bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-circulation of two viral populations under vaccination
Authors: Acuña-Zegarra Manuel A. , Núñez-López Mayra , Comas-García Andreu , Santana-Cibrian Mario , Velasco-Hernández Jorge X.
Published: January 2021

The interaction and possibly interference between viruses infecting a host population is addressed in this work. We model two viral diseases with a similar transmission mechanism and for which a vaccine exists. The vaccine is characterized by its coverage, induced temporary immunity, and efficacy. The population dynamics of both diseases consider infected individuals of each illness and hosts susceptible to one but recovered from the other. We do not incorporate co-infection. Two main transmission factors affecting the effective contact rates are postulated: i) the virus with a higher reproduction number can superinfect the one with a lower reproduction number, and ii) there exists some induced (indirect) protection induced by vaccination against the weaker virus that reduces the probability of infection by the stronger virus. Our results indicate that coexistence of the viruses is possible in the long term, even considering the absence of superinfection. Influenza and SARS-CoV-2 are employed to exemplify this last point, observing that the time-dependent effective contact rate may induce either alternating outbreaks of each disease or synchronous outbreaks. Finally, for a particular parameter range, a backward bifurcation has been observed for dynamics without vaccination.
Laboratory Biomarkers of COVID-19 Disease Severity and Outcome: Findings from a Developing Country
Authors: Leulseged Tigist W. , Hassen Ishmael S. , Ayele Birhanu T. , Tsegay Yakob G. , Abebe Daniel S. , Edo Mesay G. , Maru Endalkachew H. , Zewde Wuletaw C. , Naylor Lydia K. , Semane Dejene F. , Deresse Menayit T. , Tezera Bereket B.
Published: January 2021

Aim

To identify laboratory biomarkers that predict disease severity and outcome among COVID-19 patients admitted to the Millennium COVID-19 Care Center in Ethiopia.

Methods

A retrospective cohort study was conducted among 429 RT-PCR confirmed COVID- 19 patients who were on follow up from July to October 2020 and with complete clinical and laboratory data. Data was described using frequency tables. Robust Poisson regression model was used to identify predictors of COVID-19 disease severity where adjusted relative risk (RR), P-value and 95% CI for RR were used to test significance and interpretation of results. Binary Logistic regression model was used to assess the presence of statistically significant association between the explanatory variables and COVID-19 disease outcome where adjusted odds ratio, P- value and 95% CI for adjusted odds ratio were used for testing significance and interpretation of results

Results

Among the 429 patients studied, 182 (42.4%) had Severe disease at admission and the rest 247 (57.6%) had Non-severe disease (15.6% mild and 42.0% moderate). Regarding disease outcome, 45 (10.5%) died and 384 (89.5%) were discharged alive. Age group (ARR= 1.779, 95% CI= 1.405- 2.252, p-value < 0.0001), Neutrophil to Lymphocyte ratio (NLR) (ARR= 4.769, 95% CI= 2.419 - 9.402 p-value <0.0001), Serum glutamic oxaloacetic transaminase (SGOT) (ARR= 1.358, 95% CI= 1.109- 1.662 p-value=0.003), Sodium (ARR= 1.321, 95% CI= 1.091- 1.600 p-value=0.004) and Potassium (ARR= 1.269, 95% CI= 1.059-1.521 p-value=0.010) were found to be significant predictors of COVID-19 disease severity.

The following factors were significantly associated with COVID-19 disease outcome; age group (AOR= 2.767, 95% CI= 1.099 - 6.067, p-value=0.031), white blood cell count (AOR= 4.253, 95% CI= 1.918 - 9.429, p-value=0.0001) and sodium level (AOR= 3.435, 95% CI= 1.439, 8.198, p-value=0.005).

Conclusions

The laboratory markers of NLR of above three, raised SGOT and deranged sodium and potassium levels (both hypo- and hyper-states) were found to be significant predictors of developing severe COVID-19 disease. In addition, deranged values of white blood cell count and sodium levels were significantly associated with worse outcome of the disease. Therefore, assessing and monitoring these laboratory markers at the earliest stage of the disease could have a considerable impact in halting disease progression and death.
Insights into the molecular mechanism of anticancer drug ruxolitinib repurposable in COVID-19 therapy
Authors: Mandal Manisha , Mandal Shyamapada
Published: January 2021

Due to non-availability of specific therapeutics against COVID-19, repurposing of approved drugs is a reasonable option. Cytokines imbalance in COVID-19 resembles cancer; exploration of anti-inflammatory agents, might reduce COVID-19 mortality. The current study investigates the effect of ruxolitinib treatment in SARS-CoV-2 infected alveolar cells compared to the uninfected one from the GSE5147507 dataset. The protein-protein interaction network, biological process and functional enrichment of differentially expressed genes were studied using STRING App of the Cytoscape software and R programming tools. The present study indicated that ruxolitinib treatment elicited similar response equivalent to that of SARS-CoV-2 uninfected situation by inducing defense response in host against virus infection by RLR and NOD like receptor pathways. Further, the effect of ruxolitinib in SARS-CoV-2 infection was mainly caused by significant suppression of IFIH1, IRF7 and MX1 genes as well as inhibition of DDX58/IFIH1-mediated induction of interferon-I and -II signalling.
An Intrinsic and Extrinsic Evaluation of Learned COVID-19 Concepts using Open-Source Word Embedding Sources
Authors: Parikh Soham , Davoudi Anahita , Yu Shun , Giraldo Carolina , Schriver Emily , Mowery Danielle L.
Published: January 2021

Introduction

Scientists are developing new computational methods and prediction models to better clinically understand COVID-19 prevalence, treatment efficacy, and patient outcomes. These efforts could be improved by leveraging documented, COVID-19-related symptoms, findings, and disorders from clinical text sources in the electronic health record. Word embeddings can identify terms related to these clinical concepts from both the biomedical and non-biomedical domains and are being shared with the open-source community at large. However, it’s unclear how useful openly-available word embeddings are for developing lexicons for COVID-19-related concepts.

