Hanna , Carr Will J , Averill George G , Radtke Oliver , Selwood James , Williams Rachel , Ford Elizabeth , McCullagh Liz , McErlane James , O’Donnell Cian , Durant Claire , Bartsch Ullrich , Jones Matt W , Muñoz-Neira Carlos , Wearn Alfie R , Grogan John P , Coulthard Elizabeth J
Published: May 2020

The human brain selectively stores knowledge of the world to optimise future behaviour, automatically rehearsing, contextualising or discarding information to create a robust record of experiences. Storage or forgetting evolves over time, particularly during sleep. We have previously shown that dopamine given in the form of L-DOPA tablets improves long-term memory in Parkinson’s disease, but only when given overnight. L-DOPA is already prescribed widely with a good safety profile and could potentially be rapidly repurposed to improve cognitive performance and improve quality of life in, for example, early Alzheimer’s Disease, if we understood the best time of day to prescribe. Therefore, we sought to test how dopamine shaped long-term memory formation before and during sleep in a double-blind randomised placebo-controlled cross-over trial of healthy older adults (n = 35). We administered L-DOPA after word-list learning to be active during repeat exposure to a proportion of the words and during subsequent nocturnal sleep. Nocturnal dopamine accelerated forgetting for words presented once but it did not affect memory for words presented twice. During slow wave sleep, L-DOPA also increased spindle amplitude around slow oscillation peaks. Larger dopamine-induced difference in word memory was associated with a larger increase in spindle amplitude. Dopamine-dependent memory processing may therefore modulate spindles dependent on slow-oscillation phase. Further, overnight dopamine increased total slow wave sleep duration by approximately 11%. This pharmaceutical modification of slow wave sleep may have potential health-enhancing benefits in old age that could include cognitive enhancement and Alzheimer’s prevention.

One Sentence Summary

Dopamine before sleep promotes forgetting of weak memory traces associated with increased spindle amplitude around the peak of a slow oscillations.
Dependence of the stimulus-driven microsaccade rate signature on visual stimulus polarity
Authors: Malevich Tatiana , Buonocore Antimo , Hafed Ziad M.
Published: May 2020

Microsaccades have a steady rate of occurrence during maintained gaze fixation, which gets transiently modulated by abrupt sensory stimuli. Such modulation, characterized by a rapid reduction in microsaccade frequency followed by a stronger rebound phase of high microsaccade rate, is often described as the microsaccadic rate signature, owing to its stereotyped nature. Here we investigated the impacts of stimulus polarity (luminance increments or luminance decrements relative to background luminance) and size on the microsaccadic rate signature. We presented brief visual flashes consisting of large or small white or black stimuli over an otherwise gray image background. Both large and small stimuli caused robust early microsaccadic inhibition, but only small ones caused a subsequent increase in microsaccade frequency above baseline microsaccade rate. Critically, small black stimuli were always associated with stronger modulations in microsaccade rate after stimulus onset than small white stimuli, particularly in the post-inhibition rebound phase of the microsaccadic rate signature. Because small stimuli were also associated with expected direction oscillations to and away from their locations of appearance, these stronger rate modulations in the rebound phase meant higher likelihoods of microsaccades opposite the black flash locations relative to the white flash locations. Our results demonstrate that the microsaccadic rate signature is sensitive to stimulus polarity, and they point to dissociable neural mechanisms underlying early microsaccadic inhibition after stimulus onset and later microsaccadic rate rebound at longer times thereafter. These results also demonstrate early access of oculomotor control circuitry to sensory representations, particularly for momentarily inhibiting saccade generation.

New and noteworthy

Microsaccades are small saccades that occur during gaze fixation. Microsaccade rate is transiently reduced after sudden stimulus onsets, and then strongly rebounds before returning to baseline. We explored the influence of stimulus polarity (black versus white) on this “rate signature”. We found that small black stimuli cause stronger microsaccadic modulations than white ones, but primarily in the rebound phase. This suggests dissociated neural mechanisms for microsaccadic inhibition and subsequent rebound in the microsaccadic rate signature.
Flow-Mediated Olfactory Communication in Honey Bee Swarms
Authors: Nguyen Dieu My T. , Iuzzolino Michael L. , Mankel Aaron , Bozek Katarzyna , Stephens Greg J. , Peleg Orit
Published: May 2020

