bluuebunny/crossref_metadata_2025 huggingface dataset:
S218. TAURINE DOES NOT PREVENT SOCIAL DEFICITS INDUCED BY MK-801 IN ADULT ZEBRAFISH
Authors: Kich Giongo Franciele , Benvenutti Radharani , Gallas-Lopes Matheus , Sachett Adrieli , Piato Angelo , Paula Herrmann Ana
Published: May 2020

Background

Cognitive and negative symptoms are the core reason for the functional deficits experienced by patients with schizophrenia. Drugs that can modulate these symptoms are especially needed since no progress has been achieved in the last few decades with currently available antipsychotics. Taurine is an amino acid not used for protein synthesis but widely distributed in mammalian tissues. In the central nervous system, it has been shown to act as an inhibitory neuromodulator and possess neuroprotective, antioxidant and immunomodulatory properties. Decreased plasma and brain levels of taurine have been reported in patients as well as in animal models of schizophrenia. Furthermore, taurine improved symptoms and was well tolerated in a clinical trial of patients with first-episode psychosis. We investigated whether taurine counteracts social deficits in a zebrafish model of social interaction following acute exposure to MK-801 (dizocilpine), an NDMA antagonist commonly used in schizophrenia animal models.

Methods

Ninety-six 3-month-old wild-type zebrafish (Danio rerio, 50:50 male:female ratio) were used. For the social interaction test, animals were individually placed in a beaker with 200 mL of tank water (control) or taurine solution (42, 150 and 400 mg/L) for 20 minutes, and then exposed to water or MK-801 (5 µM) for another 20 minutes (n = 12 animals per group). Immediately after the treatments, zebrafish were transferred to the social interaction apparatus, a tank virtually divided in 3 vertical zones and sided by an empty tank and a tank containing 10 zebrafish. Behavior was recorded for 7 minutes and the last 5 were analyzed by automated tracking with the software ANY-Maze. The time spent in the stimulus zone was measured as a proxy for social interaction; total distance traveled was also computed. Data were analyzed by two-way ANOVA.

Results

MK-801 increased the total distance traveled (F1,88 = 4.935, p = 0.0289) and reduced the time spent in the tank zone next to the conspecifics (F1,88 = 23.14, p < 0.0001). No main effects of taurine or interaction effects were observed on locomotor or social interaction parameters.

Discussion

Although taurine has been shown to increase social interaction in rats and modulate shoaling behavior in ethanol-exposed zebrafish, it had not been tested against social deficits induced by NMDA antagonists. We observed that taurine did not counteract the hyperlocomotion and social deficit induced by acute exposure to MK-801 in zebrafish. As schizophrenia etiology has been linked to cortical and hippocampal disruption in GABAergic signaling, taurine may be effective as a preventive treatment in early neurodevelopmental stages. Further testing using animal models that more closely resemble the course of schizophrenia are thus needed to investigate the potential of this molecule.
S245. BRAIN CONNECTIVITY CHANGES AFTER COGNITIVE REMEDIATION: A RESTING-STATE STUDY
Authors: Penadés Rafael , Segura Barbara , Inguanzo Anna , Garcia-Rizo Clemente , Catalán Rosa , Masana Guillem , Bernardo Miquel , Junqué Carme
Published: May 2020

Background

Some studies have showed how Cognitive Remediation is able to improve activation patterns in the frontal lobe. However, only few data on neuroconnectivity has been reported yet. Resting-state fMRI approach seems to be a promising methodology with potentiality for testing neuroconnectivity.

Methods

A randomized and controlled trial was carried out with three groups: patients receiving Cognitive Remediation Therapy (CRT), patients receiving Social Skills Training (SST) as an active control, and a healthy control (HC) group. A resting-state fMRI data was acquired in part of the sample (n = 26 patients, n = 10 healthy controls) of a partner study (NCT 02341131). A data-driven approach using independent component analysis (ICA) was used to identify functional brain networks, which were compared between groups and group per time using a dual-regression approach.

Results

ICA results revealed reduced functional connectivity between patients and controls in sensorimotor, basal ganglia, default mode and visual networks at baseline (p<0.05 FEW-corrected). After treatment, time per group analyses evidenced increased connectivity in sensorimotor network. Furthermore, group comparison at follow-up showed similar connectivity patterns between patients and healthy controls in sensorimotor network, but also in default mode and basal ganglia networks.

Discussion

Cognitive remediation could be able to strengthen some aspects of brain connectivity networks. Our data could be in line of the hypothesis of disconnectivity in schizophrenia. However, cognitive remediation but also social skills training seemed to be able to induce detectable changes in brain functioning in terms of restoring some aspects on the connectivity pattern.
Isolating the role of time in bed restriction in the treatment of insomnia: a randomized, controlled, dismantling trial comparing sleep restriction therapy with time in bed regularization
Authors: Maurer Leonie Franziska , Espie Colin Alexander , Omlin Ximena , Reid Matthew James , Sharman Rachel , Gavriloff Dimitri , Emsley Richard , Kyle Simon David
Published: May 2020

Study Objectives

Sleep restriction therapy (SRT) is one of the most effective treatments for insomnia. Restriction of time in bed (TIB) is assumed to be the central mechanism through which SRT improves sleep consolidation and reduces insomnia symptoms. This hypothesis has never been directly tested. We designed a randomized, controlled, dismantling trial in order to isolate the role of TIB restriction in driving both clinical and polysomnographic sleep outcomes.