Objective

Given an initial lexicon of COVID-19-related terms, characterize the returned terms by similarity across various, open-source word embeddings and determine common semantic and syntactic patterns between the COVID-19 queried terms and returned terms specific to word embedding source.

Materials and Methods

We compared 7 openly-available word embedding sources. Using a series of COVID-19-related terms for associated symptoms, findings, and disorders, we conducted an inter-annotator agreement study to determine how accurately the most semantically similar returned terms could be classified according to semantic types by three annotators. We conducted a qualitative study of COVID-19 queried terms and their returned terms to identify useful patterns for constructing lexicons. We demonstrated the utility of applying such terms to discharge summaries by reporting the proportion of patients identified by concept for pneumonia, acute respiratory distress syndrome, and COVID-19 cohorts.

Results

We observed high, pairwise inter-annotator agreement (Cohen’s Kappa) for symptoms (0.86 to 0.99), findings (0.93 to 0.99), and disorders (0.93 to 0.99). Word embedding sources generated based on characters tend to return more lexical variants and synonyms; in contrast, embeddings based on tokens more often return a variety of semantic types. Word embedding sources queried using an adjective phrase compared to a single term (e.g., dry cough vs. cough; muscle pain vs. pain) are more likely to return qualifiers of the same semantic type (e.g., “dry” returns consistency qualifiers like “wet”, “runny”). Terms for fever, cough, shortness of breath, and hypoxia retrieved a higher proportion of patients than other clinical features. Terms for dry cough returned a higher proportion of COVID-19 patients than pneumonia and ARDS populations.

Discussion

Word embeddings are a valuable technology for learning terms, including synonyms. When leveraging openly-available word embedding sources, choices made for the construction of the word embeddings can significantly influence the phrases returned.
Argon Laser Photocoagulation for Treatment of Presumed Trematode-induced Granulomatous Anterior Uveitis in Children
Authors: Alsmman AlahmadyHamad , Abdalla Abdelsalam , Ezzeldawla Mohamed , Elmatin Shaimaa Abd , Abozaid Mortada Ahmed
Published: January 2021

Background/Aims

To assess the safety and efficacy of argon laser photocoagulation as a new modality for the treatment of presumed trematode-induced granulomatous anterior uveitis (PTGAU) in children.

Methods

Forty-eight eyes of 48 children with PTGAU with pearl-like nodule(s) in the anterior chamber were included in this prospective non- randomised controlled clinical trial. Patients were divided into two groups: group A (23 eyes) was treated with one session of argon laser applied to the anterior chamber nodules, and group B (25 eyes) received medical treatment in the form of topical steroid and cycloplegic eye drops with trans-septal triamcinolone injection.All cases were followed up for 3 monthswith measurement of VA, assessment of anterior chamber reaction, and size of the pearl-like nodules.

Results

In group A, 22 eyes (95.65%) showed regression of the pearl- like nodules with resolution of the anterior chamber reaction (flare and cells) and improvement in visual acuity from 0.52±0.12 to 0.06 ± 0.08logMAR (p value <0.001). Such improvement was maintained within the 3-month follow-up period. In group B, 23 eyes (92%) showed initial regression of the granulomas,whichwas maintained in only 14 eyes (56%),with 9 eyes experiencing recurrence after 3 months of follow-up.

Conclusion

Argon laser photocoagulation is a safe and effective novel treatment for PTGAU with pearl-like nodules in the anterior chamber in children. Larger studies with longer follow-up periods are needed to confirm these results.

PRECIS

Argon laser photocoagulation is a novel non-invasive line of treatment that can be added to the armamentarium for presumed trematode-induced granulomatous anterior uveitis in children.
Cardiometabolic risks of SARS-CoV-2 hospitalization using Mendelian Randomization
Authors: Lorincz-Comi Noah , Zhu Xiaofeng
Published: January 2021

Intro

Many cardiometabolic conditions have demonstrated associative evidence with COVID-19 hospitalization risk. However, the observational designs of the studies in which these associations are observed preclude causal inferences of hospitalization risk. Mendelian Randomization (MR) is an alternative risk estimation method more robust to these limitations that allows for causal inferences.

Methods & materials

We applied four MR methods (MRMix, IMRP, IVW, MREgger) to publicly available GWAS summary statistics from European (COVID-19 GWAS n=2,956) and multi-ethnic populations (COVID-19 GWAS n=10,808) to better understand extant causal associations between Type II Diabetes (GWAS n=659,316), BMI (n=681,275), diastolic and systolic blood pressure, and pulse pressure (n=757,601 for each) and COVID-19 hospitalization risk across populations.