Honey bee swarms are a landmark example of collective behavior. To become a coherent swarm, bees locate their queen by tracking her pheromones, but how can distant individuals exploit these chemical signals which decay rapidly in space and time? Here, we combine a novel behavioral assay with the machine vision detection of organism location and scenting behavior to track the search and aggregation dynamics of the honey beeApis melliferaL. We find that bees collectively create a communication network to propagate pheromone signals, by arranging in a specific spatial distribution where there is a characteristic distance between individuals and a characteristic direction in which individuals broadcast the signals. To better understand such a flow–mediated directional communication strategy, we connect our experimental results to an agent–based model where virtual bees with simple, local behavioral rules, exist in a flow environment. Our model shows that increased directional bias leads to a more efficient aggregation process that avoids local equilibrium configurations of isotropic communication, such as small bee clusters that persist throughout the simulation. Our results highlight a novel example of extended classical stigmergy: rather than depositing static information in the environment, individual bees locally sense and globally manipulate the physical fields of chemical concentration and airflow.
Intercalative DNA binding governs fluorescence enhancement of SYBR Gold
Authors: Kolbeck Pauline J. , Vanderlinden Willem , Nicolaus Thomas , Gebhardt Christian , Cordes Thorben , Lipfert Jan
Published: May 2020

SYBR Gold is a commonly used and particularly bright fluorescent DNA stain, however, its binding mode to DNA remains controversial. Here, we quantitate SYBR Gold binding to DNA using two complementary approaches. We use mechanical micromanipulation with magnetic tweezers (MT) to determine the effects of SYBR Gold binding on DNA length, twist, and mechanical properties. The MT assay reveals systematic lengthening and unwinding of DNA upon SYBR Gold binding, consistent with an intercalative binding mode where every SYBR Gold molecule unwinds DNA by 19.1° ± 0.7°. We complement the MT data with a spectroscopic characterization of SYBR Gold fluorescence upon addition to DNA. The data are well described by a global binding model for dye concentrations ≤1 μM, with binding parameters that quantitatively agree with the MT results. The fluorescence signal increases linearly with the number of intercalated SYBR Gold molecules. At dye concentrations >1 μM, fluorescence quenching and inner filter effects become relevant and it is required to correct the SYBR Gold fluorescence signals for quantitative assessment of DNA concentrations. In summary, we provide a mechanistic understanding of DNA-SYBR Gold interactions and present practical guidelines for optimal DNA detection and quantitative DNA sensing applications using SYBR Gold.
Fevers Are Rarer in the Morning—Could We Be Missing Infectious Disease Cases by Screening for Fever Then?
Authors: Harding Charles , Pompei Francesco , Bordonaro Samantha F , McGillicuddy Daniel C , Burmistrov Dmitriy , Sanchez Leon D
Published: May 2020

We retrospectively studied US emergency department visits (n=295,406), including nationally representative results. Patients were less likely to have detectable fevers during mornings, with especially large morning-evening differences during influenza outbreaks (national RR=0.56, 95%CI=0.47-0.66). This suggests morning screenings could miss otherwise-detectable cases. Twice-daily screenings could be a simple solution. However, similar COVID-19 research is needed.

Article Summary Line

Fevers were about half as common in the morning as in the evening during influenza outbreaks, suggesting that mornings may be a bad time to perform once-daily fever screenings for infectious diseases, and that twice-daily screenings could be preferable.
Is there hope for the Hajj? Using the SIR Model to Forecast COVID-19 Progression in the City of Makkah
Authors: Mujallad Alaa F , khoj haitham
Published: May 2020

Abstract:
Background: The Hajj is the largest annual gathering in the world, and it is a very important event for every Muslim. Makkah annually receives three million pilgrims who perform Hajj. Although precautionary measures have been taken in Saudi Arabia to slow down the spread of COVID-19, such as locking down the most affected cities, practicing social distancing, and applying the infection-control precautions, the number of cases has increased. The total confirmed number of cases in Makkah was 10,709 with 127 deaths as of May 16, 2020.