Methods

Participants aged 25–55 who met diagnostic criteria for insomnia disorder were block-randomized (1:1) to 4 weeks of SRT or time in bed regularization (TBR), a treatment that involves the prescription of a regular but not reduced TIB. The primary outcome was assessed with the insomnia severity index (ISI) at baseline, 4-, and 12-weeks post-randomization. Secondary outcomes included sleep continuity (assessed via polysomnography, actigraphy, and diary) and quality of life. We performed intention-to-treat analyses using linear mixed models.

Results

Fifty-six participants (39 females, mean age = 40.78 ± 9.08) were assigned to SRT (n = 27) or TBR (n = 29). Daily monitoring of sleep via diaries and actigraphy confirmed large group differences in TIB (d range = 1.63–1.98). At 4-weeks post-randomization, the adjusted mean difference for the ISI was −4.49 (d = −1.40) and −4.35 at 12 weeks (d = −1.36), indicating that the SRT group reported reduced insomnia severity relative to TBR. Robust treatment effects in favor of SRT were also found for objective and self-reported sleep continuity variables (d range = 0.40–0.92) and sleep-related quality of life (d = 1.29).

Conclusions

For the first time, we demonstrate that TIB restriction is superior to the regularization of TIB on its own. Our results underscore the centrality of the restriction component in reducing insomnia symptoms and consolidating sleep.
Coevolution of cognitive abilities and identity signals in individual recognition systems
Authors: Miller Sara E. , Sheehan Michael J. , Reeve H. Kern
Published: May 2020

Social interactions are mediated by recognition systems, meaning that the cognitive abilities or phenotypic diversity that facilitate recognition may be common targets of social selection. Recognition occurs when a receiver compares the phenotypes produced by a sender with a template. Coevolution between sender and receiver traits has been empirically reported in multiple species and sensory modalities, though the dynamics and relative exaggeration of traits from senders versus receivers have received little attention. Here, we present a coevolutionary dynamic model that examines the conditions under which senders and receivers should invest effort in facilitating individual recognition. The model predicts coevolution of sender and receiver traits, with the equilibrium investment dependent on the relative costs of signal production versus cognition. In order for recognition to evolve, initial sender and receiver trait values must be above a threshold, suggesting that recognition requires some degree of pre-existing diversity and cognitive abilities. The analysis of selection gradients demonstrates that the strength of selection on sender signals and receiver cognition is strongest when the trait values are furthest from the optima. The model provides new insights into the expected strength and dynamics of selection during the origin and elaboration of individual recognition, an important feature of social cognition in many taxa.

This article is part of the theme issue ‘Signal detection theory in recognition systems: from evolving models to experimental tests’.
Signal detection and optimal acceptance thresholds in avian brood parasite–host systems: implications for egg rejection
Authors: Ruiz-Raya Francisco , Soler Manuel
Published: May 2020

Signal detection theory addresses the challenge of successfully identifying informative signals in noisy information contexts, allowing optimal behavioural decisions in diverse ecological contexts. The optimal acceptance threshold hypothesis proposed by Reeve (Reeve 1989
Am. Nat.
133
, 407–435. (
doi:10.1086/284926
)) is an elegant theoretical model to predict the flexibility of acceptance thresholds for conspecific discrimination. This model has provided a robust framework used to explore recognition systems in a broad range of contexts such as animal communication, nest-mate discrimination or anti-parasitic host responses. In this review, we discuss key concepts related to the optimal acceptance threshold hypothesis applied to egg rejection decisions in avian brood parasite–host interactions. We explore those factors determining signal detectability in parasitized nests and how hosts adjust their rejection decisions to both the risk of parasitism and the potential costs associated with egg rejection. In addition, we discuss recent results that challenge some traditional assumptions of the optimal acceptance threshold hypothesis and provide a novel perspective to explore rejection decisions, such as the existence of single-threshold decision rules or acceptance decisions. An integrative view combining current evidence with traditional theory is needed to further advance the comprehension of optimal acceptance thresholds.

This article is part of the theme issue ‘Signal detection theory in recognition systems: from evolving models to experimental tests'.
Noisy communities and signal detection: why do foragers visit rewardless flowers?
Authors: Lichtenberg Elinor M. , Heiling Jacob M. , Bronstein Judith L. , Barker Jessica L.
Published: May 2020

Floral communities present complex and shifting resource landscapes for flower-foraging animals. Strong similarities among the floral displays of different plant species, paired with high variability in reward distributions across time and space, can weaken correlations between floral signals and reward status. As a result, it should be difficult for foragers to discriminate between rewarding and rewardless flowers. Building on signal detection theory in behavioural ecology, we use hypothetical probability density functions to examine graphically how plant signals pose challenges to forager decision-making. We argue that foraging costs associated with incorrect acceptance of rewardless flowers and incorrect rejection of rewarding ones interact with community-level reward availability to determine the extent to which rewardless and rewarding species should overlap in flowering time. We discuss the evolutionary consequences of these phenomena from both the forager and the plant perspectives.