Results

Although no significant causal effect evidence was observed, our data suggested a trend of increasing hospitalization risk for Type II diabetes (IMRP OR, 95% CI: 1.67, 0.96-2.92) and pulse pressure (OR, 95% CI: 1.27, 0.97-1.66) in the multi-ethnic sample.

Conclusions

Type II diabetes and Pulse pressure demonstrates a potential causal association with COVID-19 hospitalization risk, the proper treatment of which may work to reduce the risk of a severe COVID-19 illness requiring hospitalization. However, GWAS of COVID-19 with large sample size is warranted to confirm the causality.
Estimation of Daily Reproduction rates in COVID-19 Outbreak
Authors: Demongeot Jacques , Oshinubi Kayode , Seligmann Hervé , Thuderoz Florence
Published: January 2021

(1) Background

The estimation of daily reproduction rates throughout the infectivity period is rarely considered and only their sumRois calculated to quantify the level of virulence of an infectious agent;

(2) Methods

We give the equation of the discrete dynamics of epidemic growth and we obtain an estimation of the daily reproduction rates, by using a technique of deconvolution of the series of observed new cases of Covid-19;

(3) Results

We give both simulation results as well as estimations for several countries for the Covid-19 outbreak;

(4) Conclusions

We discuss the role of the noise on the precision of the estimation and we open on perspectives of forecasting methods to predict the distribution of daily reproduction rates along the infectivity period.
Primary care during the COVID-19 pandemic – observations and challenges identified through a survey and interviews with community paediatricians: the calm before the storm
Authors: Vasconcelos Malte Kohns , Weil Katharina , Vesterling-Hörner Daniela , Klemm Mehrsad , Scheich Tarik el , Renk Hanna , Remke Katharina , Bosse Hans Martin
Published: January 2021

Background

Globally, the COVID-19 pandemic has a major impact on healthcare provision. The effects in primary care are understudied.

Aim

To document changes in consultation numbers and patient management during the COVID-19 pandemic, and to identify challenges for patient care.

Methods

Survey of 44 paediatric primary care practices on consultation numbers and patient management changes (response rate 50%), and semi-structured interviews to identify challenges for patient care.

Results

Numbers of consultations for scheduled developmental examinations remained unchanged compared to the previous year while emergency visits were strongly reduced (mean 87.3 less/week in March–May 2020 compared to 2019, median reduction 55.0%). Children dependent on developmental therapy and with chronic health conditions were identified as patient groups receiving deteriorated care. High patient numbers, including of mildly symptomatic children presenting for health certificates, in combination with increased organisational demands and expected staff outages are priority concerns for the winter.

Conclusion

Primary care paediatricians offered stable service through the early pandemic but expect strained resources for the upcoming winter. Unambiguous guidance on which children should present to primary care and who should be tested would help to allocate resources appropriately, and this guidance needs to consider age group specific issues including high prevalence of respiratory symptoms, dependency on carers and high contact rates.
Is sickle cell disease a risk factor for severe COVID-19 : a multicenter national retrospective cohort
Authors: Abdulrahman Abdulkarim , Wael Mohammed , AlAmmadi Fajer , AlMosawi Zahra , Alsherooqi Reem , AlSayed Manal , Kumar Nitya , AlQahtani Manaf
Published: January 2021

Introduction

Coronavirus disease (COVID-19) caused by the novel coronavirus SARS-CoV-2 is an infectious disease which has evolved into a worldwide pandemic. Growing evidence suggests that individuals with pre-existing comorbidities are at higher risk of a more serious COVID-19 illness. Sickle cell disease (SCD) is an inherited hemoglobinopathy which increases the susceptibility to infections and as a consequent has higher risks of morbidity and mortality.

The impact of COVID-19 on SCD patients could lead to further increase in disease severity and mortality. Studies that examine the effect of SCD on COVID-19 outcomes are lacking. This study aims to determine whether SCD is a risk factor for severe COVID-19 infection in regards to the requirement of non-invasive ventilation/high flow nasal cannula (NIV/HFNC), mechanical intubation (MV) or death.

Methods

Retrospective cohort study which included COVID-19 patients admitted to four Ministry of Health COVID-19 treatment facilities in Bahrain during the period of 24, February 2020, to 31, July 2020. All SCD patients with COVID-19 were included and compared to randomly selected non-SCD patients with COVID-19. Data for the selected patients were collected from the medical records. Multivariate logistic regression models were used to control for confounders and estimate the effect of SCD on the outcomes.

Results

A total of 1,792 patients with COVID-19 were included; 38 of whom were diagnosed with SCD as well. In the SCD group, one (2.6%) patient required NIV/HFNC, one (2.6%) required MV and one (2.6%) death occurred. In comparison, 56 (3.2%) of the non-SCD patients required NIV/HFNC, 47 (2.7%) required MV and death occurred in 58 (3.3%) patients. Upon adjusting for confounders, SCD had an odds ratio of 1.847 (95% CI: 0.39 – 8.83; p=0.442).

Conclusion

Our results indicate that SCD is not a risk factor for worse disease outcomes in COVID-19 patients.
Evaluation of three rapid lateral flow antigen detection tests for the diagnosis of SARS-CoV-2 infection
Authors: Jääskeläinen AE , Ahava MJ , Jokela P , Szirovicza L , Pohjala S , Vapalahti O , Lappalainen M , Hepojoki J , Kurkela S
Published: January 2021

Introduction

The COVID-19 pandemic has led to high demand of diagnostic tools. Rapid antigen detection tests have been developed and many have received regulatory acceptance such as CE IVD or FDA markings. Their performance needs to be carefully assessed.