Aims of the study: Forecasting the COVID-19 progression in the city of Makkah will help the policymakers decide if the Hajj will be able to operate this year. Thus, to see a clear picture of the fight against COVID-19 for the economy and healthcare industry in Saudi Arabia, specifically in Makkah, the SIR model will predict COVID-19 progression in the city of Makkah.
Method: The Susceptible, Infected, and Recovered (SIR) model has been used to track the transmission dynamics and growth among the city of Makkah. The growth index was calculated, according to the data from March 16 until May 9. The estimated vital epidemiological parameters, such as forecasting works and transmission rates, were done.
Result: The data showed an interesting result about the peak of the disease progression. It is projected to occur around the 12th day after running the model. According to the model, the peak time will be around the 22nd of May. Then, the number of cases will start to decrease.

Conclusion: Using the SIR model, the result predicts the disease progression peak and an estimated end of COVID-19 in the city of Makkah to help the policymakers decide if the Hajj will be able to operate this year.
Protocol for a retrospective, comparative effectiveness study of the association between transesophageal echocardiography (TEE) monitoring used in coronary artery bypass graft (CABG) surgery and clinical outcomes
Authors: Mackay Emily J. , Zhang Bo , Heng Siyu , Ye Ting
Published: May 2020

Background

Coronary artery bypass graft (CABG) surgery is the most widely performed adult cardiac surgery in the US. Transesophageal echocardiography (TEE) is an ultrasound-based cardiac imaging modality used in CABG surgery for hemodynamic monitoring and management of complications related to cardiopulmonary bypass. However, there are no comparative effectiveness studies (randomized or non-randomized) that have investigated the relationship between TEE monitoring and clinical outcomes among patients undergoing CABG surgery. Because of this lack of evidence, recommendations for TEE in CABG surgery remain indeterminate (Class II). We aim to compare the clinical outcomes of patients undergoing CABG surgery with vs without TEE monitoring. This protocol will detail how we plan to investigate the hypothesis that TEE monitoring in CABG surgery will be associated with improved clinical outcomes.

Methods and Analysis

This investigation will be an observational retrospective, comparative effectiveness, cohort study using Centers for Medicare and Medicaid Services (CMS) claims data from January 1, 2013 to October 15, 2015. The aim is to determine if TEE monitoring during CABG surgery is associated with improved 30-day survival, lower incidence of stroke, shorter length of hospitalization, and incidence of esophageal perforation. To alleviate the potential bias from unmeasured confounding, we propose leveraging hospitals’ (or surgeons’) preference for TEE in CABG surgery as an instrumental variable (IV). We will combine this IV technique with statistical-matching-based methods by pairing hospitals (or surgeons) with similar observed confounding variables but considerably different preference for TEE monitoring in CABG surgery. Our research design is meant to emulate a cluster-randomized encouragement experiment. The following a priori protocol will detail how we plan to execute this analysis.
Verification of two Alternative Do-it-yourself Equipment Respirators Seal as COVID-19 Protection (VADERS-CoV): a quality assessment pilot study
Authors: Pettinger Marco , Momeni Mona , Michaud Clemence , Van Dyck Michel , Kahn David , Lemaire Guillaume
Published: May 2020

Background

During the ongoing COVID-19 pandemic, healthcare workers are facing shortage in personal protective equipment, especially adequate respirators. Alternative do-it-yourself respirators (ADR) emerge, without any proof of protection.

Objective

Verify seal potential of two ADR compared to a common FFP2 respirator.

Design

Quality assessment pilot study.

Setting

Tertiary Care Hospital.

Participants

Ten anaesthesiology residents.

Interventions

Participants performed quantitative face-fit tests (QNFT) with three respirators to evaluate seal. A common FFP2 respirator was used as baseline (control group). ADR tested in this study are an Anaesthesia Face Mask (AFM) and a full-face Modified Snorkelling Mask (MSM) with a 3D-printed connector, both in conjunction with a breathing system filter.

Main outcome measures

Non-inferior seal performance of ADR over FFP2, assessed by calculated QNFT based on measured individual fit factors, as defined by the Occupational Safety and Health Administration.

Results

For each respirator a total of 90 individual fit factor measurements were taken. Within the control group, seal failed in 37 (41%) measurements but only in 10 (11%) within the AFM group and in 6 (7%) within the MSM group (P < 0.001 respectively). However, when calculating the final, mean QNFT results, no statistically significant difference was found between respirators. Successful QNFT were determined for 5 out of 10 participants in the control group, for 8 in the AFM group (P = 0.25) and for 7 in the MSM group (P = 0.69).