This article is part of the theme issue ‘Signal detection theory in recognition systems: from evolving models to experimental tests’.
Genome-based reclassification of Lactobacillus casei: emended classification and description of the species Lactobacillus zeae
Authors: Huang Chien-Hsun , Chen Chih-Chieh , Liou Jong-Shian , Lee Ai-Yun , Blom Jochen , Lin Yu-Chun , Huang Lina , Watanabe Koichi
Published: May 2020

Taxonomic relationships between

Lactobacillus casei

,

Lactobacillus paracasei

and

Lactobacillus zeae

have long been debated. Results of previous analyses have shown that overall genome relatedness indices (such as average nucleotide identity and core nucleotide identity) between the type strains

L. casei

ATCC 393T and

L. zeae

ATCC 15820T were 94.6 and 95.3 %, respectively, which are borderline for species definition. However, the digital DNA‒DNA hybridization value was 57.3 %, which was clearly lower than the species delineation threshold of 70 %, and hence raised the possibility that

L. casei

could be reclassified into two species. To re-evaluate the taxonomic relationship of these taxa, multilocus sequence analysis (MLSA) based on the concatenated five housekeeping gene (dnaJ, dnaK, mutL, pheS and yycH) sequences, phylogenomic and core genome multilocus sequence typing analyses, gene presence and absence profiles using pan-genome analysis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling analysis, cellular fatty acid compositions, and phenotype analysis were carried out. The results of phenotypic characterization, MLSA, whole-genome sequence-based analyses and MALDI-TOF MS profiling justified an independent species designation for the

L. zeae

strains, and supported an emended the description of the name of

Lactobacillus zeae

(ex Kuznetsov 1956) Dicks et al. 1996, with ATCC 15820T (=DSM 20178T=BCRC 17942T) as the type strain.
Study of Non-Pharmacological Interventions on COVID-19 Spread
Authors: Singh Avaneesh , Chandra Saroj Kumar , Bajpai Manish Kumar
Published: May 2020

COVID-19 disease has emerged as one of the life threatening threat to the society. It is caused by a novel beta coronavirus. It began as unidentified pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. No vaccine has been produced till now. Mathematical models are used to study impact of different measures used to decrease pandemic. Mathematical models have been designed to estimate the numbers of spreaders in different scenarios in the present manuscript. In the present manuscript, three different mathematical models have been proposed with different scenarios such as screening, quarantine and NPIs for estimating number of virus spreaders. The analysis shows that the numbers of COVID-19 patients will be more without screening the peoples coming from other countries. Since, every people suffering with COVID-19 disease are spreaders. The screening and quarantine with NPIs have been implemented to study their impact on the spreaders. It has been found that NPI measures are able to reduce number of spreaders. The NPI measures reduces the growth of the spread function and providing decision makers more time to prepare with in dealing of the disease.
Traces of SARS-CoV-2 RNA in the Blood of COVID-19 Patients
Authors: Moustafa Ahmed , Aziz Ramy K
Published: May 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third virus that caused coronavirus-related outbreaks over the past 20 years. The outbreak was first reported in December 2019 in Wuhan, China, but rapidly progressed into a pandemic of an unprecedented scale since the 1918 flu pandemic. Besides respiratory complications in COVID-19 patients, clinical characterizations of severe infection cases showed several other comorbidities, including multiple organ failure (liver, kidney, and heart) and septic shock. To better understand COVID-19 pathogenesis in different human organs, we interrogated the presence of the virus in the blood, or any of its components, which might provide a form of trafficking or hiding to the virus. By computationally analyzing high-throughput sequence data from patients with active COVID-19 infection, we found evidence of only traces of SARS-CoV-2 RNA in peripheral blood mononuclear cells (PBMC), while the virus RNA was abundant in bronchoalveolar lavage specimens from the same patients. We also devised a "viral spike-to-actin" RNA normalization, as a metric to compare across various samples and minimize errors caused by intersample variability in human RNA. To the best of our knowledge, the presence of SARS-CoV-2 RNA in the PBMC of COVID-19 patients has not been reported before, and this observation could suggest immune presentation, but discounts the possibility of extensive viral infection of lymphocytes or monocytes.
FLNC and MYLK2 gene mutations in a Chinese family with different phenotypes of cardiomyopathy
Authors: Qin Xianyu , Li Ping , Qu Huiqi , Liu Yichuan , Xia Yu , Chen Shaoxian , Yang Yongchao , Huang Shufang , Wen Pengju , Zhou Xianwu , Li Xiaofeng , Wang Yonghua , Tian Lifeng , Hakonarson Hakon , Wu Yueheng , Zhuang Jian
Published: May 2020

Background: Mutations in the sarcomeric protein filamin C (FLNC) gene have been linked to hypertrophic cardiomyopathy (HCM), in which they increase the risk of ventricular arrhythmia and sudden death. In this study, we identified a novel missense mutation of FLNC in a Chinese family with HCM and interestingly a second novel truncating mutation of MYLK2 in one family member with different phenotype.
Methods: We performed whole-exome sequencing in a Chinese family with HCM of unknown cause. To validate the function of a novel mutation of FLNC, we introduced the mutant and wild-type gene into AC16 cells (human cardiomyocytes), and used western blotting to analyze the expression of FLNC in subcellular fractions, and confocal microscope to observe the subcellular distribution of the protein.
Results: We identified a novel missense single nucleotide variant (FLNC c.G5935A [p.A1979T]) in the family, which segregates with the disease. FLNC expression levels were equivalent in both wild type and p.A1979T cardiomyocytes. However, expression of the mutant protein resulted in cytoplasmic protein aggregations, in contrast to wild type FLNC, which was distributed in the cytoplasm and did not form aggregates. Unexpectely, a second truncating mutation, NM_033118:exon8:c.G1138T:p.E380X of the MYLK2 gene, was identified in the mother of the proband with dilated cardiomyopathy, but absent in other subjects.
Conclusion: We identified the FLNC A1979T mutation as a novel pathogenic variant associated with HCM in a Chinese family, as well as a second causal mutation in a family member with a distinct phenotype. The possibility of more than one causal mutations in cardiomyopathy warrants clinical attention, especially for patients with atypical clinical features.
Prevalence of SARS-CoV-2 infection in the Luxembourgish population: the CON-VINCE study.
Authors: Snoeck Chantal J. , Vaillant Michel , Abdelrahman Tamir , Satagopam Venkata P. , Turner Jonathan D. , Beaumont Katy , Gomes Clarissa P. C. , Fritz Joelle Veronique , Schröder Valerie E. , Kaysen Anne , Pavelka Lukas , Stute Lara , Ramos Meyers Guilherme , Pauly Laure , Hansen Maxime , Pauly Claire , Aguayo Gloria A. , Perquin Magali , Hanff Anne-Marie , Ghosh Soumyabrata , Gantenbein Manon , Huiart Laetitia , Ollert Markus , Krüger Rejko
Published: May 2020