Materials and Methods

158 positive and 40 negative retrospective samples collected in saline and analyzed by a laboratory-developed RT-PCR test were used to evaluate Sofia (Quidel), Standard Q (SD Biosensor), and Panbio™ (Abbott) rapid antigen detection tests (RADTs). A subset of the specimens was subjected to virus culture.

Results

The specificity of all RADTs was 100% and the sensitivity and percent agreement was 80% and 85% for Sofia, 81% and 85% for Standard Q, and 83% and 86% for Panbio™, respectively. All three RADTs evaluated in this study reached a more than 90% sensitivity for samples with a high viral load as estimated from the low Ct values in the reference RT-PCR. Virus culture was successful in 80% of specimens with a Ct value <25.

Conclusions

As expected, the RADTs were less sensitive than RT-PCR. However, they benefit from the speed and ease of testing, and lower price as compared to RT-PCR. Repeated testing in appropriate settings may improve the overall performance.
WITHDRAWN:Staphylococcus aureus-serineprotease-like protein B (SplB) activates PAR2 and induces endothelial barrier dysfunction
Authors: Chandrabalan Arundhasa , Thibeault Pierre E , Smiljanov Bojan , Mittmann Laura A , Deinhardt-Emmer Stefanie , Nordengrün Maria , Iqbal Jawad , Mrochen Daniel M , Chamling Bishwas , Rauch Bernhard H , Reichel Christoph A , Ramachandran Rithwik , Bröker Barbara M , Darisipudi Murty N
Published: January 2021

Withdrawal Statement

The authors have withdrawn their manuscript owing to the following reason: Unfortunately, the preparation of the recombinant serine protease-like protein B (SplB) used in this study was found to contain impurities, so that the effects presented cannot be unambiguously attributed to the protease SplB. We therefore retract the manuscript from bioRxiv. We apologize for any inconvenience this may have caused. Therefore, the authors do not wish this work to be cited as reference for the project. We want to clarify that the issue was identified in the preparation of the SplB protein and does not reflect on the contributions of individual authors. If you have any questions, please contact the corresponding author.
Tele-Rehabilitation for People with Visual Disabilities During COVID-19 Pandemic: Lesson Learned
Authors: Senjam Suraj Singh , Manna Souvik , Vashist Praveen , Gupta Vivek
Published: January 2021

Background

The COVID-19 outbreak poses a global crisis in health care delivery system, including habilitation and rehabilitation services. In the present study, we shared our experiences on telerehabilitation services established primarily for students with visual disabilities (SwVD) amidst COVID-19 pandemic and its outputs.

Methods

Following the lockdown declared on March 23, 2020, the rehabilitative team of a tertiary eye center in north India received information that many VCS were stranded in schools for the blind in Delhi, and feeling with anxiety and panic in absence of teachers. Shortly, the room for vision rehabilitation clinic was set-up for tele-facilities. The intended services was explained while disseminating the mobile numbers. A semi-structured questionnaire consisting of closed and open-ended was developed to record COVID-19 knowledge and concerns. Inductive content analysis was used to report the qualitative information.

Results

As of June 30, 2020, a total of 492 clients contacted the team, with maximum from Delhi (41.5%), and predominantly males (78.8%). Around 80.3% of callers were VCS with age range of 11 to 30 years. The two most frequently encountered health needs were itching in eyes (36.1%) and headache (29%). Television news was the most used medium among callers to get COVID-19 information. Cough is a less frequently known mode of transmission (28%), similarly handwashing as a less known for prevention (17.2%). Eight concerns were recorded based on qualitative data analysis.

Conclusion

Tele-rehabilitation provides valuable insights and has the potential to address various concerns, uncertainty, anxiety, and fear among SVD during the pandemic.
Time- and cell-dependent atypia and cell death are caused by progressive deficiency in DNA replication
Authors: Lin Alex Y. , Thomas Georgia K. , Ang Khai Chung , van Rossum Damian B. , Canfield Victor A. , Cheng Keith C.
Published: January 2021

Pleiotropy caused by single-gene mutations is common and poorly understood. A zebrafish null mutant of DNA polymerase α subunit B,huli hutu(hht), evolves a complex pleiotropy associated with DNA damage and S phase arrest across multiple organ systems over 5-7 days, including nuclear atypia, a common cellular feature in human cancers and pre-cancers, in gastrointestinal organs, and nuclear fragmentation in the eye and brain. The pleiotropic pattern ofhhtphenotypes is explained by progressive loss of wild-type maternalpola2function in homozygous mutant embryos whosepola2mRNA becomes undetectable by 24 hours post-fertilization (hpf). Inhibition of DNA synthesis by aphidicolin or hydroxyurea in wild-type embryos from 24 hpf phenocopied the pleiotropic pattern ofhht. These results are consistent with a model in which time-sensitive, reduced capacity for DNA synthesis results in cell death in fast-replicating cells, and nuclear atypia in tissues with fewer and larger cells.
On the lag between deaths and infections in the first phase of the Covid-19 pandemic
Authors: Chruściel Piotr T. , Szybka Sebastian J.
Published: January 2021

One of the key issues in fighting the current pandemic, or the ones to come, is to obtain objective quantitative indicators of the effectiveness of the measures taken to contain the epidemic. The aim of this work is to point out that the lag between the daily number of infections and casualties provides one such indicator. For this we determined the lag during the first phase of the Covid-19 pandemic for a series of countries using the data available at the server of the John Hopkins University using three different methods. Somewhat surprisingly, we find a lag varying substantially between countries, taking negative values (thus the maximum daily number of casulties preceding the maximum daily namber of new infections) in countries where no steps to contain the epidemic have been taken at the outset, with an average lag of 7 ± 0.3 days. Our results can be useful to health authorities in a search for the best strategy to fight the epidemic.