Conclusion

Both ADR do have the potential to provide non inferior seal compared to a common FFP2 respirator. While AFM respirators are easily assembled, snorkelling masks must undergo significant but feasible modifications. Our results suggest that those ADR masks might be further investigated as they seem to be viable alternatives for situations when certified respirators are not available.

Trial registration

Clinicaltrials.gov identifier: NCT04375774
Do Face Masks Create a False Sense of Security? A COVID-19 Dilemma
Authors: Yan Youpei , Bayham Jude , Fenichel Eli P. , Richter Aaron
Published: May 2020

Face masks have become an emblem of the public response to COVID-19, with many governments mandating their use in public spaces. The logic is that face masks are low cost and might help prevent some transmission. However, from the start, the assumption that face masks are “low cost” was questioned. Early on, there were warnings of the opportunity cost of public use of medical masks given shortages of personal protective equipment for healthcare providers. This led to recommendations for cloth masks and other face coverings, with little evidence of their ability to prevent transmission. However, there may also be a high cost to these recommendations if people rely on face masks in place of other more effective ways to break transmission, such as staying home. We use SafeGraph smart device location data to show that the representative American in states that have face mask mandates spent 20-30 minutes less time at home, and increase visits to a number of commercial locations, following the mandate. Since the reproductive rate of SAR-COV2, the pathogen that causes COVID-19 is hovering right around one, such substitution behavior could be the difference between controlling the epidemic and a resurgence of cases.

Highlights

We use smart device location data to show the behavioral response to face mask mandates during the 2020 COVID-19 epidemic.

We find face mask mandates lead people to spend 20-30 minutes less time at home per day.

We find face mask mandates increase trip taking to a variety of locations, chief among them are restaurants.

This substitution behavior is concerning given the limited information on the protective value of casual face coverings.
No evidence for allelic association between Covid-19 and ACE2 genetic variants by direct exome sequencing in 99 SARS-CoV-2 positive patients
Authors: Novelli Antonio , Biancolella Michela , Borgiani Paola , Cocciadiferro Dario , Colona Vito Luigi , D’Apice Maria Rosaria , Rogliani Paola , Zaffina Salvatore , Leonardis Francesca , Campana Andrea , Raponi Massimiliano , Andreoni Massimo , Grelli Sandro , Novelli Giuseppe
Published: May 2020

Background

Coronaviruses (CoV) are a large family of viruses that are common in people and many animal species. Animal coronaviruses rarely infect humans with the exceptions of the Middle East Respiratory Syndrome (MERS-CoV), the Severe acute respiratory syndrome coronavirus (SARS-CoV), and now SARS-CoV-2, which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Many studies suggested that genetic variants in ACE2 gene may influence the host susceptibility/resistance to SARS-CoV-2 virus according to the functional role of ACE2 in human pathophysiology. However, all these studies have been conducted in silico based on epidemiological and population data. We therefore investigated the occurrence of ACE2 variants in a cohort of 99 Italian unrelated individuals clinically diagnosed with coronavirus disease 19 (COVID-19) to experimental demonstrate allelic association with disease severity.

Methods

By whole-exome sequencing we analysed 99 DNA samples of severely and extremely severely COVID-19 patients hospitalized at the University Hospital of Rome “Tor Vergata” and Bambino Gesù Hospital in Rome.

Results

We identified three different germline variants, one intronic (c.439+4G>A) and two missense (c.2158A>G, p.Asn720Asp; c.1888G>C, p.Asp630His), in 26 patients with a similar frequency between male and female and a not statistically different frequency, except for c.1888G>C, (p.Asp630His) with the ethnically matched populations (EUR).