BACKGROUND:
After the World Health Organization declared the outbreak of coronavirus disease to be a public health emergency of international concern on January 30, 2020, the first SARS-CoV-2 infection was detected in Luxembourg on February 29, 2020. Representative population-based data, including asymptomatic individuals for assessing the viral spread and immune response were, however, lacking worldwide.
METHODS:
Using a panel-based method, we implemented a representative sample of the Luxembourgish population based on age, gender and residency for testing for SARS-CoV-2 infection and antibody status in order to define prevalence irrespective of clinical symptoms. Participants were contacted via email to fill an online questionnaire before biosampling at local laboratories. All participants provided information related to clinical symptoms, epidemiology, socioeconomic and psychological assessments and underwent biosampling, rRT-PCR testing and serology for SARS-CoV-2.
RESULTS:
We included a total of 1862 individuals in our representative sample of the general Luxembourgish population. Of these, 5 individuals had a current positive result for infection with SARS-CoV-2 based on rRT-PCR. Four of these individuals were oligosymptomatic and one was asymptomatic. Overall we found a positive IgG antibody status in 35 individuals (1.97%), of which 11 reported to be tested positive by rRT-PCR for SARS-CoV-2 previously and showed in addition their IgG positive status also a positive status for IgA. Our data indicate a prevalence of 0.3% for active SARS-CoV-2 infection and an infection rate of 2.15% in the Luxembourgish population between 18 and 79 years of age.
CONCLUSIONS:
Luxembourgish residents show a low rate of acute infections after 7 weeks of confinement and present with an antibody profile indicative of a more recent immune response to SARS-CoV-2. All infected individuals were oligo- or asymptomatic. Bi-weekly follow-up visits over the next 2 months will inform about the viral spread by a- and oligosymptomatic carriers and the individual changes in the immune profile.
Internet-based tool for visualizing county and state level COVID-19 trends in the United States
Authors: Hinz S , Basam MM , Aguilera KY , LaBarge MA
Published: May 2020

The novel COVID-19 outbreak started in 2019 in Wuhan China and quickly spread to at least 185 countries. We developed an interactive web application that allows users to visualize the spread of COVID-19 in the Unites States at state and county levels. This tool allows visualization of how the virus spreads over time and how state-wide efforts to reduce transmissions have affected the curve in local areas. The downloadable application data allows users to conduct additional analyses. We demonstrate exemplars of trend analyses comparing the daily infection and death rates before and after safer at home orders were implemented per state. The goal was to develop a COVID-19 tracking tool that informs users about the spread of the virus to enable them to make informed decisions after better understanding the presented data.
Adjusting Coronavirus prevalence estimates for laboratory test kit error
Authors: Sempos Christopher , Tian Lu
Published: May 2020

Testing representative populations to determine the prevalence or percent of the population with active SARS-Cov-2 (COVID-19) infection and/or antibodies to infection is being recommended as essential for making public policy decisions to open-up or to continue enforcing national, state and local government rules to shelter-in-place. However, all laboratory tests are imperfect and have estimates of sensitivity and specificity less than 100% - in some cases considerably less than 100%. That error will lead to biased prevalence estimates. If the true prevalence of COVID-19 is low, possibly in the range of 1-5%, then testing error will lead to a constant background of bias that will most likely be larger and possibly much larger than the true prevalence itself. As a result, what is needed is a method for adjusting prevalence estimates for testing error. In this paper we outline methods for adjusting prevalence estimates for testing error both prospectively in studies being planned and retrospectively in studies that have been conducted. The methods if employed would also help to harmonize study results within countries and around the world. Adjustment can lead to more accurate prevalence estimates and to better policy decisions.
Accessibility and allocation of public parks and gardens during COVID-19 social distancing in England and Wales
Authors: Shoari Niloofar , Ezzati Majid , Baumgartner Jill , Malacarne Diego , Fecht Daniela
Published: May 2020