Key Messages

The lags between the maximum daily infections and casualties during the first phase of the Covid-19 pandemic differ widely between countries.

These lags are clear for some countries, but impossible to determine confidently for most.

In some countries the day at which the maximal number of daily deaths is attained precedes the day of the maximal number of casualties, indicating a failure to protect the most vulnerable part of the population.

The lags can serve as an objective quantitative measure of the effectiveness of the measures taken to contain the epidemic.
“The drug development pipeline for glioblastoma - a cross sectional assessment of the FDA Orphan Drug Product designation database”
Authors: Johann Pascal , Lenz Dominic , Ries Markus
Published: January 2021

Background

Glioblastoma multiforme (GBM) is the most common malignant brain tumor among adult patients and represents an almost universally fatal disease. Novel therapies for GBM are being developed under the orphan drug legislation and the knowledge on the molecular makeup of this disease has been increasing rapidly. However, the clinical outcomes in GBM patients with currently available therapies are still dismal. An insight into the current drug development pipeline for GBM is therefore of particular interest.

Objectives

To provide a quantitative clinical-regulatory insight into the status of FDA orphan drug designations for compounds intended to treat GBM.

Methods

Quantitative cross-sectional analysis of the U.S. Food and Drug Administration Orphan Drug Product database between 1983 and 2020. STROBE criteria were respected.

Results

Four orphan drugs out of 161 (2,4%) orphan drug designations were approved for the treatment for GBM by the FDA between 1983 and 2020. Fourteen orphan drug designations were subsequently withdrawn for unknown reasons. The number of orphan drug designations per year shows a growing trend. In the last decade, the therapeutic mechanism of action of designated compounds intended to treat glioblastoma shifted from cytotoxic drugs (median year of designation 2008) to immunotherapeutic approaches and small molecules (median year of designation 2014 and 2015 respectively) suggesting an increased focus on precision in the therapeutic mechanism of action for compounds the development pipeline.

Conclusion

Despite the fact that current pharmacological treatment options in GBM are sparse, the drug development pipeline is steadily growing. In particular, the surge of designated immunotherapies detected in the last years raises the hope that elaborate combination possibilities between classical therapeutic backbones (radiotherapy) and novel, currently experimental therapeutics may help to provide better therapies for this deadly disease in the future.

Article summary

Strengths and limitations

This study provides a quantitative overview on the drug development pipeline for pediatric and adult oncology in general and specifically for the indication glioblastoma

Analyzing the therapeutic mechanisms of designated compounds in glioblastoma reveals an increased focus on personalized and targeted therapies

The precise reasons for failure of approved drugs and for withdrawal of approved drugs in glioblastoms are unknown

For the analysis, only the databases “FDALabel” (https://nctr-crs.fda.gov/fdalabel/ui/search) and the FDA Orphan drug product designation database (https://www.accessdata.fda.gov/scripts/opdlisting/oopd/) were considered
Mining underutilized whole-genome sequencing projects to improve 16S rRNA databases
Authors: Nolan Ben , Abram Florence , Brennan Fiona , Holmes Ashleigh , O’Flaherty Vincent , Pritchard Leighton , Waters Nicholas R.
Published: January 2021

Current approaches to interpreting 16S rDNA amplicon data are hampered by several factors. Among these are database inaccuracy or incompleteness, sequencing error, and biased DNA/RNA extraction. Existing 16S rRNA databases source the majority of sequences from deposited amplicon sequences, draft genomes, and complete genomes. Most of the draft genomes available are assembled from short reads. However, repeated ribosomal regions are notoriously difficult to assemble well from short reads, and as a consequence the short-read-assembled 16S rDNA region may be an amalgamation of different loci within the genome. This complicates high-resolution community analysis, as a draft genome’s 16S rDNA sequence may be a chimera of multiple loci; in such cases, the draft-derived sequences in a database may not represent a 16S rRNA sequence as it occurs in biology. We present Focus16, a pipeline for improving 16S rRNA databases by mining NCBI’s Sequence Read Archive for whole-genome sequencing runs that could be reassembled to yield additional 16S rRNA sequences. Using riboSeed (a genome assembly tool for correcting rDNA misassembly), Focus16 provides a way to augment 16S rRNA databases with high-quality re-assembled sequences. In this study, we augmented the widely-used SILVA 16S rRNA database with the novel sequences disclosed by Focus16 and re-processed amplicon sequences from several benchmarking datasets with DADA2. Using this augmented SILVA database increased the number of amplicon sequence variants that could be assigned taxonomic annotations. Further, fine-scale classification was improved by revealing ambiguities. We observed, for example, that amplicon sequence variants (ASVs) may be assigned to a specific genus where Focus16-correction would indicate that the ASV is represented in two or more genera. Thus, we demonstrate that improvements can be made to taxonomic classification by incorporating these carefully re-assembled 16S rRNA sequences, and we invite the community to expand our work to augment existing 16S rRNA reference databases such as SILVA, GreenGenes, and RDP.
Spatial-temporal relationship between population mobility and COVID-19 outbreaks in South Carolina: A time series forecasting analysis
Authors: Zeng Chengbo , Zhang Jiajia , Li Zhenlong , Sun Xiaowen , Olatosi Bankole , Weissman Sharon , Li Xiaoming
Published: January 2021