Conclusions

Our results suggest that there is not any ACE2 exonic allelic association with disease severity. It is possible that rare susceptibility alleles are located in the non-coding region of the gene able to control ACE2 gene activity. It is therefore of interest, to explore the existence of ACE2 susceptibility alleles to SARS-Co-V2 in these regulatory regions. In addition, we found no significant evidence that ACE2 alleles is associated with disease severity/sex bias in the Italian population.
Visualizing the invisible: The effect of asymptomatic transmission on the outbreak dynamics of COVID-19
Authors: Peirlinck Mathias , Linka Kevin , Costabal Francisco Sahli , Bhattacharya Jay , Bendavid Eran , Ioannidis John P.A. , Kuhl Ellen
Published: May 2020

Understanding the outbreak dynamics of the COVID-19 pandemic has important implications for successful containment and mitigation strategies. Recent studies suggest that the population prevalence of SARS-CoV-2 antibodies, a proxy for the number of asymptomatic cases, could be an order of magnitude larger than expected from the number of reported symptomatic cases. Knowing the precise prevalence and contagiousness of asymptomatic transmission is critical to estimate the overall dimension and pandemic potential of COVID-19. However, at this stage, the effect of the asymptomatic population, its size, and its outbreak dynamics remain largely unknown. Here we use reported symptomatic case data in conjunction with antibody seroprevalence studies, a mathematical epidemiology model, and a Bayesian framework to infer the epidemiological characteristics of COVID-19. Our model computes, in real time, the time-varying contact rate of the outbreak, and projects the temporal evolution and credible intervals of the effective reproduction number and the symptomatic, asymptomatic, and recovered populations. Our study quantifies the sensitivity of the outbreak dynamics of COVID-19 to three parameters: the effective reproduction number, the ratio between the symptomatic and asymptomatic populations, and the infectious periods of both groups. For nine distinct locations, our model estimates the fraction of the population that has been infected and recovered by Jun 15, 2020 to 24.15% (95% CI: 20.48%-28.14%) for Heinsberg (NRW, Germany), 2.40% (95% CI: 2.09%-2.76%) for Ada County (ID, USA), 46.19% (95% CI: 45.81%-46.60%) for New York City (NY, USA), 11.26% (95% CI: 7.21%-16.03%) for Santa Clara County (CA, USA), 3.09% (95% CI: 2.27%-4.03%) for Denmark, 12.35% (95% CI: 10.03%-15.18%) for Geneva Canton (Switzerland), 5.24% (95% CI: 4.84%-5.70%) for the Netherlands, 1.53% (95% CI: 0.76%-2.62%) for Rio Grande do Sul (Brazil), and 5.32% (95% CI: 4.77%-5.93%) for Belgium. Our method traces the initial outbreak date in Santa Clara County back to January 20, 2020 (95% CI: December 29, 2019 - February 13, 2020). Our results could significantly change our understanding and management of the COVID-19 pandemic: A large asymptomatic population will make isolation, containment, and tracing of individual cases challenging. Instead, managing community transmission through increasing population awareness, promoting physical distancing, and encouraging behavioral changes could become more relevant.
COVID-19 in Latin America: Contrasting phylodynamic inference with epidemiological surveillance. (Molecular epidemiology of COVID-19 in Latin America)
Authors: Rojas-Gallardo Diana M. , Garzón-Castaño Sandra C. , Millán Natalia , Jiménez-Posada Erika V. , Martínez-Gutiérrez Marlen , Ruiz-Saenz Julian , Cardona-Ospina Jaime A.
Published: May 2020

Background

SARS-CoV-2 revealed important gaps in infectious disease surveillance. Molecular epidemiology can help monitoring and adapting traditional surveillance to surpass those limitations. This work aims to contrast data driven from traditional surveillance with parameters inferred from molecular epidemiology in Latin America (LATAM)

Methods

We obtained epidemiological data up to 4th June, 2020. We estimated Effective Reproductive Number (Re) and epidemic curves using maximum likelihood (ML). SARS-CoV-2 genomes were obtained from GISAID up to June 4th 2020. We aligned sequences, generated a ML phylogenetic tree, and ran a coalescent model Birth Death SIR. Phylodynamic analysis was performed for inferring Re, number of infections and date of introduction.

Findings

A total of 1,144,077 cases were reported up to 4th June 2020. Countries with the largest cumulative cases were Chile, Peru and Panama. We found at least 18 different lineages circulating, with a predominance of B.1 and B.1.1. We inferred an underestimation of the daily incident cases. When contrasting observed and inferred Re, we did not find statistically significant differences except for Chile and Mexico. Temporal analysis of the introduction of SARS-CoV-2 suggested a detection lag of at least 21 days.