Visiting parks and gardens may attenuate the adverse physical and mental health impacts of social distancing implemented to reduce the spread of COVID-19. We quantified access to public parks and gardens in urban areas of England and Wales, and the potential for park crowdedness during periods of high use. We combined data from the Office for National Statistics and Ordnance Survey to quantified (i) the number of parks within 500 and 1,000 metres of urban postcodes (i.e., availability), (ii) the distance of postcodes to the nearest park (i.e., accessibility), and (iii) per-capita space in each park for people living within 1,000m. We examined variability by city and share of flats. Around 25.4 million people can access public parks or gardens within a ten-minute walk, while 3.8 million residents live farther away; of these 21% are children and 13% are elderly. Areas with a higher share of flats on average are closer to a park but people living in these areas are potentially less able to meet social distancing requirements while in parks during periods of high use. Cities in England and Wales can provide residents with access to green space that enables outdoor exercise and play during social distancing. Keeping public parks and gardens open, might require measures such as dedicated park times for different age groups or entry allocation systems that, combined with smartphone apps or drones, can monitor and manage the total number of people using the park.
Incidence and etiology of clinically-attended, antibiotic-treated diarrhea among children under five years of age in low- and middle-income countries: evidence from the Global Enteric Multicenter Study
Authors: Lewnard Joseph A , Rogawski McQuade Elizabeth T , Platts-Mills James A , Kotloff Karen L , Laxminarayan Ramanan
Published: May 2020

Background: Diarrhea is a leading cause of antibiotic consumption among children in low- and middle-income countries. While vaccines may prevent diarrhea infections for which children often receive antibiotics, the contribution of individual enteropathogens to antibiotic use is minimally understood. We used data from the Global Enteric Multicenter Study (GEMS) to estimate pathogen-specific incidence of antibiotic-treated diarrhea among children under five years old residing in six countries of sub-Saharan Africa and South Asia before rotavirus vaccine implementation.

Methods and findings: GEMS was an age-stratified, individually-matched case-control study. Stool specimens were obtained from children presenting to sentinel health clinics with newly-onset, acute diarrhea (including moderate-to-severe and less-severe diarrhea) as well as matched community controls without diarrhea. We used data from conventional and quantitative molecular diagnostic assays applied to stool specimens to estimate the proportion of antibiotic-treated diarrhea cases attributable to each pathogen. Antibiotics were administered or prescribed to 9,606 of 12,109 moderate-to-severe cases and 1,844 of 3,174 less-severe cases. Across all sites, incidence rates of clinically-attended, antibiotic-treated diarrhea were 12.2 (95% confidence interval: 9.0-17.8), 10.2 (7.4-13.9) and 1.9 (1.3-3.0) episodes per 100 child-years at risk at ages 6 weeks to 11 months, 12-23 months, and 24-59 months, respectively. Based on the recommendation for antibiotic treatment to be reserved for cases with dysentery, we estimated a ratio of 12.6 (8.6-20.8) inappropriately-treated diarrhea cases for each appropriately-treated case. Rotavirus, adenovirus serotypes 40/41, Shigella, sapovirus, Shiga toxin-producing Escherichia coli, and Cryptosporidium were the leading antibiotic-treated diarrhea etiologies. Rotavirus caused 29.2% (24.5-35.2%) of antibiotic-treated cases, including the largest share in both the first and second years of life. Shigella caused 14.9% (11.4-18.9%) of antibiotic-treated cases, and was the leading etiology at ages 24-59 months.

Conclusions: Our findings should inform the prioritization of vaccines with the greatest potential to reduce antibiotic exposure among children.
SARS-CoV-2 spillover into hospital outdoor environments
Authors: Zhang Dayi , Yang Yunfeng , Huang Xia , Jiang Jingkun , Li Miao , Zhang Xian , Ling Haibo , Li Jing , Liu Yi , Li Guanghe , Li Weiwei , Yi Chuan , Zhang Ting , Jiang Yongzhong , Xiong Yan , Hu Zhenyu , Wang Xinzi , Deng Songqiang , Zhao Peng , Qu Jiuhui
Published: May 2020

The outbreak of coronavirus infectious disease-2019 (COVID-19) pandemic has rapidly spread throughout over 200 countries, posing a global threat to human health. Till 15th May 2020, there are over 4.5 million confirmed cases, with roughly 300,000 death1. To date, most studies focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in indoor environment owing to its main transmission routes via human respiratory droplets and direct contact2,3. It remains unclear whether SARS-CoV-2 can spill over and impose transmission risks to outdoor environments despite potential threats to people and communities. Here, we investigated the presence of SARS-CoV-2 by measuring viral RNA in 73 samples from outdoor environment of three hospitals in Wuhan. We detected SARS-CoV-2 in soils (205-550 copies/g), aerosols (285-1,130 copies/m3) and wastewaters (255 to 18,744 copies/L) in locations close to hospital departments receiving COVID-19 patients or in wastewater treatment sectors. These findings reveal significant viral spillover in hospital outdoor environments that was possibly caused by respiratory droplets from patients or aerosolized particles from wastewater containing SARS-CoV-2. In contrast, SARS-CoV-2 was not detected in other areas or on surfaces with regular disinfection implemented. Soils may behave as viral warehouse through deposition and serve as a secondary source spreading SARS-CoV-2 for a prolonged time. For the first time, our findings demonstrate that there are high-risk areas in hospital outdoor environments to spread SARS-CoV-2, calling for sealing of wastewater treatment unit and complete sanitation to prevent COVID-19 transmission risks.
Anti-Spike, anti-Nucleocapsid and neutralizing antibodies in SARS-CoV-2 inpatients and asymptomatic carriers
Authors: Brochot Etienne , Demey Baptiste , Touzé Antoine , Belouzard Sandrine , Dubuisson Jean , Schmit Jean-Luc , Duverlie Gilles , Francois Catherine , Castelain Sandrine , Helle Francois
Published: May 2020

Objective

The objective of this study was to monitor the anti-SARS-CoV-2 antibody response in infected patients.