Background

Population mobility is closely associated with coronavirus 2019 (COVID-19) transmission, and it could be used as a proximal indicator to predict future outbreaks, which could inform proactive non-pharmaceutical interventions for disease control. South Carolina (SC) is one of the states which reopened early and then suffered from a sharp increase of COVID-19.

Objective

To examine the spatial-temporal relationship between population mobility and COVID-19 outbreaks and use population mobility to predict daily new cases at both state- and county- levels in SC.

Methods

This longitudinal study used disease surveillance data and Twitter-based population mobility data from March 6 to November 11, 2020 in SC and its top five counties with the largest number of cumulative confirmed cases. Daily new case was calculated by subtracting the cumulative confirmed cases of previous day from the total cases. Population mobility was assessed using the number of users with travel distance larger than 0.5 mile which was calculated based on their geotagged twitters. Poisson count time series model was employed to carry out the research goals.

Results

Population mobility was positively associated with state-level daily COVID-19 incidence and those of the top five counties (i.e., Charleston, Greenville, Horry, Spartanburg, Richland). At the state-level, final model with time window within the last 7-day had the smallest prediction error, and the prediction accuracy was as high as 98.7%, 90.9%, and 81.6% for the next 3-, 7-, 14- days, respectively. Among Charleston, Greenville, Horry, Spartanburg, and Richland counties, the best predictive models were established based on their observations in the last 9-, 14-, 28-, 20-, and 9- days, respectively. The 14-day prediction accuracy ranged from 60.3% to 74.5%.

Conclusions

Population mobility was positively associated with COVID-19 incidences at both state- and county- levels in SC. Using Twitter-based mobility data could provide acceptable prediction for COVID-19 daily new cases. Population mobility measured via social media platform could inform proactive measures and resource relocations to curb disease outbreaks and their negative influences.
Burden of predominant psychological reactions among the healthcare workers and general during COVID-19 pandemic phase: a systematic review and meta-analysis
Authors: Thakur Bhaskar , Pathak Mona
Published: January 2021

Aim

Present systematic review and meta-analysis examined the burden of psychological reactions predominantly anxiety, depression, stress and insomnia during novel COVID-19 pandemic phase among the frontline healthcare, non-frontline healthcare and general.

Methodology

PubMed, EMBASE and SCOPUS were searched for studies between Jan 1, 2020 to May 25, 2020. Brief protocol of the systematic review was registered with the PROSPERO database, (CRD42020186229).Any study that reported the burden of at least one of psychological reactions including anxiety or depression or stress or insomnia was eligible. Heterogeneity was assessed using I2statistic and results were synthesized using random effect meta-analysis.

Results

Out of 52eligible studies, 43 reported anxiety, 43 reported depression, 20 reported stress and 11 reported insomnia. Overall prevalence for anxiety, depression, stress and insomnia were 26.6%, 26.2%,26.2% and 34.4% respectively. Anxiety and depression were found highest among the COVID-19 patients (43.3% and 51.75 respectively). Apart from COVID-19 patients, prevalence of anxiety, depression, stress and insomnia were found highest among the frontline healthcare (27.2%, 32.1%,55.6% and 34.4% respectively) as compared to general healthcare workers (26.9%, 15.7%, 7.0% and 34.0% respectively) and general population (25.9%, 25.9%,25.4% and 29.4% respectively).

Conclusion

Anxiety and depression were found highest among the COVID-19 patients. Apart from COVID-19 patients, the anxiety, depression, stress and insomnia were more prevalent among frontline healthcare workers compared to general. Such increased prevalence is prompting towards the global mental health emergency. Therefore a call of urgent attention and pan-region effective mental-health intervention are required to mitigate these psychological reactions.
Race/ethnicity differences in vitamin D levels and impact on cardiovascular disease, bone health, and oral health
Authors: Thamattoor Ajoy
Published: January 2021