Interpretation

Our results support that epidemiological and genomic surveillance are two complementary approaches. Even with a low number of genomes proper estimations of Re could be performed. We suggest that countries, especially developing countries, should consider to add genomic surveillance to their systems for monitoring and adapting epidemiological control of SARS-CoV-2.
Estimation of the case fatality rate based on stratification for the COVID-19 outbreak
Authors: Kim Byungwon , Kim Seonghong , Jang Woncheol , Jung Sungkyu , Lim Johan
Published: May 2020

This work is motivated by the recent worldwide pandemic of the novel coronavirus disease (COVID-19). When an epidemiological disease is prevalent, estimating the case fatality rate, the proportion of deaths out of the total cases, accurately and quickly is important as the case fatality rate is one of the crucial indicators of the risk of a disease. In this work, we propose an alternative estimator of the case fatality rate that provides more accurate estimate during an outbreak by reducing the downward bias (underestimation) of the naive CFR, the proportion of deaths out of confirmed cases at each time point, which is the most commonly used estimator due to the simplicity. The proposed estimator is designed to achieve the availability of real-time update by using the commonly reported quantities, the numbers of confirmed, cured, deceased cases, in the computation. To enhance the accuracy, the proposed estimator adapts a stratification, that allows the estimator to use information from heterogeneous strata separately. With the COVID-19 cases of China, South Korea and the United States, we numerically show the proposed stratification-based estimator plays a role of providing an early warning about the severity of a epidemiological disease that estimates the final case fatality rate accurately and shows faster convergence to the final case fatality rate.
Energy efficiency and biological interactions define the core microbiome of deep oligotrophic groundwater
Authors: Mehrshad Maliheh , Lopez-Fernandez Margarita , Sundh John , Bell Emma , Simone Domenico , Buck Moritz , Bernier-Latmani Rizlan , Bertilsson Stefan , Dopson Mark
Published: May 2020

Extremely oligotrophic deep groundwaters host organisms attuned to the low-end of the bioenergetics spectrum. While all domains of life along with viruses are active in this habitat, the evolutionary and ecological constraints on colonization and niche shifts and their consequences for the microbiome convergence are unknown. Here we provide a comparative genome-resolved analysis of the prokaryotic community in disconnected fracture fluids of the Fennoscandian Shield. The data show that the oligotrophic deep groundwaters flowing in similar lithologies offer fixed niches that are occupied by a common deep groundwater core microbiome. Based on this high resolution “multi-omics” enabled understanding of the underlying mechanisms via functional expression analysis, we conclude that deep groundwater ecosystems foster highly diverse, yet cooperative microbial communities adapted to this setting. The fitness of primary energy producers is increased by ecological traits such as aggregate or biofilm formation. This also facilitates reciprocal promiscuous partnerships with diverse and prevalent epi-bionts, alleviating the “tragedy of common goods”. Hence, instead of a lifestyle where microbes predominantly invest in functions related to maintenance and survival, an episodic and cooperative lifestyle ensures the subsistence of the deep groundwater microbiome. We suggest the name “halt and catch fire” for this way of life.
Learning is shaped by abrupt changes in neural engagement
Authors: Hennig Jay A. , Oby Emily R. , Golub Matthew D. , Bahureksa Lindsay A. , Sadtler Patrick T. , Quick Kristin M. , Ryu Stephen I. , Tyler-Kabara Elizabeth C. , Batista Aaron P. , Chase Steven M. , Yu Byron M.
Published: May 2020

Internal states such as arousal, attention, and motivation are known to modulate brain-wide neural activity, but how these processes interact with learning is not well understood. During learning, the brain must modify the neural activity it produces to improve behavioral performance. How do internal states affect the evolution of this learning process? Using a brain-computer interface (BCI) learning paradigm in non-human primates, we identified large fluctuations in neural population activity in motor cortex (M1) indicative of arousal-like internal state changes. These fluctuations drove population activity along dimensions we term neural engagement axes. Neural engagement increased abruptly at the start of learning, and then gradually retreated. In a BCI, the causal relationship between neural activity and behavior is known. This allowed us to understand how these changes impacted behavioral performance for different task goals. We found that neural engagement interacted with learning, helping to explain why animals learned some task goals more quickly than others.
Regenerating motor neurons prime muscle stem cells for myogenesis by enhancing protein synthesis and mitochondrial bioenergetics
Authors: Choi Jeongmoon J. , Shin Eun Jung , Han Woojin M. , Anderson Shannon E. , Mohiuddin Mahir , Lee Nan Hee , Tran Thu , Nakhai Shadi , Jeong Hyeonsoo , Shcherbina Anna , Jeong Gunjae , Oh Dong Gun , Weinstock Laura D. , Sankar Sitara B. , Ogle Molly E. , Katsimpardi Lida , Rao Tata Nageswara , Wood Levi , Aguilar Carlos A. , Wagers Amy J. , Jang Young C.
Published: May 2020