Methods

In order to assess the time of seroconversion, we used 151 samples from 30 COVID-19 inpatients and monitored the detection kinetics of anti-S1, anti-S2, anti-RBD and anti-N antibodies with in-house ELISAs. We also monitored the presence of neutralizing antibodies in these samples as well as 25 asymptomatic carrier samples using retroviral particles pseudotyped with the spike of the SARS-CoV-2.

Results

We observed that specific antibodies were detectable in all inpatients two weeks post-symptom onset. The detection of the SARS-CoV-2 Nucleocapsid and RBD was more sensitive than the detection of the S1 or S2 subunits. Neutralizing antibodies reached a plateau two weeks post-symptom onset and then declined in the majority of inpatients. Furthermore, neutralizing antibodies were undetectable in 56% of asymptomatic carriers.

Conclusions

Our results raise questions concerning the role played by neutralizing antibodies in COVID-19 cure and protection against secondary infection. They also suggest that induction of neutralizing antibodies is not the only strategy to adopt for the development of a vaccine. Finally, they imply that anti-SARS-CoV-2 neutralizing antibodies should be titrated to optimize convalescent plasma therapy.

Highlights

Specific antibodies are detectable in 100% COVID-19 inpatients two weeks post-symptom onset.

The detection of the SARS-CoV-2 Nucleocapsid and Receptor Binding Domain is more sensitive than the detection of the S1 or S2 subunits.

Neutralizing antibodies reach a plateau two weeks post-symptom onset and then decline in the majority of inpatients.

Neutralizing antibodies are undetectable in the majority of asymptomatic carriers.
Unequal impact of structural health determinants and comorbidity on COVID-19 severity and lethality in older Mexican adults: Looking beyond chronological aging
Authors: Bello-Chavolla Omar Yaxmehen , González-Díaz Armando , Antonio-Villa Neftali E. , Fermín-Martínez Carlos A. , Márquez-Salinas Alejandro , Vargas-Vázquez Arsenio , Bahena-López Jessica Paola , García-Peña Carmen , Aguilar-Salinas Carlos A. , Gutiérrez-Robledo Luis Miguel
Published: May 2020

BACKGROUND: COVID-19 has had a disproportionate impact on older adults. The population of Mexico is younger, yet the impact of COVID-19 on older adults is comparable to countries with older population structures. Here, we aim to identify health and structural determinants that increase susceptibility to COVID-19 in older Mexican adults beyond chronological aging.
METHODS: We analyzed confirmed COVID-19 cases in older adults using data from the General Directorate of Epidemiology of Mexican Ministry of Health. We modeled risk factors for increased COVID-19 severity and mortality, using mixed models to incorporate multilevel data concerning healthcare access and marginalization. We also evaluated structural factors and comorbidity profiles compared to chronological age for improving COVID-19 mortality risk prediction.
RESULTS: We analyzed 7,029 confirmed SARS-CoV-2 cases in adults aged ≥60 years. Male sex, smoking, diabetes, and obesity were associated with pneumonia, hospitalization and ICU admission in older adults, CKD and COPD were associated with hospitalization. High social lag indexes and access to private care were predictors of COVID-19 severity and mortality. Age was not a predictor of COVID-19 severity in individuals without comorbidities and structural factors and comorbidities were better predictors of COVID-19 lethality and severity compared to chronological age. COVID-19 baseline lethality hazards were heterogeneously distributed across Mexican municipalities, particularly when comparing urban and rural areas.
CONCLUSIONS: Structural factors and comorbidity explain excess risk for COVID-19 severity and mortality over chronological age in older Mexican adults. Clinical decision-making related to COVID-19 should focus away from chronological aging onto more a comprehensive geriatric care approach.
Establishing health-based Biological Exposure Limits for pesticides: a proof of principle study using Mancozeb
Authors: Mandić-Rajčević Stefan , Rubino Federico Maria , Colosio Claudio
Published: May 2020

Pesticides represent an economical, labor-saving, and efficient tool for pest management, but their intrinsic toxic properties may endanger workers and the general population. Risk assessment is necessary, and biological monitoring represents a potentially valuable tool. Several international agencies propose biological exposure indices (BEI), especially for substances which are commonly absorbed through the skin. Biological monitoring for pesticide exposure and risk assessment seems a natural choice, but biological exposure limits (BEL) for pesticides are lacking.
This study aims at establishing equivalent biological exposure limits (EBEL) for pesticides using real-life field data and the Acceptable Operator Exposure Level (AOEL) of mancozeb as the reference.
This study included a group of 16 vineyard pesticide applicators from Northern Italy, a subgroup of a more extensive study of 28 applicators. Their exposure was estimated using "patch" and "hand-wash" methodologies, together with biological monitoring of free ethylene-bis-thiourea (ETU) excretion in 24-hour pre- and post-exposure urine samples. Modeling was done using univariate linear regression with ETU excretion as the dependent variable and the estimated absorbed dose as the independent variable.
The median skin deposition of mancozeb in our study population was 125 μg, leading to a median absorbed dose of 0.9 μg/kg. The median post-exposure ETU excretion was 3.7 μg. The modeled EBEL for mancozeb was 148 μg of free ETU or 697 μg of total ETU, accounting for around 75% of the maximum theoretical excretion based on a mass balance model. Although preliminary and based on a small population of low-exposed workers, our results demonstrate a procedure to develop strongly needed biological exposure limits for pesticides.
Repeatability of a Dual-Scheimpflug Placido Disc Corneal Tomographer/Topographer in Eyes with Keratoconus
Authors: Poulsen Anne , Jang Diane , Khan Mahmood , Al-Mohtaseb Zaina Nabil , Chen Michael , Zhan Xiang , Banerjee Kalins , Scott Ingrid U , Pantanelli Seth M
Published: May 2020

Purpose

To investigate the repeatability of a combined Dual-Scheimpflug placido disc corneal topographer (Zeimer Galilei G4) with respect to keratometric indices used to monitor progression of keratoconus (KCN).