Vitamin D and its biomarker 25(OH)D are known to vary by race/ethnicity with African Americans (AAs) having significantly lower levels than non-Hispanic whites (white Americans). However, AAs have better bone mineral density (BMD) and less arterial calcification, one marker of cardiovascular risk, than white Americans, with some studies showing higher vit. D levels harmful to AAs. This study analyzes NHANES data from 2011 to 2014, NHANES being a biennially published national survey of nearly 10,000 people, with interview, examination, and lab data components. The analyses, using count regression and linear regression models to avoid thresholding of variables, find that abdominal aortic calcification scores rise with 24(OH)D in white Americans, with no statistically significant effect in AAs; femoral BMD falls with 25(OH)D in both groups; osteoporotic fracture risks fall with 25(OH)D in white Americans; and periodontal attachment loss falls with rising 25(OH)D in both groups. Overall, higher 25(OH)D seems protective for oral and skeletal health in white Americans, protective for periodontal health in AAs, negative for their skeletal health, and negative for arterial calcification in white Americans, after controlling for the demographic factors of age and sex, the physiological elements of blood pressure and BMI, the biochemical variables of LDL and cholesterol levels, the socioeconomic indicators of income-to-poverty-level ratio and education levels, and the environmental influence of the season. As periodontitis is low on the disease hazard scale compared to arterial calcification and skeletal health, the results point to a lack of significant protection with rising OH(D) levels in AAs, even after their low base levels, and some harmful impact from those higher levels. That combination should trigger a closer look at the single population-wide vitamin D threshold of 30 to 50 ng/mL currently recommended in the US.
Priming mycobacterial ESX-secreted protein B to form a channel-like structure
Authors: Gijsbers Abril , Vinciauskaite Vanesa , Siroy Axel , Gao Ye , Tria Giancarlo , Mathew Anjusha , Sánchez-Puig Nuria , López-Iglesias Carmen , Peters Peter J. , Ravelli Raimond B. G.
Published: January 2021

ESX-1 is a major virulence factor ofMycobacterium tuberculosis, a secretion machinery directly involved in the survival of the microorganism from the immune system defence. It disrupts the phagosome membrane of the host cell through a contact-dependent mechanism. Recently, the structure of the inner-membrane core complex of the homologous ESX-3 and ESX-5 was resolved; however, the elements involved in the secretion through the outer membrane or those acting on the host cell membrane are unknown. Protein substrates might form this missing element. Here, we describe the oligomerisation process of the ESX-1 substrate EspB, which occurs upon cleavage of its C-terminal region and is favoured by an acidic environment. Cryo-electron microscopy data are presented which show that EspB from different mycobacterial species have a conserved quaternary structure, except for the non-pathogenic speciesM. smegmatis. EspB assembles into a channel with dimensions and characteristics suitable for the transit of ESX-1 substrates, as shown by the presence of another EspB trapped within. Our results provide insight into the structure and assembly of EspB, and suggests a possible function as a structural element of ESX-1.
Humoral and cell-mediated response in colostrum after exposure to severe acute respiratory syndrome coronavirus 2
Authors: Narayanaswamy Vignesh , Pentecost Brian , Alfandari Dominique , Chin Emily , Minor Kathleen , Kastrinakis Alyssa , Lieberman Tanya , Arcaro Kathleen F. , Leftwich Heidi
Published: January 2021

Background

Colostrum provides an immune sharing between a mother and her infant. The transfer in colostrum of antibodies against SARS-CoV-2 and the elicited cytokines may provide crucial protection to the infant. There is limited literature on the immune response to SARS-CoV-2 present in colostrum.

Objective

To evaluate the presence of antibodies specific to SARS-CoV-2 and the associated cytokines in colostrum from women who tested positive for the virus.

Study Design

Between March and September 2020 we obtained bilateral colostrum samples collected on spot cards within 48 hours of delivery from 15 new mothers who had previously tested positive for SARS-CoV-2. Five of these 15 COVID-19 positive women also provided bilateral liquid colostrum within 1-2 days of providing the spot card samples. Archived bilateral colostrum samples collected from 8 women during 2011-2013 were used as pre-COVID-19 controls. All samples were tested for reactivity to the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein using an ELISA that measures SARS-CoV-2 RBD-specific IgA, IgG, and IgM, and for concentrations of 10 inflammatory cytokines (IFNγ, TNFα, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13) using a multiplex electrochemiluminescent sandwich assay.

Results

Bilateral colostrum samples from 73%, 73% and 33% of the 15 COVID-19 mothers exhibited IgA, IgG, and IgM reactivity to RBD respectively. Colostrum samples from two of the 8 pre-pandemic controls showed IgA and IgG reactivity to RBD. Additionally, COVID-19 mothers had significantly higher levels of 9 of the 10 inflammatory markers (all except IFNγ) as compared to the pre-COVID-19 controls. Comparable results were obtained with both the spot card-eluates and liquid samples.

Conclusions

A strong humoral immune response is present in the colostrum of women who were infected with SARS-CoV-2 before delivering. High levels of 9 inflammatory markers were also present in the colostrum. The evolution and duration of the antibody response, as well as dynamics of the cytokine response, remain to be determined. Our results also indicate that future large-scale studies can be conducted with milk easily collected on paper spot cards.
How vaccination and contact isolation might interact to suppress transmission of Covid-19: a DCM study
Authors: Friston Karl J. , Costello Anthony , Flandin Guillaume , Razi Adeel
Published: January 2021