Throughout life, skeletal muscle, the arbiter of voluntary movements, is maintained by a population of skeletal muscle-dedicated stem cells, called muscle satellite cells (MuSCs). Similar to other adult stem cells, the function of MuSCs is tightly coordinated by the cellular and acellular components of their microenvironment, or the niche. While the processes that control the coupling of neurotransmission and muscle contraction have been well characterized, little is known on the reciprocal crosstalk between neural cells and MuSCs within the muscle microenvironment. Here, we report that mild peripheral nerve injury enhances MuSC myogenic function and muscle regeneration by synergistically augmenting MuSC mitochondrial bioenergetics and upregulating anabolic protein synthesis pathways. We also demonstrate that chronic disruption or degeneration of neuromuscular synapses, such as in muscular dystrophy and biological aging, abolishes MuSC and motor neuron interactions, causing significant deficits in muscle regeneration following injury. These results underscore the importance of neuromuscular junction and neural network as an essential niche of MuSCs. Determining the significance of MuSC-nerve interactions and their functional outcomes, as well as the possibility of modulating these connections, have important implications for our understanding of neuromuscular disease pathology and development of therapeutic interventions.

Highlights

Mild peripheral nerve injury increases muscle stem cell bioavailability of healthy muscle.

Nerve perturbation stimulates myogenesis by enhancing protein synthesis and mitochondrial metabolism in young, healthy muscle.

Synergistic crosstalk within neuromuscular niche boosts muscle regeneration in young, healthy muscle.

Positive influences from the neural network on muscle stem cells are abolished in pathological denervation manifested in dystrophic and aging muscle.
The visual ecology of Holocentridae, a nocturnal coral reef fish family with a deep-sea-like multibank retina
Authors: de Busserolles Fanny , Cortesi Fabio , Fogg Lily , Stieb Sara M. , Luerhmann Martin , Marshall N. Justin
Published: May 2020

The visual systems of teleost fishes usually match their habitats and lifestyles. Since coral reefs are bright and colourful environments, the visual systems of their diurnal inhabitants have been more extensively studied than those of nocturnal species. In order to fill this knowledge gap, we conducted a detailed investigation of the visual systems of the coral reef fish family Holocentridae (squirrelfish and soldierfish). In addition to their nocturnality, this family is particularly interesting for dim-light vision studies due to its ecological and evolutionary connection to deeper habitats. Results showed that the visual system of holocentrids is well adapted to their nocturnal lifestyle with a rod-dominated retina. Surprisingly, rods in all species were arranged into 6-17 well-defined banks, a feature most commonly found in deep-sea fishes, that may increase the light sensitivity of the eye and/or allow colour discrimination in dim-light. Holocentrids also have the potential for dichromatic colour vision during the day with the presence of at least two spectrally different cone types: single cones expressing the blue-sensitiveSWS2Agene, and double cones expressing one or two green-sensitiveRH2genes. Some differences were observed between the two subfamilies, with Holocentrinae having a slightly more developed photopic visual system than Myripristinae. Moreover, retinal topography of both ganglion cells and cone photoreceptors showed specific patterns for each cell type, likely highlighting different visual demands at different times of the day, such as feeding. Overall, their well-developed scotopic visual systems and the ease of catching and maintaining holocentrids in aquaria, make them ideal models to investigate teleost dim-light vision and more particularly shed light on the function of multibank retina and its potential for dim-light colour vision.
Inferring the effective start dates of non-pharmaceutical interventions during COVID-19 outbreaks
Authors: Kohanovski Ilia , Obolski Uri , Ram Yoav
Published: May 2020