Methods

Patients with KCN were prospectively enrolled. For each eye lacking history of corneal surgery, 5 measurements were taken in succession. Eyes in which 3 or more measurements could be obtained (defined by the device’s 4 image quality metrics) were included in the analysis. The repeatability limits (RL) and interclass correlation coefficients (ICC) were calculated for various parameters.

Results

32 eyes from 25 patients met all image quality metrics, and 54 eyes from 38 patients met at least 3/4 criteria (all except the placido image quality metric). RLs for key parameters when 4/4 or ≥3/4 image quality metrics were met included: 0.37 and 0.77 diopters (D) for steep simulated keratometry, 0.79 and 1.65 D for maximum keratometry, 13.80 and 13.88 degrees for astigmatism axis, 0.64 and 0.56 μm for vertical coma magnitude, and 3.76 and 3.84 μm for thinnest pachymetry, respectively. The ICCs for all parameters were excellent [above 0.87 except for spherical aberration (0.77)].

Conclusions

The dual-Scheimpflug placido disc corneal topographer is highly repeatable in quantifying parameters used in monitoring KCN. Excellent placido images are difficult to capture in eyes with KCN, but when available, increase the reliability of the measurements. The RLs may be especially helpful in detecting progression in mild KCN when interventions such as corneal cross-linking or intrastromal corneal ring segments are most beneficial.
A citizen science initiative for open data and visualization of COVID-19 outbreak in Kerala, India
Authors: Ulahannan Jijo Pulickiyil , Narayanan Nikhil , Thalhath Nishad , Prabhakaran Prem , Chaliyeduth Sreekanth , Suresh Sooraj P , Mohammed Musfir , Rajeevan E , Joseph Sindhu , Balakrishnan Akhil , Uthaman Jeevan , Karingamadathil Manoj , Thomas Sunil Thonikkuzhiyil , Sureshkumar Unnikrishnan , Balan Shabeesh , Vellichirammal Neetha Nanoth
Published: May 2020

Objective

India reported its first COVID-19 case in the state of Kerala and an outbreak initiated subsequently. The Department of Health Services, Government of Kerala, initially released daily updates through daily textual bulletins for public awareness to control the spread of the disease. However, this unstructured data limits upstream applications, such as visualization, and analysis, thus demanding refinement to generate open and reusable datasets.

Materials and Methods

Through a citizen science initiative, we leveraged publicly available and crowd-verified data on COVID-19 outbreak in Kerala from the government bulletins and media outlets to generate reusable datasets. This was further visualized as a dashboard through a frontend web application and a JSON repository, which serves as an API for the frontend.

Results

From the sourced data, we provided real-time analysis, and daily updates of COVID-19 cases in Kerala, through a user-friendly bilingual dashboard (https://covid19kerala.info/) for non-specialists. To ensure longevity and reusability, the dataset was deposited in an open-access public repository for future analysis. Finally, we provide outbreak trends and demographic characteristics of the individuals affected with COVID-19 in Kerala during the first 138 days of the outbreak.

Discussion

We anticipate that our dataset can form the basis for future studies, supplemented with clinical and epidemiological data from the individuals affected with COVID-19 in Kerala.

Conclusion

We reported a citizen science initiative on the COVID-19 outbreak in Kerala to collect and deposit data in a structured format, which was utilized for visualizing the outbreak trend and describing demographic characteristics of affected individuals.
Treatment Response to Hydroxychloroquine, Lopinavir–Ritonavir, and Antibiotics for Moderate COVID-19: A First Report on the Pharmacological Outcomes from South Korea
Authors: Kim Min Seo , Jang Soon-Woo , Park Yu-Kyung , Kim Bong-Ok , Hwang Tae-Ho , Kang Seok Ho , Kim Won Jun , Kyu Park Sung , Park Hea-Woon , Yang Wonjong , Jang Joonyoung , An Min Ho
Published: May 2020

The authors have withdrawn this manuscript because of the controversy about hydroxychloroquine and potential changes in results after peer-review, the authors intend to share their results in formal publication. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Excess Out-Of-Hospital Mortality and Declining Oxygen Saturation: The Sentinel Role of EMS Data in the COVID-19 Crisis in Tijuana, Mexico
Authors: Friedman Joseph , Calderon-Villarreal Alheli , Bojorquez Ietza , Vera Hernandez Carlos , Schriger David , Tovar Hirashima Eva
Published: May 2020

Objective:
Emergency medical services (EMS) may serve as a key source of real-time data about the evolving health of COVID-19 affected populations, especially in low-and-middle-income countries (LMICs) with less rapid and reliable vital statistic registration systems. Although official COVID-19 statistics in Mexico report almost exclusively in-hospital mortality events, excess out-of-hospital mortality has been identified in other settings, including one EMS study in Italy that showed a 58% increase. EMS and hospital reports from several countries have suggested that silent hypoxemia--low oxygen saturation (SpO2) in the absence of dyspnea--is associated with COVID-19 outbreaks. It is unclear, however, how these phenomena can be generalized to LMICs. We assess how EMS data can be used in a sentinel capacity in Tijuana, a city on the Mexico-United States border with earlier exposure to COVID-19 than many LMIC settings.