This report describes a dynamic causal model that could be used to address questions about the rollout and efficacy of vaccines in the United Kingdom. For example, is suppression of community transmission a realistic aspiration? And, if not, what kind of endemic equilibrium might be achieved? What percentage of the population needs to be vaccinated? And over what timescale? It focuses on the synergies among (i) vaccination, (ii) the supported isolation of contacts of confirmed cases and (iii) restrictions on contact rates (i.e., lockdown and social distancing). To model these mitigations, we used a dynamic causal model that embeds an epidemiological model into agent-based behavioural model. The model structure and parameters were optimised to best explain responses—to the first and subsequent waves—enabling predictions over the forthcoming year under counterfactual scenarios. Illustrative analyses suggest that the full potential of vaccination is realised by increasing the efficacy of contact tracing: for example, under idealised (best case) assumptions—of an effective vaccine and efficient isolation of infected pre-symptomatic cases— suppression of community transmission would require 50% herd immunity by vaccinating 22% by the end of 2021; i.e., 15 million people or about 50,000 per day. With no change in the isolation of contacts, 36% would require vaccination, i.e., 25 million people. These figures should not be read as estimates of the actual number of people requiring vaccination; however, they illustrate the potential of this kind of model to quantify interactions among public health interventions. We anticipate using this model in a few months—to estimate the average effectiveness of vaccines when more data become available.
Age-seroprevalence curves for the multi-strain structure of influenza A virus
Authors: Vinh Dao Nguyen , Duy Nhat Nguyen Thi , de Bruin Erwin , Thao Vy Nguyen Ha , Nhu Thao Tran Thi , Phuong Huynh Thi , Anh Pham Hong , Todd Stacy , Quan Tran Minh , Le Thanh Nguyen Thi , Nam Lien Nguyen Thi , Hong Ha Nguyen Thi , Kim Hong Tran Thi , Thai Pham Quang , Choisy Marc , Nguyen Tran Dang , Simmons Cameron P , Thwaites Guy E , Clapham Hannah E , Van Vinh Chau Nguyen , Koopmans Marion , Boni Maciej F
Published: January 2021

The relationship between age and seroprevalence provides the simplest and least expensive approach to computing the annual attack rate of an infectious disease. However, many pathogens circulate as multiple serologically distinct strains, with no single assay able to determine seropositivity or seronegativity to an entire clade or family of co-circulating pathogens. An approach is needed to describe population exposure to an antigenically variable group of pathogens without focusing on any particular strain or serotype in the group. In this study, we focus on the two-subtype multi-strain taxonomy of human influenza A virus. We describe a data set of 24,402 general-population serum samples collected in central and southern Vietnam between 2009 to 2015, and assayed for influenza HA1 antibodies to eleven different strains of human influenza A (both H3 and H1 subtypes). We find that a principal components decomposition of the data results in the first principal component PC1 being an appropriate surrogate for seroprevalence (or composite antibody titer) which can be further decomposed for H1 and H3 contribution to the serological profile. Using this approach, we are able to provide the first ELISA-based standardized measurements of serology to reconstruct population exposure history, which correlates well with known influenza epidemiology. Annual attack rates in Vietnam are estimated at 25.6% (95% CI: 24.1% – 27.1%) for H3 and 16.0% (95% CI: 14.7% – 17.3%) for H1, with some variation in location-specific attack rates. The remaining principal components act as descriptors of influenza history and sort the population by birth year. The novel contributions of this analysis are (1) the introduction of dimensionality reduction on human antibody profiles to construct an age-seroprevalence relationship for an antigenically variable pathogen, (2) an analysis of >24,000 individuals, using >260,000 serological data points in total, allowing us to construct age-seroprevalence relationships with the precision of modern big data studies, and (3) a description of long-term attack rates in a non-vaccinated setting showing the natural history of influenza A virus in a densely-populated tropical country.
Saving Lives with Pre-Financed Rules-Based Disaster Aid: Evidence from Mexico
Authors: Valle Alejandro del
Published: January 2021

Developing economies are not disproportionately exposed to natural disasters, but they experience significantly more deaths. Exploiting a discontinuity in the eligibility rules to Mexico’s pre-financed indexed disaster fund (Fonden), I show that accelerated reconstruction of public infrastructure can fully reduce postdisaster excess mortality in the short-run and up to 75 percent two years after. I also find that Fonden’s impact is concentrated in areas with medical infrastructure and among conditions responsive to basic medical interventions. These findings suggest that Fonden operates by restoring access to health services after a disaster. Annual benefits from Fonden amount to 197 thousand life-years saved. (JEL: G22, H12, H84, Q54, I15, O18.)
Mental health of health care workers during the COVID-19 pandemic and evidence-based frameworks for mitigation: A rapid review
Authors: Major Ajay , Hlubocky Fay J.
Published: January 2021

Background

The ongoing COVID-19 pandemic has profoundly affected the mental health of health care workers (HCWs), and optimal strategies to provide psychological support for HCWs are not currently established.

Aims

To rapidly review recently-published literature on the mental health of HCWs during the COVID-19 pandemic.

Methods

Query of all quantitative research through the PubMed database on the mental health of HCWs during the COVID-19 pandemic which utilized validated mental health instruments. 723 articles were screened and 87 articles were included.

Results

Nearly all included studies were cross-sectional, survey-based assessments of the prevalence of and risk factors for mental illness. Only one interventional study was identified. Prevalence of mental health outcomes varied widely: 7.0-97.3% anxiety, 10.6-62.1% depression, 2.2-93.8% stress, 3.8-56.6% post traumatic stress, 8.3-88.4% insomnia, and 21.8-46.3% burnout. Risk and protective factors were identified in personal and professional domains, including degree of COVID-19 exposure, adequacy of protective equipment, and perception of organizational support.

Conclusions

The myriad risk factors for poor mental health among HCWs suggests that a comprehensive psychosocial support model with individual- and organization-level interventions is necessary. Further longitudinal research on specific evidence-based interventions to mitigate adverse mental health outcomes among HCWs is urgently needed as the pandemic continues.