During Feb-Apr 2020, many countries implemented non-pharmaceutical interventions, such as school closures and lockdowns, with variable schedules, to control the COVID-19 pandemic caused by the SARS-CoV-2 virus. Overall, these interventions seem to have successfully reduced the spread of the pandemic. We hypothesise that the official and effective start date of such interventions can significantly differ, for example due to slow adoption by the population, or because the authorities and the public are unprepared. We fit an SEIR model to case data from 12 countries to infer the effective start dates of interventions and contrast them with the official dates. We find mostly late, but also early effects of interventions. For example, Italy implemented a nationwide lockdown on Mar 11, but we infer the effective date on Mar 17 (±2.99 days 95% CI). In contrast, Germany announced a lockdown on Mar 22, but we infer an effective start date on Mar 19 (± 1.05 days 95% CI). We demonstrate that differences between the official and effective start of NPIs can distort conclusions about their impact, and discuss potential causes and consequences of our results.
Ataxia as a presenting manifestation of COVID -19: Report of a single case
Authors: Mukherjee Debaleena , Sarkar Peyalee , Dubey Souvik , Ray Biman Kanti , Pandit Alak , Lahiri Durjoy
Published: May 2020

Even though various neurological presentations of COVID-19 have surfaced up, ataxia as a presenting feature has rarely been reported so far. We hereby describe a confirmed case of SARS-CoV-2 infection which not only presented with ataxia but also had delayed onset of typical respiratory features. This case represents an atypical manifestation of COVID-19.
Risk of infection and hospitalization by Covid-19 in Mexico: a case-control study
Authors: Berumen Jaime , Schmulson Max , Alegre Jesus , Guerrero Guadalupe , Olaiz Gustavo , Wong-Chew Rosa M. , Larriva-Sahd Jorge , Cantu-Brito Carlos , Ochoa-Guzman Ana , Garcilazo-Avila Adrian , Gonzalez-Carballo Carlos , Chiquete Erwin
Published: May 2020

Objective. During the onset of a novel epidemic, there are public health priorities that need to be estimated, such as risk factors for infection, hospitalization, and clinical severity to allocate resources and issue health policies. In this work we calculate the risk of infection and hospitalization by Covid-19 conferred by demographic, lifestyle, and co-morbidity factors. Material and methods. This is a case-control study including the tested individuals for SARS-Cov-2 by RT-PCR officially reported by the Health Secretary of Mexico from January 01 to May 8, 2020 (102,875 subjects). Demographic (sex, age, foreign and immigrant status, native speaking, place of residence), life-style (smoking), and co-morbidities [diabetes, obesity, high blood pressure (HBP), asthma, immunosuppression, chronic obstructive pulmonary disease (COPD), cardiovascular disease other than HBP, chronic kidney disease (CKD), and other not specified diseases (other diseases)] variables were included in this study. The risk of infection and hospitalization conferred by each variable was calculated with univariate (ULR) and multivariate (MLR) logistic regression models. Results. The place of residence (OR=4.91 living in Tijuana City), followed by advanced age (OR=6.71 in 61-70 years-old), suffering from diabetes (OR=1.87) or obesity (OR=1.61), being male (OR=1.55), having HBP (OR=1.52), and notoriously being indigenous (OR=1.49) conferred a higher risk of becoming infected by SARS-CoV-2 in Mexico. Unexpectedly, we found that having asthma (OR=0.63), immunosuppression (OR=0.65) or smoking (OR=0.85) are protective factors against infection, while suffering from COPD does not increase the risk for SARS-CoV-2 infection. In contrast, advanced age (OR=11.6 in ≥ 70 years-old) is the main factor for hospitalization due to Covid-19, followed by some co-morbidities, mainly diabetes (OR=3.69) and HBP (OR=2.79), being indigenous (OR=1.89), male sex (OR=1.67) and the place of residence (OR=4.22 for living in Juarez City). Unlike the protective risk against infection, immunosuppression (OR=2.69) and COPD (OR=3.63), contribute to the risk of being hospitalized, while having asthma (OR=0.7) also provides protection against hospitalization. Conclusions. In addition to confirming that older age, diabetes, HBP and obesity are the main risk of infection and hospitalization by Covid-19, we found that being indigenous, immunosuppression, smoking and asthma protect against infection, and the latter also against hospitalization.