Methods:
We calculated numbers of weekly out-of-hospital deaths and respiratory cases seen by EMS in Tijuana, and estimate the difference between peak-epidemic rates (during April 14th-May 11th) and forecasted 2014-2019 trends. Results were compared with official COVID-19 statistics, stratified by neighborhood socioeconomic status (SES), and examined for changing demographic or clinical features, including mean (SpO2).
Results: An estimated 194.7 (95%CI: 135.5-253.9) excess out-of-hospital deaths events occurred, representing an increase of 145% (70%-338%) compared to forecasted trends. During the same window, only 8 COVID-19-positive, out-of-hospital deaths were reported in official statistics. This corresponded with a rise in respiratory cases of 274% (119%-1142%), and a drop in mean SpO2 to 77.7%, from 90.2% at baseline. The highest out-of-hospital death rates were observed in low-SES areas, although respiratory cases were more concentrated in high-SES areas.

Conclusions:
EMS systems may play an important sentinel role in monitoring excess out-of-hospital mortality and other trends during the COVID-19 crisis in LMICs. Using EMS data, we observed increases in out-of-hospital deaths in Tijuana that were nearly threefold greater magnitude than increases reported using EMS data in Italy. Increased testing in out-of-hospital settings may be required to determine if excess mortality is being driven by COVID-19 infection, health system saturation, or patient avoidance of healthcare. We also found evidence of worsening rates of hypoxemia among respiratory patients seen by EMS, suggesting a rise in silent hypoxemia, which should be met with increased detection and clinical management efforts. Finally, we observed that social disparities in out-of-hospital death that warrant monitoring and amelioration.
Analytical performance of lateral flow immunoassay for SARS-CoV-2 exposure screening on venous and capillary blood samples
Authors: Black Margaret A. , Shen Guomiao , Feng Xiaojun , Garcia Beltran Wilfredo F. , Feng Yang , Vasudevaraja Varshini , Allison Douglas , Lin Lawrence H. , Gindin Tatyana , Astudillo Michael , Yang Diane , Murali Mandakolathur , Iafrate A. John , Jour George , Cotzia Paolo , Snuderl Matija
Published: May 2020

Objectives

Numerous serologic immunoassays have been launched to detect antibodies to SARS-CoV-2, including rapid tests. Here, we validate use of a lateral flow immunoassay (LFI) intended for rapid screening and qualitative detection of anti-SARS-CoV-2 IgM and IgG in serum, plasma, and whole blood, and compare results with ELISA. We also seek to establish the value of LFI testing on blood obtained from a capillary blood sample.

Methods

Samples collected by venous blood draw and capillary finger stick were obtained from patients with SARS-CoV-2 detected by RT-qPCR and control patients negative for SARS-CoV-2. Samples were tested with the 2019-nCoV IgG/IgM Detection Kit (Colloidal Gold) lateral flow immunoassay, and antibody calls were compared with results obtained by ELISA.

Results

The Biolidics LFI kit shows clinical sensitivity of 92% at 7 days after PCR diagnosis of SARS-CoV-2 on venous blood. Test specificity was 92% for IgM and 100% for IgG. There was no significant difference in detecting IgM and IgG with Biolidics LFI and ELISA at D0 and D7 (p=1.00), except for detection of IgM at D7 (p=0.04). Finger stick whole blood of SARS-CoV-2 patients showed 93% sensitivity for antibody detection.

Conclusions

Clinical performance of Biolidics 2019-nCoV IgG/IgM Detection Kit (Colloidal Gold) is comparable to ELISA and showed consistent results across different sample types. Furthermore, we show that capillary blood obtained by finger stick shows similar sensitivity for detecting anti-SARS-CoV-2 IgM and IgG antibodies as venous blood samples. This provides an opportunity for decentralized rapid testing in the community and may allow point-of-care and longitudinal self-testing for the presence of anti-SARS-CoV-2 antibodies.
Transmission of aerosols through pristine and reprocessed N95 respirators
Authors: Chen Paul Z. , Ngan Aldrich , Manson Niclas , Maynes Jason T. , Borschel Gregory H. , Rotstein Ori D. , Gu Frank X.
Published: May 2020

During the Covid-19 pandemic, pristine and reprocessed N95 respirators are crucial equipment towards limiting nosocomial infections. The NIOSH test certifying the N95 rating, however, poorly simulates aerosols in healthcare settings, limiting our understanding of the exposure risk for healthcare workers wearing these masks, especially reprocessed ones. We used experimental conditions that simulated the sizes, densities and airflow properties of infectious aerosols in healthcare settings. We analyzed the penetration and leakage of aerosols through pristine and reprocessed N95 respirators. Seven reprocessing methods were investigated. Our findings suggest that pristine and properly reprocessed N95 respirators effectively limit exposure to infectious aerosols, but that care must be taken to avoid the elucidated degradation mechanisms and limit noncompliant wear.